,text,label
0,"Infection in total joint replacement.
 Although a small number of infections in total joint replacements are blood borne from distant sources, most infections appear to have been derived at operation.
 Strenuous attempts to reduce this risk by cleaning the air in the wound environment, coupled with prophylactic antibiotics, have reduced infection rates by an order of magnitude in a decade.
 During that time the potential for exchange arthroplasty in established infection has been shown, and the results are encouraging.
 Rigorous infection control is the key to containing this difficult and expensive problem.
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1,"Analysis of the immune response to lipopolysaccharide. Existence of an interspecies cross-reactive idiotype associated with anti-lipid A antibodies.
 LPS is the major surface glycolipid on gram-negative bacteria.
 In this work, we have idiotypically characterized the antibody response against LPS in different species.
 To do this, we have produced mAb against LPS.
 Binding of many of these antibodies to LPS could be inhibited by LPS and lipid A, indicating that the monoclonals are specific for lipid A, the toxic moiety of the LPS molecule.
 One anti-lipid A antibody, IC9, proved protective against gram-negative bacteremia and endotoxic shock in murine protection models.
 We generated anti-idiotypic antibodies against IC9.
 The binding of several of these anti-Id to IC9 was specifically inhibited by lipid A.
 We used these anti-Id to characterize the anti-LPS response, and the results revealed that the IC9 Id is conserved in different species.
 The importance of an interspecies cross-reactive Id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed.
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2,"Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist.
 BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its capacity to block PAF, endotoxin and recombinant human tumor necrosis factor-alpha (rTNF)-mediated effects.
 In vitro, BN 50739 blocked PAF-induced platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), respectively.
 In the conscious rat, pretreatment (30 min) with BN 50739 (n = 5-13) dose-dependently attenuated PAF-induced hypotension (-5 +/- 5 vs.
 - 43 +/- 2 mm Hg, P less than .01) and shortened the recovery time of mean arterial pressure (22 +/- 13 vs.
 325 +/- 46 sec, P less than .01).
 BN 50739 (10 mg/kg i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 +/- 1 vs.
 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs.
 60%, P less than .05).
 Only partial protection was conveyed by BN 50739 against the hypotensive response to endotoxin (115 +/- 3 vs.
 91 +/- 4 mm Hg, P less than .03).
 Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of plasma thromboxane B2 (21.2 +/- 0.8 vs.
 46.7 +/- 11.8 pg/100 microliters, P less than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs.
 26,430 +/- 3541 U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained unchanged.
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3,"The direct costs of universal precautions in a teaching hospital.
 An analysis of the increase in expenditures for barrier isolation materials before and after the institution of universal precautions at our 900-bed university hospital was used to generate a national estimate of the cost of implementation of the new Centers for Disease Control guidelines.
 Following the institution of universal precautions, use of rubber gloves at our hospital increased from 1.64 million pairs of 2.81 million pairs annually.
 A 5-year review of hospital purchasing and supply records in both inpatient and outpatient areas indicated that the total annual costs for isolation materials increased by $350,900.
 This represented an increase from $13.70 to $22.89 per admission (60%) after adjustment for inflation.
 The cost of isolation materials increased from $98 to $215 per 1000 outpatient visits, an adjusted increase of 92%.
 Two thirds of the increase (64%) was due to rubber gloves and an additional 25% was due to disposable isolation gowns.
 Universal precautions are estimated to have cost at least $336 million in the United States in fiscal year 1989 after adjustment for inflation.
 If expenditures for isolation materials at our medical center are representative, previous estimates may have significantly underestimated costs nationwide.
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4,"Epidemiologic, clinical, and laboratory findings of human ehrlichiosis in the United States, 1988.
 In 1988, the Centers for Disease Control and the Oklahoma State Department of Health identified 40 patients who had a fourfold or greater change in antibody titer in response to Ehrlichia canis.
 The median age of these patients was 42 years, 83% were male, 76% became ill between May and July, and 92% reported recent exposures to ticks.
 Patients resided in or were exposed to ticks in 14 states, including five where ehrlichiosis had not been reported before 1988.
 Thirty-four patients (85%) were hospitalized, and many had serious complications, including acute respiratory failure (seven patients), encephalopathy (six patients), and acute renal failure (four patients).
 Pulmonary infiltrates were demonstrated in 14 patients, cerebrospinal fluid pleocytosis was seen in 10 patients, and elevated levels of serum creatinine were demonstrated in eight patients.
 Two patients, both of whom had preexisting medical problems, died.
 Nonhospitalized patients received tetracycline therapy earlier in the course of their illness than hospitalized patients.
 There was no significant difference in the interval from initiation of antibiotic therapy to the first day of defervescence between patients treated with tetracyclines and those treated with chloramphenicol.
",0
5,"Ecology, life cycle, and infectious propagule of Cryptococcus neoformans 
 Cryptococcus neoformans is a biotrophic smut-like fungus, and the epidemiology of cryptococcosis can mainly be explained by exposure to an infective aerosolised inoculum.
 For C neoformans var gattii it is postulated that the principal infectious propagule is the basidiospore and that exposure to Eucalyptus camaldulensis, the host tree, is required to initiate infection in man and animals.
 C neoformans var gattii may have been exported from Australia by infected seeds of E camaldulensis containing dormant dikaryotic mycelium of the fungus.
 For C neoformans var neoformans both the basidiospore and desiccated encapsulated yeast cells are postulated to act as infectious propagules, the basidiospores showing a seasonal distribution in association with an as yet unidentified host plant, and the encapsulated yeast cells dispersed from accumulations of dried bird (mainly pigeon) droppings which act as a year-round vector.
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6,"Borrelia burgdorferi infection of the brain: characterization of the organism and response to antibiotics and immune sera in the mouse model 
 To learn more about the neurologic involvement in Lyme disease, we inoculated inbred mice with the causative agent of Lyme disease, Borrelia burgdorferi.
 We cultured brains and other organs, and measured anti-B burgdorferi antibody titers.
 We further studied a brain isolate for its plasmid DNA content and its response in vitro to immune sera and antibiotics.
 One strain of B burgdorferi, N40, was consistently infective for mice, and resulted in chronic infection of the bladder and spleen.
 SJL mice developed fewer culture-positive organs and had lower antibody titers than Balb/c and C57Bl/6 mice.
 Organism was cultured from the brain early in the course of infection, and this isolate, named N40Br, was further studied in vitro.
 The plasmid content of N40Br was different from that of the infecting strain, implying either a highly selective process during infection or DNA rearrangement in the organism in vivo.
 N40Br was very sensitive to antibiotics, but only after prolonged incubation.
 Immune sera from both mice and humans infected with B burgdorferi were unable to completely kill the organism by complement-mediated cytotoxicity.
 These data demonstrate that B burgdorferi infects the brain of experimental animals, and is resistant to immune sera in vitro but sensitive to prolonged treatment with antibiotics.
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7,"Cefazolin for hysterectomy prophylaxis.
 Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy.
 For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial.
 Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach.
 Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma.
 The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy.
 Postoperative infection was unrelated to route of cefazolin administration.
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8,"Safety and immunogenicity of Haemophilus influenzae type b oligosaccharide-CRM197 conjugate vaccine in infants aged 15 to 23 months.
 A total of 268 infants aged 15 to 23 months received one dose of a vaccine composed of Haemophilus influenzae type b oligosaccharides covalently linked to the nontoxic diphtheria toxin variant CRM197 (HbOC; HibTITER).
 Side effects associated with vaccination were infrequent, transient, and mild.
 One month after a single vaccination, the anti-H influenzae type b capsular polysaccharide antibody concentration rose from a geometric mean prevaccination level of 0.20 microgram/mL to 13.77 micrograms/mL.
 Of these infants, 99% had a postvaccination level greater than or equal to 1.00 microgram/mL, a level associated with long-term protection.
 The immune response was long-lived: all of the children who were monitored 17 to 27 months after vaccination had concentrations greater than or equal to 1.00 microgram/mL.
 The anti-H influenzae type b capsular polysaccharide antibody generated was predominantly of the IgG isotype and IgG1 subclass.
 The immune sera had bactericidal activity in vitro and conferred passive protection in the infant rat meningitis model.
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9,"Poor compliance with universal precautions: a universal phenomenon?
 An anonymous survey was conducted in order to examine compliance with universal precautions in the Department of Pediatrics at Loyola University Medical Center in Maywood, Illinois.
 Completed questionnaires were returned by 23 faculty members, 29 residents, and 22 medical students.
 Gloves were worn consistently during venipuncture or intravenous catheterization by 13, 7, and 18% of attending physicians, residents, and students, respectively.
 Most physicians wear gloves only occasionally and cite presence of high-risk factors as their selection criterion.
 Interference with the performance of procedures is the most common cause of noncompliance.
 In view of poor compliance with universal precautions, further efforts are needed in order to decrease the incidence of preventable exposure to blood-borne infections.
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10,"A study to assess the efficacy of chemoprophylaxis in the prevention of endoscopy-related bacteraemia in patients aged 60 and over.
 Five hundred and fifteen patients aged 60 and over (mean age 74.7; 278 men and 237 women) underwent routine endoscopic procedures (gastroscopy, bronchoscopy and cystoscopy).
 Alternate patients were given antibiotics before the procedure, as currently recommended, and blood was taken for culture from all patients within five minutes of completion of the procedure.
 Of 74 patients who underwent bronchoscopy, only one culture, from one of 37 controls was positive.
 Of 262 who underwent gastroscopy, cultures were negative in the 130 who received antibiotics but positive in 13 of the 132 controls (9.8 per cent p less than 0.001).
 Cystoscopy was performed in 179; one culture was positive in the 88 given antibiotics (1.1 per cent) compared to 25 in the 91 controls (27.5 per cent; p less than 0.001).
 Bacteraemia rates appear to be low following bronchoscopy (less than 5 per cent) but higher with gastroscopy (10 per cent) and cystoscopy (28 per cent).
 Chemoprophylaxis was effective in reducing these rates in this patient group.
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11,"Health issues at the US-Mexican border 
 With a rapidly growing population, increasing manufacturing activity, and increased interdependence, health issues on the US-Mexican border are demanding greater attention.
 It is unlikely that any other border in the world separates two nations having such variety in health status, entitlements, and utilization.
 Binational initiatives in the areas of environmental health and sanitation are clearly needed.
 Further cooperation between the United States and Mexico in provision of health services is warranted and will probably require enhanced federal funding or subsidies to be successful.
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12,"Breast milk and neonatal necrotising enterocolitis 
 In a prospective multicentre study on 926 preterm infants formally assigned to their early diet, necrotising enterocolitis developed in 51 (5.5%).
 Mortality was 26% in stringently confirmed cases.
 In exclusively formula-fed babies confirmed disease was 6-10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk.
 Pasteurised donor milk seemed to be as protective as raw maternal milk.
 Among babies born at more than 30 weeks' gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk; it was 20 times more common in those fed formula only.
 Other risk factors included very low gestational age, respiratory disease, umbilical artery catheterisation, and polycythaemia.
 In formula-fed but not breast-milk-fed infants, delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis.
 With the fall in the use of breast milk in British neonatal units, exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year.
 About 100 of these infants would die.
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13,"Lipid infusion increases oxygen consumption similarly in septic and nonseptic patients.
 This investigation compared the metabolic effects of lipid infusion in five septic and five nonseptic patients.
 Oxygen consumption was determined by indirect calorimetry over 1 h of rest and during 2 h when Intralipid (20%) was infused [166 mL/h; 23 kJ/min (5.5 kcal/min)].
 Septic patients had a resting metabolic rate 17% higher than that of their nonseptic control subjects and a significant (P less than 0.05) rise (13%) in oxygen uptake was measured in both groups of subjects during the 2-h infusion of lipid.
 Preinfusion respiratory quotient (RQ) was 7% higher in the septic patients (P less than 0.05), and during the infusion period RQ decreased similarly (approximately 6%; P less than 0.05) in both groups.
 Plasma catecholamines were elevated in the septic patients preinfusion and the concentrations remained unaltered during the infusion.
 Norepinephrine rose significantly in the nonseptic group with the lipid infusion.
 The results show that sepsis has little or no influence on the characteristic rise in metabolic rate that occurs with intravenous lipid.
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14,"Methicillin-resistant staphylococcal colonization and infection in a long-term care facility 
 OBJECTIVE: To determine the natural history of colonization by methicillin-resistant Staphylococcus aureus (MRSA) among patients in a long-term care facility.
 We specifically sought to determine if MRSA colonization was predictive of subsequent infection.
 DESIGN: Cohort study.
 SETTING: Long-term Veterans Affairs Medical Center.
 PATIENTS: A total of 197 patients residing on two units were followed with regular surveillance cultures of the anterior nares.
 MAIN OUTCOME MEASUREMENT: The development of staphylococcal infection.
 RESULTS: Thirty-two patients were persistent carriers of MRSA and 44 were persistent carriers of methicillin-susceptible strains (MSSA).
 Twenty-five percent of MRSA carriers had an episode of staphylococcal infection compared with 4% of MSSA carriers and 4.5% of non-carriers (P less than 0.01; relative risk 3.8; 95% CI, 2.0 to 6.4).
 The rate of development of infection among MRSA carriers was 15% for every 100 days of carriage.
 Using logistic regression analysis, persistent MRSA carriage was the most significant predictor of infection (P less than 0.001; odds ratio, 3.7).
 Seventy-three percent of all MRSA infections occurred among MRSA carriers.
 Isolates of MRSA from 7 patients were typed.
 Colonizing and infecting strains had the same phage type in all 7 patients and the same pattern of plasmid EcoRI restriction endonuclease fragments in 5 patients.
 CONCLUSIONS: Colonization of the anterior nares by MRSA predicts the development of staphylococcal infection in long-term care patients; most infections arise from endogenously carried strains.
 Colonization by MRSA indicates a significantly greater risk for infection than does colonization by MSSA.
 The results offer a theoretic rationale for reduction in MRSA infections by interventions aimed at eliminating the carrier state.
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15,"Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates 
 We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae.
 That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations.
 During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice.
 None of these strains was found to be dapsone resistant.
 Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone.
 We have concluded that primary dapsone resistance still does not appear to be a significant problem in California.
 Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed.
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16,"Hepatic abscess. Changes in etiology, diagnosis, and management.
 Most recent reviews of pyogenic hepatic abscess emphasize percutaneous versus open surgical management and devote little time to studying the etiology or the clinical condition of the patient.
 In this study a detailed review was performed with a computerized analysis of multiple clinical parameters in 73 patients treated for pyogenic hepatic abscess during a 17-year period.
 The mean age of the patients was 55 years and 38 of them (52%) were male.
 The mortality rate was comparable for solitary (17%) and multiple (23%) abscesses.
 The likelihood of death was higher with antibiotic treatment alone (45%) or percutaneous treatment (25%) than with surgical treatment (9.5%).
 The primary determinant of outcome, however, was the underlying disease, i.e., malignancy or an immunocompromised patient, rather than solitary versus multiple abscesses.
 In addition the incidence of hepatic abscess seen at this center has doubled from the first half to the second half of the review, reflecting a population of more severely ill patients.
 It is apparent that in current clinical practice several methods of management are effective, and the choice of therapy should be determined by individualized selection.
 The principle of timely diagnosis and prompt institution of treatment appropriate to the specific patient remains the standard of care in this potentially grave disease.
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17,"Staphylococcus aureus infection of human endothelial cells potentiates Fc receptor expression.
 Vasculitis, a recognized complication of staphylococcal-endovascular infections, may result in part, from the expression of FcR by Staphylococcus aureus-infected endothelial cells.
 FcR were measured using [51]Cr labeled SRBC preincubated with rabbit anti-SRBC IgG.
 FcR were not detected on uninfected endothelial cells, but were demonstrated on S.
 aureus infected cells using IgG, but not IgM labeled SRBC.
 FcR expression was dependent on the initial bacterial density (greater than or equal to 8 x 10(7) cfu/ml) and on phagocytosis of the staphylococci, but not on new protein synthesis.
 IgG labeled SRBC binding was blocked by aggregated IgG but not IgM.
 SRBC coated with the F(ab')2 portion of IgG did not bind, thus confirming that FcR were specifically involved in this interaction.
 FcR are expressed after S.
 aureus invasion of human endothelial cells and may contribute to the vasculitis which often accompanies S.
 aureus-endovascular infections.
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18,"Immunization of mice with antibiotic-treated Escherichia coli results in enhanced protection against challenge with homologous and heterologous bacteria.
 The murine immune response to Escherichia coli exposed to subminimal inhibitory concentrations of four antibiotics was investigated.
 Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E.
 coli.
 Mice receiving saline only (controls) died within 24 h.
 The mortality of mice immunized with ciprofloxacin-treated E.
 coli was significantly lower than that of mice immunized with E.
 coli untreated or treated with other antibiotics.
 Sera from mice immunized with ciprofloxacin-treated bacteria showed better bacteriostatic capacity and enhanced production of antibodies that bound to homologous and heterologous lipopolysaccharide isolated from several smooth and rough gram-negative strains.
 The better protection observed in mice immunized with ciprofloxacin-treated E.
 coli was probably due to an enhanced production of antibodies to epitopes on lipopolysaccharide that became better exposed and so more accessible after treatment with ciprofloxacin.
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19,"Instillation of vancomycin into a cerebrospinal fluid reservoir to clear infection: pharmacokinetic considerations.
 Vancomycin instilled in an Ommaya reservoir was used to treat a reservoir-associated infection.
 Vancomycin concentrations in cerebrospinal fluid (CSF) were measured, and derivation of pharmacokinetic parameters allowed tailoring of dosing.
 First-order kinetics were observed.
 The calculated half-life of 3.52 h was less than reported by others, and the apparent volume of distribution (60 ml) was less than anticipated.
 The elimination constant was 0.197 h-1.
 Empiric dosing based on schedules suggested in the literature would have led to high peak and low mean concentrations of intrareservoir vancomycin.
 Patients with reservoir-associated infections have a variety of pathophysiologic conditions that can result in alteration of normal CSF dynamics.
 Pharmacokinetic analysis is useful to individualize dosing and to optimize therapy with intrareservoir vancomycin.
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20,"Contaminant blood cultures and resource utilization. The true consequences of false-positive results.
 To determine whether contaminant blood cultures increase resource utilization, we studied charge and length of stay data for episodes in which blood cultures were obtained from hospitalized adults.
 Compared with 1097 negative episodes, 94 false-positive episodes were associated with increased subsequent length of stay (median, 12.5 vs 8 days) and subsequent total charges (median, $13,116 vs $8731), pharmacy charges (median, $1456 vs $798), and laboratory charges (median, $2057 vs $1426).
 In multivariate analyses, contaminants were independently correlated with 20% and 39% increases in total subsequent laboratory charges and intravenous antibiotic charges, respectively.
 Thus, the true costs of contaminants may greatly exceed those of the test itself.
 Identifying patients at very low risk of bacteremia and attention to sterile technique may reduce costs by decreasing the frequency of contaminants.
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21,"Fluconazole: a new triazole antifungal agent.
 Fluconazole is a fluorine-substituted, bis-triazole antifungal agent.
 Its mechanism of action, like that of other azoles, involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes.
 Activity against Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, and Paracoccidioides brasiliensis has been demonstrated in several animal models.
 Fluconazole can be administered both orally and intravenously.
 Mean peak serum concentrations achieved in human volunteers after 50 and 100 mg (oral) are 3.1 and 7.0 mumols/L respectively.
 Protein binding is low (11 percent) and cerebrospinal fluid to serum ratio is 0.58 to 0.89.
 Serum half-life is long (22-32 hours) and elimination is via renal clearance of unchanged drug.
 Clinical trials and reports support the use of fluconazole in treatment of candidiasis, particularly oropharyngeal and esophageal infections in immunocompromised hosts.
 Fluconazole is also approved for initial and suppressive therapy of cryptococcal meningitis.
 Its role in management of systemic fungal infections will be further defined once results of other comparative trials become available.
 Fluconazole is well tolerated and its effects on steroidogenesis are markedly less than those of ketoconazole.
 Antipyrine clearance is not altered at low doses (50 mg) of fluconazole; however, drug interactions with the use of larger doses can be anticipated with agents such as cyclosporin, phenytoin, oral hypoglycemics, and warfarin.
 Rifampin appears to decrease metabolic clearance of fluconazole.
 Fluconazole is available as oral and parenteral formulations.
 Once-daily doses of 100-400 mg are recommended.
 Dosage reduction is advised for patients with impaired renal function.
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22,"Transmission of 'toxic strep' syndrome from an infected child to a firefighter during CPR.
 Several cases of a toxic shocklike syndrome have been reported in the United States during the past five years in association with Streptococcus pyogenes infection.
 We report a case of a firefighter exposed during attempted CPR to the secretions of an S pyogenes-infected child.
 The firefighter developed an infection of the hand and subsequent febrile illness with hypotension, erythematous rash, renal failure, and hypocalcemia.
 Bacterial isolates of blood and cerebrospinal fluid from the deceased child were identical in type and exotoxin production with isolates grown from the hand wound of the firefighter.
 This is the first reported case of documented transmission of S pyogenes, causing a toxic shocklike syndrome in an emergency medical technician.
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23,"Audit of major colorectal and biliary surgery to reduce rates of wound infection.
 OBJECTIVE--To reduce the rates of wound infection for major colorectal and biliary surgery.
 DESIGN--Prospective audit of antibiotic prophylaxis by keeping copies of typed notes of operations and annotating them at discharge and at first follow up visit and annual review of prophylactic regimen according to yearly rate of wound infection and modification if necessary.
 SETTING--The work of one consultant surgeon working in a district general hospital.
 PATIENTS--All patients having major colorectal resection during 1976-89 (400) and cholecystectomy during 1981-9 (500).
 MAIN OUTCOME MEASURES--Wound infection, defined as any discharge from the wound as detected by observation during inpatient stay and by specific questioning at the first follow up visit six weeks later.
 RESULTS--Serial changes in prophylaxis for colorectal surgery resulted in a progressive reduction in the rate of wound infection from 43% in 1976, with no prophylaxis, to 1% during 1986-9 with single intravenous doses of metronidazole and cefuroxime intraoperatively and with lavage of the peritoneal cavity and wound with 0.1% tetracycline.
 During 1981-7, with no prophylaxis, the rate of infection in biliary surgery was 12% whereas in 1988-9, after the introduction of lavage with tetracycline alone, the rate was reduced to 2%.
 IMPLICATIONS AND ACTION--Simple prospective audit identified the need for changes in antibiotic prophylaxis; successive rounds of audit resulted in improved rates of wound infection, and lavage with 0.1% tetracycline seemed to be a major factor in achieving this.
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24,"Behavior of the pulmonary circulation at rest and during exercise in miliary tuberculosis.
 We studied the hemodynamic behavior of the pulmonary circulation at rest and during exercise in six patients with MTB.
 As a group, in contrast to advanced fibrocaseous tuberculosis, these patients exhibited normal pulmonary hemodynamics at rest and during exercise.
 Only minor abnormalities in pulmonary vascular resistance at exercise (increased PAd-PWP gradient) were noted in two of the patients.
 The increase in Rp during exercise does not appear to be related to acute hypoxic vasoconstruction but rather to functional changes (compliance or recruitment or both) of the pulmonary microvasculature.
 In the genesis of these functional changes, chronic alveolar hypoxia and the inflammatory-fibrotic process might be interacting.
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25,"Rabbit skeletal muscle PO2 during hypodynamic sepsis.
 We measured skeletal muscle tissue PO2 (PtO2) in anesthetized rabbits (n = 7) following infusion of an intravenous bolus of E coli endotoxin.
 An array of surface PO2 microelectrodes was placed over the hindlimb biceps femoris muscle and sufficient readings were obtained to construct a PtO2 histogram.
 Changes in the histogram standard deviation were used to characterize micro-circulatory maldistribution.
 Systemic O2 consumption (VO2) was measured by the expired gas method.
 Cardiac output (Q) and systemic O2 transport (TO2) were calculated.
 Samples of arterial, right atrial (ra), and hindlimb venous blood, from a catheter placed in the infrarenal portion of the vena cava, were simultaneously obtained for measurement of blood gases and saturations.
 Following the administration of endotoxin, there were decreases in Q and TO2 of approximately 50 percent.
 The VO2 initially decreased 23 percent, but returned to baseline levels 30 minutes after endotoxin administration.
 Systemic O2 extraction ratio (ERO2 = VO2/TO2) increased from 0.32 +/- .03 to 0.54 +/- .07 (p less than 0.01), whereas hindlimb ERO2 increased from 0.42 +/- .03 to 0.60 +/- .02 (p less than 0.01).
 The arithmetic mean of the PtO2 histograms decreased after endotoxin infusion (43 +/- 4 to 7 +/- 2 mm Hg; p less than 0.01), but PLO2 remained at baseline levels (35 +/- 2 vs.
 33 +/- 2 mm Hg; p = NS).
 The standard deviation of the PtO2 histograms remained constant during the experiment.
 This finding supports the notion that skeletal muscle microcirculatory heterogeneity does not increase during endotoxin induced hypodynamic sepsis.
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26,"Enhancement of antibiotic concentrations in gastric mucosa by H2-receptor antagonist. Implications for treatment of Helicobacter pylori infections.
 We measured the effects of cimetidine on antibiotic concentrations in the luminal portion of gastric mucosa.
 Guinea pigs were premedicated with cimetidine 4 mg/kg intramuscularly.
 Clindamycin, an antibiotic previously characterized under physiologic pH conditions, was administered intramuscularly and levels measured in serum and tissue using a high-pressure liquid chromatography (HPLC) technique.
 The luminal mucosa concentration of clindamycin at 1 hr (pH 5.9) was fivefold greater compared to the concentrations seen under physiologic (pH 2.0) conditions (81.5 micrograms/g vs 15.9 micrograms/g; P less than 0.05) and 10-fold greater at 2 hr (82.7 micrograms/g vs 8.09 micrograms/g; P less than 0.05).
 There was no difference in peak serum levels between the groups.
 The finding that an antibiotic with characteristics of a base is thus affected by a nonconservative acid inhibitor such as cimetidine supports the presence of an acidic storage pool as proposed by other investigators.
 H2-receptor antagonists may be useful therapeutic adjuncts in H.
 pylori infections by virtue of increasing gastric concentrations of antibiotics that behave as weak bases.
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27,"Computer-generated physician and patient reminders. Tools to improve population adherence to selected preventive services.
 Despite an emerging consensus on appropriate preventive services, a minority of patients receive them.
 A study was undertaken to assess the impact of computer-generated reminders to adult patients, their physicians, or both patients and physicians on adherence to five recommended preventive services: cholesterol measurements, fecal occult blood testing, mammography, Papanicolaou smears, and tetanus immunization.
 During the academic year 1988-1989, all 7397 adult patients and their 49 physicians in a university family medicine clinical practice were randomized by practice group into one of four study groups: control, physician reminders, patient reminders, and both physician and patient reminders.
 Adherence was defined in community-oriented terms: the percentage of patients within each group who had received the preventive service in the recommended interval.
 During the study period, adherence to four of the five preventive services increased significantly, with the largest increases in the physician and patient reminder group: cholesterol measurements increased from 19.5% to 38.1%, fecal occult blood testing 9.3% to 27.0%, mammography 11.4% to 27.1%, and tetanus immunization 23.4% to 35.4% (for each increase, P less than .0001, McNemar's chi-square test).
 In general, increases were greater in blacks and in patients with any form of insurance coverage.
 Computer-based physician and patient reminder systems have great promise of improving adherence to preventive services in primary care settings.
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28,"Person-to-person transmission of Brucella melitensis 
 Human brucellosis is primarily an occupational hazard in the USA; in the Middle East and Africa ingestion of contaminated dairy products is an important route of infection.
 Whether human beings can become infected via person-to-person spread is uncertain.
 During an investigation of a commonsource, laboratory-associated outbreak due to Brucella melitensis, biotype 3, the wife of a microbiologist with serologically proven brucellosis became infected.
 Her blood isolate was indistinguishable from the epidemic strain.
 In the absence of other risk factors, we suggest that sexual intercourse is a possible means of transmission.
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29,"Utility of collecting blood cultures through newly inserted intravenous catheters.
 We prospectively examined the utility of obtaining blood cultures through newly inserted intravenous catheters in 99 children who required both a blood culture and placement of an intravenous catheter.
 Two blood cultures were collected from each patient, one through a freshly inserted intravenous catheter and another through a butterfly needle at a separate venipuncture site.
 A standardized technique of skin preparation with povidone-iodine was used.
 The rate of contamination was 1.0% (95% confidence intervals, 0 to 3.0%) for each method.
 Ten patients had blood cultures yielding true pathogens; in five of these bacteremic children, only one of two sets of blood cultures was positive.
 We conclude that blood cultures can be collected through freshly placed intravenous catheters without increasing the risk of contamination.
 These results also raise the possibility that obtaining two blood cultures instead of a single culture may improve the detection of bacteremia in children.
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30,"Syphilis. A new visit from an old enemy.
 Syphilis has a number of stages, including a latent one, and may be overlooked or misdiagnosed if the possibility is not kept in mind.
 Adequate treatment during the primary stage results in a very high cure rate.
 The latent stage may last for years, during which time a woman may still give birth to an infected child.
 Symptomatic neurosyphilis occurs more often in men than women.
 Penicillin G is preferred to treat all stages of the disease; other antibiotics can be used for patients sensitive to penicillin.
",0
31,"Metabolic changes in patients severely affected by tetanus.
 Metabolic changes in six severely affected tetanus patients suffering from characteristic labile hypertension (maximum systolic blood pressure greater than 200 mmHG, maximum diurnal change in systolic pressure greater than 100 mmHg) were investigated.
 Daily urinary excretion of urea nitrogen increased gradually from the onset of opisthotonus, reached a peak value (10.4 to 15.4 g/m2) in 8 to 20 days, and decreased subsequently.
 Average cumulative excretion in 30 days reached 239.6 +/- 32.7 g/m2.
 Urine catecholamine excretion was elevated in each patient and remained elevated during this period.
 Plasma cortisol and glucagon concentrations were not increased markedly except in a case complicated other systemic bacterial infection.
 Increased protein catabolism in these patients could not be explained by the metabolic effects of 'stressed hormones' alone, and neurologic factors must be considered.
",0
32,"Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats.
 The biologic behavior of human polyclonal immunoglobulin (IgG) radiolabeled with technetium-99m (99mTc) by a novel method, via a nicotinyl hydrazine derivative, was evaluated in rats.
 Technetium-99m- and indium-111-IgG were co-administered to normal rats and biodistribution was determined at 2, 6, and 16 hr.
 The inflammation imaging properties of the two reagents were compared in rats with deep-thigh infection due to Escherichia coli.
 Blood clearance of both antibody preparations was well described by a bi-exponential function: (99mTc-IgG: t1/2 = 3.82 +/- 0.89 and 57.52 +/- 1.70 hr.
 111In-IgG: 3.93 +/- 0.117 and 40.71 +/- 1.26 hr).
 Biodistributions in the solid organs were similar, however, small but statistically significant differences were detected: 99mTc-IgG greater than 111In-IgG in lung, liver, and spleen; 99mTc-IgG less than 111In-IgG in kidney and skeletal muscle (p less than 0.01).
 At all three imaging times, target-to-background ratio and percent residual activity for the two compounds were remarkably similar.
 These studies establish that human polyclonal IgG labeled with 99mTc via a nicotinyl hydrazine modified intermediate is equivalent to 111In-IgG for imaging focal sites of infection in experimental animals.
",0
33,"Modern chemotherapy for brucellosis in humans.
 The most effective, least toxic chemotherapy for human brucellosis is still undecided.
 In vitro, the antibiotics most active against Brucella include the tetracyclines, the aminoglycosides, the aminopenicillins, some cephalosporins, trimethoprim-sulfamethoxazole, erythromycin, rifampin, and some new fluorinated quinolones.
 Because Brucella species are facultative intracellular parasites, the penetration of drugs into and within phagocytes and phagosomes can be problematic and can best be studied in experimental animals or tissue cultures.
 In humans, the effectiveness of various regimens of chemotherapy has been compared best in acute bacteremic infections by assessment of the control of symptoms, bacteremia, complications, and relapses.
 The standard therapy against which all other therapies have been judged is a combination of tetracycline and streptomycin, which is almost universally effective but fails to prevent relapse in 10% of cases.
 A combination of oral doxycycline and rifampin is convenient and currently popular; it is highly effective, with an average relapse rate of only 8.4%.
 Trimethoprim-sulfamethoxazole is less effective in controlling bacteremia and other manifestations: in collected series, 5.7% of cases did not respond and 12% relapsed.
 Drug-resistant Brucella strains are rarely a cause of therapy failure.
 Localized brucellosis poses special problems, often requiring surgery in addition to prolonged combined chemotherapy.
",0
34,"Absence of bacteremia during nasal septoplasty.
 Episodes of staphylococcal bacteremia resulting in metastatic infection have occurred in association with nasal septoplasty, and this has suggested the possible need for antimicrobial prophylaxis.
 In a study designed to measure the actual frequency with which transient staphylococcal bacteremia occurs during nasal septoplasty, 50 healthy patients had blood cultures drawn immediately prior to and during the procedure.
 Although 46% of the 50 patients studied had their nasal mucosa colonized with Staphylococcus aureus, some of the blood cultures obtained from the 50 patients showed bacterial growth.
 The authors conclude that staphylococcal bacteremia during nasal septoplasty is a rare occurrence, and that antimicrobial prophylaxis is unnecessary.
",0
35,"Correlation of gross and microscopic appearance of skin buttons in total artificial heart animals.
 Pneumatic artificial hearts are powered by compressed air that is delivered through percutaneous tubes.
 A stress relief device, termed a skin button, surrounds these tubes as they exit from the recipient's tissues.
 The skin button is designed to protect the tissues from damage and provide a secure material-tissue interface.
 Prevention of superficial and invasive infection is the primary goal of the skin button.
 Eight calves were studied prospectively to identify gross or microscopic infection with the skin button.
 All animals who survived more than sixty days (62-136) had both gross and microscopic evidence of infection.
 All animals surviving less than 60 days (13-43) had no gross evidence of infection but one had subcutaneous microscopic abscess formation.
 No animal died secondary to a skin button infection.
 Skin buttons cannot prevent infection but they can contain the pathologic process in the superficial tissues with no evidence of systemic effects.
",0
36,"The effects of three serotypes of Ureaplasma urealyticum on spermatozoal motility and penetration in vitro [published erratum appears in Fertil Steril 1991 Jun;55(6):1214]
 The effects of incubation of spermatozoa with three serotypes of Ureaplasma urealyticum on spermatozoal motility and penetration in vitro were investigated.
 Using computer-assisted video microscopy, three parameters of motility were determined: individual path lengths, individual vectorial distances, and percentage motility.
 Polyacrylamide gels were used as a medium for assessment of spermatozoal penetration.
 Ureaplasma-infected spermatozoa did have significantly greater path lengths and individual distances than did uninfected controls, but ureaplasma infection had no significant effect on percentage motility.
 Overall, there were no significant differences in penetration distances between ureaplasma-infected spermatozoa and their corresponding uninfected controls.
 Our conclusion is that the ureaplasmas did not adversely affect motility or penetration when spermatozoa were incubated with ureaplasmas for 45 minutes at ureaplasma:sperm ratios as high as 100:1.
",0
37,"Tumor necrosis factor-independent IL-6 production during murine listeriosis.
 We report that TNF, IL-6, and IFN-alpha/beta are produced by mice during either sublethal or lethal Listeria monocytogenes infections.
 The quantities of these cytokines in infected spleens increase and decrease in concordance with bacterial numbers in these organs.
 While all of these cytokines were present in Listeria-infected spleens, only IL-6 and IFN-alpha/beta were found in the peripheral circulation.
 Inasmuch as TNF has been reported to be responsible for the production of IL-6 in vivo following the inoculation of a lethal dose of the Gram-negative bacterium, Escherichia coli (Fong et al., 1989.
 J.
 Exp.
 Med.
 170: 1627), experiments were undertaken to determine whether IL-6 production elicited by the Gram-positive bacterium, L.
 monocytogenes, was also TNF-dependent.
 It was found that the passive immunization of mice with neutralizing antibodies specific for TNF shortly before i.v.
 injection of a lethal or sublethal Listeria inoculum resulted in the complete neutralization of endogenously produced TNF, and in the progressive multiplication of bacteria in infected organs.
 It was also found that the anti-TNF IgG treatment resulted in a progressive increase in the amounts of Listeria-induced IL-6 present in spleen and blood, until the death of the host.
 These findings indicate that Listeria-induced IL-6 production in mice occurs primarily through a TNF-independent pathway, and correlates directly with the severity of the infection.
",0
38,"Lymphoproliferative responses to Borrelia burgdorferi in Lyme disease.
 OBJECTIVE: To compare lymphocyte proliferative responses to Borrelia burgdorferi in healthy controls and patients with Lyme disease.
 PATIENTS: Twelve patients fulfilling case-definition criteria for Lyme disease.
 Twelve healthy volunteers and two newborns served as controls.
 MEASUREMENTS: Antibodies to B.
 burgdorferi were measured by enzyme-linked immunosorbent assay (ELISA).
 Proliferation of peripheral blood lymphocytes cultured for 5 days with B.
 burgdorferi, recall antigens, or pokeweed mitogen was measured by radioactive thymidine uptake.
 RESULTS: Lymphocytes from 11 patients with Lyme disease, 8 healthy seronegative controls, and two newborns showed elevated responses when stimulated with B.
 burgdorferi.
 When a patient and a control were studied on the same day, the patient's lymphocyte response to B.
 burgdorferi exceeded the control's in only 5 of 12 cases.
 Lymphocytes from both patients and controls responded to B.
 burgdorferi isolates from three different sources.
 CONCLUSIONS: Heightened lymphocyte responses to B.
 burgdorferi are found in patients with Lyme disease but elevated responses also frequently occur in healthy controls.
 At present, the interpretation of a positive lymphocyte response to B.
 burgdorferi would be difficult in ambiguous clinical situations.
",0
39,"Effect of steroids on cerebrospinal fluid penetration of antituberculous drugs in tuberculous meningitis.
 Sixteen patients with oral isoniazid, pyrazinamide, rifampin, and intramuscular streptomycin for tuberculous meningitis were studied.
 The concentrations of isoniazid, pyrazinamide, rifampin, and streptomycin in cerebrospinal fluid (CSF) obtained 3 hours after administration were 2.40, 34.78, 0.29, and 3.78 micrograms/ml, respectively.
 The CSF concentrations of isoniazid and pyrazinamide were well above the minimum inhibitory concentration for Mycobacterium tuberculosis.
 Concentrations of rifampin and streptomycin were above the minimal inhibitory concentration initially but declined below the minimal inhibitory concentration at later times.
 The CSF penetration of isoniazid, pyrazinamide, rifampin, and streptomycin was about 89%, 91%, 5%, and 20%, respectively.
 In eight patients who received antituberculous drugs in combination with steroids, the mean CSF and serum concentrations, as well as CSF/serum ratios at various intervals of treatment, were not statistically different (p greater than 0.05) from those of the eight patients who did not receive steroids.
",0
40,"Endothelin immunoreactivity in mice with gram-negative bacteraemia: relationship to tumour necrosis factor-alpha.
 1.
 To investigate the role of endothelin in Gram-negative bacteraemia and the possible involvement of tumour necrosis factor-alpha in its pathophysiology, we measured plasma and tissue (lung, kidney and spleen) immunoreactive endothelin levels in Gram-negative bacteraemic mice, with and without passive immunization by anti-(tumour necrosis factor-alpha) antibody.
 2.
 Plasma immunoreactive endothelin levels were greatly increased after the Escherichia coli injection.
 Pretreatment with anti-(tumour necrosis factor-alpha) antibody did not suppress elevated plasma immunoreactive endothelin levels (P greater than 0.1).
 3.
 Lung tissue immunoreactive endothelin levels in mice were increased 16 h after the E.
 coli injection and were not affected by prior passive immunization with anti-(tumour necrosis factor-alpha) antibody.
 Immunoreactive endothelin in spleen and kidney was undetectable (less than 34 fmol/g wet weight).
 4.
 Injection of rMu tumour necrosis factor-alpha into mice did not increase plasma immunoreactive endothelin levels.
 5.
 Antibody to endothelin given 30 min after a 90% lethal dose challenge with E.
 coli did not affect mortality.
 6.
 We conclude that the rise in plasma and tissue endothelin that occurs in Gram-negative bacteraemia is independent of tumour necrosis factor-alpha.
",0
41,"Non-invasive assessment of the cardiovascular eicosanoids, thromboxane A2 and prostacyclin, in randomly sampled males, with special reference to the influence of inheritance and environmental factors.
 1.
 We studied, in a random sample of 385 nonsmoking men born in 1968-1969 and 31 men born in 1913 or 1923, whether inheritance and environmental factors influenced platelet activity and vessel wall prostacyclin formation, as reflected non-invasively by the urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 (2,3-dinor-thromboxane B2, Tx-M) and prostacyclin (2,3-dinor-6-keto-prostaglandin F1 alpha, PGI-M), respectively.
 2.
 Fathers of young men with high platelet activity did not excrete more Tx-M than fathers of young men with low platelet activity.
 Men born in 1913 or 1923 displayed higher Tx-M (563 versus 128 pg/mg of creatinine, P less than 0.001) and PGI-M (163 versus 130 pg/mg of creatinine, P less than 0.01) excretion than those born in 1968-1969.
 Excretion of both Tx-M and PGI-M was correlated to the urinary output of noradrenaline and adrenaline.
 3.
 Well-trained subjects did not differ in their excretion of Tx-M or PGI-M from those who did not exercise regularly.
 A recent acute infection was also unrelated to the excretion of Tx-M or PGI-M.
 PGI-M excretion was, however, significantly correlated to Tx-M excretion (r = 0.51, P less than 0.001).
 4.
 This study provides the first non-invasive evidence that advancing age and sympathoadrenal tone are positively correlated to platelet activity in randomly sampled men, and that paternal inheritance, physical fitness and recent infection lack correlation to platelet activity.
",0
42,"Malassezia furfur fungemia associated with central venous catheter lipid emulsion infusion.
 Malassezia furfur has been associated with fungemias in infants after prolonged intravenous lipid emulsion alimentation.
 Most cases of M.
 furfur fungemia reported in the literature involved neonates and required catheter removal for cure.
 M.
 furfur is probably an underreported problem in neonates as well as adults with central venous catheters, receiving lipid emulsions, because the organism requires selective enrichment media for growth, for example, Sabouraud's dextrose agar with sterile olive oil overlay.
 This case report of M.
 furfur fungemia in a neonates is unique because the neonate recovered on discontinuation of the lipid emulsion, without removal of the central venous catheter.
",0
43,"Comparison of functional activities between IgG1 and IgM class-switched human monoclonal antibodies reactive with group B streptococci or Escherichia coli K1.
 The influence of valence and heavy chain on antibody activity was investigated using transfectoma-derived, class-switched IgG1 and IgM human monoclonal antibodies (MAbs) reactive with the bacterial pathogens Escherichia coli K1 and group B Streptococcus species.
 IgG-IgM pairs were compared in vitro for antigen binding and opsonic activities and in vivo for protective efficacy in neonatal rats.
 For the anti-E.
 coli pair, the IgM MAb was 1000-fold more potent in all assay formats.
 Importantly, the 50% protection dose (PD50) of the IgM MAb was 10-20 ng/rat, while 100 micrograms of the IgG MAb was only minimally protective.
 For the group B streptococcal MAbs, the IgM was 100- and 4500-fold more potent in binding and opsonization assays, respectively.
 However, while 20 micrograms of IgM protected neonatal rats, 100 micrograms of IgG MAb was partly protective.
 These experiments demonstrate the utility of recombinant DNA technology for creating a panel of antibodies that may aid in selecting potential immunotherapeutic candidates.
",0
44,"Macrophage- and oxidant-mediated inhibition of the ability of live Blastomyces dermatitidis conidia to transform to the pathogenic yeast phase: implications for the pathogenesis of dimorphic fungal infections.
 Conidia, produced by the mycelial phase of dimorphic fungi, are thought to represent the infectious form of the organism but must complete a transition to the tissue-invasive, yeast-like phase for infection to ensue.
 Preventing such transition should effectively eliminate pathogenicity.
 Using Blastomyces dermatitidis as a target, murine bronchoalveolar macrophages preferentially blocked phase transition after 4 h of incubation with conidia, relatively sparing the ability of conidia to produce hyphae.
 H2O2, in relatively high concentrations, demonstrated the same activity.
 The effects of H2O2 seem irreversible, since H2O2-treated conidia that germinated at 48 h at 25 degrees C were still unable to produce yeasts over the next 5 days when incubated at 37 degrees C.
 Catalase could not reverse the macrophage-induced inhibition of phase transition, suggesting that nonoxidative defense mechanisms may be operative in vivo.
 Since conidia do not form mycelia at temperatures found in mammalian hosts, these effects may represent a novel host defense mechanism against dimorphic fungal pathogens.
",0
45,"Three new serovars of Chlamydia trachomatis: Da, Ia, and L2a.
 Three new Chlamydia trachomatis serovars were identified by several monoclonal antibodies in the microimmunofluorescence test and are proposed to be called Da, Ia, and L2a.
 Each was clearly distinguishable from the related serovars D, I, and L2.
 To date, 7, 41, and 4 isolates of the respective serovars have been identified.
 Each appears to be distributed worldwide.
 The findings meet previously established criteria for establishment of new serovars.
",0
46,"Molecular epidemiologic techniques in analysis of epidemic and endemic Shigella dysenteriae type 1 strains.
 During 1988 the number of Shigella dysenteriae type 1 infections reported in the United States increased fivefold.
 To determine if recent isolates from Mexico were related to those that caused epidemics of dysentery worldwide, Southern hybridization analysis was done with Shiga toxin and ribosomal RNA gene probes.
 Western hemisphere and Eastern Hemisphere strains differed by the size of a single EcoRI fragment carrying the Shiga toxin genes.
 Three ribosomal DNA (rDNA) patterns were observed, which correlated with the strain's continental origin for 81 of 83 isolates tested.
 Together the Shiga toxin and rDNA probe results indicated that recent Mexican isolates were chromosomally similar to earlier Central American isolates and distinct from Asian and African strains.
 This suggests there has been no significant exchange of organisms between continents in recent decades and that the 1988 outbreak in Mexico was caused by strains present in Central America since at least 1962.
",0
47,"Combined use of released proteins and lipopolysaccharide in enzyme-linked immunosorbent assay for serologic screening of Yersinia infections.
 An ELISA for the screening of serum antibodies to Yersinia species was developed using plasmid-encoded released proteins of Yersinia enterocolitica O:8 and lipopolysaccharide of Y.
 enterocolitica O:3 as a combined antigen.
 Of 43 sera from patients infected with one of six different Yersinia serotypes, 40 (93%) were positive in this assay.
 When tested using six serotype-specific ELISAs with the corresponding Yersinia bacteria as antigens, 38 (88%) were positive.
 This screening ELISA detects antibodies to all virulent yersiniae in one assay and offers the possibility for diagnosis of infections caused by Yersinia serotypes seen only occasionally and not usually included in the serotype-specific ELISAs.
 Thus, this ELISA offers a substantial advantage by saving time and money in routine laboratory work.
",0
48,"Indium-111-labeled leukocyte scan in detection of synthetic vascular graft infection: the effect of antibiotic treatment.
 To determine the sensitivity and specificity of the indium-111-(111In) labeled leukocyte scan for prosthetic vascular graft infection in patients treated with antibiotic therapy, a retrospective study was performed.
 Of 41 consecutive 111In-labeled leukocyte scans performed to evaluate possible vascular graft infection, 23 scans were performed in patients treated with antibiotics.
 The average duration of antibiotic therapy was 21 days.
 Twelve positive and 11 negative scans for graft infection were found.
 By surgical and autopsy correlation of all positive cases, and clinical correlation (of all negative cases), there were 10 true-positive, 11 true-negative, 2 false-positive, and no false-negative scans for graft infections, for an overall sensitivity of 100% and specificity of 85%.
",0
49,"Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group 
 BACKGROUND.
 HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia.
 METHODS.
 To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection.
 The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin).
 Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol.
 RESULTS.
 Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture.
 For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014).
 For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017).
 Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients.
 Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038).
 No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia.
 For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24).
 All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected.
 CONCLUSIONS.
 HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.
",0
50,"Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients.
 Two rapid group B streptococcal antigen tests were compared with nonselective blood agar culture in 1062 unselected patients admitted to labor and delivery.
 Vaginal specimens taken from each patient on admission were used to perform each of two rapid tests and corresponding cultures.
 The rapid tests were the Streptex latex agglutination assay and the Equate Strep B test, which uses a solid-phase immunoassay.
 Overall, 105 patients (9.9%) had at least one positive culture.
 The sensitivities for the rapid tests were 15.1% for Streptex and 21.5% for Equate.
 Specificities were 99.3 and 98.7%, respectively.
 Sensitivity was minimally increased in the setting of ruptured membranes for both tests.
 Likewise, use of separate swabs for streaking the culture plate and performing the rapid test increased the sensitivity, but this was not significant for either test.
 In control experiments, the limit of sensitivity of both rapid tests was 5 x 10(6) colony-forming units.
 We conclude that at present, these tests are not sensitive enough for routine use in this type of clinical setting.
",0
51,"Use of the Pediatric Risk of Mortality score to predict nosocomial infection in a pediatric intensive care unit.
 OBJECTIVE: To define infection rates in patients with Pediatric Risk of Mortality (PRISM) scores greater than and less than 10 on admission to the pediatric ICU (PICU).
 DESIGN: Descriptive.
 SETTING: An 18-bed PICU admitting patients of all ages except nonsurgical neonates; within a 585-bed tertiary care pediatric hospital.
 PATIENTS: Patients admitted to the PICU from July 1987 to February 1988 inclusive.
 Of 685 admitted, 480 were followed for greater than or equal to 72 hr.
 METHODS: The baseline state of the patients on admission was determined by a designated intensivist using the PRISM score.
 Other variables included age, length of stay, and hospital day of onset of infection.
 Infections were identified by a designated intensivist who undertook prospective daily bedside observation, chart, radiographic, and laboratory review.
 MEASUREMENTS AND MAIN RESULTS: Equal portions of patients had PRISM scores less than and greater than 10.
 Significantly more infections occurred in the high PRISM population (10.8% vs.
 3.4%, p less than .001).
 This association held through age, service, and length of stay.
 Sensitivity, specificity, positive and negative predictive values of a PRISM score greater than 10 were 75%, 53%, 11%, and 97%, respectively.
 Bacteremias accounted for 36% of infections, skin/eye/drain site 22%, respiratory 16%, wound 15%, and urine 9%.
 The most prevalent organisms were coagulase-negative staphylococci (32%), Pseudomonas aeruginosa (23%), Candida sp.
 (20%), and S.
 aureus (9%).
 CONCLUSIONS: A PRISM score greater than 10 on PICU admission characterizes a population within the PICU at increased risk of infection.
 However, 93% of patients did not develop infection and thus, a negative predictive value of 97% yields little additional information.
",0
52,"Systemic and muscle oxygen uptake/delivery after dopexamine infusion in endotoxic dogs 
 BACKGROUND AND METHODS: This study was designed to test whether dopexamine, a dopaminergic and beta 2-adrenergic agonist, would a) increase systemic oxygen delivery (DO2) in endotoxic dogs, and b) interfere with the ability of resting skeletal muscle to extract oxygen.
 There were three treatment groups (n = 6 in each group): control, endotoxin alone (E) 4 mg/kg iv, and endotoxin + dopexamine (E + D) 12 micrograms/kg.min.
 Data were analyzed between and within groups by split-plot analysis of variance with significance of identified differences tested post hoc by Duncan's multiple range test.
 Donor RBC and dextran were used after endotoxin to maintain adequate perfusion pressures, with Hct kept near 40%.
 Blood flow to left hindlimb muscles was decreased in controlled steps of 15 min each after stabilization.
 RESULTS: In E group, cardiac output (Qt), mean arterial pressure (MAP), systemic DO2, and oxygen uptake (VO2) decreased despite blood volume expansion.
 In E + D group with similar volume expansion, dopexamine maintained Qt, systemic DO2, and VO2 near the control levels, although MAP and systemic vascular resistance were reduced.
 In comparison with control subjects, endotoxin increased critical DO2 in the isolated limb muscles from 4.6 to 7.
 mL/kg.min and decreased critical oxygen extraction from 81% to 68%.
 The pressure/flow relationship in the limb became flattened, indicating loss of vascular reactivity.
 In the E + D group, there was no further change in the pressure/flow curve nor in the critical oxygen extraction level.
 CONCLUSIONS: Dopexamine provided hemodynamic support for endotoxic dogs, thereby increasing total DO2 and VO2, while not altering oxygen extraction in the muscle.
",0
53,"Gram-negative infection increases noninsulin-mediated glucose disposal.
 Peripheral glucose uptake can occur by either insulin- or noninsulin-mediated mechanisms, and the two pathways appear to be regulated independently.
 Using the euglycemic hyperinsulinemic clamp technique, we have previously demonstrated that sepsis induces whole body insulin resistance.
 The purpose of the present study was to determine whether infection also alters noninsulin-mediated glucose uptake (NIMGU) and, if so, which tissues are affected.
 Studies were performed in chronically catheterized conscious rats under either basal (6 mM glucose, 30 microU/ml insulin) or insulinopenic conditions to determine NIMGU.
 Hypermetabolic sepsis was induced by sc injections of live Escherichia coli, and 24 h later a tracer amount of [U-14C]deoxy-2-glucose was injected for the determination of the in vivo glucose metabolic rate (Rg) in selected tissues.
 Our results indicate that NIMGU is the predominant route of glucose disposal in both septic and nonseptic rats, accounting for 79-83% of the total rate of glucose disposal.
 Because the rate of whole body glucose disposal was increased by sepsis, the absolute rate of NIMGU was 46% higher in septic rats than in nonseptic animals.
 This increase was the result of the elevated Rg in liver, spleen, ileum, and lung.
 Sepsis also increased whole body insulin-mediated glucose uptake by 88% under basal conditions, and this was due to an enhanced glucose uptake by muscle and skin.
 In insulinopenic animals in which the plasma glucose concentration was elevated to 17 mM, whole body glucose disposal increased by 107% in nonseptic animals, but by only 32% in septic rats.
 The hyperglycemic-induced increment in organ Rg was smaller in all tissues examined from septic animals.
 However, the absolute rate of whole body and tissue glucose utilization was not different between the two groups.
 These results indicate that gram-negative infection increases whole body NIMGU, which results from an enhanced rate of glucose utilization by tissues rich in mononuclear phagocytes, including the liver, spleen, ileum, and lung, but not by muscle.
",0
54,"Terconazole for the treatment of vulvovaginal candidiasis.
 A double-blind, randomized trial was conducted to evaluate the efficacy and safety of terconazole for vulvovaginal candidiasis.
 Treatment consisted of daily intravaginal application of one of the following regimens: 80-mg terconazole suppositories for 3 days, miconazole nitrate suppositories for 7 days or placebo suppositories for 7 days.
 The terconazole and miconazole nitrate groups had significantly higher therapeutic cure rates than did the placebo group.
 Evaluation of vaginal secretions with microscopic examination showed no evidence of leukocyte proliferation.
 Proline aminopeptidase activity, present in patients who have bacterial vaginosis, could not be detected in the vaginal secretions from patients with yeast vulvovaginitis.
",0
55,"The challenge of prophylaxis in cesarean section in the 1990s.
 Physicians have evaluated the role of antibiotics in the prevention of perioperative infections since these drugs were discovered, but not until it was determined that antibiotics prevented staphylococcal wound infections in the animal model did surgeons consider their use for prophylaxis.
 In the 1970s, improved techniques in isolating and identifying anaerobic microorganisms and the unacceptably high incidence of infection-related complications convinced obstetricians to study, and ultimately accept, the use of perioperative antibiotic administration to prevent these infections.
 Recent progress has included refinement of the guidelines for patient selection and drug regimens.
 Although a single dose of an antibiotic given to the patient undergoing primary cesarean section has been demonstrated to be effective prophylaxis when administered after clamping the umbilical cord, this practice has not been widely accepted.
 With the discovery of cephamycins the role of these broad-spectrum antibiotics in obstetric and gynecologic surgery was investigated.
 One of the studies compared the efficacy of cefmetazole with that of cefotetan in preventing post-cesarean section infection.
 Eighteen patients in each group received a 2-g dose of one of the two drugs when the umbilical cord was clamped.
 Predetermined elevations in temperature were used to evaluate the presence of ensuing infections.
 Four subjects in each group developed some type of morbidity.
 Postoperative complications included wound infection, endometritis, bladder infection and cellulitis.
 Cefmetazole and cefotetan seemed equally effective in preventing post-cesarean section infections.
",0
56,"Cefmetazole and cefonicid. Comparative efficacy and safety in preventing postoperative infections after vaginal and abdominal hysterectomy.
 A single 1-g dose of cefmetazole was compared with a single 1-g dose of cefonicid for prophylaxis in vaginal and abdominal hysterectomy to determine their efficacy and safety.
 The antibiotics were administered intramuscularly 15-90 minutes before the incision was made.
 Cefmetazole and cefonicid had similar activity against most of the aerobic organisms recovered, but cefmetazole was significantly more active against anaerobic gram-negative microorganisms.
 The patterns of regrowth of vaginal flora were similar in the two treatment groups.
 Patient demographic characteristics and surgical procedures were similar in both groups.
 The difference in primary prophylactic failure (e.g., cuff cellulitis) with the two study drugs (1 of 53 [1.9%] with cefmetazole and 2 of 28 [7.1%] with cefonicid) did not reach statistical significance, and the results were similar for the two routes of hysterectomy.
 Cefmetazole, at a dose of 1 g intramuscularly preoperatively, is a safe and effective agent for prophylaxis during hysterectomy.
",0
57,"Changes in the differential white blood cell count in screening for group B streptococcal sepsis.
 We compared several previously defined scoring systems using white blood cell indices as part of a retrospective evaluation of infants with early onset Group B streptococcal (GBS) sepsis.
 Nineteen newborns were diagnosed with GBS sepsis between January, 1988, and April, 1990.
 Case controls (n = 33) were selected from patients admitted to the Neonatal Intensive Care Unit for suspected sepsis.
 Complete blood counts obtained at admission and between 12 and 24 hours of age were reviewed.
 There was a significant change in the ratio of immature to total neutrophils in the GBS group over time.
 Scoring systems for neonatal sepsis by Manroe et al., Rodwell et al.
 and Spector et al.
 had poor sensitivity, specificity, positive predictive value and negative predictive value when initial white blood cell count criteria were used, but scoring systems by Manroe and Rodwell were 100% sensitive and had 100% negative predictive value when applied to the repeat white blood cell count.
 We conclude that a single early complete blood count may not be an adequate screening tool for early onset GBS sepsis and should not be used to rule out infection.
 Optimal screening for GBS sepsis requires a repeat complete blood count within the first 24 hours of age.
",0
58,"Cytokines and glucocorticoids in the regulation of the ""hepato-skeletal muscle axis"" in sepsis.
 Sepsis results in muscle catabolism and peripheral release of amino acids with a concomitant uptake of amino acids in liver and acute-phase protein synthesis.
 In addition, there appears to be a cytokine-induced process that blocks muscle amino acid uptake in sepsis, further diverting amino acids from the periphery to the liver.
 In this article, evidence that cytokines and glucocorticoids play an important role in the regulation of hepatic and muscle protein metabolism during sepsis is presented.
",0
59,"An outbreak of tuberculosis in a shelter for homeless men. A description of its evolution and control.
 An outbreak of tuberculosis at a shelter for homeless men was studied in detail to further the understanding of the epidemiology of tuberculosis in this setting.
 The shelter provides evening accommodations for men aged 50 yr and older.
 The capacity is approximately 200 clients, and the client pool is approximately 1,000 men/yr.
 During a 6-wk period in December 1986 and January 1987, seven cases of tuberculosis were diagnosed in shelter clients.
 Nine cases were reported in clients during the preceding 12 months, and four cases in the year previous to that.
 The majority of outbreak cases were pulmonary tuberculosis, sputum smear positive.
 Drug resistance was rare.
 Phage typing of 15 Mycobacterium tuberculosis isolates revealed one predominant type and four other types.
 The goals of the control plan (and the steps taken to achieve them) were to render known infectious cases noninfectious (directly observed therapy); to find undiagnosed infectious cases (repetitive mass screenings); to protect exposed clients (repetitive tuberculin skin testing and isoniazid preventive therapy); and to make the shelter environment safe (exclude infectious, noncompliant clients and improve the shelter's ventilation system).
 Implementation of this plan rapidly terminated the outbreak; following the first mass screening in January 1987, at which six asymptomatic cases were detected, only five additional cases occurred in shelter clients during a 2-yr period of follow-up.
 The investigation suggested that the outbreak evolved during 1986 as a result of the presence at the shelter of an increasing number of men with undiagnosed infectious pulmonary tuberculosis.
",0
60,"Role of prophylactic antibiotics in uncontaminated neck dissections.
 The use of perioperative prophylactic antibiotics in uncontaminated head and neck surgery remains controversial.
 We performed a retrospective analysis of 192 patients undergoing uncontaminated neck dissections from 1976 to 1989.
 Wound infection developed in 10% (10/99) of patients who did not receive antibiotics, while only three (3.3%) of 93 patients who received antibiotics developed infections.
 This difference was not statistically significant.
 We correlated the use of flaps, length of surgery, prior radiation treatment, and postoperative complications with rate of wound infection.
 The difference was not statistically significant for any of these variables.
 Our beta error was, however, greater than 0.2.
 Our data do not demonstrate efficacy of prophylactic antibiotics in uncontaminated neck dissections with statistical significance; however, a trend exists suggesting its possible value.
",0
61,"Helicobacter pylori infection rates in relation to age and social class in a population of Welsh men.
 The seroprevalence of IgG antibodies to Helicobacter pylori was determined using a standard enzyme linked immunosorbent assay in a population of 749 randomly selected men, aged 30-75 years, from Caerphilly, South Wales.
 The overall prevalence of H pylori was 56.9%, increasing sharply in middle age from 29.8% in those aged 30-34 to over 59% in those aged 45 or older (p less than 0.0001).
 Age standardised seroprevalence rates were lowest in combined social class categories I and II (49.2%), intermediate in categories IIIN and M (57.5%), and highest in categories IV and V (62.2%) (p = 0.01).
 In those aged 30-34 years, the prevalence rate for those in combined social class categories IV and V was 57.9% - double the rate for social class categories IIIM and N (28.3%) and five times the prevalence rate in those in social class categories I and II (11.1%).
 These differences in the infection patterns of H pylori by social class are consistent with patterns of peptic ulcer disease and gastric cancer.
",0
62,"Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral NG-monomethyl-L-arginine.
 Murine macrophage oxidation of L-arginine guanidino nitrogen to nitrite/nitrate yields an intermediate effector, possibly nitric oxide, with antimicrobial activity.
 Total body nitrogen oxidation metabolism (NOM) was measured in vivo by determining the urinary nitrate excretion of mice ingesting a chemically defined nitrite/nitrate-free diet.
 As reported previously, mycobacterial infection with bacillus Calmette-Guerin led to a large increase in urinary nitrate excretion.
 This increase was temporally related to macrophage activation in vivo.
 The substrate for macrophage nitrogen oxidation metabolism in vitro, L-arginine, was deleted from the diet without ameliorating the urinary nitrate excretion response induced by BCG.
 This suggested that L-arginine was synthesized endogenously because there are no other known natural substrates for NOM.
 A competitive inhibitor of NOM, the L-arginine analog, NG-monomethyl-L-arginine was fed to mice in their drinking water.
 NG-monomethyl-L-arginine ingestion blocked both basal and bacillus Calmette-Guerin-induced urinary nitrate excretion over a 2-4 week time span.
 These experimental conditions should prove useful for further investigation on the role of macrophage NOM in host defense against intracellular microorganisms.
",0
63,"Nosocomial Pseudomonas pickettii bacteremias traced to narcotic tampering. A case for selective drug screening of health care personnel 
 Three patients in a university hospital developed nosocomial infusion-related Pseudomonas pickettii bacteremia.
 Investigation identified six additional patients who had received intravenous fluid contaminated by P pickettii but did not become ill.
 All nine patients had had surgery, and each of these patients but only nine of 19 operated-on control patients had received intravenous fentanyl citrate in the operating room; the mean dose given to the nine case patients was far greater than that given to control patients.
 Fentanyl in 20 (40%) of 50 predrawn 30-mL syringes was shown to be contaminated by P pickettii.
 Contamination was caused by theft of fentanyl from predrawn synringes and replacement by distilled water contaminated by P pickettii.
 Narcotic theft by health care personnel may cause patients to suffer pain needlessly and can also result in dire unanticipated consequences, such as nosocomial bacteremia.
 Whereas drug testing in the workplace is highly controversial, we believe that testing of health care personnel is indicated when drug abuse or theft is suspected.
",0
64,"Recombinant fusion protein identified by lepromatous sera mimics native Mycobacterium leprae in T-cell responses across the leprosy spectrum.
 Pooled polyvalent sera from lepromatous leprosy patients were used to screen a lambda gt11 recombinant DNA expression library of Mycobacterium leprae in order to identify the relevant antigens recognized by the human immune response.
 Of the 300,000 phages screened, 4 clones were identified that coded for fusion proteins of the same molecular mass.
 The fusion protein from clone LSR2 was tested for immunoreactivity in assays using peripheral blood cells and sera from 11 laboratory personnel and 105 patients across the leprosy spectrum.
 LSR2 protein appears to be predominantly a T-cell antigen.
 It evokes similar lymphoproliferative responses as the native bacillus both at the individual level and in the leprosy spectrum as a whole.
 Though only 50% of patient sera with anti-M.
 leprae antibodies reacted with the fusion protein, the pattern of reactivity in the antibody responses was also similar for the various clinical types.
 The coding regions of clones LSR1 and LSR2 are identical.
 They show no homology with sequences stored in data banks and encode a protein of 89 amino acids with a calculated molecular mass of approximately 10 kDa.
",0
65,"Clinical spectrum of fungal infections after orthotopic liver transplantation.
 During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%).
 Candida species accounted for 83.5% of cases.
 Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16).
 The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation.
 Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications.
 Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%).
 Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.
",0
66,"Effect of dietary fish oil on plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha levels in septic rats.
 Increased mortality from sepsis is associated with high levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha).
 Linoleic acid, an n-6 essential fatty acid, is the usual precursor of TXB2 and PGF1 alpha, while fish oil is rich in n-3 essential fatty acid, the precursor of less active moieties.
 Rats were fed chow, an essential fatty acid-deficient diet, or an essential fatty acid-deficient diet supplemented with linoleic acid or fish oil for 2 weeks.
 The animals then underwent a sham operation or cecal ligation and puncture to induce sepsis.
 Six hours later, blood was obtained for analysis.
 The chow and linoleic acid diets produced significant (twofold to fivefold) increases in levels of both TXB2 and PGF1 alpha after sepsis.
 The essential fatty acid-deficient diet and fish oil diet protected against increases in levels of TXB2 or PGF1 alpha during sepsis.
 Dietary restriction of linoleic acid or fish oil supplementation may play an important role in altering the inflammatory mediator response to sepsis.
",0
67,"Hepatic extraction of indocyanine green is depressed early in sepsis despite increased hepatic blood flow and cardiac output.
 Although active hepatocellular function is depressed during sepsis, it is not known whether this occurs in the very early stages of sepsis and whether it is due to depressed cardiac output or hepatic blood flow.
 To study this, rats were subjected to sepsis by cecal ligation and puncture and hepatocellular function was determined at various intervals thereafter by assessing the ability of the liver to clear different doses of indocyanine green.
 The indocyanine green concentration was continuously measured in vivo with a fiberoptic catheter and an in vivo hemoreflectometer.
 Maximal velocity and kinetic constant of the clearance of indocyanine green, hepatic blood flow, and cardiac output were determined in experimental and sham-operated rats.
 The results demonstrate that hepatic blood flow and cardiac output increased 2 to 10 hours after cecal ligation and puncture, while hepatocellular function (maximum velocity and kinetic constant) was decreased even 2 hours following cecal ligation and puncture.
 No linear correlation between hepatocellular function and hepatic blood flow or cardiac output was found under such conditions.
 The extremely early depression in active hepatocellular function, despite the increased hepatic blood flow and cardiac output, may form the basis for cellular dysfunctions leading to multiple organ failure during sepsis.
",0
68,"Effects of high-dose IgG on survival of surgical patients with sepsis scores of 20 or greater.
 Sixty-two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater (day 0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or human albumin (controls; 33 patients), repeated on days +1 and +5, in a prospective, double-blind, multicenter study.
 The two groups were similar in age, initial sepsis scores, and acute physiology and chronic health evaluation II score.
 A significantly lower mortality was recorded in the IgG-treated group (38%) than in controls (67%).
 Septic shock was the cause of death in 7% of IgG-treated patients and in 33% of controls.
 The results of this study indicate that high-dose IgG improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater.
",0
69,"Clostridium difficile disease in a department of surgery. The significance of prophylactic antibiotics.
 A clustering of Clostridium difficile-associated disease in a department of surgery prompted a program of infection control and the evaluation of contributing factors.
 Fifty patients had diarrhea and positive assays for C difficile cytotoxin during the study period.
 Twenty-one of the 36 cases that developed among patients admitted to the surgical services occurred on two adjacent general surgery wards that shared attending surgeons and house staff.
 Perioperative prophylactic antibiotics predated C difficile-associated disease in 20 patients, 12 of whom had short courses (less than 24 hours).
 Symptoms were typically nonspecific and early diagnosis may be difficult.
 Incidence remained high, despite infection control measures, until the coincidental closure of two surgical wards.
 Clostridium difficile-associated disease is a nosocomial infection that can be associated with short courses of prophylactic antibiotics.
 Recommendations regarding the use of perioperative prophylaxis should recognize C difficile-associated disease as a significant potential complication.
",0
70,"Clinical and immunologic responses to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants injected at 3, 5, 7, and 18 months of age.
 The safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (Hib-TT) were evaluated in 77 healthy infants receiving injections at 3, 5, 7, and 18 months of age.
 No serious local or systemic reactions were noted.
 After the first injection the geometric mean Hib antibody level rose to 0.55 micrograms/ml, and each subsequent injection elicited a statistically significant rise in the geometric mean.
 The percentage of vaccinees with Hib antibody levels greater than 0.15 micrograms/ml serum was 75.5% after the first, 97.4% after the second, and 100% after the third Hib-TT injection.
 This percentage fell to 90.9% at 18 months of age but rose again to 100% after the fourth injection.
 Control infants (n = 10) injected with diphtheria-tetanus toxoid-pertussis vaccine only had nondetectable levels after the second injection.
 Hib-TT elicited increases of Hib antibody in all isotypes: IgG greater than IgM greater than IgA.
 Among IgG subclasses the highest increases were of IgG1.
 All vaccinated subjects had greater than 0.01 U/ml of TT antibody (estimated protective level) throughout the study.
 We conclude that Hib-TT, injected at 3, 5, 7, and 18 months, is safe and induces protective levels of antibodies during the age of highest incidence of meningitis caused by Hib.
",0
71,"Splenectomy does not influence outcome of pneumococcal septicemia in a porcine model.
 The existence of the overwhelming postsplenectomy infection syndrome in adults after traumatic splenectomy is controversial.
 Due to the similarity of the porcine immune system to man we chose the pig to study subsets of peripheral mononuclear cells after splenectomy and resistance to experimental Pneumococcal infection after splenic surgery and specific immunization.
 Female miniature pigs were assigned to four operative groups: sham operation, splenectomy, splenic resection, and heterotopic splenic autotransplantation.
 Hematologic and flow cytometric analysis of mononuclear cells and their subsets revealed a marked leukocytosis following splenectomy and autotransplantation but no significant shift in monocyte and B-cell numbers.
 Response of leukocytes to septicemia, bacterial elimination from peripheral blood, and mortality were not affected by splenectomy or spleen-preserving operations.
 Mortality of splenectomized animals was 18%, compared to 42% in sham-operated controls (difference not significant).
 Immunization protected animals from development of leukopenia, and led to an enhanced bacterial elimination, and a significantly decreased mortality of 5%, compared to 48% in nonimmune animals.
 Thus our data do not show significant effects of splenectomy on subsets of porcine mononuclear cells or on resistance to experimental Pneumococcal septicemia.
",0
72,"Epidural tuberculoma of the spine: case report 
 Epidural tuberculomas of the spine have been reported only rarely during the past few decades.
 A case of a surgically treated epidural tuberculoma of the thoracic spine in a 76-year-old women is presented.
",0
73,"Factors affecting outcome in meningococcal infections.
 A prognostic score for evaluating meningococcal infections in patients consists of the following five features that indicate a poor prognosis: onset of petechiae within 12 hours of presentation; shock; normal or low peripheral leukocyte count; normal or low erythrocyte sedimentation rate; and absence of meningitis.
 Based on our experience and some published data, we suspected that the score may no longer be reliable.
 We reviewed the charts of 73 children with meningococcal infection from December 19, 1979 to December 19, 1987 and applied the prognostic score mentioned previously.
 Our findings indicate that although a low score is generally associated with a good outcome, a higher score is less predictive of poor outcome than previously suggested.
 A rash with petechiae or purpura, the presence of shock, and a normal or low peripheral leukocyte count continue to be predictors of poor outcome.
 Erythrocyte sedimentation rate was not evaluated owing to a limited amount of data.
 The absence of meningitis did not correlate with a worse outcome in our patients.
 Most patients who died had evidence of meningeal involvement at the time of presentation.
 Instead, altered mental status at presentation, particularly obtundation or coma, was an ominous sign.
 We conclude that absence of meningitis is not a good predictor of outcome, as was previously thought.
 Altered mental status at the time of presentation may prove to be a stronger indicator of poor outcome.
",0
74,"Antibody responses to four Haemophilus influenzae type b conjugate vaccines.
 Serum antibody responses to four Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines (PRP-D, HbOC, C7p, and PRP-T) were studied and compared in 175 infants, 85 adults and 140 2-year-old children.
 Antibodies to the H influenzae type b polysaccharide vaccines were determined with a Farr-type radioimmunoassay.
 The infants received two doses of vaccine at the ages of 4 and 6 months.
 After the first dose of vaccine, the geometric mean antibody concentration measured at the age of 6 months was 0.09 to 0.10 mg/L, only marginally higher than that measured before immunization in all infants who had received PRP-D, HbOC, or C7p but increased to 0.82 mg/L in those who had received PRP-T.
 One month after the second dose, the geometric mean antibody concentration was increased in all vaccine groups.
 No significant differences were noted between recipients of HbOC, C7p, or PRP-T (geometric mean antibody concentrations, 4.32, 3.10, and 6.10 mg/L, respectively), whereas the PRP-D recipients had a significantly lower geometric mean antibody concentration (0.63 mg/L).
 In contrast, PRP-D, HbOC, C7p, and PRP-T were all highly immunogenic in adults, with no differences noted among them.
 The 2-year-old children also responded to one dose of these vaccines with a high antibody concentration.
",0
75,"Efficacy of short courses of oral novobiocin-rifampin in eradicating carrier state of methicillin-resistant Staphylococcus aureus and in vitro killing studies of clinical isolates.
 Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial infection problem.
 Colonization appears to be more common than invasive disease is.
 Eradication of colonization or the carrier state could limit the spread of MRSA, thus reducing the potential for mortality and morbidity in other patients.
 The detection of patients with MRSA infection in a rehabilitation ward led to a study of the combination of novobiocin-rifampin in vivo and in vitro.
 We found that 300 mg of rifampin plus 500 mg of novobiocin orally twice daily for 5 days, in 18 courses of treatment given to 12 patients, resulted in the clearing of MRSA in 79% of the evaluable courses and 81% of the evaluable sites.
 A second course cleared MRSA from one of the patients with a treatment failure.
 Side effects were not noted.
 All 18 pretherapy isolates were susceptible to either drug in vitro, but 1 of 2 posttherapy isolates was rifampin resistant.
 Timed-kill studies demonstrated that the rate of killing was the same with either drug alone or both drugs together.
 Pretherapy isolates from treatment successes or failure were killed at the same rate by the drug combination.
 However, with the rifampin-resistant isolate killing ceased after 48 h.
 Results of this study suggest that previously untreated patients are likely to have isolates that are susceptible to the combination of drugs and that the combination is commonly effective in eradicating MRSA carriage.
 Since the regimen is orally administered, and thus convenient, in conjunction with other measures it has the promise of reducing the spread of MRSA in hospitals.
",0
76,"Ampicillin-resistant enterococcal species in an acute-care hospital.
 A prospective review of all enterococcal isolates for 13 months showed that 9.0% were resistant to ampicillin (MIC, greater than or equal to 16 micrograms/ml; zone diameter, less than 15 mm), as determined by the Vitek system, disk diffusion, microdilution MIC testing, and macrodilution MIC testing.
 All were beta-lactamase negative.
 A total of 19 and 3 resistant isolates were from urine and intravascular sites, respectively.
 Ampicillin-resistant enterococci appear to be a growing clinical problem.
",0
77,"Endogenous colonization by gentamicin-resistant gram-negative bacilli elaborating aminoglycoside (3)-5-acetyltransferase.
 Members of the family Enterobacteriaceae that elaborate aminoglycoside 3-5-acetyltransferase [AAC(3)-5] caused a nosocomial outbreak at the Vanderbilt University Medical Center and have persisted.
 To see whether the gene for AAC(3)-5 was present in the community, stool cultures of newly admitted patients and ambulatory persons were examined with a specific gene probe.
 AAC(3)-5-positive strains were present in the intestinal flora examined.
",0
78,"Increasing resistance of Staphylococcus aureus to ciprofloxacin.
 We demonstrated the marked emergence of resistance to ciprofloxacin among Staphylococcus arueus strains isolated at the Ann Arbor Veterans Administration Medical Center.
 All S.
 aureus isolates tested from 1984 to 1985 were susceptible, whereas 55.1% of methicillin-resistant and 2.5% of methicillin-susceptible strains from 1989 had high-level resistance to ciprofloxacin.
",0
79,"Prevalence of Chlamydia trachomatis infection in women having cervical smear tests 
 OBJECTIVE--To determine the prevalence of sexually transmitted diseases in patients with normal and abnormal cervical smears.
 DESIGN--A prospective study of asymptomatic women with normal cervical smears attending their general practitioner and newly referred patients with abnormal smears attending a colposcopy clinic.
 SETTING--A hospital based colposcopy clinic and an urban general practice (list size 5500) in north west Glasgow.
 SUBJECTS--197 asymptomatic women attending their general practitioner for cervical smear tests and 101 randomly selected patients attending the colposcopy clinic for investigation of abnormal smears.
 MAIN OUTCOME MEASURES--Presence of various sexually transmitted infections as determined by culture and serological tests.
 RESULTS--Of the 101 women with cytological abnormalities, six had current chlamydial infection proved by culture and none had gonococcal infection; of the 197 women with normal smears, 24 (12%) had a chlamydial infection and two had gonorrhoea.
 Serological studies for Chlamydia trachomatis specific antibody also indicated that a large proportion of patients had been exposed to this agent in both groups.
 There was no significant difference between the groups in the prevalence of any sexually transmitted disease studied.
 CONCLUSION--A high prevalence of chlamydial infection is present in women in north west Glasgow irrespective of their cervical cytological state.
",0
80,"Reversible decrease of oxygen consumption by hyperoxia.
 The hemodynamic and metabolic effects of 90 minutes normobaric hyperoxia were studied in 20 critically ill patients (11 septic, 9 nonseptic) requiring mechanical ventilation with inspired O2 fraction (FIO2) less than 0.40.
 Thirty minutes after increasing the FIO2 to 1.0, arterial PO2 had increased from about 100 to about 400 mm Hg, and whole body oxygen uptake (VO2) was decreased 10 percent (p less than 0.05) due to an 18 percent decrease in O2 extraction ratio.
 During the subsequent 60 minutes of hyperoxia, there was no further significant change in VO2.
 Cardiac index did not change in hyperoxia, but it increased 10 percent (p less than 0.05) in recovery as systemic vascular resistance decreased.
 VO2 returned to baseline after 30 minutes recovery at original FIO2 due to increased O2 extraction as well as the increased cardiac output.
 The decrease in VO2 without a decrease in O2 delivery may reflect maldistribution of blood flow and functional O2 shunting to protect tissue from unphysiologically high PO2.
 While brief oxygenation is advisable before periods of hypoventilation, the present data suggest that hyperoxic ventilation in these patients with already adequate O2 delivery was counterproductive.
",0
81,"Serologic diagnosis of human ehrlichiosis using two Ehrlichia canis isolates.
 Ehrlichia canis or a closely related rickettsial organism has been implicated serologically and morphologically as the causative agent of human ehrlichiosis in the United States.
 Although E.
 canis has been serially propagated in primary canine monocytes, only a limited quantity of antigen is obtained by this method.
 A continuous canine macrophage cell line, DH82, supports the growth of a new isolate of E.
 canis established from the whole blood of a carrier dog in Oklahoma.
 Serologic comparison of the Oklahoma isolate in the continuous canine cell line with a Florida isolate in commercial antigen slides revealed 100% specificity and 87.5% sensitivity.
",0
82,"Clinical disease, drug susceptibility, and biochemical patterns of the unnamed third biovariant complex of Mycobacterium fortuitum.
 Previous studies of Mycobacterium fortuitum identified isolates that did not fit its two recognized biovariants.
 Eighty-five clinical isolates of this group, the ""third biovariant complex"", were evaluated.
 They represented 16% of 410 isolates of M.
 fortuitum submitted to a Texas laboratory and 22% of 45 isolates in Queensland, Australia.
 Most infections (76%) involved skin, soft tissue, or bone and occurred after metal puncture wounds or open fractures.
 Isolates differed from biovar fortuitum in resistance to pipemidic acid and use of mannitol and inositol as carbon sources.
 Two subgroups were present, and examples were deposited in the American Type Culture Collection.
 Isolates were resistant to doxycycline and one-third were resistant to cefoxitin.
 All were susceptible to amikacin, ciprofloxacin, sulfamethoxazole, and imipenem.
 Surgical debridement combined with drug therapy based on in vitro susceptibilities resulted in cures of cutaneous disease or osteomyelitis.
 DNA homology studies are needed to determine the taxonomic status of these organisms.
",0
83,"Urinary phenolic glycolipid 1 in the diagnosis and management of leprosy.
 A simplified assay to measure the phenolic glycolipid 1 (PGL-1) of Mycobacterium leprae in the urine was applied to the diagnosis of leprosy and the monitoring of antileprosy chemotherapy.
 One hundred seventy-nine previously untreated patients and 25 normal controls were tested.
 The specificity of the assay was 100%.
 There were no false-positive results.
 The sensitivity of the assay varied with the type of leprosy from 92% for lepromatous leprosy to 56% for borderline lepromatous and 18% for borderline tuberculoid patients.
 After the onset of chemotherapy in lepromatous leprosy patients, there was often a transient increase of urinary PGL-1, followed by a steady decline.
 Within 3 months of multiple drug therapy, urinary PGL-1 levels were reduced by 90%-99% and were often undetectable.
 This assay appears to have considerable potential for monitoring chemotherapy and detecting treatment failure and relapse in patients with Hansen's disease.
",0
84,"Virola: a promising genus for ethnopharmacological investigation.
 Data are now available on the antifungal use of Virola from four countries and some 14 different tribes of Indians in these countries who employ the Virola exudate for the same or similar purposes.
 Three of the five methods of ethnobotanical investigation proposed by Schultes and Swain in 1976 have been employed in this ethnobotanical research.
 Furthermore, both of the present authors have successfully employed this antifungal treatment themselves.
 Given that deep fungal infections of the skin are often considered incurable with medications currently in use, further laboratory analysis of Virola resin should be undertaken as soon as possible.
",0
85,"Issues in cerebrospinal fluid management. CSF Venereal Disease Research Laboratory testing.
 Three policies for decreasing unnecessary cerebrospinal fluid (CSF) management Venereal Disease Research Laboratory (VDRL) tests were compared.
 The first policy attempted to educate physicians about the use of serologic tests for diagnosing neurosyphilis but allowed the CSF VDRL to be performed either as a screening test or as a retrospective test.
 The second policy required that the CSF VDRL be performed as a retrospective test without regard to the patient's serologic status.
 The third policy required that a patient be seropositive by either rapid plasma reagin (RPR) or fluorescent treponemal antibody absorbance (FTA-ABS) before a CSF VDRL could be performed.
 Before these policies were instituted, VDRL testing was performed on 18.2% of all CSF samples.
 The optional and required retrospective policies decreased the CSF VDRL rate to 13.0% and 8.5%, respectively, but the percentages of seropositive patients for whom these procedures were performed were only 7.3% and 12.9%.
 The third policy decreased the CSF VDRL test rate to 1.8% (P less than 0.001) with seropositivity improving to 90%.
 To assure serologic tests are obtained in the evaluation of neurosyphilis, requirement for seropositivity must be implemented with the use of retrospective CSF VDRL testing.
",0
86,"Issues in cerebrospinal fluid management. Acid-fast bacillus smear and culture.
 Meningeal tuberculosis is an uncommon disease in the United States with an annual incidence of fewer than 200 cases.
 This study evaluates three approaches to improving the use of the cerebrospinal (CSF) acid-fast bacillus (AFB) smear and culture procedure: (1) education alone; (2) optional screening by which physicians can select to have the AFB analysis stopped if the initial CSF findings are unremarkable; and (3) mandatory screening before the performance of all CSF AFB analyses.
 With education alone, the CSF AFB culture rate decreased from 20.6% of all CSF acquisitions to 15.7% (P less than 0.001); however, the effect may have been related to a decrease in all types of AFB testing.
 Optional screening had no impact on the AFB testing rate.
 Mandatory screening significantly decreased the CSF AFB rate to 6.7% (P less than 0.001), unrelated to changes in other types of AFB testing.
 Laboratories that employ mandatory screening should report the screening results immediately and have a mechanism whereby physicians can bypass the screen, providing CSF AFB analysis on unremarkable fluid from high-risk patients.
",0
87,"Closed suction drainage following knee arthroplasty. Effectiveness and risks.
 A prospective investigation was performed to determine when to remove a suction drain following total knee arthroplasty (TKA).
 Forty-one TKAs were randomly allocated to closed suction drainage for either 24 or 48 hours.
 The drain was removed and the tip was cut off and processed by a method giving quantitative cultures.
 In the 48-hour group, 85% of the total volume was drained during the first 24 hours.
 During the following 24-hour period, a mean volume of only 50 ml was drained.
 No organism was isolated from cultures of drain tips sampled at 24 hours.
 However, at 48 hours, 25% of the drain tips yielded light growths of coagulase-negative staphylococci (four drain tips) and Staphylococcus aureus (one drain tip).
 Clinical evaluations of wound healing were comparable in the two groups.
 Clearly, nothing is to be gained by continuing drainage beyond 24 hours.
 If drainage is maintained for longer periods, there is an increased risk of contamination by bacteria.
",0
88,"The office laboratory.
 Few areas of medicine are experiencing such tremendous growth as the office-based laboratory.
 Recent advances in technology and changes in reimbursement practices have greatly expanded the potential of this segment of patient care.
 In the 1990s the physician has opportunity to introduce many testing procedures to the office laboratory that were not available 20 years ago.
 Requirements in the areas of quality assurance and quality control are constantly changing.
 These regulations vary from state to state and each laboratory should know what is required by their respective certifying agency.
 In today's market, the physician must choose between the referral laboratory or the resources in the office and consider which option provides the best in care and cost to the patient.
",0
89,"Antibiotics and infectious diseases.
 Selection of antibiotics in clinical practice has become increasingly complex because more patients have underlying predispositions to infection, a greater variety of microorganisms with varying antibiotic resistance patterns cause these infections, and more antibiotics are available to treat these pathogens.
 A practical approach to antibiotic decision-making involves comparing the advantages and disadvantages of each group of antibiotics available while remembering the patient population being treated and the common pathogens encountered in one's practice.
 It is helpful to study the penicillin derivatives in approximately chronologic order of development and the cephalosporins in terms of generations because this puts the use of each individual agent in perspective.
 Familiarity with commonly encountered adverse antibiotic reactions, dosage guidelines, and special situations (pregnancy, pediatric patients) will help avoid problems associated with antibiotic use.
 Finally, having one or more useful references at hand will aid in resolving questions about antibiotic use.
",0
90,"Infectious skin diseases.
 Descriptions of individual diseases, including impetigo, scarlet fever, and toxic shock syndrome, are presented in the context of the specific organisms that cause them.
 Pictures are used to show some of the diseases.
 Testing and treatment information for these diseases are included.
",0
91,"Antibiotics for common infections in the elderly.
 A decline in host defense mechanisms and concurrent diseases combine to make the elderly patient particularly susceptible to common infections.
 The bacterial cause and antimicrobial sensitivity patterns may also be different in the elderly.
 The appropriate selection and dosing of antibiotics for elderly patients with such common infections as pneumonia, bronchitis, urinary tract infections, and skin and soft-tissue infections will optimize the patient's response while minimizing adverse consequences.
",0
92,"Antistaphylococcal activities of teicoplanin and vancomycin in vitro and in an experimental infection.
 The efficacies of vancomycin and teicoplanin in an experimental Staphylococcus aureus infection in granulocytopenic mice were related to their activities in vitro and their pharmacokinetic profiles.
 In vitro teicoplanin had a higher intrinsic activity than vancomycin did; and it also had a more favorable pharmacokinetic profile, resulting in higher peak concentrations in plasma, a longer elimination half-life, and a larger area under the concentration-time curve than those of vancomycin.
 To predict the antibacterial efficacies of the drugs in vivo on the basis of their activities in vitro and pharmacokinetics, a mathematical model was applied.
 In the model the in vitro effect was expressed as the difference in growth rate between control cultures and those in the presence of the antibiotic (ER), and the in vivo effect was expressed as the difference between numbers of CFU in control and antibiotic-treated animals (EN).
 The integral of ER against time, ERt, was calculated by using the concentrations found in vivo.
 A significant linear relationship was found between EN and ERt for different dosages at the same times (4 h) after drug administration as well as for the same doses at consecutive times, although at the lowest doses of teicoplanin the observed effect was less than the predicted effect.
",0
93,"Pharmacokinetics and tissue penetration of a single dose of ornidazole (1,000 milligrams intravenously) for antibiotic prophylaxis in colorectal surgery.
 Levels in serum and tissue penetration of ornidazole were studied after a single intravenous injection of 1,000 mg given to 14 patients for prophylaxis of surgical infection.
 They were scheduled for elective colorectal surgery.
 Adequate levels in blood (greater than or equal to MIC for 90% of Bacteroides fragilis strains tested) were found in all patients throughout the procedure and up to hour 24.
 Mean-maximal (15 min) and last-determined (24 h) ornidazole levels in serum were 24 +/- 5.2 and 6.3 +/- 1.4 mg/liter, respectively.
 beta-Phase elimination half-life was 14.1 +/- 2.7 h, and clearance and apparent volume of distribution were 47 +/- 12 ml/min and 0.9 +/- 0.13 liters/kg, respectively.
 In all patient, adequate levels in tissue were found in the abdominal wall and the epiploic fat at time of incision and in the colonic wall at time of anastomosis.
 At time of closure, all but one patient had adequate levels in tissue in the abdominal wall and the epiploic fat.
 No anaerobic nor aerobic infection occurred in the study patients.
",0
94,"Comparative study of the effects of four cephalosporins against Escherichia coli in vitro and in vivo.
 A thigh muscle infection induced with Escherichia coli in irradiated mice was used as a model to compare the in vivo pharmacodynamics of the antibacterial effect of four cephalosporins (i.e., cefepime, ceftriaxone, ceftazidime, and cefoperazone) with the in vitro antibacterial pharmacodynamics of these drugs.
 The following in vitro pharmacodynamic parameters were determined: the maximum effect as a measure for efficacy, the 50% effective concentration as a parameter for potency, and the slope of the concentration-effect relationship.
 For analysis of the in vivo antibacterial pharmacodynamics, the same parameters were applied for the dose instead of the concentration.
 For the detection of a relationship between concentration and antibacterial effect in vivo, we determined the pharmacokinetics of the four cephalosporins in the plasma of mice.
 The results showed that, in general, there is a direct relationship between the in vivo and in vitro pharmacodynamics of these cephalosporins.
 The maximum effects of cefepime, ceftazidime, and cefoperazone were approximately similar in vivo and in vitro.
 The sequence of potency of these drugs was, in descending order, cefepime, ceftazidime, and cefoperazone.
 Ceftriaxone differed from the other three cephalosporins in that it displayed unexpected in vivo pharmacodynamics.
 Ceftriaxone was just as efficacious as the other three in vitro, but its maximum effect in vivo was much lower.
 This relatively low maximum effect of ceftriaxone in vivo was not explained by the pharmacokinetic characteristics of the drug.
 From the present results it can be concluded that the in vitro efficacy of cephalosporins does not necessarily have a predictive value for the in vivo efficacy.
",0
95,"Thoracoscopic debridement and pleural irrigation in the management of empyema thoracis.
 As a sequel to a paper reporting good results obtained in 12 patients with empyema thoracis treated by thoracoscopic debridement and irrigation in our department, subsequent experience with a further 18 patients is reported.
 Drainage of pus and irrigation resulted in resolution of pyrexia with improvement in general condition in all patients.
 Overall, complete resolution was obtained by this technique alone in 60% (18/30).
 Of the 12 patients in whom complete resolution was not obtained, secondary surgical measures resulted in resolution of empyema in 8.
 Four patients died; all were elderly and severely debilitated, 3 with advanced malignancy.
 Their deaths were not related to the technique, which was well tolerated in all cases.
 Thoracoscopic debridement and irrigation used routinely as a first-line measure in empyema thoracis is a safe and relatively atraumatic procedure, does not exclude the use of any subsequent surgical measure, and provides valuable time to improve the condition of debilitated patients so that they may tolerate more aggressive surgical procedures.
",0
96,"Successful treatment of disseminated cutaneous cytomegalic inclusion disease associated with Hodgkin's disease.
 A case of disseminated cutaneous cytomegalic inclusion disease associated with Hodgkin's disease is described.
 The patient had a diffuse eruption of pruritic, erosive erythematous nodules.
 Histologically, many inclusion bodies were observed in perivascular areas of the skin lesions.
 Immunohistologically, the inclusion bodies positively stained with both anticytomegalovirus antibody and anti-factor VIII-related antibody.
 On electron microscopy many virus particles and dense bodies were found in the area where inclusion bodies were observed.
 Treatment with high-dose intravenous acyclovir and a large amount of immunoglobulin resulted in prompt healing of the skin lesions.
 Subsequently, the patient's Hodgkin's disease was well controlled on chemotherapy.
 The patient steadily improved without relapse of skin lesions 1 year after antiviral therapy was administered.
",0
97,"Cortisol response to corticotropin and survival in septic shock 
 Corticotropin stimulation tests were used to assess adrenocortical function in 32 patients with septic shock.
 13 patients had a poor cortisol response (rise less than 250 nmol/l) to corticotropin, all of whom died.
 However, there were only 6 deaths among the 19 patients with adequate responses (p less than 0.001).
 These results suggest that some patients with septic shock may have relative adrenocortical insufficiency.
",0
98,"A case of neonatal tetanus.
 The morbidity and mortality from neonatal tetanus are preventable.
 It is largely a disease of developing countries.
 This single case of neonatal tetanus in southern Florida must serve as an indicator for the need for health care professionals to evaluate the degree of utilization of maternal health services and the impact of immunization programs for those women at risk, in this case, women who have migrated from developing countries.
",0
99,"Bacterial translocation from the gut impairs systemic immunity.
 The goal of this study was to determine the influence of bacterial translocation on systemic immunity, since bacteria and their products play a major role in the development and maintenance of the host's immune system.
 To test this hypothesis, we measured the blastogenic response of mononuclear cells harvested from the blood, spleen, Peyer's patches, and mesenteric lymph nodes of control and Escherichia coli C25 monoassociated mice to a battery of mitogens.
 The E.
 coli C25 monoassociation model was used because this bacterial translocation model is not associated with experimental manipulations that are likely to affect the systemic immune system.
 The mitogenic response of lymphocytes isolated from the E.
 coli C25 monoassociated mice was significantly depressed compared to the control groups (p less than 0.01).
 Since the biologic significance of depressed in vitro mitogen responsiveness is difficult to determine, we assessed the ability of the mice to control a bacterial challenge using an in vivo Staphylococcus aureus abscess model.
 It appears that the observed changes in mitogen responsiveness may be of biologic significance, since the ability of the E.
 coli C25 monoassociated mice to control the injected S.
 aureus was impaired (p less than 0.01).
 These results suggest that an association exists between bacterial translocation and decreased systemic immune responsiveness.
",0
100,"Cephalosporins: rationale for clinical use.
 Cephalosporins, the most widely used class of antibiotics, are more resistant than penicillins to inactivation by beta-lactamases.
 Based on their spectrum of activity against gram-negative bacteria, cephalosporins are classified into three generations.
 The generation classification, however, does not correlate with activity against gram-positive bacteria or anaerobes.
 First-generation cephalosporins have a narrow gram-negative spectrum but are most active against gram-positive bacteria, particularly Staphylococcus aureus.
 Third-generation compounds have excellent activity against gram-negative bacteria.
 The cephamycins, a second-generation subgroup that includes cefoxitin, cefotetan and cefmetazole, have the best activity against anaerobes.
",0
101,"Empiric antibiotic selection by physicians: evaluation of reasoning strategies.
 The objectives of the study were to evaluate the appropriateness of empiric antibiotic selection by housestaff treating medical patients with bacteremia.
 The design was a prospective, observational study at a university-affiliated hospital.
 Seventy-eight patients with bacteremia were evaluated.
 A clinical grade of acceptable or not acceptable was assigned to each antibiotic prescription by a consensus panel.
 The consensus panel found that 34.6% of antibiotic prescriptions were unacceptable (clinical grade).
 At least one flaw in the chain of reasoning was found in 56.4% of the 78 cases evaluated.
 Assessment of the clinical setting was correct in 94.9% of the cases; the portal of entry was identified in 91%; adequate knowledge of the bacterial flora at the suspected site of infection was found in 69%; the diagnostic workup was appropriate in 81%, and the correct antibiotic susceptibility patterns were given in 72%.
 A correct chain of reasoning was more likely to result in an acceptable clinical grade than flawed reasoning (p less than 0.005).
 However, an appropriate antibiotic selection was made by some physicians despite flawed reasoning, and inappropriate antibiotic selection occurred in a few cases despite fautless reasoning.
 In 3.8% of cases, unexpected organisms appeared in blood culture.
 Prescription of broad spectrum antibiotics may then be learned response.
 If so, educational efforts that emphasize narrow, rather than broad spectrum prescribing may be inadequate to change physician prescribing habits.
",0
102,"Assessment of platelet antibody by flow cytometric and ELISA techniques: a comparison study.
 Two different methods for evaluating platelet antibody were used to study 12 normal subjects and 24 patients consisting primarily of intravenous drug users (IVDUs) who were positive for human immunodeficiency virus (HIV).
 Total platelet-associated immunoglobulin G (IgG) and immunoglobulin M (IgM) were measured by enzyme-lined immunosorbent assay on platelet lysate, and platelet surface-associated IgG and IgM were measured by semiquantitative flow cytometry.
 IgG and IgM values showed significant correlations between the two measurement methods.
 Mean platelet surface IgG and total IgG were 3.6 and 4.3 times greater, respectively, in IVDUs than in controls, and platelet IgM was also significantly higher in IVDUs than in controls as measured by both techniques.
 Although mean platelet immunoglobulin levels were higher in the IVDUs with thrombocytopenia than in IVDUs with normal platelet counts, these differences did not achieve significance.
 These data show that platelet IgG and IgM levels are increased in IVDU-associated HIV infection and suggest that these increases are not confined to patients manifesting thrombocytopenia.
 The herein described platelet surface antibody and total platelet antibody measurements appear to be equally useful in studying this patient population.
 Specific details for generating platelet-associated immunofluorescence units are discussed.
",1
103,"A report of eight HIV-seropositive patients with major depression responding to fluoxetine.
 This pilot study examined the effectiveness of fluoxetine in depressed human immunodeficiency virus (HIV)-seropositive asymptomatic patients.
 Eight patients, participating in an AZT trial who met criteria for major depression syndrome (DSM-III-R), were treated with fluoxetine (20 or 40 mg/day) for 4 weeks.
 Initially, mean Hamilton Depression scores were 23.8 (range of 17-31), and improved to 6.4 (range of 3-10).
 All subjects maintained their remission over a 2-month follow-up.
 Fluoxetine treatment may be effective in treating major depression in HIV-seropositive asymptomatic patients.
",1
104,"Antibody persistence in Gambian children after high-dose Edmonston-Zagreb measles vaccine.
 Measles antibody concentrations in Gambian children immunised at 4 months of age with a high-dose Edmonston-Zagreb (EZ) measles vaccine or at 9 months with conventional Schwarz vaccine were measured 5 months after vaccination, and at 18 and 36 months of age.
 Schwarz vaccinees produced, on average, a 2.4-fold higher concentration of measles haemagglutinin inhibiting (HAI) antibody than EZ vaccinees, but at 36 months of age 82 of 93 (88%) EZ vaccinees and 83 of 87 (95%) Schwarz vaccinees had measles plaque-neutralising antibody concentrations above the assumed protective level of 200 mIU/ml (p greater than 0.1).
 HAI antibody concentrations 5 months after vaccination were inversely related to the presence of maternal antibody at vaccination, but above protective levels; at 18 and 36 months of age there was no relation to antibody concentration at vaccination, and decay of HAI antibody between 18 and 36 months of age was similar for EZ and Schwarz vaccinees.
",1
105,"Oral and pharyngeal herpes simplex virus infection after allogeneic bone marrow transplantation: analysis of factors associated with infection.
 This study analyzed factors associated with acute oropharyngeal herpes simplex virus (HSV) infection in 627 patients who had undergone allogeneic bone marrow transplantation for leukemia, lymphoma, or aplastic anemia.
 HSV infection developed in 233 (37%) of the patients; all but two were seropositive for HSV before transplant.
 Sixty-two percent of the seropositive patients had at least one episode of HSV reactivation during the first 100 days after transplant.
 Other factors that placed patients at increased risk for HSV infection were a pretransplant diagnosis of leukemia, being in remission at the time of transplant, and/or having been conditioned for transplant with chemoradiotherapy.
 Recognition of factors that may predispose patients to HSV infection helps determine those transplant recipients who might benefit most from antiviral prophylaxis or other approaches to prevention of HSV reactivation.
",1
106,"Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion.
 Individuals infected by the human immunodeficiency virus type 1 (HIV-1) demonstrate progressive depletion and qualitative dysfunction of the helper T4 (CD4+) cell population.
 Mechanisms proposed for attrition of CD4+ T cells include direct cytopathicity of these mature cells following infection as well as infection of early T-lymphocyte progenitors.
 The latter mechanism could lead to failure to regenerate mature functioning CD4+ T cells.
 The present study determines the susceptibility of thymocytes at various stages of maturity to infection with HIV-1.
 Various normal thymocyte populations were inoculated with HIV-1, including unfractionated (UF), CD3- CD4- CD8- [""triple negative"" (TN)], CD4+ CD8+ [""double positive"" (DP)] thymocytes, and thymocyte populations obtained by limited dilution cloning.
 Cultures were studied for the presence of HIV-1 DNA by polymerase chain reaction in addition to examination for reverse transcriptase activity.
 We determined that transformed T-cell and thymocyte cell lines completely lacking CD4 were not susceptible to infection by HIV-1, whereas all of the following lines were: UF thymocytes (70-90% CD4hi+); DP thymocytes (99% CD4hi+); TN thymocytes (0% CD4hi+); and TCR alpha beta +, TCR gamma delta +, or CD16+ CD3- (natural killer) thymocyte clones expressing variable levels of CD4 and representing the progeny of TN thymocytes.
 [TCR alpha beta + and TCR gamma delta + refer to the chains of the T-cell antigen receptor (TCR), and CD4hi refers to a strong rightward shift (greater than 30 linear channels) of the CD4 curve on flow cytometric analysis compared with control.] Monoclonal antibodies (mAbs) to CD4 (T4a epitope) but not to CD3 (T3) were capable of blocking infection of mature and immature CD4hi+ thymocytes.
 Moreover, anti-CD4(T4a) mAbs also inhibited infection of CD4hi- TN thymocytes, indicating that these T-cell precursors--despite their apparent ""triple negativity"" (CD3- CD4hi- CD8-)--expressed sufficient CD4 molecules to become infected.
 Cell sorter analysis with a panel of CD4 mAbs demonstrated a mean shift of the mean fluorescence channel (MFC) with CD4 mAbs on TN thymocytes of 6 +/- 4 MFC units.
 Thus, intrathymic T-cell precursors and their progeny representing many stages of T-cell ontogeny are susceptible to infection by HIV-1, including early TN thymocytes, which express very low levels of CD4.
 Infection of multiple stages and multiple subsets of the T-cell lineage in man, mediated via the CD4 molecule, may explain the inability of the T-cell pool to regenerate in the setting of progressive HIV infection.
",1
107,"Subacute sclerosing panencephalitis in black children--a review of 18 cases.
 Despite the fact that measles is severe and presents in very young Black children in Natal, South Africa, no case of subacute sclerosing panencephalitis was reported from this region prior to 1982.
 A retrospective study was therefore made over the six-year period 1982-1987 of 18 patients who presented to the King Edward VIII teaching hospital, Durban, with clinical and laboratory features of subacute sclerosing panencephalitis.
 The majority of patients (66 per cent) were between 8 and 12 years of age.
 The mean age of onset was 9.3 years, the youngest patient being four years nine months and the oldest 14 years.
 The male to female ratio was 1.25:1.
 A previous history of primary measles infection was obtained in 44.4 per cent of cases; 62.5 per cent occurred before the second birthday.
 The commonest mode of presentation was personality, intellectual and behaviour disorders (83 per cent) followed by myoclonic seizures (61 per cent) and choreiform movements (28 per cent).
 Measles antibody was present in the CSF in all cases.
 The EEG was abnormal in all recorded cases with pathognomonic periodic complexes being found in 56.2 per cent.
 Confirmation of the diagnosis was provided by brain biopsy in two cases and by necropsy in one case.
 The findings of this study suggest that subacute sclerosing panencephalitis may not be as uncommon in Black children as has hitherto been thought.
",1
108,"Preliminary report: protection of cynomolgus macaques against simian immunodeficiency virus by fixed infected-cell vaccine 
 Cynomolgus macaques were vaccinated with inactivated simian immunodeficiency virus-infected cells and 'Quil-A' as adjuvant at 0, 4, 8, and 36 weeks or at 0, 4, 8, and 16 weeks.
 2 weeks later these animals, together with a similar unvaccinated group, were challenged with 10 MID50 (50% monkey infectious doses) of a pool of SIVmac251 previously titrated in vivo.
 Virus was repeatedly isolated from unvaccinated animals on at least five separate occasions and proviral DNA was detected in circulating lymphocytes by polymerase chain reaction amplification.
 By contrast, virus and proviral DNA were not found in any of the vaccinated animals.
 However, the same vaccination regimen used after live virus challenge did not eliminate virus from previously infected macaques.
",1
109,"The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network.
 OBJECTIVE: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp 160) candidate vaccine in humans.
 SUBJECTS: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups.
 INTERVENTIONS: The subjects were randomly assigned to receive 40 or 80 micrograms of rgp 160, 10 micrograms of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540.
 MEASUREMENTS AND MAIN RESULTS: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months.
 No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity.
 Serum antibody responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-micrograms doses of rgp160 and were most commonly of weakly reactive intensity.
 Responses were first noted by Western blot after the second dose.
 They markedly increased in frequency after the third dose and declined over the next 12 to 18 months.
 The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 to 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%).
 Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time.
 CONCLUSIONS: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.
",1
110,"Abnormal function of CD4+ helper/inducer T lymphocytes in a patient with widespread human papillomavirus type 3-related infection.
 Human papillomavirus-induced infections may be associated with cellular immunodeficiency.
 However, very little is known about the dysfunctional interactions among T lymphocytes, B lymphocytes, and antigen-presenting cells.
 A 30-year-old heterosexual man with a 10-year history of persistent multiple refractory flat wart lesions containing human papillomavirus type 3-related DNA sequence was studied.
 The patient had a severe depletion of CD4+ T lymphocytes and a compensatory increase in the number of CD8+ T lymphocytes.
 Impaired T-lymphocyte response to various stimuli was found.
 Depletion of the increased number of CD8+ T lymphocytes, which suppressed immunoglobulin production in vitro, did not restore the impaired T-lymphocyte response.
 Immobilized anti-CD3 beads that stimulate the T lymphocyte antigen complex in the absence of antigen-presenting cells indicated a T-lymphocyte defect, rather than a decreased antigen-presenting cell function.
 Thus, the pronounced cellular immunodeficiency was due to abnormal function of the CD4+ helper/inducer T lymphocytes.
",1
111,"Antibody-dependent cellular cytotoxicity against HIV-coated target cells by peripheral blood monocytes from HIV seropositive asymptomatic patients.
 Cytotoxic effector cells like cytotoxic T cells, NK cells, monocytes/macrophages, and neutrophils can lyse directly HIV-infected or HIV-coated cells in the absence or presence of anti-HIV antibodies.
 Therefore, these cytotoxic mechanisms can be invoked either in the control of HIV infection at early stages of the disease or in the generalized immunosuppression observed at later stages of the disease.
 The relationship between anti-HIV effector mechanisms and disease, however, remains elusive.
 The present study investigates in HIV+ seropositive asymptomatic patients peripheral blood monocytes (PBM)-mediated antibody dependent cellular cytotoxicity (ADCC) against HIV-coated target cells in the presence of heterologous or autologous anti-HIV serum.
 To test for specific ADCC against HIV Ag, a T4+ CEM.TR line resistant to TNF and macrophage-mediated cytotoxicity was selected in vitro.
 ADCC was performed in an 18-h 51Cr-release assay using CEM.TR cells coated with inactivated HIV.
 Unlike PBM from normal controls, significant ADCC was observed by PBM from HIV+ seropositive patients in the presence of pooled HIV+ antiserum.
 The ADCC activity was specific for HIV and was dependent on the E:T ratio and the antiserum dilution used.
 Upon activation of PBM with rIFN-gamma, both normal and HIV+ PBM-mediated ADCC against HIV-coated CEM.TR.
 Furthermore, ADCC activity by PBM from HIV+ seropositive patients in the presence of their autologous serum was examined.
 Significant ADCC activity was observed and was dependent on the E:T ratio and serum dilution used.
 The findings demonstrating anti-HIV ADCC activity by PBM from HIV+ seropositive individuals and their autologous sera support the notion that monocyte-mediated ADCC may be operative in vivo.
",1
112,"Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi's sarcoma: clinical consequences and side effects.
 Interferon alpha (IFN-alpha) has been shown to be effective in treating HIV-associated KS in at least 30% of patients, and Zidovudine has proved beneficial for AIDS patients.
 Moreover, both drugs have demonstrated an inhibitory effect on HIV replication.
 Based on the above, we combined IFN-alpha and zidovudine for treatment of HIV-associated KS in order to evaluate tolerance and clinical efficacy.
 Twenty-one homosexual men with histologically proved HIV-associated KS were treated in an open trial with rIFN-alpha-2a 18 X 10(6) IU every second day and zidovudine 800-1200 mg/d.
 Treatment was discontinued within the first month in six patients: three of them developed subjective intolerance, and three others contracted severe opportunistic infections or HIV-cachexia.
 Fifteen evaluable patients received combination treatment over a period of 2-20 months (average 10 months).
 The dosage was reduced as required based on drug-induced cytotoxicity.
 Complete remission was observed in four patients, partial remission in three, stable disease in two, and progression in six, resulting in an overall response rate of 46%.
 Negative p24 expression prior to treatment was a positive predictor.
 Although extracutaneous involvement had a negative influence on tumor remission, even patients with a mean initial T-helper cell count below 100 mm3 responded positively.
 In conclusion, combination therapy of rIFN-alpha-2a with AZT may effectively control HIV-related Kaposi's sarcoma in more than 40% of patients.
 In contrast to monotherapy with IFN-alpha, patients with severely reduced immune systems will also benefit from combined treatment.
",1
113,"Biologic effects of interferons.
 If one were to review articles on IFN published between 1957 and 1967 it would become apparent that virtually none of the tenets held then are still valid today.
 Whereas IFN was long considered to be a specific antiviral substance without any effect on normal cellular metabolism, we accept today that it affects normal cell division and many specialized cellular functions.
 In this respect it is not unique; IFN is a prototype of a family of similar substances now called cytokines that all appear to function as regulatory molecules.
 It was held that the production of IFN constituted a specific response to a viral infection.
 Today we believe that IFN is an integral part of a cytokine network and that they and other cytokines may be produced constitutively at low levels.
 These substances exert multiple effects on virtually all cells.
 They play an important role in host defense against viral and parasitic infections, and in the resistance to experimental tumors.
 IFN can be shown to exert effects on the immune system and on lymphocyte circulation.
 Lastly, because of the multiplicity of their biologic effects, they may even contribute to the pathogenesis of certain diseases.
 Thus, when large amounts of IFN are administered or induced in newborn mice they can cause liver, kidney, and pulmonary disease.
 The field of IFN and cytokine research continues to expand and there is an increasing number of therapeutic applications.
 Twenty years from now, scientists and clinicians may be surprised that we understood so little of how IFN act and how inadequately we used them to treat disease.
",1
114,"Mucosal immunity induced by enhance-potency inactivated and oral polio vaccines.
 Oral polio vaccine (OPV) is recommended for routine immunization in the United States in part because of its ability to induce intestinal and pharyngeal immunity to reinfection.
 Mucosal immunity produced by OPV and enhanced-potency inactivated polio vaccine (E-IPV) was compared by challenging vaccines with type 1 OPV.
 Fewer OPV (25%) than E-IPV (63%) vaccinees excreted OPV virus in stool after challenge.
 The mean stool virus titer was higher and the duration of shedding longer among E-IPV excreters.
 Only one E-IPV and three OPV vaccinees shed virus in the pharynx after challenge.
 Prechallenge serum neutralizing antibody levels were not statistically different among E-IPV vaccinees who did and did not shed virus; these levels were much higher than those of OPV vaccinees.
 Poliovirus-specific IgA levels in stool did not correlate with viral excretion.
 E-IPV was less effective than OPV in preventing and limiting intestinal infection, even though it induced higher postvaccination serum antibody levels.
",1
115,"Measles among the Amish: a comparative study of measles severity in primary and secondary cases in households.
 An outbreak of measles among a predominantly unvaccinated and susceptible Amish population in Lebanon County, Pennsylvania, offered the opportunity to test the hypothesis that secondary cases in households are more severe than primary cases because the former have more intense exposure and receive a greater virus inoculum.
 Of 130 measles cases reported between April and June 1988, 119 (92%) constituted a study of disease severity.
 Severity was assessed by determining frequency and duration of symptoms, length of any hospitalization, and number of days in bed.
 In a univariate analysis, fewer secondary cases had conjunctivitis (relative risk [RR], 0.67; 95% confidence interval [CI], 0.48-0.96) and headache (RR, 0.37; CI, 0.15-0.86), but more had earache (RR, 9.69; CI, 1.8-202.9) compared with primary cases.
 Secondary cases had a shorter mean duration of coryza (4.0 vs.
 5.0 days, Student's t test, P = .08).
 However, a logistic regression model that matched by family and controlled for age and sex indicated that there were no significant differences in measles severity among primary and secondary cases in households.
",1
116,"Use of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis: a statistical model and its clinical implications. NIAID Collaborative Antiviral Study Group.
 Using the decision analysis technique and multivariate regression methods, a statistical model was established to define the utility of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis (HSE).
 Two strategies were compared: strategy I, brain biopsy with acyclovir (ACV) treatment for 10 days in biopsy-positive patients, and strategy II, ACV therapy without brain biopsy.
 Strategy I resulted in a greater 6-month survival rate when the likelihood of patients having HSE was less than 70%.
 Based on the current estimated prevalence of HSE (for patients with suspected HSE) of 35%, strategy I showed a slight advantage of a 3.2% increase in 6-month survival rate.
 An individual patient's chance of a positive brain biopsy can be predicted using a mathematical equation based on several important clinical assessments.
 This equation in conjunction with the decision analysis is a useful guide for the clinical management of patients with regard to brain biopsy.
",1
117,"The role of secretory immunity in hepatitis A virus infection.
 Because the role of intestinal immunity remains uncertain in hepatitis A, samples of feces and saliva from infected primates and humans were tested for virus neutralizing activity.
 Only two of eight owl monkeys infected by the intragastric route developed neutralizing antibody detectable in extracts of feces collected up to 88 days after viral challenge, although serum neutralizing antibody was present in all monkeys by day 33.
 Similarly, neutralizing antibody was detected in fecal extracts from none of three experimentally infected human volunteers and only 1 of 15 naturally infected humans.
 The single positive human specimen contained occult blood.
 Only 2 of 19 saliva samples from naturally infected humans had significant viral neutralizing activity.
 In contrast, neutralizing antibody to type 2 poliovirus was present in most human fecal or saliva specimens tested.
 These data suggest that intestinal immunity does not play a significant role in protection against hepatitis A.
",1
118,"Unexplained rabies in three immigrants in the United States. A virologic investigation 
 BACKGROUND.
 Extensive investigation of three patients who died of rabies in the United States failed to reveal any source of exposure to the disease.
 The three patients had immigrated to the United States from areas in Laos, the Philippines, and Mexico where rabies is endemic.
 METHODS.
 We studied rabies viruses isolated from the three patients, other patients with a known source of exposure, and animals in the United States, Thailand (as a proxy for Laos), the Philippines, and Mexico.
 The viruses were characterized by indirect immunofluorescence and neutralization tests according to their reactions to panels of monoclonal antibodies.
 Transcribed complementary DNA from these isolates was amplified by the polymerase chain reaction; the DNA product was then analyzed by differential digestion with restriction enzymes.
 RESULTS.
 The viral isolate from each of the three patients was a rabies variant with distinctive antigenic or genetic characteristics.
 For each of the three isolates, identical variants were found in specimens from rabid animals obtained from or near the country in which the patient lived before immigrating to the United States.
 None of these variants were found among the isolates collected from rabid animals in the United States.
 CONCLUSIONS.
 Rabies infection in these three patients did not originate in the United States but resulted from exposures in Laos, the Philippines, and Mexico.
 Since the three patients had lived in the United States for 4 years, 6 years, and 11 months, our findings suggest that the onset of the clinical manifestations of rabies occurred after long incubation periods.
",1
119,"Antibodies to HIV-1 nef(p27): prevalence, significance, and relationship to seroconversion.
 A sensitive and specific enzyme-linked immunoassay for antibodies to the human immunodeficiency virus type 1 (HIV-1) nef gene product, p27, has been developed using recombinant Escherichia coli-derived protein from the LAV-1-Bru sequence.
 Of 92 HIV-1 infected hemophiliacs, 72 (78%) produced anti-nef antibodies in this assay; the early appearance of anti-nef prior to full seroconversion was a rare event in this population, occurring in only one subject (approximately 1%).
 Anti-nef antibodies were not detected in any of 500 sera from 98 repeatedly HIV seronegative subjects who had been exposed to sexually transmitted modes of HIV infection (45 subjects) or through blood products (53 subjects).
 There was no significant association of titer or anti-nef antibody with protection from disease in HIV infection (p = 0.1).
 Although the nef protein is relatively immunogenic in natural infection, this study cannot confirm the previously reported high prevalence of anti-nef antibodies prior to seroconversion, nor the finding of anti-nef antibodies in HIV seronegative but exposed subjects.
",1
120,"Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid.
 With the aim of improving early diagnosis of herpes simplex encephalitis a polymerase chain reaction (PCR) assay with two ""nested"" primer pairs was developed for the amplification of herpes simplex virus DNA in cerebrospinal fluid (CSF).
 Southern blotting was used to confirm the specificity of the amplification.
 The assay was applied to 151 CSF samples from 43 consecutive patients with herpes simplex encephalitis verified by the finding of herpes simplex virus/viral antigen in a brain biopsy sample or at necropsy (13) and/or intrathecal production of IgG antibody to the virus (40).
 As controls, 87 CSF samples from 60 patients with acute febrile focal encephalopathy (initially suspected to be herpes simplex encephalitis but excluded by the absence of intrathecal antibody synthesis) were tested.
 PCR detected herpes simplex virus DNA in 42 of the 43 patients with proven herpes simplex encephalitis; all but 1 were positive in the first CSF sample taken.
 The 1 PCR-negative patient had been treated with acyclovir from 20 h after the onset of symptoms.
 All the control subjects were PCR negative, as were 270 internal contamination controls.
 The PCR result remained positive in samples drawn up to 27 days after the onset of neurological symptoms.
 This method is a rapid and non-invasive means to diagnose herpes simplex encephalitis; it is highly sensitive and specific.
",1
121,"Antiviral drug therapy.
 Major advances in molecular virology have led to the development of new antiviral compounds.
 These drugs include ribavirin, used in the treatment of severe respiratory syncytial virus infection in children; amantadine, used in the prophylaxis and treatment of influenza A infection; acyclovir, used in a variety of herpesvirus infections, including primary gingivostomatitis, genital herpes and herpes zoster; ganciclovir, used in the treatment of retinitis due to cytomegalovirus, and zidovudine, used in the prophylaxis and treatment of human immunodeficiency virus infection.
",1
122,"Detection of salivary HIV-1-specific IgG antibodies in high-risk populations in Zaire.
 Saliva and blood samples were tested for human immunodeficiency virus-1 (HIV-1) antibodies in two high-risk populations in Kinshasa, Zaire.
 In a seroprevalence study of 458 sexually transmitted disease (STD) clinic attendees, 142 of 145 seropositive individuals had enzyme-linked immunosorbent assay (ELISA)-positive saliva samples (97.9% sensitivity).
 All saliva samples from seronegative patients were ELISA-negative (100% specificity).
 Of the 142 ELISA-positive saliva specimens, 137 were also Western blot-positive (94.5% sensitivity).
 In a subsequent seroincidence study of 315 initially seronegative female prostitutes followed during 183 woman-years of observation, 9 of 14 women who seroconverted (7.7% seroincidence) had ELISA-positive saliva samples at the time seroconversion was detected.
 Only three of these saliva specimens could be confirmed by Western blot.
 Although salivary testing for HIV-1 antibodies using conventional assays was not sensitive in detecting recent seroconversions, screening of salivary samples for HIV-1 antibody provides a convenient alternative method for conducting seroprevalence surveys in populations in whom venipuncture is not possible or convenient.
",1
123,"Clinical manifestations of primary herpes simplex virus type 1 infection in a closed community.
 The clinical features and the molecular epidemiology of primary herpes simplex virus type 1 (HSV-1) infection among children younger than 3 years of age were investigated in day-care nursery.
 Serial sera were assayed for anti-HSV-1 glycoprotein B antibody by enzyme-linked immunosorbent assay.
 Serologic examinations revealed 55 cases of primary HSV infection during the observation period.
 Fifty-one of them (93%) had typical herpetic gingivostomatitis, showing a high rate of clinically overt infection.
 Four outbreaks of herpetic gingivostomatitis were observed during the observation period.
 Forty-one children were infected with HSV-1 in the outbreaks.
 The rates of infection in the susceptible children were 81%, 73%, 78%, and 100%, respectively, in the four outbreaks.
 Restriction endonuclease analysis of DNA of isolated HSV revealed that only one strain of HSV-1 had been transmitted among children for a long period.
",1
124,"Vaccination for disease.
 Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response.
 Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine.
 Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.
",1
125,"The effect of anti-neoplastic drugs on murine acquired immunodeficiency syndrome.
 The murine acquired immunodeficiency syndrome (MAIDS) is associated with proliferation of target cells that have been infected by a defective retrovirus.
 To control the growth of this primary neoplasia, virus-inoculated mice were treated with anti-neoplastic drugs.
 Paradoxically, cyclophosphamide, which is also immunosuppressive, was very effective in preventing the appearance and progression of the disease, in restoring a normal T cell function, and in depleting the number of infected target cells.
 This result suggests that the proliferating infected target cells were responsible for the immunodeficiency.
",1
126,"Epidemiologic patterns of wild-type hepatitis A virus determined by genetic variation.
 Hepatitis A virus (HAV) isolates from different parts of the world are a single serotype.
 However, genetic analysis of the VP1 genome region of published HAV sequences suggested that distinct genotypes of HAV could be defined based upon the geographic source of the original isolates.
 To circumvent the process of cell culture adaptation or animal passage, a 247-bp segment within the VP1 genome region of wild-type HAV was amplified by reverse transcription followed by polymerase chain reaction amplification in the presence of negative- and positive-sense primers.
 From the sequences obtained from 22 epidemiologically distinct HAV isolates, three genetic groups of HAV could be delineated.
 Two of the groups differed by 10%, while the third group differed from other isolates by approximately 20%.
 These investigations indicate that HAV isolates from different parts of the world can be differentiated genetically, which will facilitate studies of epidemiologic transmission.
",1
127,"Genome analysis of adenovirus type 31 strains from immunocompromised and immunocompetent patients.
 Adenovirus type 31 (Ad31) was isolated from 15 immunocompromised patients in 12 of whom seroconversion was also recorded.
 Ad31 infection has a substantial clinical relevance since 8 of 10 with lower respiratory tract infection and 4 of 4 with hepatitis died.
 Therefore, Ad31 isolates from immunocompetent and immunodeficient hosts were compared by restriction endonuclease analysis.
 Nine genome types were identified among the 79 Ad31 isolates.
 Pairwise comparison of comigrating restriction fragments indicated that the genome types could be divided into three genomic clusters.
 Several Ad31 genome types were isolated from immunocompromised patients, but no highly virulent genome type could be found.
 A genome type was identified in a child with severe combined immunodeficiency who originally was infected with another genome type.
 This observation is suggested to have evolutionary implications.
",1
128,"Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by attenuated and inactivated vaccines to A/Chile/83-like viruses.
 Children (n = 192) aged 3-19 years from 98 families completed this double-blind, placebo-controlled study comparing the efficacy of a bivalent attenuated (CR) vaccine with trivalent inactivated (TI) vaccine.
 Both vaccines contained A/Chile/83 (H1N1)-like antigens.
 After vaccination the geometric mean titer to A/Taiwan/86 (H1N1) was 1:36 in the CR group, 1:92 in the TI group, and 1:5 in the placebo group.
 During the influenza A/Taiwan/86 (H1N1) epidemic, 21.4% of CR recipients, 16.7% of TI recipients, and 43.9% of placebo recipients were infected with influenza A/Taiwan.
 TI vaccine provided better heterotypic protection than did CR vaccine for children aged 10-18 years (infection rate, 0 vs.
 24%, respectively; P less than .025); in contrast, in the younger children (3-9 years), CR vaccine tended to be more protective (19% vs.
 26% for TI).
",1
129,"Antiidiotypic responses to immunization with anti-Leu 3a in human immunodeficiency virus-seropositive individuals.
 Anti-idiotypic antibodies to anti-CD4 monoclonal antibodies (MAbs) have been reported to bind to the human immunodeficiency virus (HIV) envelope glycoprotein gp120.
 To establish whether HIV-infected patients can mount an anti-idiotypic response to murine MAb, four individuals with symptoms of AIDS-related complex (ARC) were immunized over 10 weeks with six intramuscular injections of anti-Leu 3a (1 mg).
 Despite their immunocompromised state, all patients made anti-constant region and anti-idiotypic antibodies, although the amplitude of the responses varied between individuals.
 No significant toxic or allergic reactions were seen, and there were no changes in clinical status during the 6 months after immunization.
 No increase in serum HIV-neutralization titers was seen, and purified anti-idiotypic antibodies did not bind gp120.
",1
130,"Encephalitogenicity for rats of myelin basic protein without the aid of water-in-oil emulsions.
 The induction of experimental allergic encephalomyelitis (EAE) with purified myelin basic protein (MBP) has, heretofore, required its incorporation in a water-in-oil emulsion or adsorption on particulate adjuvants.
 In the present work, the absorption of a saline solution of MBP from the peritoneal cavity into the mediastinal lymph nodes was increased by giving repeated inoculations or by pretreating rats with a peritoneal irritant.
 Under these conditions, the only adjuvant needed for production of EAE was aqueous pertussis vaccine which was injected separately a few hours or one day after the MBP.
 Pertussis vaccine was also necessary for production of EAE with intradermal injection of aqueous MBP.
 By injecting the aqueous MBP directly into pre-enlarged popliteal lymph nodes, it was possible to produce EAE without the pertussis vaccine.
 Thus, EAE can be induced in rats using MBP without the addition of Freund's adjuvant or pertussis vaccine.
",1
131,"Depression, distress, lymphocyte subsets, and human immunodeficiency virus symptoms on two occasions in HIV-positive homosexual men.
 We evaluated the extent to which depressive disorders, psychiatric distress, and psychosocial stressors are related to three measures of human immunodeficiency virus (HIV) illness, both cross-sectionally and during a 6-month period, in a community sample of 124 HIV-positive homosexual men.
 The dependent variables are immune status measured by CD4 and CD8 cell subsets, number of signs and symptoms commonly associated with HIV infection, and a cumulative index of HIV illness stage.
 We chose to focus on CD4 cell count because it is the immune marker most closely linked to the clinical consequences of HIV infection.
 We found no relationships between the independent variables and immune status or illness stage.
 The HIV-positive men who were depressed or distressed or who reported more life stressors had no greater immunosuppression or more advanced illness stage than did the others, either concurrently or across occasions.
 We did find a suggestive pattern of association between depressive disorders, distress, and stressors and the number of HIV-related symptoms, which warrants further study.
",1
132,"Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. I. Overview of study design.
 Although much is known about the virus believed by most experts to be the cause of the acquired immunodeficiency syndrome and about its pathogenic actions, major areas of ignorance remain.
 Among these are the reasons for the varying time between infection with human immunodeficiency virus and development of acquired immunodeficiency syndrome, the relationship between neurologic and medical aspects of the disease, the time course of neuropsychological findings, and the prevalence of psychiatric morbidity.
 We assessed 124 homosexual men who were positive for human immunodeficiency virus and 84 who were negative for the virus.
 In this article we describe the study design, method of recruitment, and medical and demographic characteristics of the cohort, which will be followed up for 5 years.
",1
133,"Effectiveness of psychoeducational interventions in reducing emotional distress after human immunodeficiency virus antibody testing.
 To examine the effectiveness of three psychoeducational interventions in reducing emotional distress after voluntary serologic testing for human immunodeficiency virus-1,307 physically asymptomatic adults were randomly assigned to standard counseling, counseling plus a three-session interactive video program, or counseling plus six individual sessions of stress prevention training.
 Subjects were evaluated using five standardized distress measures at entry and 3 months later.
 Among the 204 human immunodeficiency virus-seronegative subjects, mean distress measures decreased significantly after all three interventions without differential treatment effects.
 Among the 103 human immunodeficiency virus-seropositive subjects, mean distress measures decreased significantly after the stress prevention training and did not significantly increase in the other two interventions.
 We conclude that stress prevention training is particularly helpful after notification of human immunodeficiency virus seropositivity.
",1
134,"Should family physicians test for human papillomavirus infection? An opposing view.
 Recent advances in the field of molecular biology have expanded the knowledge of HPV manifestations.
 We have attempted to separate those circumstances when HPV testing may be useful in patient management and when it may not.
 Routine screening for HPV has not yet been shown to be useful.
 One must weigh informing 10% of patients that they have a potentially oncogenic virus against the ability of a repeat Papanicolaou smear to detect the lesion.
 On the other hand, HPV detection in the setting of an abnormal Papanicolaou smear and an acetowhite lesion that on biopsy lacks the histologic features of CIL does predict who is at high risk for CIL.
 HPV typing should not affect clinical management, and we do not recommend it.
 HPV detection by in situ hybridization is a very useful adjunct to histological analysis in genital tract lesions that are clinically suggestive of an HPV lesion but where the histological analysis is equivocal.
 This ability to distinguish true HPV lesions from its mimics is often crucial to the patient, given the implications of having a sexually transmitted disease.
",1
135,"Voluntary human immunodeficiency virus testing: acceptance levels and identification of seropositive individuals.
 Of 4340 clients of a clinic for those with sexually transmitted diseases who were eligible for voluntary, confidential, serologic testing for the human immunodeficiency virus, 4246 (97.8%) consented to testing; 23 (0.5%) were seropositive.
 Of 94 persons who declined voluntary testing but who were tested in a blinded study, nine (9.6%) were seropositive.
 Seropositive persons who declined voluntary testing did not conceal their association with a risk group, while only 61% of seropositive individuals who accepted voluntary testing admitted to inclusion in a risk group before the test.
 Voluntary testing appears to be insufficient, because 28% of the seropositive individuals were not identified as being seropositive; also, there was a significant deficiency associated with identification of risk at pretest counseling among persons agreeing to voluntary testing.
",1
136,"Bronchial hyperresponsiveness in normal subjects during attenuated influenza virus infection.
 Fourteen healthy male subjects with hemagglutination-inhibition antibody titers of 1:8 or less to homologous influenza A virus were studied.
 Six subjects received live, attenuated influenza virus by nasal drops and by aerosol.
 Although infection occurred in these six subjects, with the development of 4-fold or greater increases in hemagglutination-inhibition antibody titers, they remained asymptomatic.
 Eight subjects received placebo via the same route, and did not develop symptoms and showed no increase in antibody titer.
 Prior to administration of virus or placebo, histamine diphosphate aerosol increased airway resistance only slightly, and there was no difference between the virus and placebo groups.
 Two days after inoculation, bronchomotor responses in the placebo group were unchanged (p greater than 0.05), but in the virus-infected group, bronchomotor responses were significantly greater than in the preinfected state (p less than 0.01).
 Isoproterenol hydrochloride reversed and prevented the increase in airway resistance after histamine, suggesting that the bronchoconstriction was caused by smooth muscle contraction.
 Our findings indicate that transient, asymptomatic respiratory virus infection augments airway smooth muscle responses.
",1
137,"Induction of CD4+, human T lymphotropic virus type-1-specific cytotoxic T lymphocytes from patients with HAM/TSP. Recognition of an immunogenic region of the gp46 envelope glycoprotein of human T lymphotropic virus type-1.
 Although the humoral response to human T lymphotropic virus type-1 (HTLV-I) has been well characterized in patients with HTLV-I-associated neurologic disease (HAM/TSP), little is known about a functional HTLV-I-specific human T cell response, such as CTL, in these patients.
 To define both the phenotype of the responding CTL and the fine specificity of this response, long term T cell lines were generated from two HAM/TSP patients who were from two different countries.
 Patient's peripheral blood lymphocytes were repeatedly stimulated in vitro with an HTLV-I expressing autologous T cell line.
 The resultant long term T cell culture was shown to be CD4+ and cytotoxic for targets expressing HTLV-I Ag.
 Using a panel of synthetic peptides that span hydrophilic regions of the HTLV-I gp46 envelope glycoprotein, the CTL lines generated from both patients were shown to recognize the same region of the HTLV-I envelope between amino acids 196-209 as defined by the synthetic peptide sp4a1.
 Interestingly, this sequence overlaps a region of HTLV-I envelope that had also been shown to elicit a strong B cell response in HAM/TSP patients (amino acids 190-203).
 One CTL line recognized this HTLV-I epitope in the context of HLA DQ5 whereas the other CTL line was restricted by HLA DRw16.
 The generation of two independent CTL lines from two HAM/TSP patients from different geographic areas that recognize the same region of the HTLV-I envelope glycoprotein highlights the immunogenic nature of this envelope region.
",1
138,"HTLV-I-associated myelopathy associated with blood transfusion in the United States: epidemiologic and molecular evidence linking donor and recipient.
 Six months after receiving 58 units of blood components, a 65-year-old white man from New York City, with no other risk factors for human T-lymphotropic virus type I (HTLV-I) infection, developed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
 Investigation of blood donors identified a 25-year-old white Hispanic woman from Florida whose platelets had been given to the patient and who was seropositive for the virus on a serum specimen obtained 2 years after the donation.
 She was born in Cuba and had had 2 sexual relationships with men who either had been born in or had resided in the Caribbean.
 Polymerase chain reaction (PCR) studies of peripheral blood mononuclear cells indicated that both donor and recipient were infected with HTLV-I.
 Molecular studies of a 595-nucleotide sequence in the 5' envelope region of HTLV-I indicated that the viruses from donor and recipient were identical in each of 32 positions in which published HTLV-I sequences demonstrate molecular heterogeneity; the donor and recipient viruses were also identical in 2 additional positions in which they differed from all published sequences.
 Transfusion-associated HAM/TSP has occurred in the United States, but additional cases should be prevented by screening blood donations for HTLV-I.
 Molecular studies of HTLV-I may prove useful in defining the genetic heterogeneity of HTLV-I isolates in the United States and in studying transmission of this virus.
",1
139,"Peptide-induced antiviral protection by cytotoxic T cells.
 A specific antiviral cytotoxic immune response in vivo could be induced by the subcutaneous injection of the T-cell epitope of the lymphocytic choriomeningitis virus (LCMV) nucleoprotein as an unmodified free synthetic peptide (Arg-Pro-Gln-Ala-Ser-Gly-Val-Tyr-Met-Gly-Asn-Leu-Thr-Ala-Gln) emulsified in incomplete Freund's adjuvant.
 This immunization rendered mice into a LCMV-specific protective state as shown by the inhibition of LCMV replication in spleens of such mice.
 The protection level of these mice correlated with the ability to respond to the peptide challenge by CD8+ virus-specific cytotoxic T cells.
 This is a direct demonstration that peptide vaccines can be antivirally protective in vivo, thus encouraging further search for appropriate mixtures of stable peptides that may be used as T-cell vaccines.
",1
140,"Influence of inhaled cadmium on the immune response to influenza virus.
 Cadmium may exacerbate pulmonary infections.
 In a previous study, however, cadmium appeared to enhance mouse resistance to influenza pneumonia.
 We report herein on the influence of cadmium intoxication in mice on different factors of anti-influenza immunity, e.g., antibody response, local production of interferon, pulmonary cellular response, and the interaction between pulmonary alveolar macrophages and the influenza virus.
 Cadmium inhalation did not affect production of antibodies or interferon.
 The protective effect appeared to be related to an enhanced supply to phagocytic cells into the lung.
",1
141,"Early and specific diagnosis of seropositivity to HIVs by an enzyme-linked immunosorbent assay using env-derived synthetic peptides.
 We describe and evaluate the sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA) using a 22-amino-acid peptide corresponding to the carboxy-terminal end of HIV-1 gp120 and two 30-amino-acid long cyclic peptides including the two vicinal cysteines present on HIV-1 gp41 and on HIV-2 gp36.
 This test was evaluated.
 Data obtained with the Western blot (WB) and the peptide-based ELISA on a first panel composed of sera from 547 patients attending a specialized outpatient clinic (high-risk population) are in perfect agreement; moreover, 39 samples that had falsely been found positive with a viral lysate-based ELISA were not detected by peptide-based ELISA.
 The second panel was composed of 309 sera which were difficult to resolve using both WB and viral lysate-based ELISA.
 Using the peptide-based ELISA, 134 were found clearly positive and 173 clearly negative; only two were falsely positive.
 Finally, sera from 16 individuals examined at the time of seroconversion gave high absorbancy readings even if they were weakly reactive by WB (weak gp160 band).
 This test is thus highly sensitive and specific, and capable of detecting early seroconversion.
 It is also instrumental in clearly defining samples that are found indeterminate in the WB, and consequently it avoids the unnecessary follow-up required when a false-positive result is obtained using viral lysate-based ELISA.
",1
142,"Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein.
 In order to identify the target epitopes recognized by specific CTL in the NEF protein of HIV-1, 33 peptides derived from the HIV-BRU sequence were tested with NEF-specific CTL generated from HIV-seropositive donors.
 Six different epitopes were identified and several points were remarkable: 1) They were all located in two regions of the central part of the NEF protein corresponding to residues 73 to 94 and 113 to 147, respectively.
 2) The CTL issued from a single donor could recognize several peptides of the NEF protein.
 3) Some of these peptides could be recognized in association with at least two or three different HLA class I molecules.
 4) Two different overlapping epitopes were present in a relatively short sequence of 15 amino acids.
 These results suggest that multiple epitopes corresponding to different HLA restrictions could coexist in a relatively small region of the NEF protein.
 The implications of these results in vaccine strategies using synthetic peptides bearing CTL epitopes are discussed.
",1
143,"A measles outbreak at a college with a prematriculation immunization requirement.
 BACKGROUND.
 In early 1988 an outbreak of 84 measles cases occurred at a college in Colorado in which over 98 percent of students had documentation of adequate measles immunity (physician diagnosed measles, receipt of live measles vaccine on or after the first birthday, or serologic evidence of immunity) due to an immunization requirement in effect since 1986.
 METHODS.
 To examine potential risk factors for measles vaccine failure, we conducted a retrospective cohort study among students living in campus dormitories using student health service vaccination records.
 RESULTS.
 Overall, 70 (83 percent) cases had been vaccinated at greater than or equal to 12 months of age.
 Students living in campus dormitories were at increased risk for measles compared to students living off-campus (RR = 3.0, 95% CI = 2.0, 4.7).
 Students vaccinated at 12-14 months of age were at increased risk compared to those vaccinated at greater than or equal to 15 months (RR = 3.1, 95% CI = 1.7, 5.7).
 Time since vaccination was not a risk factor for vaccine failure.
 Measles vaccine effectiveness was calculated to be 94% (95% CI = 86, 98) for vaccination at greater than or equal to 15 months.
 CONCLUSIONS.
 As in secondary schools, measles outbreaks can occur among highly vaccinated college populations.
 Implementation of recent recommendations to require two doses of measles vaccine for college entrants should help reduce measles outbreaks in college populations.
",1
144,"Safety and prophylactic efficacy of low-dose rimantadine in adults during an influenza A epidemic.
 A placebo-controlled, double-blind study to evaluate the safety and prophylactic efficacy of a low dose (100 mg) of rimantadine hydrochloride against naturally occurring influenza in adults was conducted at two sites.
 After the onset of the influenza season, volunteers (ages, 18 to 55 years) were assigned randomly to receive rimantadine or placebo daily.
 Subjects were monitored for adverse effects and evidence of influenza virus infection weekly for six weeks.
 Only 10 (8.7%) of 114 rimantadine recipients and 5 (4.4%) of 114 placebo control recipients reported one or more mild to moderate adverse symptoms, most of which were related to the gastrointestinal or central nervous system.
 Compared with placebo, low-dose rimantadine was highly effective in the prevention of influenza A virus infection (20 of 110 versus 7 of 112 participants; P less than 0.01) and influenza illness (7 of 110 versus 1 of 112 participants; P = 0.04).
 Influenza A/Leningrad/87-like (H3N2) virus was recovered from the nasopharynxes of only five placebo recipients.
 These findings indicate that low-dose rimantadine is well tolerated and highly effective for the prevention of influenza A illness in healthy adults.
",1
145,"Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome.
 The therapeutic efficacies of human recombinant alpha interferon (IFN-alpha), IFN-alpha plus zidovudine (AZT), and AZT alone were evaluated in presymptomatic cats with established feline leukemia virus (FeLV)-acquired immunodeficiency syndrome (FAIDS) infection and high levels of persistent antigenemia.
 Subcutaneous injection of 1.6 x 10(6) U of human recombinant IFN-alpha 2b per kg delivered peak concentrations in plasma of 3,600 U/ml at 2 h postadministration with a half-life of elimination of 2.9 h.
 This dosage of IFN-alpha could be delivered to cats for up to 12 weeks without significant clinical toxicity.
 Oral administration of AZT (20 mg/kg three times daily) resulted in peak concentrations in plasma of 3 micrograms/ml at 2 h with a half-life of elimination of approximately 1.60 h.
 Treatment of FeLV-FAIDS-infected cats with IFN-alpha, either alone or in combination with orally administered AZT, resulted in significant decreases in circulating p27 core antigen beginning 2 weeks after the initiation of therapy.
 AZT alone had no effect on circulating virus antigen.
 Depending upon whether high (1.6 x 10(6) U/kg)- or low (1.6 x 10(4) to 1.6 x 10(5) U/kg)-dosage IFN-alpha was used, cats became refractory to therapy 3 or 7 weeks after the beginning of treatment.
 At these times, IFN-alpha-treated animals developed antibodies to IFN-alpha that were neutralizing, specific for human recombinant IFN-alpha, and dose dependent in magnitude.
 The results of this study indicate that human recombinant IFN-alpha is effective in reducing circulating virus antigenic load in cats persistently infected with FeLV-FAIDS.
",1
146,"Preparation and characterization of an intravenous solution of IgG from human immunodeficiency virus-seropositive donors.
 An intravenous solution of 99% pure globulin (hyperimmune IgG, HIVIG) was obtained from pooled plasma of selected human immunodeficiency virus (HIV-1)-seropositive asymptomatic donors with greater than 400 CD4+/microliters cells per microliter and a high titer of antibody to HIV-1 p24 protein.
 HIVIG had high titers of antibody to p24, glycoprotein 41 (gp41), and gp120, group-specific neutralizing activity, and binding to the gp120 hypervariable loop region.
 It inhibited syncytia formation.
 At low concentration, it enhanced viral production of HIV-1 in infected peripheral blood monocytes but was inhibitory at higher concentration.
 HIVIG directed group-specific antibody-dependent cellular cytotoxicity against HIV-infected targets.
 For a period of 6 to 28 months, plasma donors kept stable antibody titers and had a 1.0% decrease in CD4+ cells per month.
 One gram per kilogram HIVIG injected in two juvenile chimpanzees was well tolerated and did not transmit HIV, as measured by negative cell culture, IgM immune response to HIV proteins, and polymerase chain reaction.
 The mean half-life of HIV-1 p24 antibody was 15 days.
 These preliminary data suggest that HIVIG is a safe product suitable for clinical trial in HIV-1-infected individuals.
",1
147,"Cytomegalovirus infection in sexually active adolescents.
 To determine whether cytomegalovirus (CMV) infection in teenage girls is related to sexual activity, 254 girls 12-18 years old (mean, 15.8) attending a contraceptive counseling clinic were studied.
 Participants were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, and serum antibody to CMV was determined.
 Demographic and sexual history data were collected by interview.
 The mean number of lifetime sex partners was 2.2; 173 (68%) were seropositive.
 Race, greater than 3 years of sexual activity, and greater than 2 lifetime sex partners were significant risk factors for CMV infection (odds ratios [OR], 1.8-4.7; P less than .05).
 Using logistic regression analysis, a composite sexual activity variable was the most important risk factor for CMV infection (OR, 4.8; P = .003), followed by race (OR, 3.4; P = .004) and a sexually transmitted disease composite variable (OR, 2.4; P = .016).
 Sexual activity is an important risk factor for CMV infection in adolescent girls.
",1
148,"Pattern of respiratory syncytial virus epidemics in Finland: two-year cycles with alternating prevalence of groups A and B.
 Time-resolved fluoroimmunoassay with monoclonal antibodies distinguishing between respiratory syncytial virus (RSV) group A and B strains was used to analyze their prevalence in Finland during 1981-1990 among 3285 patients with laboratory diagnosis of RSV, most of them hospitalized.
 The group typing of antigens in 608 RSV-positive nasopharyngeal aspirates showed a regular alternation of group prevalence, following the cyclic occurrence of the virus.
 Group A predominated in 73%-90% of specimens from 1981-1982, 1985-1986, and 1989-1990, whereas group B predominated in 70%-100% of specimens from 1983-1984 and 1987-1988.
 The epidemiologic occurrence of verified reinfections in hospitalized children and the group typing results indicated that children greater than 6 months of age during the first infection were more resistant to severe reinfection with the homologous than with the heterologous group of virus.
 The study shows that group antigenic variation of RSV has a significant effect on the epidemiology of the virus.
",1
149,"HIV prevalence in a midwestern emergency department.
 STUDY OBJECTIVE: To determine the prevalence of human immunodeficiency virus (HIV) seropositivity of patients 15 years of age and older in our emergency department.
 DESIGN: HIV status was determined anonymously, and the seroprevalence rate was calculated.
 The 95% confidence intervals also were calculated.
 Twenty demographic and predictor categorical variable were cross-tabulated with HIV status to determine associations.
 Only gender and male homosexual preference were significantly associated by Fisher's exact test.
 TYPE OF PARTICIPANTS: Excess serum samples from 454 randomly selected patients 15 years of age and older who required venipuncture for their ED evaluation were included in the study.
 MEASUREMENTS AND MAIN RESULTS: Of the 454 serum specimens, six (1.32%) were positive for HIV.
 The 95% confidence interval was from 0.27% to 2.37%.
 All six positive patients were men.
 The only statistically significant risk factors associated with HIV seropositivity were male sex (P = .00112) and male homosexual preference (P = .0000).
 CONCLUSION: HIV seropositivity occurs in 1.32% of our ED population over the age of 15 years.
 The only factors that correlate with HIV seropositivity are male homosexual preference and male sex.
",1
150,"Apparent response of subacute sclerosing panencephalitis to intrathecal interferon alpha.
 An 8-year-old boy with subacute sclerosing panencephalitis (SSPE) was treated with 1.0 to 3.0 x 10(6) IU human interferon alpha (IFN) by the intrathecal route weekly or fortnightly.
 Pronounced improvement of clinical and electroencephalographic findings were observed in a dose-dependent manner.
 Our patient raises hope that IFN can induce sustained remission in patients with SSPE.
",1
151,"Counseling patients seropositive for human immunodeficiency virus. An approach for medical practice.
 Persons at risk for infection with the human immunodeficiency virus are being encouraged to learn their serostatus.
 While such knowledge can help patients seek appropriate medical care, it can also be distressing.
 We describe an approach, based on crisis counseling, for physicians to use in working with patients infected with HIV.
 It can help physicians in assisting patients with emotional reactions to the diagnosis as well as in directing patients to manage practical issues of concern.
 Methods for discussing safer sex or injection practices are also presented.
",1
152,"Acanthamoeba keratitis with two species of Acanthamoeba.
 We describe a case of Acanthamoeba keratitis related to soft contact lens wear.
 The patient presented with a 3-week history of severe uniocular pain, radial stromal infiltrates and subepithelial infiltrates with no epithelial defect.
 Acanthamoeba was cultured from the corneal biopsy specimen, contact lens and lens case.
 The corneal biopsy culture grew both A.
 castellani and A.
 polyphaga as well as Escherichia coli.
 The patient was treated with topical dibromopropamidine isethionate (Brolene) drops, neomycin and polymyxin B drops and fortified gentamicin drops.
 Gradual clinical improvement ensued.
",2
153,"Prenatal diagnosis of congenital toxoplasmosis.
 Prenatal diagnosis of congenital toxoplasmosis was attempted in 50 pregnant women at risk for giving birth to an affected child.
 Fifteen of these patients seroconverted during pregnancy and 35 had a high initial antibody level in their first serum sample.
 Prenatal diagnosis consisted of a combination of ultrasound screening, amniocentesis, and funipuncture at about 20 weeks' gestation.
 Diagnosis of congenital toxoplasmosis was based on a positive toxoplasma culture of amniotic fluid or fetal blood and on the presence of specific immunoglobulin M antibodies in fetal blood.
 In addition, alterations in fetal hematology, cellular immunology, and fetal liver tests were indicative of infection.
 Fetal infection was detected in six fetuses; two died in utero as a consequence of the infection and four were born after 37 weeks' gestation.
 Despite antibiotic treatment with pyrimethamine and sulfadiazine, one child has internal hydrocephalus and chorioretinitis and another has unilateral chorioretinitis.
 In the two other children, the disease is still subclinical.
 Of the 44 children born after a negative prenatal diagnosis, 35 have reached the age of 1 year; toxoplasma antibodies have disappeared in all of them.
 Investigation of the remaining nine children showed a decrease in toxoplasma antibodies, suggesting that none of them are affected.
 Prenatal diagnosis was never associated with fetal loss, and premature delivery occurred in only two cases.
 We conclude that prenatal diagnosis of congenital toxoplasmosis is safe and reliable.
",2
154,"Filarial-specific IgG4 response correlates with active Wuchereria bancrofti infection.
 The filarial-specific humoral immune response of adult residents of two areas of Papua New Guinea, differing in transmission of Wuchereria bancrofti infection was compared.
 The majority of residents of the village of Bonahoi, in an area where transmission of filariasis had been interrupted by a 20-year insecticide spray program to control malaria, showed no parasitologic signs of active W.
 bancrofti infection and were negative for both circulating phosphorylcholine Ag and peripheral blood microfilariae.
 In contrast, adult residents of the village of Nanaha were in an area exposed to infection, and were phosphorylcholine-Ag- and microfilariae-positive.
 The antibody response of these two groups to both adult worm excretory/secretory (ES) Ag and somatic antigen extract was examined to determine which components of the filarial-specific immune response were dependent on active infection.
 Identification of these immune responses may point to immunologic methods to evaluate control programs for lymphatic filariasis.
 Adults from Bonahoi were found to have significant immune responses to [35S] methionine-labeled ES Ag by immunoprecipitation and to adult somatic antigen extracts by ELISA and by immunoblotting.
 This result is consistent with the fact that these individuals were previously exposed to and/or infected with W.
 bancrofti.
 Similarly, residents of the endemic village had detectable immune responses to these Ag irrespective of if they were microfilaremic.
 The most striking immunologic difference observed between the two groups was that residents of Bonahoi had a dramatically reduced filarial-specific IgG4 antibody response to both adult somatic Ag and adult ES Ag.
 These data suggest that longitudinal measurement of filarial-specific IgG4 levels may be a useful seroepidemiologic indicator of changes in W.
 bancrofti infection status.
",2
155,"Serum resistance of metacyclic stage Leishmania major promastigotes is due to release of C5b-9.
 The mechanism of serum resistance for infective promastigotes of Leishmania major was investigated.
 Prior results suggested that the mechanism of resistance was mediated at a step after C3 deposition.
 Equivalent amounts of C3b were deposited on serum-susceptible, noninfective promastigotes harvested from log stage cultures (LOG) and on C-resistant, infective, metacyclic promastigotes (MP) purified from stationary stage cultures.
 Whereas binding of C9 to LOG was stable during incubation in serum, C9 binding to MP was minimal and unstable, because molecules bound initially to MP were released with continued incubation.
 Failure to bind C9 was not a result of inability to activate C; the kinetics of C3, C6, and C9 consumption were similar for LOG and MP.
 Deposition of C5b-7 on MP was stable, indicating that the initial steps in terminal complex formation were intact.
 Instead, the majority of C5b-9 formed on MP was spontaneously released into the serum as SC5b-9.
 Residual C5b-9 on MP was released with 1 M NaCl.
 These data show that developmental modification of the promastigote membrane during transition from a noninfective to an infective stage blocks insertion of lytic C5b-9 into the promastigote membrane.
",2
156,"Analysis of the permissive association of a malaria T cell epitope with DR molecules.
 In this study we examined the association of a promiscuous malaria T cell epitope, CS.T3, to different HLA-DR alleles.
 A large series of singly substituted or truncated variants of CS.T3 was prepared and tested for the ability to be recognised in association with, or to bind to, three distinct HLA-DR alleles (DR1, DRw11, and DRw14(w6)) and three natural variants of HLA-DRw11.
 We found that although association with the different DR molecules mapped to identical or closely overlapping regions of the peptide, distinct substitutions could drastically influence the capacity of the peptide to interact with one but not another of the three DR molecules tested.
 Based on analysis of the distribution of residues recognized by T cell clones restricted to the different DR alleles, we suggest that the peptide CS.T3 is not bound, at least for the three DR examined, as an alpha-helix.
 In addition we tested three subtypes of DRw11 as APC for the CS.T3 analogues and observed that the peptide is most likely bound in the same conformation to the three natural variants of the DRw11 molecule.
",2
157,"Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Need for a better dosing regimen 
 To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly.
 Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine.
 Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection.
 All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months.
 Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia.
 No serious adverse reactions were observed.
 The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.
",2
158,"Imported Plasmodium falciparum malaria in American travelers to Africa. Implications for prevention strategies 
 Data from the US National Malaria Surveillance System were analyzed to assess characteristics of travelers who acquired Plasmodium falciparum infections in Africa and evaluate the impact of chloroquine resistance on the incidence of imported malaria.
 Although the number of cases acquired in East Africa has stabilized, the number of imported P falciparum infections acquired in West Africa increased threefold from 1985 to 1988, and the proportion of travelers who reported failure of chloroquine prophylaxis increased from 10% to 48%.
 Fifty-eight percent of patients who acquired malaria in West Africa had not used chemoprophylaxis.
 To curb the rising incidence of P falciparum infections in American travelers, the Centers for Disease Control revised malaria prophylaxis recommendations to include the use of mefloquine in areas of chloroquine resistance.
 Use of malaria protection measures by travelers to West Africa must also be improved.
",2
159,"Leishmania donovani chagasi: new clinical variant of cutaneous leishmaniasis in Honduras.
 During surveillance for endemic visceral leishmaniasis on an island off the Pacific coast of Honduras, an unusual form of cutaneous leishmaniasis was encountered.
 By clinical and laboratory criteria, 17 cases were identified over 5 months; children aged 4 to 15 years were primarily affected.
 Lesions were generally few in number, small, always papular, and non-ulcerative, even when present for several years.
 Patients with skin lesions seemed otherwise healthy and were well nourished.
 Montenegro skin tests with Leishmania mexicana and L major antigens were positive in 10 of 17 patients tested, and lesions from 9 patients were positive by culture.
 Since the summer of 1988, cases of atypical cutaneous leishmaniasis continue to occur on the island (8) as well as on the mainland of southern Honduras (23).
 A total of 9 parasite isolates from skin lesions, 4 from bone marrow of patients with kala-azar, and 2 from sandflies were identified as L donovani chagasi and were indistinguishable from one another by isoenzyme analysis.
",2
160,"Rapid diagnosis of malaria by fluorescence microscopy with light microscope and interference filter 
 Fluorochrome staining to detect malaria parasites in bloodfilms is more sensitive, is easier to do, and is less time-consuming than Giemsa staining.
 However, standard epi-illuminated, mercury vapour, fluorescence microscopes are expensive, especially for tropical countries where malaria is endemic.
 Fluorescence microscopy with a standard light microscope and a new interference filter specially designed for the fluorochrome stain, acridine orange, was used to detect malaria parasites in thick and thin bloodfilms.
 In this system two fluorescence colours, green (nuclei) and red (cytoplasm), were emitted from stained parasites.
 Thick and thin bloodfilms from patients with malaria were examined with this system.
 Bloodfilms had been fixed and stored for 1-5 years.
 Rapid scanning of both thick and thin bloodfilms was possible at a magnification of x200 with standard lenses, indicating that this may be a useful economic system for rapid diagnosis of malarias.
",2
161,"Exchange transfusion as an adjunct to the treatment of severe falciparum malaria: case report and review.
 Malaria associated with complications or a fatal outcome is almost always caused by Plasmodium falciparum.
 The mortality due to this disease parallels the degree of parasitemia.
 Successful use of exchange blood transfusion as a therapeutic adjunct for this infection was first reported in 1974, although the efficacy of this procedure has not been established by randomized, controlled trials.
 The rationale for this form of therapy is based on: (1) rapid reduction in the parasite load by direct removal; (2) decreased risk of severe intravascular hemolysis and its consequences (disseminated intravascular coagulation and renal dysfunction); (3) improved rheology with transfused blood and reduced microcirculatory sludging; and (4) improved oxygen-carrying capacity with transfused erythrocytes.
 We describe a case of severe falciparum malaria and review the literature describing the use of exchange transfusion for treatment of this infection.
",2
162,"Leishmania mexicana complex: human infections in the Republic of Panama.
 Parasites of the genus Leishmania responsible for human cutaneous leishmaniasis in the New World form 2 major taxonomic divisions: the Leishmania braziliensis and the L.
 mexicana complexes.
 We report the isolation and characterization of the L.
 mexicana complex among humans in the Republic of Panama.
 Characterization was based on parasite morphology, pathogenesis in infected golden hamsters, cellulose acetate isoenzyme electrophoretic mobilities, and membrane-specific monoclonal antibodies using the radioimmune binding assay technique.
",2
163,"Infectivity of the subspecies of the Leishmania braziliensis complex in vivo and in vitro.
 The infectivity of Leishmania braziliensis ssp.
 in relation to their growth kinetics in Senekjie's medium was determined using the human macrophage cell line U937 and inbred hamsters.
 In both systems, infectivity was shown to be distinctive for each subspecies.
 While L.
 b.
 panamensis promastigotes from 6-day-old cultures (early stationary phase) were more infective than parasites from any other culture day, L.
 b.
 guyanensis and L.
 b.
 braziliensis reached maximum infectivity on days 8-10 and day 10 (late stationary phase of growth), respectively.
 Although maximum infectivity occurred during stationary growth, strict growth phase dependency was not observed.
 The populations of parasites on these culture days were composed mostly of small, highly motile promastigotes with flagella 2-3 times the length of their cell bodies.
 These promastigotes resembled the infective forms transmitted by the sand fly vector.
 A distinct pathological picture characterized the disease caused by the different WHO reference strains for these subspecies in hamsters: L.
 b.
 guyanensis developed the most severe lesions, while moderate and inconspicuous lesions were observed when L.
 b.
 panamensis and L.
 b.
 braziliensis, respectively, constituted the inocula.
",2
164,"An improved serodiagnostic procedure for visceral leishmaniasis.
 The enzyme-linked immunosorbent assay (ELISA) is a sensitive and specific serodiagnostic method for leishmaniasis.
 In this report, we describe how this versatile assay can be improved by the use of protein A or protein G conjugates for the specific detection of Leishmania antibody in the sera of patients with visceral leishmaniasis.
 In direct comparisons with anti-immunoglobulin conjugate, enzyme-linked protein A gave significantly higher absorbance values for positive sera without a corresponding increase in absorbance values for sera from normal individuals or from patients with other diseases known to cross-react with leishmaniasis.
 The effect was to increase the distance between positive and negative values, which aided in the interpretation of the results.
 This also permitted visual distinction between positive sera and negative or weakly reactive sera.
 The assay was effective using either blood or serum as the source of primary antibody.
 A further advantage of protein A over anti-Ig conjugate was its ability to detect specific antibody in dog as well as human sera.
 Finally, we demonstrated the usefulness of the protein A ELISA with a recombinant leishmania antigen, gp63.
",2
165,"Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus.
 This paper assesses the effects on adult Onchocerca volvulus of monthly doses of ivermectin (150 micrograms/kg) given over 4, 8, and 12 months to patients in Guatemala.
 Nodules were removed 4 months after the last dose; the adult O.
 volvulus were extracted by collagenase digestion, studied by histological techniques, and compared with worms from untreated patients.
 Twelve monthly doses killed a proportion of the adult worms (12% of males and 22% of females), leaving the remainder relatively unaffected and the females slowly resuming embryogenesis.
 After 8 and 12 doses, a number of female worms had resumed embryogenesis in 1 genital tract only, and in 1 female a total degeneration of 1 ovary was seen.
 Ivermectin also led to a marked drop in the number of male worms in nodules.
 No serious adverse reactions occurred and the treatment was well accepted.
",2
166,"Scabies in nursing homes: an eradication program with permethrin 5% cream.
 Permethrin 5% cream was used to treat scabies in three large nursing homes under a compassionate-plea protocol for chronic, therapy-resistant infestations.
 All residents, staff, and frequent visitors were treated whether or not symptomatic.
 Family members of these groups were treated either when symptomatic or directly exposed to scabies.
 Nine hundred ninety-five persons were treated, 202 of whom were diagnosed with scabies.
 Approximately 35% (111 of 313) of nursing home residents were diagnosed with scabies.
 These were patients in whom multiple treatments with other scabicides were unsuccessful.
 At the completion of the study, 195 patients were examined for efficacy of treatment.
 Of these, 91 (46.7%) had clearing of lesions with one medication application, 77 (39.5%) with two treatments, and 23 (11.8%) with three or more treatments.
 The overall cure rate was 98%.
 Adverse experiences occurred in 2.4% of cases and were mild (i.e., pruritus and rash).
",2
167,"Monoclonal, but not polyclonal, antibodies protect against Plasmodium yoelii sporozoites.
 One of the primary strategies for malaria vaccine development has been to design subunit vaccines that induce protective levels of antibodies against the circumsporozoite (CS) protein of malaria sporozoites.
 In the Plasmodium yoelii mouse model system such vaccines have been uniformly unsuccessful in protecting against sporozoite-induced malaria.
 To demonstrate that antibodies to P.
 yoelii CS protein could provide protection we established a passive transfer model.
 Passive transfer of Navy yoelii sporozoite 1 (NYS1), an IgG3 mAb against the P.
 yoelii CS protein, protected 100% of mice against challenge with 5000 P.
 yoelii sporozoites.
 Binding of NYS1 to sporozoites was inhibited by incubation with (QGPGAP)2, a synthetic peptide derived from the repeat region of the P.
 yoelii CS protein, indicating that the epitope on sporozoites recognized by this mAb was included within this peptide.
 The levels of antibodies to (QGPGAP)2 by ELISA, and to sporozoites by indirect fluorescent antibody test and CS precipitation reaction were similar in sera from mice that received NYS1 in passive transfer and were protected against challenge with 5000 sporozoites, and from mice that had been immunized with subunit vaccines containing (QGPGAP)2 but were not protected against challenge with 40-200 sporozoites.
 To determine if antibody avidity, not absolute concentration could explain the striking differences in protection, we established a thiocyanate elution assay.
 The results suggest that NYS1, the protective mAb, has a lower avidity for (QGPGAP)2 and for sporozoites than do the vaccine-induced antibodies.
 Although the results of the conventional antibody assays did not correlate with protection, sera from the protected animals inhibited sporozoite development in mouse hepatocyte cultures significantly more than did the sera from the unprotected, subunit vaccine-immunized animals, correlating with protection.
 The data clearly demonstrate that antibodies to the CS protein can protect against intense sporozoite infection.
 Improved understanding of the differences between protective mAb and nonprotective polyclonal antibodies will be important in the further development of malaria vaccines.
",2
168,"A comparison of 6-, 12-, and 24-monthly dosing with ivermectin for treatment of onchocerciasis.
 This study was designed to examine the optimal dose and interval of administration of ivermectin, the now-accepted drug of choice for onchocerciasis.
 Two hundred Liberians with Onchocerca volvulus infection received 100, 150, or 200 micrograms/kg ivermectin or placebo and were followed for 36 months.
 The reaction after the second dose of ivermectin was significantly less than after the initial dose, although it was still significant in the 200-micrograms/kg group.
 The skin microfilaria counts in the group treated 6-monthly with 150 micrograms/kg was significantly less than in the group treated yearly (12 and 24 months after initial therapy).
 Prevalence of microfilariae in the anterior chamber and punctate corneal opacities decreased progressively in all groups over 3 years.
 There appears to be a slight advantage, in terms of antiparasitic effect over the first 2 years, of therapy given 6-monthly compared with yearly.
",2
169,"Community-based treatment of onchocerciasis with ivermectin: safety, efficacy, and acceptability of yearly treatment.
 The safety, acceptability, and efficacy of ivermectin during community-based mass treatment of onchocerciasis was assessed.
 Ivermectin was distributed three times, 1 year apart, to the population of a rubber plantation (14,000 people) in Liberia where greater than 80% of adults have Onchocerca volvulus infection.
 In a sample of adults, the microfilarial density was reduced by 84% after 2 years of treatment.
 Acceptance was as high as 98% during the third year.
 Adverse reactions occurred in 6-13 in 1000 people after first treatment and in only 3-4 in 1000 receiving their second or third annual dose of ivermectin; severe adverse reactions were not seen.
 These data show that community-based treatment with ivermectin is safe, well accepted, and effective in reducing microfilarial loads and suggest that ivermectin is the first practical drug suitable for mass treatment campaigns to control human onchocerciasis.
",2
170,"The effect of N-alkyl modification on the antimalarial activity of 3-hydroxypyridin-4-one oral iron chelators.
 The antimalaria effect of iron chelators is attributed to their interaction with a labile iron pool within parasitised erythrocytes, and it was postulated that increased affinity to iron as well as increased lipophilicity may improve antimalarial activity.
 In the present study we have examined the antimalarial effect of 3-hydroxypyridin-4-ones, a family of bidentate orally effective iron chelators whose lipophilicity may be modified by altering the length of the R2 substituent on the ring nitrogen.
 A significant dose-related suppression of Plasmodium falciparum cultures was observed with all drugs tested in vitro at concentrations of 5 mumol/L or higher.
 In contrast, there was a clear segregation of the in vivo effect on P berghei in rats (300 mg/kg/d subcutaneous) into two categories: compounds CP20, 38, and 40 failed to suppress malaria, whereas CP51, 94, and 96 had a strong antimalarial effect, similar or better than deferoxamine.
 There was a close linear correlation between the suppression of peak parasite counts and the reduction in hepatic nonheme iron induced by the various drugs tested (r = .9837).
 The most lipophilic compounds were also the most effective in suppressing malaria and in depleting hepatic iron stores.
 These data indicate that 3-hydroxypyrydin-4-ones are able to suppress malaria in vivo and in vitro.
 Because lipid solubility is an important determinant of antimalarial action, our study provides useful information regarding the selection of orally effective iron-chelating compounds that may be suitable for clinical application as antimalarial agents.
",2
171,"Changes in electrocardiographic patterns at different stages of Chagas' heart disease in rats.
 1.
 The resting electrocardiogram was obtained from 25 Trypanosoma cruzi-infected rats 30 days after infection (phase I).
 The resting electrocardiogram was abnormal in 12 (group I) and normal in 13 (group II) animals.
 Nineteen similar but non-infected animals served as controls.
 Both the resting electrocardiogram and the ajmaline test were performed 120 and 350 days after infection (phases II and III, respectively).
 2.
 With regard to the resting electrocardiogram of group I animals, left axis deviation was found in 10 of 12 (83%) in phase I, one of 12 (8%) in phase II (P less than 0.05) and in none of phase III (P less than 0.05).
 An intraventricular conduction delay was found in four of 12 (33%) rats in phase I, two of 12 rats (16%) in phase II (P greater than 0.05) and six of 12 rats (50%) in phase III (P greater than 0.05).
 The ajmaline test was abnormal in nine of 10 (90%) rats of group I with normal resting electrocardiogram in phase II, and in three of six (50%) animals in phase III (P greater than 0.05).
 3.
 An intraventricular conduction delay was found in the resting electrocardiogram of one of 13 (7%) rats of group II in phase III.
 The ajmaline test was abnormal in one of 13 (7%) rats in phase II and in one of 12 (8%) rats in phase III.
 4.
 No control rat showed pathological changes.
",2
172,"Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence.
 Saimiri monkeys immunized with a recombinant protein containing 20 copies of the nine amino acid repeat of the Plasmodium vivax circumsporozoite (CS) protein developed high concentrations of antibodies to the repeat sequence and to sporozoites, but were not protected against challenge.
 After intravenous injection of an immunoglobulin G3 monoclonal antibody (NVS3) against irradiated P.
 vivax sporozoites, four of six monkeys were protected against sporozoite-induced malaria, and the remaining two animals took significantly longer to become parasitemic.
 Epitope mapping demonstrated that NVS3 recognizes only four (AGDR) of the nine amino acids within the repeat region of the P.
 vivax CS protein.
 The monkeys immunized with (DRAADGQPAG)20 did not produce antibodies to the protective epitope AGDR.
 Thus, determination of the fine specificity of protective immune responses may be critical to the construction of successful subunit vaccines.
",2
173,"Rapid microscopic detection of malaria parasites permanently fluorochrome stained in blood smears with aluminum and morin.
 Intra- and extracellular Plasmodium parasites in fixed blood smears are easily identifiable by fluorescence microscopy after brief mordanting with aluminum ammonium sulfate and staining with morin (3,5,7,1',4'-pentahydroxyflavanol).
 The intensely fluorescent preparations of stained parasites are strongly resistant to photodegradation and remained essentially unimpaired for two years.
",2
174,"Detection of Plasmodium falciparum infection with the fluorescent dye, benzothiocarboxypurine.
 The fluorescent dye benzothiocarboxypurine (BCP) intensely stains nucleic acids.
 The dye does not penetrate viable white blood cells but does stain these cells following fixation.
 It has also been found that the dye stains the nucleic acid of viable Plasmodium falciparum.
 We have subsequently evaluated the staining of P.
 falciparum by benzothiocarboxypurine within red blood cells and have found that the red blood cell membrane is freely permeable to this dye and consequently P.
 falciparum is stained within the red blood cell.
 This finding prompted an in-depth analysis of the dye in the laboratory and in a field study as an alternative to Giemsa-stained blood smears and as a means of enhancing the microscopic diagnosis of malarial infection.
 In a field study the BCP dye allowed detection of malaria in fresh blood at a level equivalent to the Giemsa method (parasitemia ranged from 0.01% to 30%).
 The BCP staining procedure could also be used with fixed specimens although the differential staining characteristics were lost following specimen preparation.
 Of 111 blinded samples obtained in the field 22 were negative by Giemsa-stained thin smear, 16 were negative on thick smear and the same 16 were negative by BCP analysis.
 We have found that the BCP dye offers many advantages compared with the microscopic diagnosis of P.
 falciparum infection with standard Giemsa stains.
 These advantages are especially evident in conditions of low parasitemia, in the speed of staining and evaluation, and the relatively low level of training required to provide consistent results.
",2
175,"Acridine orange fluorescent microscopy and the detection of malaria in populations with low-density parasitemia.
 Detection of low-density malaria parasites with Giemsa-stained thick smears (G-TS) requires time and experience and becomes impractical with high sample loads.
 Acridine orange fluorescent microscopy (AO/FM) of capillary centrifuged blood may offer an alternative technique.
 We compared AO/FM readings with G-TS in 290 specimens from asymptomatic people in Thai villages endemic for malaria.
 AO/FM specimens were prepared in modified capillary tubes coated with acridine orange (Quantitative Buffy Coat or ""QBC tubes"") and examined under a fluorescent microscope.
 Twenty-three (85.2%) of the 27 specimens found positive by G-TS had under 100 parasites/microliters blood (less than 35 parasites/200 microscopic fields).
 The overall AO/FM sensitivity was 78.9% [range: 66.7% (10/15)-86.7% (13/15)].
 For Plasmodium falciparum, regardless of stages, the sensitivities varied from 66.7% (8/12) to 91.7% (11/12).
 AO/FM performed better for P.
 falciparum than for Plasmodium vivax and for asexual than for sexual stages of the parasite.
 However, the species- and stage-specific results must be interpreted with caution because of the small sample sizes and very low parasite densities involved.
 The test specificity was 96.6% [range: 95.6% (263/275)-97.1% (263/271)].
 These levels of accuracy plus the known advantages of AO/FM suggest that the test, supplemented with G-TS to improve species and stage differentiation, is also useful for screening low-density parasitemias.
",2
176,"Plasmodium vivax sporozoite antibodies in individuals exposed during a single malaria outbreak in a non-endemic area.
 We studied seroreactivity against Plasmodium vivax antigens in 62 individuals living in a small community near Mantena, Minas Gerais, Brazil, an area outside the endemic malaria zone Brazil.
 Eight months earlier, there had been transmission of P.
 vivax for a period of 50 days, which was then totally controlled by chemotherapy and insecticides.
 An anti-sporozoite response, measured by ELISA using a recombinant protein expressed in yeast, was detected in 45% (14 of 31) of individuals eight months after infection and persisted for 20 months in 12%.
 Eighteen individuals were treated prophylactically for malaria because they lived in houses in which an overt infection had occurred.
 Seven of these individuals were ELISA positive; of these, 5 had antibodies against the blood stage parasites.
 Among 13 other individuals in the endemic area who did not have positive smears, had not been ill, and had not received prophylaxis, five were anti-circumsporozoite positive up to a 40-fold serum dilution.
 They did not develop asexual blood stage antibodies and remained parasite-free for the following 20 months.
",2
177,"Comparison of high dose ivermectin and diethylcarbamazine for activity against bancroftian filariasis in Haiti.
 This three-phase study was designed to compare high dose ivermectin with a standard diethylcarbamazine (DEC) regimen for patient tolerability, potential to kill adult filaria, and duration of microfilarial suppression in 30 Haitian subjects with Wuchereria bancrofti microfilaremia.
 All were first given a 1-mg oral dose of ivermectin (phase 1) to reduce microfilaria densities.
 Participants were randomized into three groups: Group 1 received DEC (6mg/kg per day for 12 days), Group 2 received 200 mcg/kg of ivermectin, and Group 3 received 400 mcg/kg of ivermectin (200 mcg/kg per day for 2 days).
 All drug regimens were well tolerated with few adverse reactions.
 Most reactions occurred during phase I and consisted primarily of headache, fever, and myalgia.
 At the end of phase 1, 27 of 30 (90%) patients were microfilaria negative.
 During phase 2, four of the six men receiving DEC developed scrotal reactions suggesting killing adult worms; no such reactions were noted in 10 men receiving ivermectin (p less than 0.05).
 At one-year follow up (phase 3), all treatment groups had less than 10% return to pretreatment microfilaria levels.
 The mean percent of baseline microfilaria counts were for Group 1, 0.9% (range 0-5%); Group 2, 8.2% (range 0-31%); and Group 3, 3.8% (range 0-25%).
 Seven individuals in Group 1 were microfilaria-negative, while only one and three individuals were microfilaria-negative in Groups 2 and 3, respectively.
 These results suggest that DEC causes more damage to the adult worms and greater reduction in microfilaria densities than ivermectin, but that high doses of ivermectin may suppress microfilaremia in lymphatic filariasis for periods much longer than previously reported.
",2
178,"Immunization of owl monkeys with the ring-infected erythrocyte surface antigen of Plasmodium falciparum.
 Aotus nancymai were immunized with the 4-mer, 8-mer, and 11-mer repeat peptides of the ring-infected erythrocyte surface antigen molecule of Plasmodium falciparum conjugated to diphtheria toxoid with muramyl dipeptide (MDP) as adjuvant.
 Immunization failed to induce protective immunity against the Uganda Palo Alto strain of P.
 falciparum as judged by maximum levels of parasitemia of immunized monkeys relative to those of controls.
 The fused polypeptide FPAg632, when combined with MDP, also failed to induce protective immunity.
 However, the maximum level of parasitemia and serologic response to the 11-mer peptide were inversely correlated.
 The safety of the use of MDP was evident.
",2
179,"A spleen is not necessary to resolve infections with Plasmodium yoelii.
 The role of the spleen in resistance to infections with nonlethal Plasmodium yoelii 17x is dependent upon the genotype of the host.
 Thus, DBA/2 (D2) mice infected with P.
 yoelii 17x were not adversely affected by removal of the spleen, while splenectomized C57BL/6 (B6) or Balb/c mice failed to resolve their infections and eventually died.
 The levels of parasitemia were lower in splenectomized mice compared to intact controls; however, splenectomized mice became as anemic as did spleen-intact controls.
 Splenectomy resulted in the appearance of large aggregates of mononuclear cells in the livers of infected mice and also altered the liver/body weight ratios.
 These results indicate that D2 mice have a spleen-independent mechanism of clearing parasites which is lacking in B6 and Balb/c mice.
",2
180,"Onchocercacidal effects of amocarzine (CGP 6140) in Latin America.
 An open clinical trial of amocarzine was carried out in onchocerciasis patients in Ecuador and Guatemala.
 Administration after food was more effective than that during fasting.
 The most effective and best tolerated regimen, 3 mg/kg twice daily after food for 3 days (in 312 patients), killed 73% of 1477 female worms at nodulectomy 4 months after treatment.
 The mean microfilarial skin count was greatly reduced within a week (6-11% Of day 0 value on day 8) and it remained low at least 6 months (14-18% on day 180).
 Follow-up of a higher dose 3 day regimen taken while fasting showed microfilaridermia of 7-9% of the day 0 value 2 years after treatment.
",2
181,"Cerebellopontine angle lipoma in a teenager.
 Lipomas of the cerebellopontine angle are very rare lesions.
 To date, 18 patients have been reported, 17 of whom were adults.
 A second child is described with cerebellopontine angle lipoma.
",3
182,"The role of cellular maturation in neutrophil heterogeneity.
 Previous studies have shown that many neutrophil (PMN) characteristics are heterogeneous but the origin of PMN heterogeneity is unknown.
 It is unclear if PMN functional heterogeneity is secondary to maturational differences or due to distinct subpopulations of cells that possess different functional capacities.
 The PMN 31D8 antigen is a useful probe for evaluation of PMN subpopulations.
 The majority of PMNs (approximately 85%) exhibit a high intensity fluorescence after 31D8 monoclonal antibody (MoAb) labeling (31D8 enriched or ""bright"" PMNs) as determined by flow cytometric analysis.
 These cells are more functional than cells with low intensity fluorescence (31D8 diminished or ""dull"" PMNs).
 Various immunologic, clonogenic and functional techniques were used to study the expression of the 31D8 antigen in HL-60 cells and myeloid cells in order to evaluate antigenic and functional heterogeneity during morphologic maturation.
 The results of this study indicate that the percentage of 31D8 antigen positive (31D8 antigen enriched and diminished) bone marrow cells increases from 20 +/- 11% in myeloblast cells to 68 +/- 10% in promyelocytes, 93 +/- 2% in myelocytes and 99 +/- 1% in bands and PMNs.
 31D8 antigen enriched cells first appear at the myelocyte stage (32 +/- 10%) and increase in bands (52 +/- 13%), marrow PMNs (62 +/- 13%) and peripheral blood PMNs (88 +/- 4%).
 These data indicate that the heterogeneous expression of 31D8 antigen in PMNs is due, at least in part, to maturational differences within the PMN population and raise the possibility that other heterogeneously expressed PMN characteristics are also maturationally derived.
 They also suggest that 31D8 antigenic expression may be a more precise indicator of myeloid functional maturation than maturation as identified by cellular morphology.
",3
183,"Papillary cystic neoplasm of the pancreas: radiological and pathological characteristics in 11 cases.
 Clinical charts, radiological features, macroscopic and microscopic findings, and clinical follow-up data were retrospectively reviewed in 11 patients with papillary cystic neoplasm of the pancreas (PCNP).
 The patients were nine women and two men, aged from 13 to 51 years with a mean age of 25 years.
 The greatest diameter of the PCNPs ranged from 2.5 cm to 14.0 cm with a mean size of 7.5 cm.
 Six tumours were located in the tail of the pancreas, two in the body and three in the head.
 Most patients complained of abdominal pain or a mass.
 Ultrasonographic and/or computed tomography findings showed five solid, four mixed (solid and cystic) and two cystic types of tumour.
 Angiographically, PCNP was either a hypovascular or mild hypervascular mass with a displacement of the surrounding vessels.
 No vascular encasement was seen.
 Macroscopically all 11 tumours consisted of a well defined solid mass with degenerative change of various widths, including haemorrhage, necrosis or dystrophic calcification, and were represented by three radiological types of PCNP.
 The 11 patients with PCNP survived for from 3 to 253 months after curative resection without any signs of local recurrence or remote metastasis.
 PCNP usually affects the distal portion of the pancreas of young women.
 Despite its huge size, PCNP should be explored with aggressive surgical intent because of the inherently good prognosis.
",3
184,"CA72-4: a new tumour marker for gastric cancer.
 To date, tumour markers for gastric cancer have proved unreliable.
 In this study the value of a new serum marker, CA72-4, was compared with the serum activities of carcinoembryonic antigen (CEA) and CA19-9 in a consecutive series of patients with gastric cancer.
 The results show that the CA72-4 assay is significantly better at separating stage I and II disease from normal controls (P less than 0.01) than CEA (n.s.) or CA19-9 (n.s.).
 CA72-4 also gave better differentiation between patients with positive and negative nodes (P less than 0.01) and between those who were serosa positive and negative (P less than 0.01).
 CEA differentiated between patients with positive and negative nodes (P less than 0.05) but CA19-9 could not.
 CA19-9 and CEA could not discriminate between patients who were serosa positive and negative.
 In this study, at a specificity of 95 per cent, the sensitivities of CEA, CA19-9 and CA72-4 were 0.25, 0.41 and 0.94 respectively.
 These preliminary findings indicate that CA72-4 is a reliable tumour marker of disease stage and activity in gastric cancer.
 Further longitudinal studies are required for full evaluation of its clinical utility.
",3
185,"Treatment of adenocarcinoma of the cardia with synchronous chemotherapy and radiotherapy.
 Twenty-nine evaluable patients with adenocarcinoma of the cardia were treated with synchronously administered chemotherapy (two cycles of 5-fluouracil and cisplatin and 30-36 Gy of radiation to determine whether these tumours are responsive to such treatment.
 Complete regression of tumour was observed endoscopically in 19 patients, and partial regression in four.
 Fourteen patients had their tumours resected and in six no microscopic tumour was found in the specimen.
 Nine patients received additional radiotherapy to a total dose of 54-60 Gy instead of surgery.
 Tumour response was associated with rapid reversal of dysphagia.
 Only one patient required subsequent intervention for relief of dysphagia due to fibrous stricture.
 Enhanced survival was associated with a complete endoscopic response to initial chemotherapy and radiotherapy, and a tumour of less than 5 cm in length.
 The median survival of responding patients was 15 months.
 Synchronous chemotherapy and radiotherapy was of major palliative benefit in this series and merits further evaluation.
",3
186,"Manometric evaluation of jejunal limb after total gastrectomy and Roux-Orr anastomosis for gastric cancer.
 Total gastrectomy with Roux-Orr anastomosis is frequently performed for gastric cancer.
 Since intestinal motility of the Roux limb has never been evaluated after this operation, pressure activity was investigated in the Roux limb of ten patients (aged 51-77 years) who had undergone total gastrectomy and Roux-Orr reconstruction.
 Investigations were carried out during a 6-h fast and 3 h after a 605 kcal mixed meal.
 During fasting only two patients had activity fronts and these were abnormal.
 All ten patients displayed non-propagating bursts of contractions and three had discrete clustered contractions and high amplitude jejunal contractions.
 The fed state was characterized by a severely reduced motor activity pattern and other abnormalities.
 Total gastrectomy with Roux-Orr anastomoses provokes a relatively severe disturbance in intestinal activity.
",3
187,"Intraoperative ultrasonography and the detection of liver metastases in patients with colorectal cancer.
 A total of 213 patients with carcinoma of the colon and rectum were examined to detect liver metastases.
 The study compared preoperative ultrasonography and inspection and palpation of the liver during surgery with intraoperative ultrasonography.
 Preoperative ultrasonography, inspection and palpation identified 238 metastases in 42 patients.
 Intraoperative ultrasonography detected 116 previously unrecognized metastatic tumours during 40 surgical procedures (P less than 0.01).
 High resolution intraoperative ultrasonography is safe and more accurate than preoperative imaging and surgical exploratory methods.
 The examination is simple to perform and success appears to be related to careful attention to detail.
",3
188,"The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma.
 Gastric cancer remains a disease with a very poor prognosis, and there is no safe and effective form of therapy for advanced disease.
 Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo, and that blockade of gastrin receptors can prolong survival in xenografted nude mice.
 We have thus performed a randomized, controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma.
 Proglumide had no overall effect on survival (Mantel-Cox statistic = 0.5, P = 0.48).
 The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group.
 No significant difference was seen with proglumide, which has a relatively low affinity with the gastrin receptor and also has partial agonist activity.
 Drugs that are far more specific and potent gastrin receptor antagonists are becoming available, which may have a greater effect on survival, and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy.
",3
189,"Autopsy-documented cure of multiple myeloma 14 years after M2 chemotherapy.
 Multiple myeloma was diagnosed in a 65-year-old woman in 1974 who thereafter received five-drug M2 chemotherapy.
 All protein abnormalities subsequently returned to normal and serial bone marrow studies documented complete bone marrow remission.
 Destructive bone lesions persisted radiographically, but did not progress.
 In 1987, a localized sigmoid adenocarcinoma was resected.
 In 1988, the patient presented with multiple brain metastases associated with a primary pulmonary adenocarcinoma that proved rapidly fatal.
 At autopsy, no evidence of multiple myeloma was found.
 This report describes the first tissue-documented cure of multiple myeloma 14 years after diagnosis and initiation of M2 chemotherapy.
 The possible association of multiple myeloma with other malignancies is also discussed.
",3
190,"Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions.
 The application of fine-needle aspiration biopsy (FNAB) to the diagnosis of nonpalpable breast lesions was evaluated with a new method which uses standard needle localization under mammographic guidance to assure accurate sampling by FNAB.
 This method was prospectively applied to 100 mammographically detected breast lesions in 100 women (mean age, 53 years).
 All 100 patients underwent surgical excision of these nonpalpable lesions after cytologic aspiration.
 Sufficient aspirated material was obtained for cytologic diagnosis from 91 patients (91%).
 The histologic and cytologic interpretations were then compared.
 Twenty malignancies were ultimately diagnosed by histology (12 invasive ductal carcinoma, six ductal carcinoma in situ, and two lobular carcinoma in situ), of which 17 had been cytologically diagnosed.
 There were no false-positive diagnoses of malignancy by FNAB.
 False-negative readings (3.3%) included two cases of lobular carcinoma in situ and one case of ductal carcinoma in situ.
 This technique thus demonstrated a sensitivity of 85%, specificity of 100%, and overall diagnostic accuracy of 96.7% for the nonsurgical detection of malignancy in nonpalpable breast lesions.
 These results suggest that the established safety, reliability, and cost-effectiveness of FNAB can be maintained in this clinical setting.
 This procedure may obviate the need for open surgical biopsy in those patients with an unequivocal diagnosis of malignancy.
 It can also be done using standard techniques and equipment available in many community hospitals.
",3
191,"Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion.
 The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I).
 After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion.
 Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy.
 The mechanisms of the seroconversion are discussed.
",3
192,"Immunohistochemical studies on the main entrance-route of CA19-9 into the peripheral venous blood of gastric cancer patients. Correlation with CA19-9 levels in peripheral and portal blood.
 The correlation between CA19-9 levels of portal and peripheral venous blood, and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases.
 Immunohistochemically, CA19-9 was found in 33 (62.5%) of 53 primary lesions.
 The antigen was found in the cancer cells of invasive lymphatics and node metastases of every CA19-9 localized cancer, although the cancer cells in veins showed little or no CA19-9.
 There was little or no antigen in the cancer cells in veins, lymphatics, or metastases of 20 CA19-9 nonlocalized primary lesions.
 Patients with CA19-9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood.
 CA19-9 levels of portal blood (mean, 76.4 U/ml; positive rate, 33.3%) were not different from those of peripheral blood (mean, 91.5 U/ml; positive rate, 33.3%).
 Additionally, the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases, and every patient without the invasion showed no elevation of the antigen.
 These results suggest that production of the antigen in cancer cells may be a premise of CA19-9 elevation in peripheral blood and that CA19-9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics, but not by the hematogenous portal system.
",3
193,"Establishment of an erythroid cell line (JK-1) that spontaneously differentiates to red cells.
 The authors established a new hemopoietic cell line (JK-1) from a patient with chronic myelogenous leukemia in erythroid crisis.
 This JK-1 line predominantly consists of immature cells, but a small number of mature erythroblasts and red cells can be consistently seen without any specific differentiation inducer.
 The JK-1 cells grow in suspension culture supplemented with human plasma and carry double Philadelphia chromosomes.
 Hemoglobin staining with benzidine was positive for about 20% of cells and the type of the hemoglobin was for the most part HbF.
 Surface-marker analysis revealed JK-1 cells positive for glycophorin A, EP-1, and HAE9.
 The proportion of mature cells was elevated by the addition of delta-aminolevulinic acid.
 Erythropoietin (EPO) enhanced the growth of JK-1 cells either in the suspension or in methylcellulose semisolid culture.
 The total number of EPO receptors was 940 per cell, of which 220 sites had an affinity higher than the other 720 sites.
 This is the first report of an established human erythroid cell line which spontaneously undergoes terminal differentiation.
",3
194,"Mammographic screening of women with increased risk of breast cancer.
 Five hundred one women from Dallas County, Texas who participated in the American Cancer Society 1987 Texas Breast Screening Project were selected because of a self-reported family history of breast cancer (cases).
 They were matched with 501 randomly selected women from the same county with no family history (controls).
 Although there was a statistically significant trend with age for an increasing proportion of women to report having undergone mammography, there was no significant difference when comparing mammographic histories of cases with controls after controlling for age (31.5% versus 35.1%, P = 0.33).
 Significantly more cases (79%) perceived their risk for breast cancer to be moderate or greater compared with controls (54%, P less than 0.0001), but mammographic histories were not different when controlling for perceived risk.
 Both cases and controls cited lack of physician referral and cost as their reasons for not having undergone mammography.
 Women at increased risk for breast cancer (because of their family history) are not undergoing regular mammographic screening despite their self-awareness of the increase in their risk.
",3
195,"Murine monoclonal anti-idiotype antibody as a potential network antigen for human carcinoembryonic antigen.
 Carcinomas of the gastrointestinal tract are not curable by standard therapies.
 Thus, new therapeutic approaches for this disease are needed.
 This study proposes the use of anti-Id mAb as Ag substitutes to induce anti-tumor immunity in gastrointestinal cancer patients.
 Recently, we have generated and characterized one monoclonal anti-Id antibody, designated 3H1 (Ab2), which mimics biologically and antigenically a distinct and specific epitope of the 180,000 m.w.
 carcinoembryonic antigen (CEA) primarily expressed in high density by human pancreatic and colonic tumor cells.
 This epitope is unique to CEA and not present on other CEA-related lower m.w.
 members of the Ag family also found on normal tissues.
 The antigenic determinant as defined by the mAb 8019 (Ab1) against which the Ab2, 3H1 was raised, is absent on normal adult tissues by immunoperoxidase staining and haematopoietic cells including granulocytes by flow cytometry analysis.
 Anti-Id (Ab2) 3H1 induced CEA-specific antibodies in mice and rabbits.
 The immune sera from both mice and rabbits competed with Ab1 for binding to the colon carcinoma cell line LS174T and inhibited the binding of radioiodinated Ab1 to Ab2.
 This indicates that anti-anti-Id (Ab3) in mice and rabbits share idiotopes with Ab1 (8019).
 Furthermore, monoclonal Ab3 that bind to CEA have been generated from mice immunized with 3H1.
 The Ab3 (both polyclonal as well as monoclonal) immunoprecipitated the same 180,000 m.w.
 CEA as Ab1 (8019) by Western blotting analysis and showed almost identical immuno-staining patterns as Ab1 on colonic adenocarcinoma tissue sections from several patients.
 Collectively these data suggest that Ab2 3H1 could potentially be used clinically as a network Ag for immunotherapy of patients with CEA positive tumors.
",3
196,"Regulation of HLA class II molecule expressions by IFN-gamma. The signal transduction mechanism in glioblastoma cell lines.
 We examined the signal transduction mechanism responsible for the IFN-gamma-induced HLA class II molecule expressions on glioblastoma cell lines, T98G and A172.
 A series of experiments demonstrated that the activation of protein kinase C (PKC) is involved in the DR and DP molecule expressions on T98G cells.
 In addition to the activation of PKC, calcium influx appeared to be involved in the DR and DP molecule expressions on T98G.
 Northern blot analyses with actinomycin D or cycloheximide revealed that these second messengers induce the transcription of DRA and B and DPA and B genes without de novo protein synthesis.
 Furthermore, we examined the region of the DPB gene that is responsible for IFN-gamma-induced gene transcription by gene transfer of a series of 5' and 3' deletion mutants in which the upstream region of the DPB was linked to a reporter gene, chloramphenicol acetyltransferase.
 By using these deletion mutants, it appeared that the region between -152 and -126 bp contains a critical IFN-gamma-responsive element.
 Taken together, these results suggest that IFN-gamma activates PKC and stimulates calcium influx, resulting in the induction of transcription of DRA and B and DPA and B genes without de novo protein synthesis.
 In DPB gene, we speculate that preexiting protein(s) phosphorylated by PKC in the presence of Ca2+ might directly bind or indirectly interact with the region between -152 and -126 bp of the upstream sequence, leading to the induction of the transcription (possibly in concert with other nuclear protein(s) bound to the promoter sequences).
",3
197,"Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor-specific immune memory.
 The ability of rIL-4 to trigger host reactivity against both a chemically induced fibrosarcoma (CE-2) and a spontaneous adenocarcinoma (TS/A) of BALB/c mice was studied.
 Daily local s.c.
 administration around tumor draining lymph nodes of 10 injections of progressive amounts (0.00001 to 1000 pg/day) of rIL-4 induced appreciable inhibition of the growth of both tumors after a dose-response survival curve peaking at 0.1 pg/day.
 Inasmuch as rIL-4 has no direct antitumor activity, as shown by in vitro tests, host immune reactivity plays a fundamental role in this lymphokine activated tumor inhibition (LATI).
 LATI, in fact, is abolished when recipient mice are sublethally irradiated or treated with cyclosporin A, or when the reactivity of CD4+ lymphocytes is suppressed, whereas it is not affected by anti-asialo GM1 antibody.
 The morphologic data show that rIL-4 LATI rests on the recruitment of several cell reaction mechanisms, among which those that are nonspecific seem to predominate.
 rIL-4 LATI also leads to a state of long lasting and specific immune memory: the growth of a second contralateral tumor challenge is significantly impaired after LATI.
 This immune memory takes place after LATI of both the poorly immunogenic CE-2 fibrosarcoma and the TS/A adenocarcinoma, previously classed as nonimmunogenic on the basis of immunization-protection tests.
 In the latter case, adoptive transfer experiments show that Thy-1+ lymphocytes and, in particular, the CD4 cell-depleted T lymphocyte subpopulation, are responsible for the immune memory.
 Finally, the ability of rIL-4 to trigger LATI is greater than that of the most effective doses of rIL-2, rIL-1 beta, and IFN-gamma, whereas its association with rIL-1 beta induces a more effective immune memory.
",3
198,"Abnormal processing of pro-IGF-II in patients with hepatoma and in some hepatitis B virus antibody-positive asymptomatic individuals.
 Hepatomas are a common malignancy in countries with a high prevalence of hepatitis B virus infections.
 These tumors may present with severe persistent hypoglycemia.
 We have studied the possible relationship of production of insulin-like growth factor II (IGF-II) by these tumors and the development of hypoglycemia.
 Mean IGF-II concentration was not significantly higher in 23 patients with hypoglycemia than in nine patients with euglycemia (542 +/- 61 [SE] micrograms/L vs 382 +/- 52 micrograms/L).
 Serum IGF-I was more suppressed in patients with hypoglycemia (16 +/- 3 micrograms/L) than in patients with euglycemia (57 +/- 18 micrograms/L).
 Because an increased percentage of IGF-II in serum of patients with hypoglycemia who have other tumors is present as partially processed pro-IGF-II (""big"" IGF-II), we passed sera of patients with hypoglycemia and patients with euglycemia with hepatomas through acidic Bio-Gel P-60 columns.
 We found that 57% +/- 4.6% of the IGF-II in sera from patients with hypoglycemia was present as big IGF-II compared with 22% +/- 3% in patients with euglycemia with hepatomas (not significantly different from that in normal controls).
 Four of 11 apparently healthy control subjects who were hepatitis B virus positive also had increased percentages of big IGF-II, suggesting that abnormal processing of pro-IGF-II may result from subtle changes in liver function with this infection.
 It remains to be determined whether these subjects with increased big IGF-II are at increased risk for the development of hepatomas.
 In conclusion, we have confirmed marked suppression of IGF-I in the sera of patients with hepatoma and hypoglycemia.
",3
199,"Changes in surgical treatments: the example of hysterectomy versus conization for cervical carcinoma in situ.
 From 1969 through 1985, 4584 women in the state of New Mexico were diagnosed with carcinoma in situ of the cervix.
 Of these women, 65.5% underwent hysterectomy while 31.1% had a conservative therapy (primarily conization).
 Over the 17-year period, there was a steady increase in the percentage of women receiving conservative therapies, from 11.8% in 1969 to 50.3% in 1985.
 Younger women, unmarried women and American Indian women were more likely to receive conservative therapy.
 This marked shift in therapeutic approach occurred during a time of apparent controversy as to the optimal treatment for cervical carcinoma in situ, and illustrates a rapid change in surgical practice in the absence of any controlled trials comparing the two major treatment modalities.
",3
200,"Response of oral leukoplakia to beta-carotene.
 Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion.
 Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia.
 However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer.
 Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia.
 In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia.
 However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were ""guaranteed"" beta-carotene.
 Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months.
 Responding patients were continued for another 3 months of treatment.
 All lesions were examined histologically at entry.
 Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion.
 Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%).
 There was no significant toxicity requiring drug discontinuation or dose reduction.
 These results indicate that beta-carotene has substantial activity in oral premalignancy.
 Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer.
",3
201,"Pharmacodynamics in cancer therapy.
 Our understanding of anticancer pharmacodynamics, and the relationships between pharmacologic measurements and clinical effects, has grown markedly in recent years due to advances in analytical and computational technology.
 Although methotrexate plasma levels have been empirically used to guide leucovorin dosing during high-dose methotrexate therapy, there has been no other standard use of therapeutic drug monitoring in oncology.
 More recently, investigators have attempted to titrate precisely the dose of antineoplastic agents based on previously derived models and real-time analysis of plasma drug or tissue concentrations.
 Studies have been completed or are in progress using hexamethylene bisacetamide, etoposide, teniposide, fluorouracil (FUra), and cytarabine (ara-C).
 Future studies will focus on optimal sampling strategies, analysis of intermediate biochemical end points, combination chemotherapy, modulation by colony-stimulating factors, and more sophisticated pharmacodynamic models.
",3
202,"Characteristics and biological role of steroid hormone receptors in neuroepithelial tumors 
 Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors.
 Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively.
 Only a few tumors showed estrogen or progesterone receptors.
 A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors.
 The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors.
 For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml).
 A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture.
 No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses.
 Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status.
 All of the cultures tested for testosterone activity were negative for androgen receptors.
 This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml.
 The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins.
 Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone.
",3
203,"Lymphocele: the spectrum of scintigraphic findings in lymphoceles associated with renal transplant.
 Lymphocele is a well recognized complication of renal transplant surgery.
 We performed a retrospective review of 305 renal transplant patients with over 2,500 scintigraphic exams to describe the pattern of activity on technetium-99m-DTPA blood flow and dynamic imaging, and iodine-131-OIH studies.
 Diagnostic criteria for a lymphocele were ultrasonic evidence of a perirenal fluid collection and analysis of that fluid that demonstrated BUN, creatinine, and electrolytes similar to the patient's plasma.
 Scintigraphic findings were attributed to a lymphocele if abnormalities were in the same area as the ultrasound fluid collection.
 Scintigraphic findings attributable to lymphocele resolved in all patients following surgical drainage or peritoneal window placement.
 Six of the 11 documented lymphoceles demonstrated a cold defect on initial dynamic images that ""filled in"" to equal background activity and another exceeded background.
 Three cases showed a rim of increased activity surrounding the lymphocele (""rim sign"").
",3
204,"Scintigraphic evaluation of aggressive fibromatosis.
 Despite its benign microscopic appearance, aggressive fibromatosis has potential to recur and infiltrate neighboring tissues.
 Therefore, it is necessary to determine the exact extent before therapy.
 In the present study, 11 cases of aggressive fibromatosis were examined scintigraphically using [99mTc(V)]dimercaptosuccinic acid (11 cases) and 67Ga-citrate (7 cases).
 Technetium-99m-(V)-dimercaptosuccinic acid demonstrated all lesions, while 67Ga-citrate detected 57% of the cases.
",3
205,"N-[18F]fluoroacetyl-D-glucosamine: a potential agent for cancer diagnosis 
 Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue.
 Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide.
 We evaluated a new synthesized pharmaceutical, N-[18F]fluoroacetyl-D-glucosamine (18F-FAG), which is a structural analog of N-acetyl-D-glucosamine.
 C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study.
 At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27).
 The tumor uptake of 18F-FAG showed the highest value in all tissue.
 In the PET study, VX-2 carcinoma of the rabbit was clearly visualized.
 Our preliminary results suggest that 18F-FAG has potential as a new agent for tumor imaging.
",3
206,"Desmoplastic variant of ameloblastoma: report of a case and review of the literature.
 A case of desmoplastic variant of ameloblastoma is reported.
 The lesion, in a 36-year-old Japanese woman, was successfully treated by partial maxillectomy.
 Reconstruction was carried out with a block of hydroxyapatite about 7 years and 6 months later.
 Six cases, including our case, reported up to the present are summarized and reviewed.
",3
207,"Characterization of the effect of two 4-methyl piperidine derivatives of hemicholinium-3, A-4 and A-5, on choline transport.
 A-4 and A-5 are tertiary and N-methyl quaternary 4-methylpiperidine analogs of hemicholinium-3 (HC-3).
 Previous work in this laboratory has shown A-4 and A-5 to be inhibitors of the sodium-dependent, high affinity choline uptake system (SDHACU).
 Their effects on choline transport were characterized further using neuroblastoma 41A3 cells.
 These cells rapidly take up choline through two separate mechanisms: a SDHACU system and a sodium-independent, low affinity uptake system (SILACU).
 A-4, A-5 and HC-3 decreased 5 microM choline transport in a dose-dependent fashion.
 The compounds were unable to decrease choline transport at 250 microM choline suggesting that they are inactive with respect to SILACU.
 All three compounds significantly increased the Km but not the Vmax for the SDHACU system, suggesting a competitive mechanism of inhibition.
 Ki values ranged from 18 to 25 microM for A-4, 20 to 26 microM for A-5 and 68 to 75 microM for HC-3.
 Dose-response curves for inhibition of choline transport by A-5 and HC-3 were not changed by a 24-hr pre-exposure of the cells to each inhibitor.
 However, after a 24-hr pre-exposure to A-4, a significantly different dose-response curve was obtained compared to the dose-response curve for A-4 in untreated cells.
 After a 24-hr pre-exposure, a 4-hr recovery period was sufficient to remove the effect of each compound.
 These data suggest that A-4 and A-5, like HC-3, inhibit the SDHACU, competitively and reversibly.
",3
208,"Increasing annual incidence of primary malignant brain tumors in the elderly 
 Between 1973 and 1985, total age-adjusted cancer incidence in the United States (all races, men and women) rose by 10.7%, with an average annual percentage change of +0.9%.
 Analysis of reported age-specific incidence of primary malignant brain tumors over the same years demonstrates that incidence rates increased dramatically between 1973/1974 and 1985.
 In 1985, incidence rates for persons aged 75-79, 80-84, and 85 years of age and over were 187%, 394%, and 501%, respectively, of rates in 1973/1974.
 Similar increases were found in both men and women, analyzed separately and combined.
 Average annual percentage changes in primary brain tumor incidence were +7.0%, +20.4%, and +23.4% in these age ranges, respectively.
 Reported incidence in younger persons varied little over the same period of time.
 The most common histologic type of primary brain tumor in the elderly was of glial origin, predominantly the glioblastoma multiforme and astrocytoma.
 These tumors are highly malignant and invariably fatal.
 Two possible causes may explain the increased incidence in the elderly: the introduction and extensive use of x-ray computed tomography since 1973 and/or a true increase in incidence occurring independently of diagnostic advances.
",3
209,"Effect of prostaglandin E in multiple experimental models: V. Effect on tumor/host interaction.
 Prostaglandin E (PGE) has long been incriminated as a cause of the immunosuppression seen in cancer patients and for the increased rates of tumor growth due to the impairment of the immunologic response to the tumor.
 We have investigated the effect of PGE on tumor-host interaction by utilizing a parenterally administered long-acting PGE derivative, 16,16-dimethyl-prostaglandin E (dPGE).
 Administration of dPGE was found to decrease the rate of tumor growth but at a cost of decreasing tumor-free body mass.
 The dPGE did not alter resting metabolic rates but did alter some parts of brain dopamine metabolism and significantly decreased the serum level of multiple amino acids.
 In conclusion, elevated PGE levels may significantly alter metabolism in tumor patients.
",3
210,"Malignant melanoma occurring during pregnancy: a report of the Northern Israel Oncology Center (1968-1988).
 Medical records of seven patients treated within a 20 year period for malignant melanoma during pregnancy were reviewed.
 No significant detrimental prognostic effects could be attributed to pregnancy.
 The current literature on melanoma and pregnancy is discussed.
 Based on this, pregnancy seems not to be contraindicated in melanoma patients.
",3
211,"Renal vein leiomyosarcoma.
 The 11th case of primary leiomyosarcoma of the renal vein is reported.
 Unique features of this case included concomitant resection of an isolated hepatic metastasis, intraoperative radiation therapy, and the use of electron microscopy and immunohistochemical stains in confirming the diagnosis.
 A review of the previously reported cases shows a tendency toward slow tumor growth and infrequent recurrence (18%).
 Metastases are common (82%), primarily to the lung and liver.
 Aggressive surgical resection and adjuvant radiation therapy, including intraoperative radiation therapy, are recommended.
 Adjuvant chemotherapy should be considered, although its benefits at present are unclear.
",3
212,"Adrenal carcinosarcoma.
 The clinical and pathologic features of a case of adrenal carcinosarcoma are reported.
 Although synchronous malignancy of the adrenal gland has been described, no case of an adrenal tumor combining both carcinomatous and sarcomatous elements has been previously documented.
 This neoplasm is extremely aggressive with distant metastasis arising from the sarcomatous component, and rapid progression despite multimodal therapy.
",3
213,"Utility of surgical margins in the radiotherapeutic management of soft tissue sarcomas.
 Seventy-four adult patients with localized soft tissue sarcomas were treated with radiation therapy following surgery between 1965 and 1988.
 Fifty-three were treated after the first excision of their tumor with 6 (11.3%) local recurrences.
 Twenty-one received radiation after excision of recurrent disease with 11 (52.4%) local failures (P less than .0005).
 Metastatic disease occurred in 14 (26.4%) of the primary tumors and 8 (38.1%) with multiple previous excisions (P less than .48).
 Of those patients treated for primary sarcoma, there were no local failures with pathologically wide margins or if a single margin was microscopically positive.
 Local failure occurred in 4 of 26 (15.4%) if the tumor was merely enucleated and in 2 of 11 (18.2%) who had grossly positive surgical margins (P not significant).
 Local failure was also more common in truncal locations (33.3%) as compared with extremity locations (8.7%, P = .1359).
 Additional factors analyzed which adversely affected prognosis included tumor grade, stage, and inadequate radiation dose.
",3
214,"Acral melanoma: a review of 185 patients with identification of prognostic variables.
 One hundred eight-five patients with acral melanoma treated since 1972 were reviewed.
 These included 53 subungual lesions, 123 plantar lesions, and 9 palmar lesions.
 Eighty percent presented with stage I disease.
 Mean age was 57 years.
 Males outnumbered females 1.1:1.
 Seventeen percent (17%) were blacks.
 Actuarial 10-year survival was 58% for stage I patients and 35% for stage II patients.
 Univariate Cox regression analyses identified 5 prognostic variables affecting survival: stage at diagnosis (P less than 0.001), race (P less than 0.001), ulceration (P = 0.012), Clark's level (P = 0.014), and thickness of the primary lesion (P = 0.013).
 Factors unrelated to survival included sex of the patient, site (volar vs.
 subungual), histology, and treatment with amputation.
 Multivariate analysis for patients with stage I lesions identified race (P = 0.001) and ulceration (P = 0.018) as significant variables, with thickness approaching significance (P = 0.094).
 In an additional series of 71 patients with melanomas arising from extremity sites near the junction of glabrous and non-glabrous skin, survival was significantly poorer for those arising from glabrous skin (P = 0.024), and reflects a higher incidence of metastatic disease at diagnosis.
 Specific active immunotherapy was the principal adjuvant used for these patients, and survival was comparable to that reported with regional perfusion therapy.
 Acral melanoma a) has a strong racial predilection, b) carries a grave prognosis, and c) arises from glabrous skin.
 It is a clinical entity distinct from other extremity melanomas.
 Surgical management with either wide excision or amputation is appropriate for the primary lesion.
",3
215,"Long-term experience with a totally implanted catheter system in cancer patients.
 Long-term experience with totally implanted catheter systems (TICS) is limited.
 We retrospectively evaluated the performance and long-term complications of TICS for intravenous infusion in cancer patients; 134 systems were implanted in 128 patients.
 The median duration of implantation was 144 weeks with 49 systems implanted for more than one year.
 Complications related to surgical factors included malposition of reservoir (2%), skin perforation or wound dehiscence (1.5%) and pneumothorax (less than 1%).
 Complications not related to surgical factors included: drug extravasation (1.5%), mechanical malfunction (1.5%), vein thrombosis (less than 1%), clotting of the reservoir or catheter (2%), skin infection (1.5%), and sepsis (less than 1%).
 The total complication rate was 13%.
 Most complications resolved spontaneously or with medical treatment and only 6 patients (4.6%) required re-implantation of a second system.
 We conclude that with long-term usage of TICS, the complication rate remains low, making it a safe and viable alternative for patients requiring long-term intravenous therapy.
",3
216,"Cutaneous malignant melanoma in Rochester, Minnesota: trends in incidence and survivorship, 1950 through 1985 
 In Rochester, Minnesota, 107 incidence cases of cutaneous malignant melanoma (in 46 male and 61 female patients) were diagnosed during the years 1950 through 1985.
 Overall crude incidence rates were 6.0 and 6.6 per 100,000 males and females, respectively.
 Evaluation of trends in 9-year periods showed that the rates increased from 3.2 to 8.9 for males (P = 0.015) and from 4.4 to 11.7 for females (P less than 0.001).
 Age-specific rates suggested that the highest incidence occurs in the age-groups 50 to 59 years and 70 years or older for males and 40 to 49 years and 70 years or older for females.
 Lesions were most common in the head and neck area among males (P = 0.044) and on the lower extremities among females (P = 0.018).
 The most frequent histologic type was superficial spreading melanoma (61%).
 Five-year survival was diminished overall for patients with cutaneous malignant melanoma--0.72 in comparison with 0.88 expected for the general population.
 Statistically significant risk factors for survival were depth of invasion of the lesion (Clark level), thickness of the lesion, histologic type, and age of the patient.
",3
217,"Diagnosis of corticotropin-producing bronchial carcinoid tumors causing Cushing's syndrome 
 Cushing's syndrome due to ectopic production of adrenocorticotropic hormone (corticotropin) has been recognized for many years.
 Traditionally, clinicians have thought that most cases were due to lung carcinomas and that the clinical manifestations differed from those for pituitary-dependent Cushing's syndrome.
 We report two cases of corticotropin-producing bronchial carcinoid tumors that were clinically and biochemically indistinguishable from pituitary-dependent Cushing's syndrome.
 Review of the literature revealed that bronchial carcinoid tumors are the most common cause of Cushing's syndrome due to ectopic secretion of corticotropin.
 On biochemical and anatomic studies, they are frequently indistinguishable from pituitary-dependent Cushing's syndrome and thus may be difficult to diagnose.
 Inferior petrosal sinus sampling for corticotropin and computerized imaging of the chest may be the best aids in making the diagnosis.
",3
218,"Adult T-cell leukaemia/lymphoma in Brazil and its relation to HTLV-I 
 In a series of fourteen patients with adult T-cell lymphoma-leukaemia (ATLL) in Brazil the main features were lymphadenopathy, hepatosplenomegaly, hypercalcaemia, and high leucocyte counts, with abnormal lymphoid cells which had irregular nuclei.
 The series included the youngest patient with ATLL so far (18 months).
 Analysis with monoclonal antibodies showed a mature T-cell phenotype (CD4+, CD8-).
 Antibodies to HTLV-I and/or integration of HTLV-I proviral DNA were found in eleven patients.
 In the other three HTLV-I DNA could not be demonstrated even by means of the polymerase chain reaction; they therefore had HTLV-I-negative ATLL.
 This report of ATLL in Brazil corroborates serological reports that HTLV-I may be endemic in some parts of that country.
 Follow-up studies are required to identify precisely the main route of transmission of HTLV-I in South America and the risk factors for the development of ATLL in carriers.
",3
219,"Local control of auricular, periauricular, and external canal cutaneous malignancies with Mohs surgery.
 Three hundred ninety-seven patients with 407 cutaneous malignancies of the auricle, periauricular region, and cartilaginous external ear canal were reviewed.
 Tumors were most commonly located in the preauricular and postauricular regions, followed by the helix, concha, antihelix, and ear canal.
 All lesions were excised with Mohs microscopic control of margins.
 For lesions requiring lateral temporal bone resection, an adaptation of fresh-tissue microscopic control was used to analyze deep and anterior margins suspected of harboring residual tumor.
 Two-year minimum follow-up of 229 patients with periauricular and auricular tumors (N = 231 tumors) and 14 patients with cartilaginous ear canal tumors (N = 14 tumors) revealed recurrence rates of 6.9% and 14.3%, respectively.
 Recurrences were most common in cases of large tumors (greater than 2.5 cm), basal cell carcinomas with morphea elements, and multiply recurrent lesions.
 We conclude that Mohs surgery is comparatively effective, though not uniformly curative, and can be adapted to supplement excision of large tumors in these regions.
",3
220,"Clinical classification and staging for primary malignancies of the maxillary antrum.
 A study of 51 patients with primary malignant maxillary sinus neoplasms was conducted.
 None of the patients had neck nodes and/or metastases, and each had 5-year follow-up.
 The tumors were staged according to the 1983 and 1988 American Joint Committee on Cancer staging systems for maxillary sinus cancers.
 There were 13 early stage (T1, T2) and 38 advanced (T3, T4) tumors in both systems.
 Cox regression analyses of survival curves showed increasingly worse prognoses for advanced tumors in both T-staging systems.
 Further analyses showed a significant difference in survival between T3 and T4 in the 1988, but not in the 1983 system.
 There were no significant differences in survival according to treatment modality or histological type of malignancy.
 We conclude that the 1988 system prognosticates successfully for T-stage (1 to 4) and demonstrates significant improvement in detecting T3 versus T4 differences compared to the 1983 system.
 The 1988 system applies equally for epidermoid cancer and other malignancies of the antrum.
",3
221,"Somatostatin-receptor imaging in the localization of endocrine tumors 
 BACKGROUND AND METHODS.
 A number of different tumors have receptors for somatostatin.
 We evaluated the efficacy of scanning with 123I-labeled Tyr3-octreotide, a somatostatin analogue, for tumor localization in 42 patients with carcinoid tumors, pancreatic endocrine tumors, or paragangliomas.
 We then evaluated the response to octreotide therapy in some of these patients.
 RESULTS.
 Primary tumors or metastases, often previously unrecognized, were visualized in 12 of 13 patients with carcinoid tumors and in 7 of 9 patients with pancreatic endocrine tumors.
 The endocrine symptoms of these patients responded well to therapy with octreotide.
 Among 20 patients with paragangliomas, 8 of whom had more than one tumor, 10 temporal (tympanic or jugular), 9 carotid, and 10 vagal tumors could be visualized.
 One small tympanic tumor and one small carotid tumor were not seen on the scan.
 CONCLUSIONS.
 The 123I-labeled Tyr3-octreotide scanning technique is a rapid and safe procedure for the visualization of some tumors with somatostatin receptors.
 A positive scan may predict the ability of octreotide therapy to control symptoms of hormonal hypersecretion.
",3
222,"Intraoperative radioimmunodetection of ovarian cancer using monoclonal antibody B72.3 and a portable gamma-detecting probe.
 To assess the value of radioimmunoguided surgery in the intraoperative detection of ovarian cancer, we used monoclonal antibody B72.3, radiolabeled with 125I, and a hand-held gamma-detecting probe in 13 women with ovarian cancer undergoing exploratory laparotomy.
 B72.3, which recognizes a tumor-associated glycoprotein, TAG 72, was injected 12-29 days preoperatively (intraperitoneally in four cases, intravenously in nine, and by both routes in one).
 Intraoperatively, the abdomen was surveyed with the probe and probe counts were correlated with biopsies and excised specimens studied by routine histologic stains.
 Probe counts were positive in four of seven evaluable patients with histologically confirmed disease.
 In three of these four patients, the probe detected cancer in specimens interpreted as normal on frozen histologic sections.
 The probe also identified microscopic cancer in the one patient who had no gross disease.
 The specificity of the probe was 70%.
 Preoperative computed tomography was normal in all patients, including those with tumors as large as 3 cm.
 This pilot study shows the ability of radioimmunoguided surgery to detect occult ovarian cancer.
",3
223,"Prognostic factors for outcome of and survival after second-look laparotomy in patients with advanced ovarian carcinoma.
 In ovarian cancer stages IIB-IV, pre-treatment variables and variables obtained intraoperatively at second-look laparotomy were investigated for their prognostic influence on the outcome of 109 patients and survival after second-look laparotomy in 131 patients.
 The subjects came from a randomized trial of sequential versus alternating combination chemotherapy.
 The overall median survival after second-look laparotomy was 62 months.
 Logistic regression analysis identified stage and hysterectomy plus bilateral salpingo-oophorectomy and omentectomy as significant prognostic covariates for second-look laparotomy outcome.
 Based on a Cox multivariate stepwise analysis, independent prognostic factors for survival after second-look laparotomy were secondary residual tumor size, pre-treatment histologic differentiation grade, and performance status.
 A high differentiation grade and a good performance status at the start of therapy thus still had a prolonging effect on survival after second-look laparotomy.
 The prognostic power of these pre-treatment variables was increased substantially by the addition of the secondary residual tumor size variable.
 The 3-year survival rate after second-look laparotomy for high- and low-risk patients was 15 and 87%, respectively.
 Second-look laparotomy thus provides prognostic information in patients with advanced ovarian carcinoma, but the benefit in terms of survival is still unclear.
",3
224,"Ovarian metastases are rare in stage I adenocarcinoma of the cervix.
 Over a 32-year period at the University of California, Los Angeles Medical Center, all cases of adenocarcinoma and adenosquamous carcinoma of the uterine cervix were reviewed to determine the incidence of ovarian metastases in stage I disease.
 One of 25 patients (4.0%) who underwent an exploratory laparotomy and radical hysterectomy had a microscopic ovarian metastasis.
 A literature review identified nine additional patients who had ovarian metastases and stage I adenocarcinoma of the cervix.
 Including our series, the overall reported rate of ovarian metastases is 1.8%.
 All ten patients had at least one of the following additional characteristics: They were postmenopausal, they had adnexal pathology, or they had positive pelvic lymph nodes.
 Thus, ovarian preservation is warranted in premenopausal patients who do not have ovarian pathology or evidence of other metastatic disease at surgery.
 Bilateral oophorectomy may be performed if frozen-section examination of enlarged or suspicious nodes documents metastases.
 If the ovaries are left in the pelvis at the completion of the surgical procedure and microscopic spread to other pelvic tissues is documented, pelvic irradiation can be administered.
",3
225,"The fallacy of the screening interval for cervical smears.
 One hundred seventy-four women with invasive cervical carcinoma were interviewed about their cervical smear histories to assess the accuracy of self-reporting and to relate the smear history with patient and tumor characteristics.
 Patients reported significantly more frequent, more recent, and more normal smears than were documented in medical records.
 The interval between onset of cancer symptoms and previous smear correlated directly with advanced stage.
 Sixteen women with normal smears within 36 months had significantly more advanced cancers than did 25 women with recent abnormal smears.
 Women with recent normal and abnormal smears had similar sociodemographic and behavioral characteristics.
 Because of inaccuracies in patients' self-reported smear histories and cancers developing in women with recent normal smears, we conclude that a specific screening interval should not be relied upon.
",3
226,"Cold-knife and laser conization for cervical intraepithelial neoplasia.
 In a 5-year study, 425 women had conization performed for cervical intraepithelial neoplasia (CIN) I, II or III.
 Conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive.
 In all other cases, local destruction was the operation of choice.
 In the early years of the study, conization was done by the cold-knife method (N = 201), whereas CO2 laser was used in the latter part of the study (N = 224).
 Success and complication rates were the same for the two methods.
 Abnormal cytology after conization was found in a total of 53 cases (12.5%), but a histologic confirmation of residual or recurrent CIN was made in only 27 women (6.4%).
 This corresponds to a success rate of 92% after cold-knife and 95% after laser conization.
 The CIN grading of the residual or recurrent CIN was similar to or less than the CIN diagnosis of the cone.
 Because our success rate was comparable to that of other series with much less strict referral criteria, our policy seems adequate.
",3
227,"Primary invasive carcinoma of the vagina.
 A retrospective review was conducted of 53 women with invasive carcinoma of the vagina and without documented exposure to diethylstilbestrol who were seen at the University of California Irvine Medical Center, Long Beach Memorial Medical Center, and Saddleback Memorial Medical Center from 1976-1988.
 Forty-seven (89%) had squamous cell carcinoma and six (11%) adenocarcinoma.
 Thirty-seven (70%) were treated with whole-pelvis irradiation and brachytherapy, nine with surgery alone, and the other seven with a combination of treatments.
 The crude and corrected 2-year survival rates for the entire group were 47 and 69%, respectively.
 Those with previous pelvic surgery were more likely to develop serious treatment-related complications.
 There was a statistically significant correlation between previous hysterectomy and the diagnosis of primary invasive carcinoma of the vagina after the onset of symptoms.
 Women diagnosed during routine examination, before symptom onset, tended to have a survival advantage.
 All women, including those who have had hysterectomy, should be counseled to continue gynecologic cancer surveillance regardless of age.
",3
228,"Carbon dioxide laser vaporization of diaphragmatic metastases for cytoreduction of ovarian epithelial cancer.
 Three patients with International Federation of Gynecology and Obstetrics state IIIC ovarian adenocarcinoma underwent CO2 laser vaporization of large-volume (5-6 cm) and miliary right hemidiaphragmatic metastases at the conclusion of standard debulking surgery to effect optimal cytoreduction.
 Destruction of diaphragmatic metastases was accomplished rapidly with no added morbidity or blood loss.
 The hand-held CO2 laser is a useful modality for removal of isolated large- and small-volume diaphragmatic disease, particularly if only the peritoneum is involved, and avoids the morbidity that may accompany entry into the pleural space.
",3
229,"Detection, prevalence, and prognosis of asymptomatic carcinoma of the cervix.
 Between 1979-1986, 82 of 407 patients (20%) treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis.
 Sixteen (20%) of these 82 patients had stage IA, 60 (73%) had stage IB, and six (7%) had stage IIA disease.
 Asymptomatic patients represented 16 of 23 (70%) of stage IA, 60 of 196 (31%) of stage IB, and six of 77 (8%) of stage IIA.
 In the Netherlands, population screening for cervical carcinoma is conducted on women aged 35-55 years.
 To examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups, we studied the patients referred to our department.
 Among the patients younger than 35 years with cervical carcinoma, 20 of 70 (29%) were asymptomatic with disease detected by incidental screening, whereas eight of 177 (5%) in the group 55 years or older had been detected by incidental screening.
 In the age category 35-55 years, 54 of 160 (34%) were asymptomatic.
 Patients aged 35-55 years had undergone population screening or incidental screening.
 In the patients 55 years or older, asymptomatic disease was significantly less prevalent than in younger patients.
 Only one of the 66 asymptomatic patients in stage IB or higher suffered tumor recurrence.
 Among symptomatic patients, 25 of 136 (18%) with stage IB and 17 of 71 (24%) with stage IIA had tumor recurrence.
 Despite the favorable prognosis of patients with asymptomatic carcinoma, asymptomatic presentation could not be shown to be a significant prognostic factor, as were tumor diameter and lymph node status.
",3
230,"New findings in treatment of colon cancer.
 Patients with colon cancer involving regional lymph nodes (stage C disease) have a 5-year survival rate of only 30% to 40%, and the majority die of recurrent disease.
 Recent trials have shown increased survival rates with postoperative use of fluorouracil plus levamisole.
 The authors discuss these findings and the implications on treatment recommendations for stage C colon cancer.
",3
231,"Cloning of the cDNA for human 12-lipoxygenase.
 A full-length cDNA clone encoding 12-lipoxygenase (arachidonate:oxygen 12-oxidoreductase, EC 1.13.11.31) was isolated from a human platelet cDNA library by using a cDNA for human reticulocyte 15-lipoxygenase as probe for the initial screening.
 The cDNA had an open reading frame encoding 662 amino acid residues with a calculated molecular weight of 75,590.
 Three independent clones revealed minor heterogeneities in their DNA sequences.
 Thus, in three positions of the deduced amino acid sequence, there is a choice between two different amino acids.
 The deduced sequence from the clone plT3 showed 65% identity with human reticulocyte 15-lipoxygenase and 42% identity with human leukocyte 5-lipoxygenase.
 The 12-lipoxygenase cDNA recognized a 3.0-kilobase mRNA species in platelets and human erythroleukemia cells (HEL cells).
 Phorbol 12-tetradecanoyl 13-acetate induced megakaryocytic differentiation of HEL cells and 12-lipoxygenase activity and increased mRNA for 12-lipoxygenase.
 The identity of the cloned 12-lipoxygenase was assured by expression in a mammalian cell line (COS cells).
 Human platelet 12-lipoxygenase has been difficult to purify to homogeneity.
 The cloning of this cDNA will increase the possibilities to elucidate the structure and function of this enzyme.
",3
232,"p53 mutations in colorectal cancer.
 Immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in approximately 50% of the malignant tumors examined.
 Benign adenomas were all negative for p53 overexpression.
 To determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines.
 Six of the cell lines expressed high levels of p53 in ELISA, cell-staining, and immunoprecipitation studies.
 Direct sequencing and chemical-mismatch-cleavage analysis of p53 cDNA by using the polymerase chain reaction in these cell lines showed that all cell lines that expressed high levels of p53 were synthesizing mRNAs that encoded mutant p53 proteins.
 In two of those four cell lines where p53 expression was lower, point mutations were still detected.
 Thus, we conclude that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis.
 Mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer.
",3
233,"Chemical carcinogenesis: too many rodent carcinogens.
 The administration of chemicals at the maximum tolerated dose (MTD) in standard animal cancer tests is postulated to increase cell division (mitogenesis), which in turn increases rates of mutagenesis and thus carcinogenesis.
 The animal data are consistent with this mechanism, because a high proportion--about half--of all chemicals tested (whether natural or synthetic) are indeed rodent carcinogens.
 We conclude that at the low doses of most human exposures, where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than is commonly assumed.
",3
234,"Gd-HP-DO3A in clinical MR imaging of the brain.
 As part of a phase II clinical trial, 14 patients with presumed intracranial neoplastic disease underwent magnetic resonance (MR) imaging before and after intravenous injection of gadolinium 1,4,7-tris(carboxymethyl)-10-(2'-hydroxypropyl)-1,4,7,10-tetraazacycl ododecane (HP-DO3A).
 This neutral (nonionic) gadolinium chelate has lower osmolality, when formulated at equimolar concentrations, and superior in vitro stability compared with gadopentetate dimeglumine.
 The safety profile of Gd-HP-DO3A permitted administration of doses up to 0.3 mmol/kg, three times the dose of gadopentetate dimeglumine approved by the U.S.
 Food and Drug Administration.
 In this limited clinical trial, Gd-HP-DO3A proved to be a safe and efficacious agent in MR imaging of the head.
 The only change documented in patient monitoring was that of slight skin redness at the injection site immediately after administration in two patients.
 No statistically significant changes due to administration of the agent were noted in laboratory evaluations.
 These results differ from those obtained with gadopentetate, which induces a transient rise in serum iron and bilirubin levels in up to 26% of patients.
 Administration of higher doses of Gd-HP-DO3A, either 0.2 or 0.3 mmol/kg, appeared to provide improved enhancement.
 No decrease in efficacy at these high doses was noted.
",3
235,"Primary Ewing sarcoma: follow-up with Ga-67 scintigraphy.
 While avid accumulation of gallium-67 citrate and technetium-99m methylene diphosphonate (MDP) occurs initially in most cases of primary Ewing sarcoma, uptake after therapy is less well defined.
 Thirty patients with Ewing sarcoma who underwent Ga-67 and bone scintigraphy at diagnosis, at completion of therapy, and at relapse from 1978 to 1988 were evaluated.
 All 30 patients showed less primary site Ga-67 activity following therapy.
 Twenty-three of 28 patients who underwent corresponding bone scintigraphy showed less uptake, but residual activity was usually more intense than with Ga-67.
 Avid reaccumulation of Ga-67 occurred in four of five patients with primary site relapse, while patients who underwent bone scintigraphy showed less change.
 It was concluded that a greater decrease in Ga-67 than in Tc-99m MDP uptake often occurs in patients successfully treated for primary Ewing sarcoma.
 Information obtained at Ga-67 scintigraphy is most likely to be helpful if results of bone scintigraphy remain abnormal or if occult relapse is suspected.
",3
236,"Endorectal ultrasonographic staging of rectal carcinoma.
 Endorectal ultrasonography is a valuable imaging method for examination of the rectum and perirectal tissues.
 We assessed 50 patients with known rectal carcinoma prospectively by using a 7.0-MHz endorectal transducer to determine the depth of invasion of the rectal wall by tumor and the presence of lymphadenopathy.
 Tumors were staged by using the Astler-Coller modification of the Dukes staging system, and the results were compared with histologic staging of the surgical specimen.
 Ultrasonography had an accuracy of 80%, a sensitivity of 92%, and a specificity of 76% for detection of invasion of the perirectal fat.
 Ultrasonography was sensitive in the detection of perirectal lymphadenopathy but was not specific in distinguishing benign from malignant nodes.
",3
237,"Invasive lobular carcinoma: mammographic findings in a 10-year experience 
 From January 1, 1976 to December 30, 1985, 1,966 cases of breast carcinoma were diagnosed and treated at Malmo General Hospital, Malmo, Sweden.
 Of these cases, 185 (9.4%) involved invasive lobular carcinoma (ILC).
 Mammography in 137 cases demonstrated the following findings: spiculated opacity (53%), architectural distortion (16%), poorly defined opacity (7%), normal or benign findings (16%), and parenchymal asymmetry (4%).
 Radiographic definition of the ILC lesion varied greatly with projection: The craniocaudal view demonstrated significant findings more frequently than either the oblique or lateral views.
 Secondary radiographic findings were present in 31%, microcalcifications were rare, and physical findings were present in 89%.
 Because of its diffuse growth pattern and tendency to form lesions with opacity equal to or less than that of the parenchyma, ILC can be extremely difficult to detect mammographically.
 Therefore, the radiologist must be alert for subtle mammographic signs of malignancy and highly suspicious of any abnormal physical findings regardless of the mammographic appearance.
",3
238,"Mammographic follow-up of low-suspicion lesions: compliance rate and diagnostic yield.
 All recommendations for mammographic follow-up of low-suspicion lesions seen at mammography during a 6-month period were reviewed to establish compliance rate and eventual outcome.
 One hundred forty-four of 2,650 mammograms (5%) showed minimal abnormalities that warranted short-term and periodic mammographic follow-up.
 Rates of compliance at 4 months and at 1, 2, and 3 years were 88%, 71%, 60%, and 47%, respectively.
 Progressive mammographic change was found in 10 patients, only one of whom had a carcinoma.
 It was concluded that mammographic follow-up of low-suspicion lesions is a reasonable alternative to surgical biopsy, although patient compliance remains a significant problem.
",3
239,"Insulinomas: localization with selective intraarterial injection of calcium.
 To facilitate the noninvasive preoperative localization of islet cell tumors less than 15 mm in diameter, the authors examined the use of calcium as an insulin secretagogue in an arterial stimulation venous sampling (ASVS) technique.
 In four patients with episodic hypoglycemia, calcium gluconate (0.01-0.025 mEq Ca2+/kg) was injected directly into branches of the celiac plexus (gastroduodenal, splenic, and hepatic arteries) and the superior mesenteric artery.
 In all patients, serum levels of insulin rose abruptly in blood samples taken from the right hepatic vein 30 and 60 seconds after the infusion of calcium into the artery supplying the tumor; injection into an artery not supplying the tumor did not result in a similar rise.
 Accurate localization of the insulinomas was verified at surgery in three patients.
 In the fourth patient, who did not undergo surgery, arteriographic results were positive for insulinoma at the predicted site.
 On the basis of these results, the authors believe noninvasive ASVS may replace invasive portal venous sampling as the most effective method for the localization of occult insulinomas.
",3
240,"Selective catheterization of the inferior petrosal sinuses: new catheter design.
 Catheters for selective catheterization of the right and left inferior petrosal sinuses have been developed to replace the complex tip-deflector catheter-guide-wire system currently used.
 The new catheters are easily formed from commonly available straight catheters with the use of steam.
 They have been successfully tested in 22 patients; the only complications were minor groin hematomas.
",3
241,"Petrosal sinus sampling: technique and rationale.
 Bilateral simultaneous sampling of the inferior petrosal sinuses is an extremely sensitive, specific, and accurate test for diagnosing Cushing disease and distinguishing between that entity and the ectopic ACTH syndrome.
 It is also valuable for lateralizing small hormone-producing adenomas within the pituitary gland.
 The inferior petrosal sinuses connect the cavernous sinuses with the ipsilateral internal jugular veins.
 The anatomy of the anastomoses between the inferior petrosal sinus, the internal jugular vein, and the venous plexuses at the base of the skull varies, but it is almost always possible to catheterize the inferior petrosal sinus.
 In addition, variations in size and anatomy are often present between the two inferior petrosal sinuses in a patient.
 Advance preparation is required for petrosal sinus sampling.
 Teamwork is a critical element, and each member of the staff should know what he or she will be doing during the procedure.
 The samples must be properly labeled, processed, and stored.
 Specific needles, guide wires, and catheters are recommended for this procedure.
 The procedure is performed with specific attention to the three areas of potential technical difficulty: catheterization of the common femoral veins, crossing the valve at the base of the left internal jugular vein, and selective catheterization of the inferior petrosal sinuses.
 There are specific methods for dealing with each of these areas.
 The sine qua non of correct catheter position in the inferior petrosal sinus is demonstration of reflux of contrast material into the ipsilateral cavernous sinus.
 Images must always be obtained to document correct catheter position.
 Special attention must be paid to two points to prevent potential complications: The patient must be given an adequate dose of heparin, and injection of contrast material into the inferior petrosal sinuses and surrounding veins must be done gently and carefully.
 When the procedure is performed as outlined, both inferior petrosal sinuses can be catheterized in more than 98% of patients.
 The complication rate is low, and the theoretical risk of major morbidity or death is less than 1% (neither has yet occurred, to our knowledge).
 The most common complication is groin hematoma.
",3
242,"Spindle and epithelioid cell nevus (Spitz nevus). Natural history following biopsy.
 A clinical follow-up study of 49 cases of spindle and epithelioid cell nevus is presented to address the question about the potential for local recurrence.
 Only 19 (39%) of the 49 lesions were initially excised en toto, and the remainder (30 cases) had positive margins; six of the latter spindle and epithelioid cell nevi were reexcised, and no evidence of a residual nevus was found in five of the six cases.
 There were no recurrences in the 49 patients during an average follow-up period of 5.0 years (range, 1 to 10 years).
 The rarity of recurrent spindle and epithelioid cell nevus would justify a conservative approach to management, with clinical follow-up alone recommended after a subtotal excision, when the pathologic diagnosis is unequivocal.
",3
243,"Occupational sunlight exposure and melanoma in the U.S. Navy.
 Melanoma is the second most common cancer, after testicular cancer, in males in the U.S.
 Navy.
 A wide range of occupations with varying exposures to sunlight and other possible etiologic agents are present in the Navy.
 Person-years at risk and cases of malignant melanoma were ascertained using computerized service history and inpatient hospitalization files maintained at the Naval Health Research Center.
 A total of 176 confirmed cases of melanoma were identified in active-duty white male enlisted Navy personnel during 1974-1984.
 Risk of melanoma was determined for individual occupations and for occupations grouped by review of job descriptions into three categories of sunlight exposure: (1) indoor, (2) outdoor, or (3) indoor and outdoor.
 Compared with the U.S.
 civilian population, personnel in indoor occupations had a higher age-adjusted incidence rate of melanoma, i.e., 10.6 per 100,000 (p = .06).
 Persons who worked in occupations that required spending time both indoors and outdoors had the lowest rate, i.e., 7.0 per 100,000 (p = .06).
 Incidence rates of melanoma were higher on the trunk than on the more commonly sunlight-exposed head and arms.
 Two single occupations were found to have elevated rates of melanoma: (1) aircrew survival equipmentman, SIR = 6.8 (p less than .05); and (2) engineman, SIR = 2.8 (p less than .05).
 However, there were no cases of melanoma or no excess risk in occupations with similar job descriptions.
 Findings on the anatomical site of melanoma from this study suggest a protective role for brief, regular exposure to sunlight and fit with recent laboratory studies that have shown vitamin D to suppress growth of malignant melanoma cells in tissue culture.
 A mechanism is proposed in which vitamin D inhibits previously initiated melanomas from becoming clinically apparent.
",3
244,"Control of interleukin-1 beta expression by protein kinase C and cyclic adenosine monophosphate in myeloid leukemia cells.
 We have examined the signal transduction pathways leading to the expression of the interleukin-1 beta (IL-1 beta) gene in human myeloid leukemia cells lines.
 Two cell lines representing different stages of differentiation were used (HL-60, promyelocytic, and THP-1, mature monocytic).
 In accordance with previous studies, it was observed that a protein kinase C (PKC) activator, phorbol myristate acetate (PMA), was a sufficient stimulus for induction of the IL-1 beta messenger RNA (mRNA) expression and IL-1 beta protein production in both of these cell lines.
 A structural analog of cyclic adenosine monophosphate (dbcAMP) or agents elevating the endogenous cAMP levels (prostaglandin E2, forskolin) were not alone able to induce IL-1 beta expression, but they strongly enhanced the PMA-induced IL-1 beta production and IL-1 beta mRNA accumulation.
 Nuclear run off analysis showed that this elevation in IL-1 beta mRNA levels was due to an increased rate of transcription.
 If dbcAMP was added 6 hours before PMA to the cultures, no enhancement in the IL-1 beta production was seen, implying that for this enhancing effect both of these signals must be present simultaneously.
 PKC inhibitor, H7, also blocked effectively the PMA plus dbcAMP induced IL-1 beta production, while the protein kinase A (PKA) inhibitor, HA1004, had no effect, suggesting that PKA activation is not involved in the mechanism of action of cAMP in this case.
 Collectively, the present findings show that cAMP-dependent signals can have a positive regulatory effect on the PKC-dependent activation of the IL-1 beta gene in cells derived from different stages of myeloid differentiation.
",3
245,"Potentiation of the erythropoietin response by dimethyl sulfoxide priming of erythroleukemia cells: evidence for interaction of two signaling pathways.
 Erythropoietin (Epo) and dimethyl sulfoxide (DMSO) are believed to induce the differentiation of transformed erythroid cells by different signal transduction pathways.
 We have now obtained evidence for the interaction of these pathways.
 We used a Rauscher murine erythroleukemia cell line with a relatively low (8% to 10%) hemoglobinization response to Epo alone.
 Pretreatment of these cells for 1 day with DMSO followed by its removal and the addition of Epo resulted in a marked enhancement of the Epo specific hemoglobinization.
 We have designated this effect ""DMSO priming."" This priming effect of DMSO on the Epo response was both time-dependent and DMSO concentration-dependent.
 DMSO priming potentiated the Epo response in three ways.
 Firstly, DMSO priming increased the total number of Epo responsive cells from 8% to 10% to 40% to 60%.
 Secondly, DMSO priming reduced the time required to reach the optimal Epo-induced response from 4 days to 2 days.
 Thirdly, the Epo dose-response curve was left-shifted approximately 20-fold.
 DMSO priming was also associated with a marked increase in Epo receptor density characterized by an apparently new receptor population and by the appearance of positive cooperativity between receptors.
 Our results suggest that the DMSO priming effect is due to potentiation of the Epo signaling pathway, thus resulting in a much more rapid and dramatic Epo-induced hemoglobinization response.
",3
246,"In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions.
 The knowledge about drug resistance in childhood leukemias and acute lymphoblastic leukemia (ALL) in general is limited.
 This is because of the lack of a suitable in vitro drug sensitivity assay, which is in part due to low in vitro ALL cell survival.
 We recently adapted the highly efficient 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay to test cells from ALL patients and showed that its results were comparable with those of the DiSC assay, up to now the most valid but laborious assay.
 In this study, in vitro drug sensitivity was assessed in cells from 82 children with leukemia, 79 of whom had ALL, with the MTT assay.
 Dose response curves were obtained for 6-mercaptopurine, 6-thioguanine (6-TG), prednisolone (Pred), daunorubicin (DNR), vincristine (VCR), cytosine arabinoside (Ara-C), L-asparaginase (L-Asp), mafosfamide, and mustine.
 A cytotoxic effect of methotrexate could be detected in only a few cases.
 Large interindividual differences in drug sensitivity were detected.
 Compared with leukemia cells from newly diagnosed patients, leukemia cells from relapsed patients were significantly more in vitro resistant to 6-TG, Pred, Ara-C, mafosfamide and mustine but not to DNR, VCR, and L-Asp.
 Improvements of culture medium and methods to increase MTT reduction were studied.
 From 10 components tested, addition of insulin and bovine serum albumin to serum-containing medium improved ALL cell survival.
 Addition of succinate did not increase the amount of MTT reduction.
 We conclude that the in vitro MTT assay highly facilitates large-scale studies on drug resistance of ALL patients that can lead to rational improvements in existing treatment protocols.
",3
247,"Analysis of interferon-inducible genes in cells of chronic myeloid leukemia patients responsive or resistant to an interferon-alpha treatment.
 Recombinant human interferon-alpha (IFN-alpha) can induce a hematologic remission in patients with chronic myeloid leukemia.
 However, some patients are resistant and others develop late resistance to the IFN-alpha treatment.
 To understand the molecular mechanism of this resistance, we have analyzed the expression of 10 IFN-inducible genes in the cells of three resistant patients, two responsive patients, and six healthy controls.
 Northern blot hybridizations showed that all the genes were induced in in vitro IFN-alpha treated peripheral blood cells of the patients and healthy controls.
 These genes were also inducible in peripheral blood and bone marrow cells of two out of two resistant patients administered an injection of IFN-alpha.
 We conclude that the resistance to the IFN-alpha treatment of the chronic myeloid leukemia patients we studied is not due to (1) the absence of induction of any of the 10 IFN-inducible genes we studied, including the low-molecular-weight 2'-5'oligoadenylate synthetase; (2) the presence of an antagonist of IFN-alpha in the peripheral blood or bone marrow cells; and (3) the presence of neutralizing anti-IFN-alpha antibodies.
",3
248,"Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy.
 To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT).
 Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT.
 On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient.
 The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits.
 Epo levels were measured by radioimmunoassay (RIA).
 For each patient, baseline serum Epo levels were determined at time of admission to the hospital.
 Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT.
 Hematocrits (Hcts) were measured daily.
 All patients had an initial serum creatinine less than or equal to 1.5 mg/dL.
 Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed.
 Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased.
 The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter.
 While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period.
 Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy.
 We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post-BMT.
 Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.
",3
249,"Efficacy of interferons on bowenoid papulosis and other precancerous lesions.
 Preliminary results of an open randomized trial of recombinant interferon gamma in patients suffering from bowenoid papulosis are described.
 Recombinant interferon gamma was given subcutaneously to 12 patients at a daily dose of 4 X 10(6) I.U.
 by injection.
 Four patients each were assigned to one of three treatment groups consisting of continuous therapy (group A) with three subcutaneous injections per week for 13 weeks; intermittent block therapy (group B) with four six-week cycles consisting of five injections on days 1, 3, 5, 7, and 9 of each cycle; and intermittent single-dose therapy (group C) with six four-week cycles consisting of only one subcutaneous injection on day one of each cycle.
 At the twenty-sixth week after onset of therapy, complete responses were seen in three of four patients of treatment group A, whereas in the treatment groups B and C only one patient, respectively, responded partially.
 These results suggest that in contrast to condylomata acuminata bowenoid papulosis lesions respond better to continuous than to intermittent interferon gamma injections.
",3
250,"Non-AIDS-associated Kaposi's sarcoma (classical and endemic African types): treatment with low doses of recombinant interferon-alpha.
 In the treatment of the classical and endemic African forms of Kaposi's sarcoma (KS), radiation therapy and chemotherapy have been widely used with varying degrees of success and morbidity.
 We here report our preliminary experiences with low doses of recombinant interferon alfa-2b (rIFN alpha-2b) in the treatment of these types of KS, non-linked to the acquired immunodeficiency syndrome (AIDS).
 Ten consecutive patients (eight patients with classical and two with endemic KS) with a median age of 62 years were treated long-term with 5 X 10(6) units of rIFN alpha-2b (Introna) given subcutaneously three times weekly for at least 6 months.
 Of the 10 patients, six presented with cutaneous disease only, and four had additional visceral involvement.
 After 6 months of treatment, seven of the 10 patients had a major response of the cutaneous lesions, and three patients showed stable skin diseases.
 Of the four patients with additional visceral disease, one patient showed a complete regression of an intramyocardial tumor involving the right atrium and ventricle, whereas in the three other patients stabilization of the visceral lesions with marked symptomatic improvement occurred.
 On the whole, the long-term results over a median duration of 12 months (range, 7 to 30) are also satisfactory: IFN-alpha continued to control KS in all patients.
 The treatment was generally well tolerated; no serious side effects were observed.
 Our preliminary data suggest that low-dose rIFN alpha-2b regimens are effective in classical and endemic African KS.
 However, further studies are needed to establish the exact role for IFN-alpha as alternative to radiation and chemotherapy.
",3
251,"Clinical evaluation of interferons in malignant melanoma.
 The evaluation of interferons in the treatment of malignant melanoma has been mainly in the treatment of advanced disease using interferons as the sole agent or in combination with other agents.
 Studies of the value of interferons as adjuvant therapy in high-risk primary melanoma patients are necessary, but no results have been published to date.
 Human interferon alpha produces low response rates as a sole agent, but in combination with cimetidine, a 30% response rate has been achieved.
 Recombinant alpha interferons give responses of 15%-20% in advanced melanomas, and combination with cimetidine does not enhance the response rate.
 Recombinant alpha interferons have been used in combination with other interferons, cimetidine, monoclonal antibodies, and cytotoxics, with either no or small improvement in response rates.
 DTIC with recombinant interferon alpha-2a has been shown to produce objective response rates of 26%, with low toxicity and maintenance of quality of life.
 A randomized trial with DTIC as the sole agent, compared with combination treatment, is being conducted to determine the significance of this finding.
",3
252,"Long-term adjuvant therapy of high-risk malignant melanoma with interferon alpha 2b.
 Fifty-three high-risk melanoma patients in stage I and 15 patients in stage II were treated after standard surgical intervention with adjuvant therapy with recombinant interferon alpha-2b (rIFN alpha 2b) therapy for a total period of 20 months.
 Concomitant patients (stage I, n = 82; stage II, n = 33) with identical stages and prognostic factors without adjuvant therapy were used to evaluate the efficacy of rIFN alpha 2b therapy.
 No difference in 5-year relapse incidence and overall survival rates could be detected.
 However, it appears that patients of both stage I and stage II benefit from long-term adjuvant rIFN alpha 2b therapy, because during the treatment period (20 months), the incidence of relapses was lower in comparison to controls.
 After stopping treatment the incidence of relapse is equal in treated and control groups.
 According to the results of our study, we suggest using continuous low-dose rIFN alpha 2b therapy for adjuvant treatment of malignant melanoma.
",3
253,"Interferon alpha and etretinate combination treatment of cutaneous T-cell lymphoma.
 Eleven patients suffering from cutaneous T-cell lymphoma (mycosis fungoides) were treated with recombinant interferon alpha-2A in combination (seven patients) or alone.
 Two patients, one in combined treatment, went into clinical complete remission, and five experienced partial remission.
 Two patients progressed during therapy, and two were nonevaluable because they stopped treatment early due to side effects.
 Dosages of interferon were from 3 to 36 million units daily for 3 months, and thereafter 3 times weekly.
 Etretinate (0.7 mg/kg) was given orally.
 The study showed that recombinant interferon alpha-2A in combination with etretinate or alone can induce remission of cutaneous T-cell lymphoma.
",3
254,"Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy.
 Monolayer cultures of the human melanoma cell lines StML-12, StML-11, StML-14 (third, respectively, twenty-fifth subculture), and SKMel-28 derived from specimens representing different stages of tumor progression were treated with 10-10,000 U/ml rTNF-alpha applied for 72 h.
 The effects of rTNF-alpha on cell proliferation, DNA synthesis, cell viability, cloning efficiency, cell division, cell morphology, and the immunophenotype were studied in triplicate experiments.
 The cell line StML-14(3) revealed a significantly dose-dependent reduction of growth due to both cytostatic and cytotoxic activities of rTNF-alpha as well as a decrease of CE.
 Increased numbers of cells in prophase were observed 24 h after addition of r-TNF-alpha.
 In addition, dislocation of chromosomes in the metaphase, formation of micronuclei, and dose-dependent increases of cells exhibiting micronuclei and the DNA amount per cell were detected at the end of treatment.
 On the other hand, only a slight sensitivity to the anti-proliferative effect of rTNF-alpha was observed with StML-14(25) and SKMel-28, whereas StML-12 and StML-11 were significantly resistant.
 The last four cell lines were serially subcultivated and presented common phenotypic patterns with more malignant characteristics than the cell line StML-14(3) before treatment.
 Overall, rTNF-alpha enhanced the malignant immunophenotype of the cell lines tested.
 It increased the expression of the ""late"" melanoma progression markers A.10.33 and A.1.43, and Ki67, and it decreased the expression of the ""early"" progression marker K.1.2.
 The expression of HLA-I, HLA-DR, and ICAM-1 was also enhanced after rTNF-alpha treatment, whereas in contrast to other cytokines, rTNF-alpha did not induce the de novo expression of HLA-DR in HLA-DR-negative melanoma cell lines.
 These findings indicate that rTNF-alpha induces cytostasis and decreases cell viability of certain rTNF-alpha-sensitive melanoma cells.
 These effects may result in selection of rTNF-alpha-non-sensitive human melanoma cell populations with higher proliferation rates and a more aggressive immunophenotype in vitro.
",3
255,"High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients.
 Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I).
 Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process.
 Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors.
 To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax).
 For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05).
 The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs.
 44.2% [42/95]; P less than .005).
 Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection.
 Alternatively, it might reflect genetic differences in host susceptibility or virus strain.
",3
256,"The fastigial pressor response. Case report.
 A distinct vasomotor and cardioregulatory response first identified experimentally was elicited intraoperatively in a 6-year-old girl by local mechanical stimulation in the vicinity of the fastigial nucleus of the cerebellum.
 These findings are discussed in the light of current experimental knowledge of the anatomy and physiology of the fastigial pressor response.
",3
257,"Correlates of survival and the Daumas-Duport grading system for astrocytomas.
 In order to examine the correlation between prognosis and the histological features of nuclear atypia, mitosis, endothelial proliferation, and necrosis in supratentorial adult astrocytomas, the authors reviewed 251 such cases treated at the Massachusetts General Hospital between 1972 and 1980.
 One point was given for the presence of each feature.
 The total number of features was translated into a grade as follows: none of the four features = Grade 1 (one patient), one feature = Grade 2 (36 patients), two features = Grade 3 (33 patients), and three or four features = Grade 4 (181 patients).
 The period of survival was significantly associated with grade, the presence or absence of each of the four histological features, patient's age, type of operation, radiation therapy, and extent of tumor (log rank, p less than 0.05).
 The variables associated with grade were age (p less than 0.001) and radiation therapy (p less than 0.02).
 After adjustment for these variables using a Cox proportional-hazards model, the difference in overall survival time between patients in Grades 2 and 3 was not statistically significant.
 When comparable groups of patients were examined in terms of age or receipt of radiation therapy, the median survival times differed markedly.
 Patients 50 years of age or less had a median survival time of 68 months (Grade 2 tumors), 29 months (Grade 3 tumors), and 13 months (Grade 4 tumors).
 Patients over 50 years of age had a median survival time of 6 months (Grade 2 and 4 tumors) and 9 months (Grade 3 tumors).
 Those patients who had received radiation therapy had a median survival time of 68 months (Grade 2 tumors), 21 months (Grade 3 tumors), and 11 months (Grade 4 tumors).
 Those patients who did not receive radiation therapy had a median survival time of 1 month (Grade 2 tumors) and 2 months (Grade 3 and 4 tumors); over half of these patients died within 2 months of surgery.
 This grading system, originally proposed by Daumas-Duport, et al., is simple, objective, and reproducible, and correlates well with survival times.
 The authors recommend that astrocytomas be graded on a scale of 1 to 4, with Grade 1 reserved for the rare adult supratentorial astrocytoma with none of the four histological features.
",3
258,"Intratumoral oxygen pressure in malignant brain tumor.
 Oxygen pressure (pO2) in brain tumors, pO2 in brain cortex surrounding the tumors, and PaO2 were measured simultaneously during total resection in 16 patients with previously untreated brain tumors in order to detect hypoxic regions within the tumors.
 When the inhaled O2:N2O ratio was 1:3 under enflurane anesthesia, mean PaO2 was 109.2 +/- 5.8 mm Hg, a rather high value when compared with that obtained when air is inhaled under atmospheric pressure.
 The simultaneously measured intratumoral pO2 and pO2 in brain cortex surrounding the tumor were 15.3 +/- 2.3 and 59.8 +/- 6.5 mm Hg, respectively.
 Each intratumoral pO2 value was significantly lower than that of pO2 in brain cortex surrounding the tumor (mean less than 30 mm Hg, Wilcoxon signed rank test, p less than 0.005) and influenced the oxygen effects on radiation.
 These results appear to confirm that there are hypoxic regions within human brain tumors.
 A comparison between intratumoral pO2 and either the angiographic or contrast-enhanced computerized tomography scans of the tumor vasculature disclosed no correlation.
",3
259,"Photodynamic therapy of spontaneous cancers in felines, canines, and snakes with chloro-aluminum sulfonated phthalocyanine.
 This is the first report on the photodynamic treatment with a second-generation sensitizer, chloro-aluminum sulfonated phthalocyanine (CASPc) of spontaneously arising tumors and on the photodynamic therapy (PDT) of snake neoplasms.
 Each of 10 cats, 2 dogs, and 3 snakes presenting with a variety of tumor types (squamous cell carcinoma, mast cell malignant tumor, and mixed carcinoma/sarcoma) was given an intravenous injection of 1 mg of CASPc per kilogram body weight 48 hours prior to irradiation with 675-nm light.
 Some larger tumors (greater than 1.5 cm deep) were surgically debulked prior to PDT.
 No significant systemic toxicity or skin photosensitization was observed in any animal.
 The tumor responses were comparable to those seen with conventional cryotherapy, hyperthermia, or surgery.
 PDT with CASPc of these cases led to 67% (12 of 18) complete response, 22% (4 of 18) partial response, and 11% (2 of 18) no response (less than 50% reduction in tumor size).
 Four cases could not be evaluated.
 Since the overall tumor response to CASPc is very good, and the problem of skin photosensitivity is nonexistent, it is expected that using CASPc-PDT to eradicate human tumors would also yield comparable results.
 Further studies with long-term follow-up are necessary to optimize the use of CASPc-PDT in veterinary and human medicine.
",3
260,"Increased expression of the laminin receptor in human colon cancer.
 It has been proposed that among the various cell-surface proteins capable of interacting with laminin, the 67-kd high-affinity laminin receptor plays a crucial role during tumor invasion and metastasis.
 In this study, the expression of laminin-receptor-precursor messenger RNA (mRNA) and 67-kd protein was analyzed in human colon adenocarcinoma.
 In 22 of 23 patients with colon cancer, we found a 2- to 23-fold increase in levels of laminin-receptor-precursor mRNA in the cancer tissues compared with those in matched normal adjacent colonic mucosa.
 In 10 of 11 cases studied, the level of 67-kd laminin receptor, detected by affinity-purified anti-laminin-receptor synthetic peptide antibodies on immunoblots of matched tumor and normal tissue extracts, was higher in the colon carcinoma tissue.
 Immunodetection of laminin receptor in tissue sections using anti-laminin-receptor-peptide antibodies confirmed that the increased expression of laminin receptor was specifically associated with the cancer cells.
 In a series of 72 paraffin sections of colon lesions, we observed a correlation between the expression of the laminin receptor and the Dukes' classification.
 Our observations indicate that increased expression of laminin-receptor-precursor mRNA is associated with enhanced levels of the 67-kd laminin receptor as well as with the invasive phenotype of colon carcinoma.
 Detection of this metastasis-associated gene product may be a valuable adjunct in the evaluation of human colon cancer.
",3
261,"Effect of prior cancer chemotherapy on human tumor-specific cytotoxicity in vitro in response to immunopotentiating biologic response modifiers.
 Tumor-specific cytotoxicity was measured in fresh human biopsy specimens by a modification of the differential staining cytotoxicity assay.
 ImuVert, a cytokine inducer derived from Serratia marcescens, which produces broad-spectrum activation of both macrophages and lymphocytes, was dramatically more effective when it was tested in tumors obtained from patients with previously treated, chemotherapy-responsive adenocarcinomas (breast and ovary) than when it was tested in tumors obtained from either previously untreated patients or previously treated patients with chemotherapy-refractory adenocarcinomas (colon, lung, pancreas, stomach, kidney, gallbladder, uterus, and prostate).
 Similar findings, relating to prior chemotherapy treatment status, were obtained for tumor necrosis factor and interferon gamma, but not for interleukin-2 or interferon alpha.
 On the basis of these findings and on other evidence in the literature, we speculate that response to chemotherapy produces massive release and processing of tumor antigens.
 We further speculate that this response leads to a state in which the human immune system is primed (via in situ vaccination) to respond to exogenous macrophage-activation signals with potent, specific antitumor effects.
",3
262,"Comparisons of diet and biochemical characteristics of stool and urine between Chinese populations with low and high colorectal cancer rates.
 In an investigation of the roles of diet and stool biochemistry in human colorectal carcinogenesis, 24-hour food, urine, and stool samples were collected from randomly selected participants from two populations with a fourfold difference in colorectal cancer risk: Chinese in Sha Giao, People's Republic of China (low risk), and Chinese-Americans of similar ages in San Francisco County, Calif, in the United States (high risk).
 The findings supported the hypotheses that colorectal cancer risk is increased by the consumption of high-fat, high-protein, and low-carbohydrate diets and is associated with high levels of cholesterol in stool as well as increased daily outputs of 3-methyl-histidine and malonaldehyde in urine.
 However, risk does not increase with low stool bulk and low total stool fibers.
",3
263,"Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies.
 A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule.
 A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest.
 Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration.
 Fifty-one patients with advanced cancer were entered in the study.
 One hundred twenty-four (96%) of 129 courses were considered assessable.
 Myelosuppression proved to be the dose-limiting toxic effect.
 Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels.
 Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma.
 The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.
",3
264,"Hematoporphyrin photodynamic therapy: is there truly a future in head and neck oncology? Reflections on a 5-year experience.
 Photodynamic therapy, which consists of the selective destruction of tumors using a combination of a photosensitizer administered systemically (dihematoporphyrin ether) and an argon dye-pumped laser, has provoked profound interest amongst oncologists and has particularly titillated head and neck oncologists with its potential.
 Unfortunately, no multi-institutional trials for head and neck tumors have been introduced, and the literature is replete with anecdotal reports from individual researchers on the management of advanced cancers for palliation, superficial early cancers, and field cancerization of the mucosa (""condemned mucosa"").
 A personal 5-year experience with 41 head and neck cancers was reviewed, as was the current literature.
 An attempt was made to place in perspective the true role and future direction of this technology.
",3
265,"Extended retrolabyrinthine transtentorial approach to petroclival lesions.
 In this communication, an extension of the retrolabyrinthine approach that has permitted safe, effective access to the petrous tip and clivus is presented.
 The basic technique involved complete mastoidectomy, preservation of the middle and inner ear structures, removal of the sigmoid and middle fossa plates, middle and posterior fossa craniotomies, ligation of the superior petrosal sinus, and division of the tentorium.
 Nine cases that exemplified the versatility of this approach constituted the basis of this paper: 2 cholesteatomas, 2 basilar artery aneurysms, 2 chordomas, and 3 meningiomas.
 The indications for, and complications of, this method have been discussed.
",3
266,"A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas.
 A gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas.
 On the basis of its sequence, the product of this gene, named stromelysin-3, is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix.
 The suggestion is that stromelysin-3 is one of the stroma-derived factors that have long been postulated to play an important part in progression of epithelial malignancies.
",3
267,"Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome 
 Tumour suppressor genes, whose usual function seems to be controlling normal cell proliferation, have been implicated in many inherited and sporadic forms of malignancies Much evidence supports the concept of tumour formation by loss-of-function mutations in suppressor genes, as predicted by the two-hit model of Knudson and DeMars.
 The suppressor gene, p53, is affected in such a manner by numerous mutations, which occur in a variety of human tumours.
 These mutations usually represent the loss of one allele and the substitution of a single base in the other.
 We have now analysed the p53 gene in a family affected by Li-Fraumeni syndrome, a rare autosomal dominant syndrome characterized by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites.
 In some instances the neoplasms seem to be related to exposure to carcinogens, including ionizing radiation.
 The Li-Fraumeni family that we studied had noncancerous skin fibroblasts (NSF) with an unusual radiation-resistant phenotype.
 DNA derived from the NSF cells of four family members, spanning two generations, had the same point mutation in codon 245 (GGC----GAC) of the p53 gene.
 This mutation leads to substitution of aspartic acid for glycine in one of the regions identified as a frequent target of point mutations in p53.
 The NSF cell lines with the mutation also retained the normal p53 allele.
 This inherited p53 mutation may predispose the members of this family to increased susceptibility to cancer.
",3
268,"Intracerebral solitary plasmacytoma.
 We report a rare occurrence of intraparenchymal plasmacytoma and review the literature.
 The clonal nature of the neoplasm is demonstrated by immunohistochemical and molecular techniques.
 The importance of the latter techniques in ruling out other pathological entities is stressed.
",3
269,"Mohs micrographic surgery.
 Mohs micrographic surgery is a versatile technique for the treatment of nonmelanoma skin cancers, especially recurrent, invasive, or infiltrating basal cell carcinomas.
 It provides unsurpassed cure rates by using 100% surgical margin control, and it achieves maximal preservation of normal tissue.
 At the conclusion of tumor extirpation, the defect is ready for immediate reconstruction.
 With better understanding of the Mohs micrographic surgery technique, it can be more effectively used as part of a coordinated multidisciplinary approach to the treatment of patients with difficult cutaneous and paracutaneous neoplasms.
",3
270,"Transhepatic portal vein catheterization for localization of insulinomas: a ten-year experience.
 One of the most important factors in the management of insulinomas is the ability to localize the tumor accurately either before or during surgery.
 We prospectively carried out transhepatic portal venous sampling (THPVS) for tumor localization in 35 of 40 patients with organic hyperinsulinism during a 10-year period.
 In 32 patients who underwent THPVS and in whom a single tumor was subsequently identified surgically, the maximal insulin gradient was located in the vicinity of the tumor in 100% of cases.
 Specific regionalization of the tumor on the basis of the site of the maximal insulin gradient to one of three regions (the tail, the body/neck region, and the head/uncinate region) gave a sensitivity of 81% and a specificity of 91%.
 In contrast, the use of specific cutoff levels for the insulin gradient as a guide to the presence of a tumor in one of these three regions did not increase the accuracy, leading instead to a significant loss of sensitivity with no comparable increase in specificity.
 There were no major complications from the procedure in any patient.
 The initial use of computed tomographic/ultrasound scanning and selective angiography localized only 46% of tumors, whereas subsequent THPVS led to the accurate preoperative localization of 100% of all tumors submitted to surgery.
 Although the surgeon would have identified 81% of the tumors correctly at operation, in 19% (n = 6) he would have failed.
 Four tumors were in the uncinate and two were in the head.
 It seems that in patients with proved or established organic hyperinsulinism, THPVS may continue to be of value, if only to regionalize the tumor, especially those in the pancreatic head and uncinate process so as to preclude noncurative operations on the body and tail of the pancreas.
",3
271,"Myogenic regulatory protein (MyoD1) expression in childhood solid tumors: diagnostic utility in rhabdomyosarcoma.
 Transcripts for the muscle regulatory gene MyoD1 are expressed during normal skeletal muscle myogenesis and in rhabdomyosarcomas but not in other tissues or in soft-tissue sarcomas.
 Here we report the distribution of MyoD1 protein, determined by reactivity with anti-MyoD1 polyclonal sera in normal tissues, rhabdomyosarcoma cell lines, and in a variety of pediatric solid tumors.
 The distribution of MyoD1 protein was highly restricted in normal tissues and was detected only in fetal skeletal muscle and more faintly in adult skeletal muscle.
 All six human rhabdomyosarcoma cell lines analyzed expressed MyoD1 mRNA transcripts as well as immunoreactive protein.
 The immunohistochemical expression of MyoD1 protein was then examined in 49 surgical specimens from a variety of pediatric solid tumors.
 Each of 16 rhabdomyosarcoma specimens was positive for MyoD1, including four that did not express the intermediate filament protein desmin.
 Two of five specimens originally designated sarcoma type indeterminate (STI) and two of three specimens originally designated extraosseous Ewing's sarcoma (EOE) were positive for MyoD1, suggesting commitment to myogenic differentiation.
 Three of eight Wilms' tumors, which also expressed desmin and had clearly evident myogenic elements, also were positive for MyoD1.
 Tumors that failed to express MyoD1 protein included neuroblastoma, primitive neuroectodermal tumor, non-Hodgkins lymphoma, embryonal sarcoma of the liver, malignant fibrous histiocytoma, malignant rhabdoid tumor, and Ewing's sarcoma of the bone.
 These results indicate that expression of MyoD1 protein is highly restricted in normal human tissues and that expression of this gene product in malignant tissue may be diagnostic for rhabdomyosarcoma.
 Furthermore MyoD1 staining may be a valuable adjunct in the classification of pediatric soft-tissue sarcomas.
",3
272,"Vimentin expression appears to be associated with poor prognosis in node-negative ductal NOS breast carcinomas.
 Vimentin expression in tumors from 83 node-negative and 112 node-positive patients with infiltrative ductal not otherwise specified (NOS) breast carcinomas has been compared with 5-year survival.
 For node-negative, but not for node-positive patients, there was a significant inverse relation between vimentin expression and survival.
 Five-year survival of node-negative patients with vimentin-positive tumors was significantly worse compared with vimentin-negative tumors (P less than 0.0001).
 In the node-negative group, only 36% of patients with vimentin-positive tumors but 82% of patients with vimentin-negative tumors survived 5 years.
 Tumors of all eight node-negative patients with ductal NOS cancer who died in the first 27 months expressed vimentin.
 Multivariate analysis of the node-negative group showed a strong correlation of vimentin expression and overall survival, but weak and not significant correlation between histologic grade or size and overall survival at 5 years.
 Thus vimentin expression seems to be a strong indicator of poor prognosis in node-negative ductal NOS breast carcinomas.
",3
273,"Study of neu-protein expression in mammary Paget's disease with and without underlying breast carcinoma and in extramammary Paget's disease.
 Correlation between neu/c-erbB-2/Her-2 gene amplification and overexpression of the neu gene product has been reported in tumors of glandular origin, especially ductal breast carcinomas.
 Formalin-fixed and dewaxed sections from 23 cases of mammary (MPD) and 9 cases of extramammary (EPD) Paget's disease were immunohistochemically stained by means of the monoclonal antibody 3B5 directed against an intracellular domain of the neu gene protein.
 All MPDs exhibited a distinct membrane staining of tumor cells independent of the presence of ductal breast carcinomas found in 18 cases.
 All these breast carcinomas also were positive for neu staining.
 In contrast to MPD, all EPDs were negative.
 Normal epidermis was always negative.
 Northern blot analysis sustained the immunohistologic findings in that the presence of neu mRNA could be demonstrated in two of three cases with MPD.
 Negativity in one case was due to dilution effects by nontumor cells.
 Our results suggest that Paget cells of mammary and extramammary localization, although very similar phenotypically, derive from different genetic accidents.
 Furthermore neu positivity in all MPDs and all underlying ductal carcinomas suggests common genetic alterations for both tumors.
 However the finding of five neu protein-positive MPDs without associated ductal breast carcinomas may suggest a somewhat different transformation process.
",3
274,"Detection of HTLV-I proviral sequences in CD30-positive large cell cutaneous T-cell lymphomas.
 To investigate the possibility that cutaneous T-cell lymphomas of large cell type may be associated with human T-cell leukemia/lymphoma virus type I infection in nonendemic regions, tissue samples from six cases of large cell cutaneous T-cell lymphoma and four cases of small cell cutaneous T-cell lymphoma were screened for the presence of integrated proviral human T-cell leukemia/lymphoma virus type I DNA.
 Combined use of Southern blot hybridization and enzymatic DNA amplification revealed human T-cell leukemia/lymphoma virus type I-specific sequences in all cases of large cell cutaneous T-cell lymphoma and in none of the cases of small cell cutaneous T-cell lymphoma.
 These results suggest that in nonendemic areas, a significant proportion of large cell cutaneous T-cell lymphoma cases are associated with human T-cell leukemia/lymphoma virus type I.
",3
275,"Immunodetection of the metastasis-associated laminin receptor in human breast cancer cells obtained by fine-needle aspiration biopsy.
 Fine-needle aspiration biopsy of the breast is a very useful technique for the evaluation of a suspect lesion before surgical removal.
 Increased expression of the 67-kd laminin receptor has been associated with the metastatic phenotype of cancer cells, particularly in colon and breast cancers.
 In this study, the expression of laminin receptor was evaluated using the immunoperoxidase technique in 81 breast aspirates (26 benign and 55 neoplastic lesions).
 Cells obtained from benign samples exhibited a low level of laminin receptor antigen detected by affinity-purified antibody raised against a cDNA-derived laminin receptor peptide.
 In contrast, 71% of smears obtained from malignant breast lesions contained cells that were strongly stained by the antibody.
 Heterogeneous expression of the laminin receptor was noted in both breast aspirates and fixed tissue specimens.
 These data suggest that the immunodetection of laminin receptor in cells obtained by fine-needle aspiration of breast lesions could be a valuable adjunct in the prognostic evaluation of breast lesions.
",3
276,"Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics.
 Frozen tissue immunoreactivity with Ki-67, a monoclonal antibody that recognizes a nuclear antigen in nonresting or proliferating cells, was compared to DNA flow cytometry results (from fresh tissue) in a diverse group of 60 soft-tissue lesions.
 Both DNA index and Ki-67 score were independently reported to be associated with grade and prognosis in sarcomas, but no direct comparison of these two variables was made.
 It was attempted to measure proliferative activity in fixed paraffin-embedded tissues immunohistochemically in a subset of lesions using an antibody to another nuclear proliferation antigen, p105.
 Lesions were given a grade according to lesion category (reactive, 1; benign, 2; low-grade malignant, 3; and high-grade malignant, 4).
 Ki-67 reactivity correlated relatively well with this grading system (r = 0.59); benign lesions usually exhibited a low Ki-67 score and malignant lesions usually but not always exhibited a high score.
 For example, some malignant fibrous histiocytomas contained only rare positive cells.
 Some disparity between Ki-67 score and grade and within histologic types indicates some independence from these features, a fact that may be important when correlation with prognosis is performed.
 However Ki-67 did not correlate well with flow data such as percentage S phase (r = 0.30), percentage S + G2M phases (r = 0.37), or DNA index (r = 0.39).
 This probably is due to the fact that Ki-67 also marks cells in the G1 phase, whereas these are excluded in flow data analyses.
 Anti-p105 highlighted almost all nuclei in all cases tested, including fibromatosis, and did not correlate with Ki-67 score, histologic grade or DNA flow cytometric data.
 Results with p105 could not be favorably affected by titration experiments.
 It is reasonable to conclude that the Ki-67 score is a variable related to but independent of histologic grade, histologic type, and DNA flow values.
 Whether it is prognostically important in human sarcomas, as has been suggested, awaits further clinicopathologic study.
",3
277,"Alternative splicing of endothelial cell fibronectin mRNA in the IIICS region. Functional significance.
 Transforming growth factor-beta 1 (TGF-beta 1) is thought to play a role in modulating vascular cell function in vivo.
 In vitro, it decreases endothelial cell proliferation and migration.
 We postulated that these biologic activities could be mediated through TGF-beta 1 modulation of specific gene expression.
 Therefore we differentially screened a human umbilical vein endothelial cell cDNA library with cDNAs prepared from both untreated and TGF-beta 1-treated bovine aortic endothelial cells.
 Using this technique, we isolated many TGF-beta 1-induced cDNA clones.
 Sequence analysis of these cDNAs showed that many of them corresponded to alternatively spliced fibronectin mRNAs.
 These fibronectin clones all contained the extradomain I (ED I) but three different forms of the type III connecting segment (IIICS).
 These different fibronectin cDNAs were expressed in bacteria and the recombinant proteins used to study the effects of IIICS alternative splicing on cell attachment, spreading, and migration in bovine aortic endothelial and smooth muscle cells and B16F10 melanoma cells.
 The results of these experiments show that attachment and spreading of bovine aortic endothelial and smooth muscle cells depend primarily on the presence of the Arg-Gly-Asp-Ser (RGDS) sequence in the recombinant fibronectin proteins.
 However attachment and spreading of bovine aortic endothelial cells are modulated by alternative splicing in the IIICS region.
 Specifically splicing of the IIICS region decreases spreading and increases migration rates of the endothelial cells.
 On the contrary, using a cell line (B16F10 melanoma cells) that is known not to require the RGDS sequence for adhesion confirmed previous findings that B16F10 melanoma cells do not require the presence of the RGDS sequence for attachment and spreading.
 Indeed B16F10 cells were able to attach and spread on two recombinant proteins that did not contain the RGDS sequence.
 However attachment and spreading of B16F10 were dramatically inhibited when a 75-base pair DNA fragment was removed from the 5' end of the IIICS region.
 These results suggest that various regions of the fibronectin molecule may be able to interact with different cell populations to promote cell attachment and spreading, and that alternative splicing may modulate this process.
",3
278,"A three-dimensional system for long-term culture of human colorectal adenomas.
 Studies of the adenoma-carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression.
 Progress recently was reported in the development of monolayer culture systems.
 The principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three-dimensional in vivo growth.
 We used a calcium alginate encapsulation technique that was previously described for established tumor cell lines.
 Briefly, fresh resected specimens were washed, minced into small multicellular particles called microadenomas, and encapsulated in 1% calcium alginate pellets.
 The pellets were maintained in minimum essential medium containing 10% fetal bovine serum at 37 degrees C in humidified atmosphere of 95% air, 5% CO2.
 Ten of eleven adenomas, including six tubular, three tubulovillous, and one villous have been successfully cultured for 34 to 162 days.
 Cell viability was confirmed histologically by light and electron microscopy.
 The cells were characterized as epithelial by morphologic features and ultrastructural studies, which showed a high degree of cellular differentiation, including villous brush borders and many desmosomes.
 Both tubular and villuslike structures have been observed in vitro, correlating in some cases with the histology of the parent adenoma.
 Measurements of proliferative activity by [3H]thymidine autoradiography or immunohistochemical staining with the monoclonal antibody Ki-67 demonstrated growth fractions of 9% to 25%.
 A simple, highly efficient primary culture system was developed for the long-term maintenance of adenomas that promotes three-dimensional growth patterns and growth rates analogous to those seen in vivo.
 This model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma.
",3
279,"Chromatin structural analysis of the 5' end and contiguous flanking region of the myeloperoxidase gene.
 Myeloperoxidase (MPO) synthesis is known to be associated with the promyelocyte stage of myeloid differentiation.
 In particular the downregulation of MPO gene transcription is associated with myeloid cell maturation.
 We examined the changes in the deoxyribonuclease I hypersensitive sites within the 5' end of the MPO gene and its 5' flanking region during dimethyl sulfoxide (DMSO)-induced differentiation of HL-60 cells to determine the changes in chromatin structure that accompany this process.
 The locations of hypersensitive sites surrounding the 5' end of the gene in proliferating, uninduced cells were determined: three were observed in the 5' flanking region and one within the gene.
 Progressive changes in all sites accompanied the downregulation of MPO transcription after treatment with DMSO.
 No evidence of hypersensitivity was observed in the chromatin region examined after 8 days of DMSO exposure.
 The results provide an example of the changes that occur in the chromatin structure of a gene as it is inactivated during differentiation.
",3
280,"Six years' audit of laboratory workload and rates of referral for colposcopy in a cervical screening programme in three districts 
 OBJECTIVE--To determine laboratory workload and rates of referral for colposcopy in a three district cervical screening programme during 1983-9 to assess the feasibility of accommodating call up of all women at risk, recall at three year intervals (now five year intervals), and investigation of women with all degrees of abnormality.
 DESIGN--Analysis of computerised screening histories dating back to 1977 of women screened in the Avon cervical screening programme.
 SETTING--Three district health authorities covering the population of Bristol and Weston-super-Mare, comprising 800,000 people, of whom 250,000 were female residents aged 20 to 64.
 SUBJECTS--196,977 Women aged 20 to 64 screened in cervical screening programme since 1983.
 RESULTS--Laboratory workload devoted to follow up of women with abnormalities increased sharply between 1987-8 and 1988-9, with increases of 54% (from 2075 to 3196) in the number of smears for follow up of severe dyskaryosis and invasive cancer, 40% (from 1925 to 2695) for mild and moderate dyskaryosis, and 49% (from 1793 to 2677) for borderline change.
 The increases were partly explained by the introduction in April 1988 of protocols for follow up and investigation based on guidance in an intercollegiate working party report.
 The proportion of women with mild and moderate dyskaryosis who were recommended for referral for colposcopy increased steadily from 9.9% in 1983-4 to 79.9% in 1988-9, and for borderline change the proportions were 3.5% and 13.6% respectively.
 Of all women tested in 1988-9, referral for colposcopy was recommended in 3%.
 CONCLUSIONS--The increase in laboratory follow up work identified, if it continued, could result in half of existing laboratory capacity in Avon being devoted to follow up work by 1993, with little prospect of maintaining call, recall, and quality control.
 Investigation of all women with minor cytological abnormalities is neither justifiable nor sustainable and will undermine the benefits of screening by increasing the rate of false positive results and the financial costs.
",3
281,"How district health authorities organise cervical screening [published erratum appears in BMJ 1990 Nov 24;301(6762):1209]
 OBJECTIVES--To examine how district health authorities organised cervical screening with respect to Department of Health guidelines and to determine their assessment of the problems encountered.
 DESIGN--Postal questionnaire sent to all 190 district health authorities in England in 1989.
 PARTICIPANTS--190 District health authorities in England.
 MAIN OUTCOME MEASURES--Population coverage of screening, quality of smear testing, and follow up of abdominal test results in comparison with national guidelines for district cervical screening services, and problems encountered by districts.
 RESULTS--Replies were received from 178 (94%) of districts, in 143 of which the person named as responsible for cervical screening contributed.
 All districts implemented a computer managed scheme, 150 by the target date of 31 March 1988, but not all of these conformed with the guidelines.
 At the time of the survey only just over half called women in the target age group of 20-64 and only 70% expected to meet the target date of 13 March 1993 for completing the call.
 Considerable variation was evident among the schemes with regard to how they dealt with issues related to population coverage, quality of testing, and follow up of abnormal results.
 The problems most commonly identified by the districts (n = 174) were laboratory workload (107, 61%), computer software (104, 60%), availability of resources (78, 45%), non-attendance (77, 44%), rate of opportunistic screening (62, 36%), and investigation and treatment (60, 34%).
 CONCLUSIONS--Current practice in running cervical screening schemes needs to be examined to determine the extent to which it contributes to the goal of reducing mortality from cervical cancer.
",3
282,"Etoposide. Current and future status.
 Etoposide (VP-16-213) is an antineoplastic agent with demonstrated efficacy against a broad spectrum of human malignancies, including testicular, germ cell, lung, and other cancers.
 Etoposide can be synergistic with other agents.
 As part of combination chemotherapy, etoposide has become a so-called standard in therapies for testicular cancer and small cell lung cancer.
 Its activity in tumors such as lymphoma and leukemia, as well as solid tumors, identifies etoposide as a highly important chemotherapeutic agent.
 Cellular and animal models have shown that the cell kill and tumor response depend on both dose and time of exposure.
 Recent clinical studies again show that dose and schedule of etoposide can have important effects on clinical response to the drug.
 Further research should now continue: (1) on the use of etoposide as part of initial therapy in several cancers, and (2) in higher doses and prolonged schedules to optimize this agent's potential.
",3
283,"New chemotherapies for ovarian cancer. Systemic and intraperitoneal podophyllotoxins.
 The epipodophyllotoxin derivatives etoposide and teniposide have been evaluated intermittently for possible use in the treatment of ovarian cancer.
 Conflicting studies suggest that variables such as dose and prior treatment have a major influence on outcome.
 Response rates ranged from 0% to 40% in five series with teniposide, and from less than a 10% overall response rate to greater than a 10% complete response rate in nine studies with etoposide.
 One study documented activity with oral etoposide.
 However, because all patients had received various prior chemotherapies, firm conclusions regarding the activity of etoposide could not be drawn.
 These results, and the expectation of synergy with etoposide and cisplatin, led to several studies that combined etoposide with platin compounds by the systemic and intraperitoneal (IP) routes.
 Various studies have used intravenous drug combinations of these agents in both previously treated and untreated patients.
 One study, which used carboplatin instead of cisplatin, reported only seven failures among 26 previously untreated patients.
 Conversely, the prominent toxicities reported by another study were discouraging, and responses did not exceed what might be expected from cisplatin alone.
 Studies of analogous combinations administered IP are ongoing.
 A favorable experience, which was initially reported by the University of California (San Diego group), is being confirmed by other investigators.
 This has prompted the incorporation of etoposide into first-line strategies.
 The pharmacologic advantage of etoposide by the IP route (related to its high protein binding) may provide appropriate dose intensity against IP disease while sparing systemic toxicities.
 Finally, systemic dose intensity with autologous bone marrow support indicates some promise for etoposide in combination with high-dose alkylating drugs.
",3
284,"Current strategies in the management of locoregional and metastatic gastric carcinoma.
 Gastric carcinoma remains a significant cause of death worldwide.
 A patient's prognosis depends on the degree of gastric wall penetration, presence of lymph node metastases, and location of the primary site.
 Metastatic gastric carcinoma is currently incurable.
 However, chemotherapy continues to evolve at a rapid pace.
 Active agents include 5-fluorouracil (5-FU), doxorubicin, cisplatin, methotrexate, mitomycin, and etoposide.
 Combination etoposide, doxorubicin, and cisplatin (EAP) has been reported to result in encouragingly high response rates, including a 10% complete response rate in patients with metastatic gastric carcinoma.
 Trials are now under way to confirm these results.
 Similarly, another etoposide-based combination, etoposide, leucovorin, and 5-FU (ELF), has resulted in an equally good response rate but less toxicity than EAP.
 The 5-FU, doxorubicin, and methotrexate (FAMTX) regimen, previously reported to have an excellent response rate, is also being investigated further.
 For patients with locoregional carcinoma, curative resection rate is often unsatisfactorily low; however, curative resection is consistently associated with improved survival (between 23 and 26 months).
 In patients with potentially resectable carcinoma, two significant problems must be recognized: (1) a low rate of curative resection and (2) the development of widespread carcinoma despite curative resection.
 Despite many attempts, the postoperative strategies of adjuvant chemotherapy have been ineffective.
 New strategies must be investigated aggressively.
 Combination etoposide, 5-FU, and cisplatin (EFP) has been administered preoperatively and postoperatively to patients with resectable gastric carcinoma, resulting in an encouraging curative resection rate (greater than 70%) and manageable toxicity.
 Based on promising results reported with EAP in patients with unresectable locoregional carcinoma of the stomach, a trial of preoperative and postoperative EAP in potentially resectable carcinoma of the stomach is now under way.
",3
285,"Etoposide in the management of metastatic breast cancer.
 Etoposide, despite extensive use in other malignancies, has played a minor role in the treatment of patients with breast cancer.
 Single-agent trials in which etoposide is administered to heavily pretreated patients with metastatic breast cancer have demonstrated a low overall response rate (6.6% of 383 patients), with no convincing evidence for either schedule dependence or a relationship between dose intensity and response.
 The sole single-agent trial in previously untreated patients suggested that the drug has an approximately 15% response rate in untreated patients.
 Combination therapy trials in which etoposide has been combined with either cyclophosphamide, doxorubicin, or cisplatin have not yet convincingly demonstrated superiority over any of these drugs as single agents, although cisplatin plus etoposide appears to be superior to either agent alone.
 In vitro studies suggest that pretreating hormone-sensitive breast cancer cells with estradiol may increase their sensitivity to etoposide-induced DNA cleavage.
 This may represent a future direction in the use of etoposide in breast cancer.
 Currently, however, the use of etoposide in breast cancer should be considered investigational.
",3
286,"Etoposide in leukemia.
 Etoposide (VP16-213, NSC 141540) induces a complete response (CR) in 15% to 25% of previously treated patients with acute nonlymphocytic leukemia (ANLL) when used as a single agent.
 Etoposide has been used successfully in combination with cytarabine, daunorubicin, and amsacrine for salvage and consolidation therapies.
 Previously untreated ANLL patients 15 to 70 years of age were randomly assigned to cytarabine (100 mg/m2) on days 1 to 7 plus daunorubicin (50 mg/m2) on days 1 to 3 (7-3) or to the same drugs plus etoposide (75 mg/m2) on days 1 to 7 (7-3-7).
 Patients achieving a CR received two consolidation courses (5-2, attenuated 7-3 or 5-2-5).
 Among 264 eligible patients, there was a 56% CR rate with 7-3 therapy and a 59% CR rate with 7-3-7 therapy.
 Remission duration was significantly improved with 7-3-7 (median, 12 months with 7-3 and 18 months with 7-3-7; P = 0.01), but survival was not.
 Subset analysis in patients younger than 55 years of age revealed prolonged remission (median, 12 months with 7-3 and 27 months with 7-3-7; P = 0.01) and survival (median, 9 months with 7-3 and 17 months with 7-3-7; P = 0.04) with the 7-3-7 regimen.
 Hematologic toxicity was similar for both regimens during induction, but significantly more severe for 7-3-7 during consolidation therapy.
 Etoposide is active in ANLL and prolongs remission when used in induction therapy.
",3
287,"High-dose etoposide and marrow transplantation.
 Etoposide underwent conventional Phase I testing in the 1970s.
 The dose-limiting toxicity in these studies was mild myelosuppression; other toxicities were infrequent.
 If a greater degree of myelosuppression is accepted, higher than standard doses could be given.
 This approach takes advantage of the steep dose-response relationship for most chemotherapeutic agents, including etoposide, as shown in early in vitro and clinical studies.
 Thus, etoposide was considered an ideal agent for further dose-escalation studies, given its wide range of clinical antitumor activity at standard doses, steep dose-response curve, mild bone marrow suppression, and few nonmyeloid side effects.
 The high-dose etoposide studies that followed used improved and more intensive hematologic supportive care, including, in some trials, autologous marrow transplantation.
 When etoposide was used as a single agent in these high-dose trials, mucositis, and, to a lesser degree, hepatic dysfunction were dose-limiting.
 The maximum tolerated dose (MTD) in this setting was 2.4 to 3.0 g/m2.
 Multi-agent Phase I trials with etoposide and cyclophosphamide, total body irradiation, carmustine, or carboplatin also resulted in dose-limiting mucosal toxicity, with liver and lung problems appearing more often than with high-dose etoposide alone.
 The toxicity and MTD can be influenced markedly by the schedule of administration.
 Etoposide as a continuous intravenous infusion can be given at doses of 4.2 g/m2 (with 200 mg/kg cyclophosphamide) with similar toxicity, but without marrow support.
 The antitumor results in the lymphomas set the stage for treatment of solid tumors, where treatment of patients with ""sensitive"" relapses had the best outcome.
 Lymphoma patients had an 80% response rate; overall, long-term (greater than 2 years) disease-free survival was approximately 40%.
 Germ cell tumors were also responsive, and the same pattern of sensitive relapses and improvement in responding patients was seen (50% to 75% of patients greater than 1 year).
 In breast cancer and small cell lung cancer (SCLC), high-dose etoposide-containing regimens were used to intensify standard therapy.
 The results in these settings were not quite as good (breast cancer, 30% disease-free survival at 2 years; SCLC, 10% at 2 years).
",3
288,"The pharmacology of intravenous and oral etoposide.
 The epipodophyllotoxin derivative etoposide (VP-16) has been in widespread use both alone and in combination chemotherapy for the past decade.
 It has phase-specific cytotoxicity that acts in the last S and G2 phases of the cell cycle.
 Although its mode of action is not certain, it appears to act by causing breaks in DNA by interaction with DNA-topoisomerase II or by the formation of free radicals.
 Most studies show biexponential decay after the intravenous (IV) administration of etoposide.
 Approximately 30% to 70% of administered etoposide is excreted, with approximately 45% present in the urine.
 Etoposide is available in oral and IV preparations.
 It is highly schedule-dependent, with once-daily doses (e.g., for 5 to 8 days every 21 days) giving results superior to intermittent administration.
 The bioavailability of oral etoposide is approximately 50%, but its absorption is not linear with increasing dose (e.g., greater than 200 mg/d, bioavailability decreases).
 Factors influencing the bioavailability of oral etoposide include patient status, concurrent medications, hepatic and renal function, and nausea and vomiting.
 In numerous clinical trials, etoposide has demonstrated excellent activity against a range of tumors, including small cell lung cancer (SCLC), malignant lymphomas, gestational trophoblastic tumors, Ewing's and soft tissue sarcomas, and germ cell tumors, with more modest activity in other tumors (e.g., non-SCLC).
 Although few comparative studies have been carried out, available data suggest that oral etoposide administered daily during 5 to 8 days is similar to the IV preparation in range of activity.
 In a study of 53 elderly patients with SCLC treated with etoposide (200 mg/d for five times), there was a response rate of 79% and a median survival of 9.5 months.
 These results were similar to those achieved with more intensive IV regimens.
 Several studies of chronic oral etoposide (50 mg/m2/d for 21 times) have been reported recently.
 Responses were observed in SCLC and germ cell tumors among patients who had relapsed after standard etoposide-containing regimens.
 These data suggest that etoposide may be a ""new"" drug when given in this schedule.
 The high response rates with oral etoposide suggest that oral administration may be substituted for IV administration.
 This substitution may allow for greater flexibility in chemotherapeutic administration, less hospitalization, and more acceptable toxicity.
",3
289,"Chronic oral etoposide.
 Etoposide is an important drug that has been recently incorporated with other agents in the curative treatment of patients with advanced neoplasms, including germ cell tumors, non-Hodgkin's lymphomas (NHL), and small cell lung cancer (SCLC).
 Etoposide demonstrates remarkable schedule dependency.
 A randomized comparison has shown an impressive survival difference for patients with extensive SCLC receiving a 5-day course versus those receiving a 1-day course.
 Because of these and previous clinical and laboratory data, etoposide is now given intravenously or orally in a 3-day to 5-day schedule.
 It is generally accepted that approximately 50% of the orally administered drug is absorbed.
 The authors have initiated several etoposide studies using an extended administration schedule, believing that a prolonged schedule may be superior to the standard 3-day to 5-day schedule.
 This was initially tested in a Phase I study.
 Results showed that etoposide (50 mg/m2/d) given over 21 days was feasible and was associated with only moderate toxicity.
 Several Phase II studies have been completed or are nearing completion, including studies in patients with SCLC, NHL, germ cell tumors, soft tissue sarcoma, renal carcinoma, and ovarian carcinoma.
 Responses have been seen in all of these groups, particularly in patients with SCLC, lymphoma, and germ cell tumors.
 In these groups we saw responses in patients who were clearly resistant to etoposide plus cisplatin given in a standard schedule or in some patients who were resistant to high-dose etoposide with bone marrow transplantation.
 Investigators at Indiana University Medical Center who studied oral etoposide in a similar fashion in patients with advanced germ cell tumors and SCLC achieved results similar to those reported here.
 The authors have initiated a number of combination chemotherapy programs using the chronic oral form of etoposide.
 These include patients with SCLC, non-small cell lung cancer, and elderly patients with high-grade and intermediate forms of NHL.
 In addition, chronic intravenous oral etoposide is being used in salvage approaches for patients with acute myelocytic leukemia and recurrent resistant intermediate-grade and high-grade NHL.
 Preliminary pharmacokinetic data suggest that a 50-mg/m2 oral dose is highly bioavailable (91% to 96%).
 Therefore, during a prolonged oral course at 50 mg/m2, many patients maintain a minimum plasma concentration of 1 microgram/ml.
 Further studies of multiple dose or continuous infusion etoposide to maintain a potentially critical plasma level are in progress.
 Etoposide administered in this way could represent a ""new"" drug because many of its features are different, and its activity spectrum may be broader.
",3
290,"Future directions for etoposide therapy.
 Etoposide is an important chemotherapeutic agent in the treatment of selected patients with germ cell tumors, lymphomas, and small cell lung cancer (SCLC).
 Its optimal use is continuing to evolve.
 It is clear that schedule dependency is of critical importance.
 Recently, preliminary studies have suggested that a prolonged schedule of etoposide administration (21 days) may be more effective than the standard 3- to 5-day schedule.
 Results of several Phase II studies show chronic oral etoposide administration induces occasional responses in resistant tumors and higher-than-expected response rates in patients with germ cell tumors and SCLC.
 Preliminary data show nearly 90% etoposide absorption when given in a low-dose schedule (50 mg/m2/d) for 21 days.
 These observations indicate that etoposide may be a ""new drug"" when given in the chronic schedule.
 Further exploration of the schedule dependency of etoposide is indicated.
 Etoposide has recently been proven useful in selected patients with gastric, ovarian, and poorly differentiated carcinoma of unknown primary site.
 Several other drugs are either synergistic or additive and will be explored in combination chemotherapy.
 The possibility of adding topoisomerase I inhibitors and modulating etoposide's activity by inhibiting drug resistance is now within the realm of human testing.
",3
291,"The clinical pharmacology of etoposide.
 Etoposide, a semisynthetic derivative of podophyllotoxin, is increasingly used to treat cancer.
 Etoposide is a phase-specific, cytotoxic drug acting in the late S and early G2 phases of the cell cycle.
 It appears to cause breaks in DNA by either an interaction with DNA-topoisomerase II or the formation of free radicals.
 Most studies show a biexponential decay after the intravenous (IV) administration of etoposide.
 The peak plasma concentrations of drug and the area under the concentration versus time curve (AUC) are linearly related to the IV dose.
 Considerable interpatient variability of pharmacokinetic variables exists after IV etoposide.
 Various metabolites of etoposide have been identified, but their detection and quantitation are disputed.
 Approximately 30% to 70% of an etoposide dose is excreted.
 The bioavailability of oral etoposide is approximately 50%, but its absorption is not linear with increasing doses within the range in clinical use.
 Considerable interpatient and intrapatient variability exists in the pharmacokinetics of oral etoposide.
 There is no evidence of etoposide accumulation after multiple consecutive doses by either the IV or oral route.
 The exact roles of the liver and kidney in metabolism and excretion of etoposide are uncertain.
 Etoposide has been shown to be a highly schedule-dependent drug in clinical studies.
 This, together with the phase-specific action of etoposide and its increasingly widespread use in treating cancer, makes the clinical pharmacology of this drug of great clinical importance.
",3
292,"Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature individuals.
 Sacrifice of major growth plates during resection and fixed-length reconstruction of a limb in a skeletally immature child with osteosarcoma may result in a significant limb-length inequality as growth progresses.
 A limb-length discrepancy in the humerus may cause minor cosmetic problems but does not generally result in a significant functional deficit.
 In the lower extremity, tumors about the knee, including the distal femur and proximal tibia, usually present the dilemma of whether limb salvage by arthrodesis, osteoarticular allograft, or endoprosthetic replacement would result in a significant limb-length inequality and whether amputation of the extremity is a preferable procedure.
 The techniques of rotationplasty and an expandable endoprosthesis have been successfully used for treating skeletally immature patients with osteosarcoma of the distal femur.
 With regard to survival and function, the results obtained with these innovative methods are favorable compared with those of a high above-knee amputation.
",3
293,"The cellular biology of bone tumors.
 New knowledge in cell and molecular biology has begun to expand the understanding of the biology of osteosarcoma and Ewing's sarcoma.
 Studies on osteosarcomas have revealed abnormalities in the growth-inhibiting retinoblastoma gene, which may release cells from normal growth control.
 Abnormalities in growth factor production or response tend to inappropriately activate cell growth.
 Tumor cell DNA content and cytogenetics may affect the diagnosis and prognostic grouping of osteosarcomas.
 In Ewing's sarcomas, a characteristic translocation between Chromosomes 11 and 22 has been identified; this translocation is also found in malignant neuroepitheliomas.
 A variety of studies point to both neuroectodermal and mesenchymal origins for Ewing's sarcomas.
 Applications of new biologic knowledge and technology to clinical problems will lead to significant changes in the diagnosis, and perhaps in the treatment, of these tumors in the coming years.
 Collaborations between community and referral center physicians and scientists are critical for continued progress.
",3
294,"Osteoid osteoma of the scapula. A case report and review of the literature.
 The scapula is a rare location for osteoid osteoma, which in most cases does not involve the flat bones.
 The en bloc excision in this uncommon location can be problematic since the surgical exposure is difficult, and shoulder joint function can be affected if the lesion is subchondral.
 In an 18-year-old man, an osteoid osteoma was located in the subchondral area of the glenoid.
 A guided needle biopsy of the nidus resulted in complete healing.
 This mode of treatment, with proper follow-up examination, is acceptable for a benign lesion situated in a problematic location.
",3
295,"Cryosurgery and acrylic cementation as surgical adjuncts in the treatment of aggressive (benign) bone tumors. Analysis of 25 patients below the age of 21.
 This article reviews the clinical experience with cryosurgery (use of liquid nitrogen) and acrylic cementation (polymethylmethacrylate; PMMA) in the treatment of aggressive, benign bone sarcomas and the biologic basis of this technique.
 The results of 25 patients below the age of 21 treated by cryosurgery, with an average follow-up period of 60.8 months, are reported.
 Three approaches to surgical reconstruction were used: Group 1 (four patients) had cryosurgery with no reconstruction, Group 2 (13 patients) had bone graft reconstruction alone, and Group 3 (eight patients) had composite osteosynthesis with internal fixation, bone graft, and/or PMMA.
 The overall control rate was 96% (one recurrence).
 The tumor types were giant-cell tumor, chondroblastoma, aneurysmal bone cyst, and malignant giant-cell tumor.
 Nineteen lesions involved the lower extremity, and six lesions were located in the upper extremity.
 There were two secondary fractures (8%), one local flap necrosis, and one synovial fistula.
 There were no infections.
 Two epiphyseodeses were performed.
 The functional results were excellent (83%), good (13%), and fair (4%).
 The technique of composite osteosynthesis is recommended for all large tumors of the lower extremity.
 Cryosurgical results compare favorably with those obtained by en bloc resection and demonstrate the ability of cryosurgery to eradicate tumors while avoiding the need for extensive resections and reconstructive procedures.
",3
296,"Limb reconstruction with vascularized fibular grafts after bone tumor resection.
 Limb-salvage operations are being used with increasing frequency for patients with malignant bone tumors.
 For children, when a biologic reconstruction is desired, the choice is often between conventional and vascularized fibular grafts.
 An experimental study was performed in dogs to compare the two types of fibular grafts for bridging segmental defects in the radius and ulna.
 Twenty-six adult dogs were divided into two groups and studied at intervals of two, three, four, six, and 12 months after transplantation.
 The conventional grafts healed by creeping substitution i.e., they were first partially resorbed before new bone was laid down.
 In contrast, the vascularized fibulae maintained their normal structure and hypertrophied by subperiosteal new bone formation.
 The conventional fibulae eventually hypertrophied but much later than the vascularized grafts.
 The vascularized grafts were stronger at four and six months.
 Between six and 12 months, both grafts remodeled to resemble the size and shape of the forearm bones they were replacing.
 These experimental results have influenced the treatment of patients.
 Vascularized fibular grafts are ideal for diaphyseal defects greater than 10 cm long, especially in very young children, a poorly vascularized bed, or when bone healing is delayed by chemotherapeutic agents.
 To maximize hypertrophy, an external fixator is used to immobilize the graft rather than a plate, which acts as a stress shield.
",3
297,"Modified Van Nes rotationplasty in the treatment of malignant neoplasms in the lower extremities of children.
 A technique of modified Van Nes rotationplasty has been used since 1981 for limb salvage surgery in children and adolescents with malignant sarcoma of the lower extremity.
 The original procedure for lesions of the distal femur was further modified and adopted for selected lesions of the proximal femur and tibia.
 Sixteen skeletally immature children form the base of this report.
 The tumors were located in the distal femur in ten children, the proximal tibia in five and the proximal femur in one.
 There were no intraoperative complications and postoperative complications included one infection requiring debridement and three minor healing delays.
 There were no local recurrences, neurovascular compromises, late derotations, or psychologic decompensations.
 One patient died of metastatic disease and another died of a second malignancy (leukemia).
 The remaining patients are good, functional, below-knee prosthesis users who participate in a number of sporting and athletic activities.
 The procedure is safe, has a relatively low complication rate, allows for the functional demands of an active, growing child, and accommodates for the future growth of extremities.
",3
298,"Ewing's sarcoma. Prognostic factors, disease control, and the reemerging role of surgical treatment.
 Advances in the treatment of Ewing's sarcoma have been dramatic.
 Present treatment protocols control local disease by radiotherapy, surgery, or both; systemic spread is limited by aggressive multiagent chemotherapy.
 In patients with localized osseous Ewing's sarcoma, five-year survival rates now range from 54% to an estimated 74%.
 With late relapse not uncommon, control of the primary lesion is critical to long-term survival.
 Several studies now show improved local control and possibly improved survival of patients with surgical treatment of primary osseous Ewing's sarcoma.
",3
299,"The effect of chemotherapy on growth in the skeletally immature individual.
 One hundred twenty-two children with nonmetastatic osteogenic or Ewing's sarcoma were studied to assess the effect of multiagent adjuvant chemotherapy on skeletal growth and final stature.
 No deviations from the height distributions of a normal population were noted at diagnosis.
 There was a marked retardation of linear growth during the year of intensive chemotherapy.
 Only 15% of the patients grew at the expected rate during that year.
 The distribution of nutritional status scores was significantly different at the end of the first year than at baseline.
 The distribution of ultimate height scores was significantly different than the baseline distribution.
 The overall final distribution was also significantly different from the normal population expectation.
 Any absolute difference in height, however, is likely to be small.
 The subgroups that were observed to full adult stature showed mean heights of 162 cm for girls and 176 cm for boys.
",3
300,"The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta.
 Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells.
 Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells.
 Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells.
 Other synthetic progestins had no effect, indicating that this induction is mediated by the novel Gestodene binding site and not by the conventional progesterone receptor.
 Furthermore, in four breast cancer cell lines, the extent of induction of TGF-beta correlated with intracellular levels of Gestodene binding site.
 No induction of TGF-beta was observed with the endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but which expresses high levels of progesterone receptor.
 The inhibition of growth of T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF-beta.
 These data indicate that the growth-inhibitory action of Gestodene may be mediated in part by an autocrine induction of TGF-beta.
",3
301,"Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells.
 Human erythroblastic precursor cells adhere to fibronectin (Fn) but the exact nature of the receptors mediating this interaction has not been characterized.
 In this study, we report data showing that immature human erythroblasts express the integrins VLA-4 and VLA-5 and that both these molecules act as fibronectin receptors on these cells.
 We have recently demonstrated that adhesion to Fn of purified human CFU-E and their immediate progeny preproerythroblasts was inhibited by antibodies directed against the human fibronectin receptor (VLA-5).
 Here we have extended those results and characterized by immunoprecipitation with specific antibodies the integrins expressed on surface-labeled normal human immature erythroblasts.
 A polyclonal antibody recognizing the common VLA beta 1 subunit yielded two polypeptides of 120 and 160 kD.
 Our data further demonstrate that the polypeptide of 160 kD contains alpha subunits corresponding to both alpha 4 and alpha 5.
 Thus, erythroblast lysates prepared in 0.3% CHAPS and immunoprecipitated with antibodies which specifically recognize the alpha 4 subunit showed a heterodimer with peptides of 120 (beta 1) and 160 kD (alpha 4) and the additional peptides of 70 and 80 kD which usually coprecipitate with the alpha 4 chain.
 On the other hand, specific anti-alpha 5 antibodies immunoprecipitated an alpha 5/beta 1 complex with peptides of 120 and 160 kD which under reducing conditions migrated as a single band of 130 kD.
 Similar experiments performed with an erythroleukemic cell line (KU 812) showed that these cells also coexpress both the VLA-4 and VLA-5 members of the integrin family.
 Furthermore, monoclonal antibodies recognizing the VLA alpha 4 chain blocked the adhesion of immature erythroblasts to Fn-coated surfaces, thus demonstrating that, as VLA-5, VLA-4 is also a functional Fn receptor on these cells.
",3
302,"Measurement techniques for melanoma: a statistical comparison 
 Inter- and intra-observer variation in measuring the depth of invasion of malignant melanomas was assessed using three different techniques: eye-piece graticule, stage Vernier, and projection image analysis.
 Significant variation was found for all methods but was least pronounced with the stage Vernier.
 It is recommended that this should be the preferred technique for routine use.
",3
303,"Cartilage removal prior to skin grafting in the triangular fossa, antihelix, and concha of the ear.
 Skin grafting onto a large area of exposed ear cartilage with irregular contours poses an increased risk of inadequate re-establishment of circulation.
 Removal of cartilage not needed for structural support before grafting following Mohs surgery on the triangular fossa, antihelix, and concha of the ear decreases the risk of recurrence of the carcinoma, and increases the chances for survival of the graft.
",3
304,"Fine-needle aspiration for diagnosis of intranodal squamous-cell carcinoma metastatic from the skin.
 Fine-needle aspiration is a useful way to determine the presence of squamous-cell carcinoma in enlarged lymph nodes of patients at high risk for metastases.
 Advantages include a high degree of accuracy, outpatient as well as inpatient availability, and negligible potential for seeding of malignant cells.
 Cutaneous oncologists should consider using this technique in patients with lymphadenopathy and a previous history of cutaneous squamous cell carcinoma.
",3
305,"HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia.
 We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL).
 We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery.
 Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study.
 The rate of complete remission was 95%.
 Four patients have relapsed.
 The 2-year actuarial EFS was 75% (median follow-up, 37 months).
 Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C.
 We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL.
 EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.
",3
306,"High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study [published erratum appears in J Clin Oncol 1991 Jun;9(6):1094]
 We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission.
 During a 57-month period, we accrued 101 patients.
 We report here results for the 81 who completed treatment at least 2 years ago.
 The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses.
 Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites.
 Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically.
 Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR.
 As of October 1, 1990, follow-up was from 32 to 72 months.
 Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago.
 The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%).
 Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031).
 These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.
",3
307,"Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma [published erratum appears in J Clin Oncol 1991 May;9(5):893]
 Clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma (RMS).
 We therefore studied the cellular DNA content (ploidy) of RMS cells in relation to histology and response to therapy in 37 patients with unresectable tumors.
 Using flow cytometric techniques, we found that about one third of patients had diploid tumor stem lines, regardless of the histologic subtype.
 In the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times the DNA content of normal diploid cells) was exclusively associated with embryonal histology (P = .001).
 By contrast, near-tetraploidy (1.80 to 2.60 times the DNA content of normal cells) was strongly associated with alveolar histology (P = .001).
 Thus, in these histologic subtypes of RMS, abnormal ploidy appears to arise through different mechanisms.
 Tumor-cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable, nonmetastatic (group III) tumors.
 In this subgroup, hyperdiploidy conferred the best prognosis and diploidy the worst (P less than .0001).
 None of the eight patients with diploid tumors survived for more than 18 months.
 Tumor-cell ploidy was the best predictor of treatment outcome for patients with either embryonal (P less than .001; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1) RMS and contributed significantly after adjustment for disease stage and anatomic site.
 Patients with unresectable diploid RMS have an unacceptably high risk of treatment failure, justifying new therapeutic approaches for this distinct subgroup.
",3
308,"Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies.
 Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility.
 The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate.
 Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL).
 Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens.
 Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma.
 The compound does not appear active against most common solid tumors.
 Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity.
 Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine.
 Possible pulmonary toxicity has been suggested in several patients.
 The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity.
 Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting.
 The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined.
 Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
",3
309,"How American oncologists treat breast cancer: an assessment of the influence of clinical trials.
 The present study was designed to assess the preferred methods of treatment of breast cancer by American oncologists, and the impact of clinical trials on their practice.
 We mailed 465 questionnaires to surgical, radiation, or medical oncologists.
 The questionnaire described five hypothetic patients with breast cancer, and respondents were asked to select their preferred treatment for each patient.
 For primary breast cancer, most physicians would offer the choice of local excision followed by radiation therapy or modified radical mastectomy.
 About 80% of physicians would prescribe adjuvant chemotherapy for a premenopausal woman with estrogen receptor-negative, axillary node negative breast cancer, and for a postmenopausal woman with estrogen receptor-negative, node-positive disease.
 This policy was favored by male and female physicians of each specialty.
 Almost all respondents would treat a young woman with inflammatory breast cancer with initial chemotherapy followed by radiation and/or surgery, and about 60% would recommend chemotherapy to a postmenopausal patient with estrogen receptor-negative disease and minimally symptomatic bone metastases.
 Clinical trials have compared treatment strategies that could be applied to patients described in our questionnaire.
 Preferred treatments for primary breast cancer, and for inflammatory breast cancer are supported by the results of clinical trials.
 Recommendation of adjuvant chemotherapy for node-negative breast cancer is not based on a consistent demonstration of improvement in survival, although randomized trials with short follow-up have shown delay to recurrence.
 Recommendation of adjuvant chemotherapy for a postmenopausal woman with node-positive breast cancer is contrary to the results of large randomized controlled trials (and to a meta-analysis), which have shown that this policy does not lead to improved survival.
 Our report suggests that even large randomized clinical trials may have a minimal impact on practice if their results run counter to belief in the value of the treatment.
",3
310,"4-Hydroperoxycyclophosphamide purging of breast cancer from the mononuclear cell fraction of bone marrow in patients receiving high-dose chemotherapy and autologous marrow support: a phase I trial.
 We designed an ex vivo bone marrow treatment for breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support (ABMS), using 4-hydroperoxycyclophosphamide (4-HC), an active derivative of cyclophosphamide with known activity against breast cancer.
 This phase I bone marrow purging trial used ficoll-separated mononuclear cells (MNC) (devoid of granulocytes and RBCs), as opposed to the buffy coat.
 Twenty-five patients with metastatic breast cancer were studied.
 Patients received three cycles of the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), fluorouracil, and methotrexate (Duke AFM) regimen, followed by marrow harvest.
 An MNC fraction of marrow was prepared and treated with 4-HC in concentrations of 20 micrograms/mL (four patients), 40 micrograms/mL (four patients), 60 micrograms/mL (nine patients), or 80 micrograms/mL (eight patients) and cryopreserved.
 Patients then received high-dose systemic cyclophosphamide, cisplatin, and carmustine, followed by infusion of the purged marrow.
 The study end point was marrow engraftment, defined as WBC count greater than 1,000 cells per microliter.
 At the first three dose levels (20, 40, and 60 micrograms/mL 4-HC), there was no significant delay in time to engraftment (19, 20, and 23 days, respectively) compared with the unpurged historical controls (17 days).
 At 80 micrograms/mL, engraftment was significantly delayed compared with the lower concentrations (P = .027), and further escalation of 4-HC was not attempted.
 A significant correlation was observed between the time of leukocyte engraftment and the 4-HC concentration (P = .017).
 With a methylcellulose-based tissue culture assay, we demonstrated a statistically significant correlation between the colony-forming unit-granulocyte-macrophage (CFU-GM) content in the purged marrow and the days to engraftment.
 Ninety-five percent of patients responded clinically to the entire program, 55% of them completely.
 Longer follow-up is required to assess the ultimate benefit of intensive therapy on long-term survival.
",3
311,"Phase I clinical trial with floxuridine and high-dose continuous infusion of leucovorin calcium.
 Sixty-two patients with metastatic disease were treated with continuous infusion folinic acid (leucovorin calcium; Lv) and 2-deoxy-5-fluorouridine (floxuridine; FUDR).
 Lv was given by constant intravenous (IV) infusion at 500 mg/m2/d, days 1 to 6, while FUDR was given by IV push, days 2 to 6, at 3:00 PM daily with doses ranging from 294 to 1,214 mg/m2/d.
 This program was well tolerated with dose-limiting toxicities of diarrhea and stomatitis, while hematologic toxicity was minimal.
 Eighty-two percent of the assessable patients (46 of 56) had failed at least one chemotherapy regimen.
 One complete remission lasting 9 months and 10 partial remissions ranging from 5 to 10 months were observed in this heavily pretreated patient population for an overall response rate of 20%.
 These data suggest that the combination therapy with Lv and FUDR may have clinical use.
 Because of differing patient sensitivity to this drug combination, the recommended dose of FUDR for the initial therapy cycle is 500 mg/m2/d, days 2 to 6, with subsequent escalation to 900 mg/m2/d in those patients without extreme sensitivity.
 Phase II studies are now in progress with these doses.
",3
312,"Extraoral application of osseointegrated implants.
 The use of osseointegrated implants to provide support for craniofacial prostheses has provided the clinician with another approach to the treatment of complex craniofacial reconstructive problems.
 The surgical technique is reviewed and the Mayo Clinic experience is presented.
",3
313,"Antisecretory and antilesional effect of a new histamine H2-receptor antagonist, IT-066, in rats.
 The effects of a new histamine H2-receptor antagonist, IT-066 (3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-++ +butenylamino]- 3-cyclobutene-1,2-dione hydrochloride), were investigated on the secretagogue-induced acid secretion in vivo and in vitro, and on experimental gastric and duodenal lesion in rats.
 IT-066 (10-60 micrograms/kg) given i.v.
 inhibited histamine-stimulated acid secretion dose-dependently in gastric lumen-perfused rats, and the inhibitory effect was observed for about 12 hr.
 Famotidine (FMD) (10-60 micrograms/kg i.v.) also had an antisecretory effect, but the acid secretion recovered to the control level 4 hr after the administration.
 Cold stress plus indomethacin-induced lesion was significantly inhibited by IT-066 and FMD given i.v.
 30 min before the cold stress plus indomethacin treatment.
 IT-066 given 7 hr before the cold stress plus indomethacin treatment also inhibited lesion formation significantly, but such antilesional effect was not observed with FMD.
 In the rat isolated gastric mucosal sheet, IT-066 inhibited histamine-stimulated acid secretion dose-dependently and noncompetitively; its action was produced via a unique mechanism.
 The inhibitory effect of IT-066 remained after washing of the mucosa, and became more potent time-dependently.
 The inhibitory effects of FMD and cimetidine were not observed after washing the mucosa.
 These data suggest that IT-066 has a potent and long lasting antisecretory effect in vivo and in vitro, and that these properties are responsible for the long lasting antilesional action.
",3
314,"Potent selective inhibition of 7-O-methyl UCN-01 against protein kinase C.
 UCN-01 is a staurosporine-related compound that was isolated from the culture broth of Streptomyces sp.
 and shows potent and selective inhibitory activity against protein kinase C.
 Cellular inhibitory activity of UCN-01 against protein kinase C and cytotoxicity of UCN-01 were compared with those of staurosporine.
 When the mechanism of inhibitory activity was investigated in vitro, UCN-01 as well as staurosporine inhibited the activity of the catalytic domain of protein kinase C.
 In spite of direct inhibition against the catalytic domain of protein kinase C, cytotoxicity of UCN-01 was much lower than that of staurosporine.
 In addition, UCN-01 showed more selective inhibitory activity against protein kinase C than did staurosporine because of the sole structural difference at C-7.
 Therefore, a series of 7-O-alkyl derivatives of UCN-01 was synthesized and investigated.
 Interestingly, one of the compounds, the beta-methoxy derivative, showed 3-fold greater potency and 17-fold more selective inhibitory activity against protein kinase C than did UCN-01.
",3
315,"Stimulatory effects of maitotoxin on insulin release in insulinoma HIT cells: role of calcium uptake and phosphoinositide breakdown.
 In hamster insulinoma (HIT) cells, maitotoxin (MTX) induces a time-dependent and concentration-dependent release of insulin that requires the presence of extracellular calcium.
 The response is nearly completely blocked by cinnarizine and cadmium, but is not inhibited by the L-type calcium channel blocker nifedipine or by manganese.
 MTX induces 45Ca+ uptake in these cells in a dose-dependent mode, and the uptake is blocked with cinnarizine, nifedipine and cadmium, and is partially inhibited by manganese.
 MTX induces phosphoinositide breakdown in HIT cells, and the response is partially blocked by cadmium, but is not affected by nifedipine, cinnarizine or manganese.
 High concentrations of potassium ions also induce insulin release and calcium uptake in HIT cells.
 Both effects of potassium are blocked partially by nifedipine, cadmium and cinnarizine.
 High concentrations of potassium do not induce phosphoinositide breakdown in HIT cells.
 The results suggest that MTX-elicited release of insulin is attained by two mechanisms: 1) a nifedipine-sensitive action, which results from MTX-induced activation of L-type calcium channels, which can be mimicked with high potassium concentrations; and 2) a nifedipine-insensitive action, which may be initiated by the activation of phosphoinositide breakdown by MTX.
 Such an activation of phospholipase C would result in the formation of 1,4,5-inositol trisphosphate, a release of intracellular calcium and then release of insulin to the extracellular space.
 Cinnarizine is proposed to block both MTX-elicited mechanisms, the first by blockade of calcium channels and the second by blocking 1,4,5-inositol trisphosphate-induced release of internal calcium.
 Either mechanism alone appears capable of eliciting release of insulin.
",3
316,"Molecular surgery of the basement membrane by the argon laser.
 Although the argon laser is used successfully to weld a number of different tissues, the underlying chemical and cellular mechanisms for this process are not precisely defined.
 Consequently, a biochemical model has been developed in vitro using the well-defined extracellular matrix from the murine Engelbreth-Holm-Swarm (EHS) sarcoma.
 Control and experimental samples of EHS basement membranes were irradiated with a Trimedyne argon laser at 500-3,000 Joules/cm2 at 0 degrees C.
 The samples were diluted into cold phosphate-buffered saline and allowed to gel at 35 degrees C.
 The time course of the gelation reaction was followed in a spectrophotometer at 360 nm.
 Irradiation reduced the absorbance 7.5-15% compared to controls and was independent of the dilution over a 10-fold range.
 Gelation was also measured by determining the amount of protein by the Bradford assay that could be collected by centrifugation at 10,000g for 10 minutes.
 Argon-irradiated samples had 30-40% less protein in the precipitate than the controls.
 The addition of 5 mM beta-mercaptoethanol to the EHS extract blocked the effect of the laser on the gelation reaction.
 In addition, when gelation was carried out in the absence of calcium and magnesium, there were no differences between laser-treated samples and controls.
 The basement membrane proteins were separated by electrophoresis through polyacrylamide gels under denaturing plus reducing or denaturing and non-reducing conditions.
 No differences in the polypeptide composition were noted between irradiated and control samples using either Coomassie- or silver-staining techniques.
",3
317,"Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin 
 BACKGROUND.
 In both animal and epidemiologic studies, exposure to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD) has been associated with an increased risk of cancer.
 METHODS.
 We conducted a retrospective cohort study of mortality among the 5172 workers at 12 plants in the United States that produced chemicals contaminated with TCDD.
 Occupational exposure was documented by reviewing job descriptions and by measuring TCDD in serum from a sample of 253 workers.
 Causes of death were taken from death certificates.
 RESULTS.
 Mortality from several cancers previously associated with TCDD (stomach, liver, and nasal cancers, Hodgkin's disease, and non-Hodgkin's lymphoma) was not significantly elevated in this cohort.
 Mortality from soft-tissue sarcoma was increased, but not significantly (4 deaths; standardized mortality ratio [SMR], 338; 95 percent confidence interval, 92 to 865).
 In the subcohort of 1520 workers with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency, however, mortality was significantly increased for soft-tissue sarcoma (3 deaths; SMR, 922; 95 percent confidence interval, 190 to 2695) and for cancers of the respiratory system (SMR, 142; 95 percent confidence interval, 103 to 192).
 Mortality from all cancers combined was slightly but significantly elevated in the overall cohort (SMR, 115; 95 percent confidence interval, 102 to 130) and was higher in the subcohort with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency (SMR, 146; 95 percent confidence interval, 121 to 176).
 CONCLUSIONS.
 This study of mortality among workers with occupational exposure to TCDD does not confirm the high relative risks reported for many cancers in previous studies.
 Conclusions about an increase in the risk of soft-tissue sarcoma are limited by small numbers and misclassification on death certificates.
 Excess mortality from all cancers combined, cancers of the respiratory tract, and soft-tissue sarcoma may result from exposure to TCDD, although we cannot exclude the possible contribution of factors such as smoking and occupational exposure to other chemicals.
",3
318,"Comparison of myelography with CT follow-up versus gadolinium MRI for subarachnoid metastatic disease in children.
 We evaluated 17 children with primary intracranial neoplasms for subarachnoid metastatic disease (SAMD) using myelography with computed tomographic follow-up (Myelo + CT) and cerebrospinal fluid (CSF) histopathologic examination, as well as magnetic resonance imaging with gadolinium DTPA (MRI + Gd), between December 1988 and December 1989.
 There were 12 boys, and the median age was 5.7 years (range, 0.8 to 21.8 years).
 Tumor histology included 8 primitive neuroectodermal tumors (PNETs), 3 ependymomas, 2 low-grade astrocytomas, 1 anaplastic astrocytoma, 1 glioblastoma multiforme, 1 atypical rhabdoid tumor, and 1 malignant fibrous histiocytoma.
 Thirteen tumors originated in the posterior fossa, 2 were supratentorial, and 2 were in the spinal cord.
 The median interval between the 2 diagnostic tests was 2 days.
 MRI + Gd was positive in 11 (65%), Myelo + CT in 8 (47%), and CSF in 5 (29%) cases.
 MRI + Gd was superior in delineating spinal cord nodules and ""sugar coating"" whereas Myelo + CT more readily revealed nerve root sleeve filling defects.
 There was no case in which Myelo + CT was positive that MRI + Gd did not reveal SAMD.
 MRI + Gd is a safe, noninvasive test that should be used as the initial imaging modality for the presence of SAMD.
",3
319,"Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radiotherapy.
 In this clinical study at the University of Texas M.
 D.
 Anderson Cancer Center, unstimulated and stimulated salivary flow rates were obtained from 47 patients with head and neck cancer who had received mantle, unilateral facial, or bilateral facial field radiotherapy from 0.5 to 25 years earlier.
 The magnitude of salivary flow rate reduction compared with a healthy control group was primarily related to the radiation dosage and the amount of salivary gland tissue included in the irradiated fields.
 Flow rates were lower for women in all groups, but these differences were not statistically significant.
",3
320,"Intramuscular hemangioma in the oral region: report of three cases.
 The occurrence of intramuscular hemangioma in an intraoral or perioral localization is rare, and a thorough knowledge of these tumors is necessary for adequate diagnosis and treatment.
 Three cases are presented with discussion, and their histopathology and differential diagnosis are discussed.
 An adequate primary excision is necessary to avoid recurrence.
",3
321,"Analysis of interleukin 2 and various effector cell populations in adoptive immunotherapy of 9L rat gliosarcoma: allogeneic cytotoxic T lymphocytes prevent tumor take.
 Recombinant interleukin 2 (rIL-2) and various effector cell populations were used for adoptive immunotherapy in the Fischer strain 9L rat gliosarcoma model.
 The in vivo cytotoxicities of nonspecifically activated lymphocytes and specifically activated cytotoxic T lymphocytes (CTLs) were assessed in a modified in vivo neutralization (Winn) assay.
 Effector cells (10(6)) and 9L tumor cells (10(5] were combined with 10(4) units of rIL-2 and stereotactically implanted into the right frontal centrum semiovale of the Fischer (F344) rat.
 At 7 and 14 days, additional effector cells (10(6] and rIL-2 (10(4) units) were administered through the same burr hole.
 Nonspecifically activated splenocytes were lymphokine-activated killer (LAK) cells, both plastic-adherent and nonadherent, whereas specifically activated CTLs were either syngeneic (genetically identical) or allogeneic (genetically dissimilar).
 Syngeneic CTLs were T lymphocytes from Fischer rats primed in vivo with 9L cells and restimulated in vitro.
 Allogeneic CTLs were generated by exposing DA rat lymphocytes either to irradiated Fischer lymph node cells or to 9L Fisher tumor cells in vitro.
 Control groups included rats bearing 9L tumor who were untreated, those who received peripheral (i.p.
 or s.c.) administration of rIL-2, or those who received syngeneic unstimulated T lymphocytes and rIL-2.
 For a set of animals given the same inoculum of 9L tumor, significantly improved survival was shown for groups treated with nonadherent or adherent LAK cells (P less than or equal to 0.0003), syngeneic CTLs (P = 0.0327), or allogeneic CTLs (P = 0.0025) over untreated control animals by using Mantel-Haenzel nonparametric logrank equations.
 Only treatment with allogeneic CTLs prevented tumor take.
",3
322,"Activation of early events of the mitogenic response by a P2Y purinoceptor with covalently bound 3'-O-(4-benzoyl)-benzoyladenosine 5'-triphosphate.
 3'-O-(4-Benzoyl)benzoyl-ATP (BzATP), a photoaffinity analog of ATP, was used as a ligand for a P2Y purinoceptor (adenine nucleotide receptor) present in intact Swiss 3T3 and 3T6 cells and A-431 epidermoid carcinoma cells.
 Photolysis of serum-starved cells in the presence of 10-50 microM BzATP, followed by extensive washing to remove unincorporated BzATP, induced the release of arachidonic acid.
 A trace (less than 0.01%) of photoincorporated BzATP was as effective as when 50 microM BzATP or ATP was contained in the incubation medium during the assay.
 Photoincorporated BzATP also stimulated the production of prostaglandin E2 and the accumulation of cyclic AMP.
 In previous studies, we demonstrated that these three events are obligatory early steps in a pathway leading to DNA synthesis in the above cell lines.
 The evidence indicated that the purinoceptor activated by extracellular ATP or BzATP was linked to a pertussis toxin-sensitive GTP-binding protein.
 Consistent with these observations, we now find that pertussis toxin inhibits the effect of photoincorporated BzATP on arachidonic acid release.
 These results indicate that BzATP is an effective agonist for the P2Y purinoceptor concerned with stimulation of DNA synthesis in 3T3, 3T6, and A-431 cells.
 Furthermore, after photolysis it becomes irreversibly associated with intact cells and promotes the activation of early events required for DNA synthesis.
",3
323,"Boron neutron capture therapy of intracerebral rat gliosarcomas.
 The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested.
 Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0).
 This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT.
 Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively.
 On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors.
 Untreated rats had a median postinitiation survival time of 21 days.
 Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days.
 The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days.
 Two of these animals survived greater than 15 months.
 In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT.
 The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively.
 Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation.
",3
324,"Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone.
 Characterization of the polypeptides present in bone-inductive protein extracts from bovine bone has led to the cloning of seven regulatory molecules, six of which are distantly related to transforming growth factor beta.
 The three human bone morphogenetic proteins (BMPs) we describe herein, BMP-5, BMP-6, and BMP-7, show extensive sequence similarity to BMP-2, a molecule that by itself is sufficient to induce de novo bone formation in vivo.
 The additive or synergistic contribution of these BMP-2-related molecules to the osteogenic activity associated with demineralized bone is strongly implicated by the presence of these growth factors in the most active fractions of highly purified bone extract.
",3
325,"Adenovirus 12S E1A gene represses differentiation of F9 teratocarcinoma cells.
 The F9 teratocarcinoma cell line differentiates in vitro after treatment with retinoic acid and cAMP and has been a widely used model system for the study of the molecular events that are responsible for cellular commitment and differentiation during early development.
 Previous experiments have suggested intriguing parallels between the control of gene expression during F9 cell differentiation and the regulation of gene expression by adenovirus E1A.
 Transfection of a 12S E1A-expressing plasmid into terminally differentiated, nonproliferating F9 cells generates, at high frequency, colonies of dividing cells, each of which expresses E1A.
 Cell lines established from these colonies proliferate in the presence of retinoic acid and have lost the fully differentiated phenotype as characterized by the absence of expression of a series of differentiation-specific genes.
 We conclude that expression of the viral 12S E1A gene product interferes with retinoic acid-induced F9 cell differentiation.
 Moreover, the results suggest that the differentiation process, as defined by markers of terminal differentiation, may not be a permanent event but can be reversed by E1A expression.
",3
326,"Frequent mutation of the p53 gene in human esophageal cancer.
 Sequence alterations in the p53 gene have been detected in human tumors of the brain, breast, lung, and colon, and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene.
 To our knowledge, neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors.
 We examined four human esophageal carcinoma cell lines and 14 human esophageal squamous cell carcinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5, 6, 7, 8, and 9.
 Two cell lines and five of the tumor specimens contained a mutated allele (one frameshift and six missense mutations).
 All missense mutations detected occurred at G.C base pairs in codons at or adjacent to mutations previously reported in other cancers.
 The identification of aberrant p53 gene alleles in one-third of the tumors we tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus.
",3
327,"Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene.
 The leukemogenic membrane glycoprotein (gp55) encoded by Friend spleen focus-forming virus appears to bind to erythropoietin receptors (EpoR) sto stimulate erythroblastosis [Li, J.-P., D'Andrea, A.D., Lodish, H.F.
 & Baltimore, D.
 (1990) Nature (London) 343, 762-764].
 To directly compare the effects of gp55 with erythropoietin (Epo), we produced retrovirions that encode either gp55, Epo, or EpoR.
 After infection with EpoR virus, interleukin 3-dependent DA-3 cells bound 125I-labeled Epo and grew without interleukin 3 in the presence of Epo.
 These latter cells, but not parental DA-3 cells, became factor-independent after superinfection either with Epo virus or with Friend spleen focus-forming virus.
 In addition, Epo virus caused a disease in mice that mimicked Friend erythroleukemia.
 Although Fv-2r homozygotes are susceptible to all other retroviral diseases, they are resistant to both Epo viral and Friend viral erythroleukemias.
 These results indicate that both gp55 and Epo stimulate EpoR and that the Fv-2 gene encodes a protein that controls response to these ligands.
 However, the Fv-2 protein is not EpoR because the corresponding genes map to opposite ends of mouse chromosome 9.
 These results have important implications for understanding signal transduction by EpoR and the role of host genetic variation in controlling susceptibility to an oncogenic protein.
",3
328,"Adenocarcinoma of the colon and rectum in patients less than 40 years of age.
 From 1962 to 1988, 50 of 801 patients with adenocarcinoma of the colon and rectum treated at the National Naval Medical Center were less than 40 years old.
 Symptoms were present in 47 of the younger patients at presentation.
 The mean duration of time from the onset of symptoms to diagnosis in this group was 4.9 months.
 Risk factors for carcinoma of the colon and rectum were identified in 14 of 50 patients less than 40 years old.
 A significantly greater proportion of patients less than 40 years old had Stage C disease compared with the older group of patients (42 versus 22 per cent, p = 0.014).
 Stage B disease was more common in patients more than 40 years of age (44.8 versus 26.0 per cent, p = 0.014).
 The proportion of patients with Stages A and D disease was similar in both age groups.
 The cumulative survival rate in this group at five and ten years was 43 and 34 per cent, respectively.
 The five year survival rate in patients less than 40 years old with Stage B disease was 76 per cent and with Stage C disease, 37 per cent.
 All young patients with Stage D disease were dead at 28 months.
 Synchronous and metachronous carcinomas of the colon and rectum were uncommon in patients less than 40 years old.
 Patients less than 40 years of age with carcinoma of the colon and rectum are usually symptomatic and have advanced disease at the time of presentation.
 Survival time for these patients for each stage of disease is similar to the over-all population of patients with carcinoma of the colon and rectum.
",3
329,"The oncologic risks of skin preservation at mastectomy when combined with immediate reconstruction of the breast.
 Most oncologic surgeons agree that removal of the nipple, the areola and any recent scar at the site of the biopsy is necessary during a mastectomy for treatment of carcinoma of the breast.
 There is less agreement about what should be done with the remaining uninvolved mammary skin.
 Its preservation facilitates the performance of immediate reconstruction of the breast and can lead to improved aesthetic results, but many oncologists fear that this practice could lead to an increased incidence of local tumor recurrence.
 To determine if that fear was justified, 87 patients who had undergone unilateral or bilateral mastectomy with immediate reconstruction for treatment of early carcinoma of the breast were studied.
 Preservation of uninvolved skin was used in all instances.
 All patients had a documented follow-up study of 12 months or more; the average follow-up time was 23.1 months.
 One peripheral local recurrence was observed.
 This 1.2 per cent rate of early local recurrence is lower than that reported from several series using modified radical mastectomy without skin preservation or immediate reconstruction, and suggests that skin preservation does not confer additional risks of local recurrence of carcinoma of the breast in properly selected patients.
",3
330,"Gastric lymphoma.
 From 1976 to 1988, 35 patients were treated for Stage IE and Stage IIE primary gastric lymphoma (non-Hodgkin's).
 Pain and weight loss were the predominant symptoms, physical findings were usually absent and 20 per cent of the patients were anemic.
 The results of gastrointestinal contrast studies suggested a malignant condition in 75 per cent, but findings were not specific for lymphoma.
 Endoscopic findings suggested a malignant process in 85 per cent, but the yield for biopsy was only 60 per cent.
 Of 28 patients undergoing operative exploration, 75 per cent were resectable.
 Nine patients received postresectional adjuvant therapy.
 Five had chemotherapy; three, radiotherapy, and one patient, a combination of the two.
 Primary nonsurgical treatment consisted of chemotherapy in 11, radiotherapy in two and combined therapy in one instance.
 Three of five recurrences were successfully treated.
 The five year survival rate was 65 per cent without significant differences between surgical and nonsurgical regimens.
 Those with tumors smaller than 7 centimeters had a five year survival rate of 100 per cent versus 50 per cent for larger neoplasms.
 Patients more than 60 years of age appeared to have a more favorable course after surgical therapy compared with those who had nonsurgical treatment.
 We concluded that endoscopy is a most useful, although limited diagnostic study and since no treatment program is obviously superior, the choice of therapy can be individualized accordingly.
",3
331,"Nutritional approach to cancer prevention with emphasis on vitamins, antioxidants, and carotenoids.
 The main human cancers are associated with complex life-style related causative, enhancing, and inhibiting factors.
 Tobacco smoking or chewing exposes humans to genotoxic carcinogens and to promoting substances.
 Likewise, Western dietary traditions involve certain carcinogens and promoters, whereas Oriental traditions implicate other carcinogens and promoters.
 Importantly, in virtually all situations regular intake of fruits and vegetables appreciably lowers the risk of cancer.
 This paper reviews the causes of the main human cancers and analyzes the mechanisms of the protective effects of fruits and vegetables.
 Prevention of human cancer requires the definition of optimal levels of recommended daily allowances of micronutrients.
",3
332,"Vegetables, fruits, and carotenoids and the risk of cancer.
 Low intake of vegetables, fruits, and carotenoids is consistently associated with increased risk of lung cancer in both prospective and retrospective studies.
 In addition, low levels of beta-carotene in serum or plasma are consistently associated with the subsequent development of lung cancer.
 The simplest explanation is that beta-carotene is protective.
 Since retinol (preformed vitamin A) is not related in a similar manner to lung cancer risk, beta-carotene appears to function through a mechanism that does not require conversion into vitamin A.
 However, the importance of other carotenoids and other constituents of vegetables and fruit has not been adequately explored.
 Both prospective and retrospective studies suggest that vegetable and fruit intake may reduce the risk of cancers of the mouth, pharynx, larynx, esophagus, stomach, colon, rectum, bladder, and cervix.
 But because of fewer studies and less consistency among studies, the epidemiologic evidence is at present less persuasive than for lung cancer.
",3
333,"Prediagnostic serum levels of carotenoids and vitamin E as related to subsequent cancer in Washington County, Maryland.
 In 1974 and 1975, serum specimens were collected from 25,802 volunteers in Washington County, Maryland.
 The serum was kept frozen at -73 degrees C until the time of assay.
 Prediagnostic samples from 436 cancer cases and 765 matched control subjects have been assayed.
 Nine sites have been studied: colon, rectum, pancreas, lung, melanoma, basal cell of skin, breast, prostate, and bladder.
 Serum beta-carotene levels showed a strong protective association with lung cancer, suggestive protective associations with melanoma and bladder cancer, and a suggestive but nonprotective association with rectal cancer.
 Serum vitamin E levels had a protective association with lung cancer; none of the other sites showed impressive associations.
 Low levels of serum lycopene were strongly associated with pancreatic cancer and less strongly associated with cancer of the bladder and rectum.
",3
334,"Vitamin C and cancer prevention: the epidemiologic evidence.
 Epidemiologic evidence of a protective effect of vitamin C for non-hormone-dependent cancers is strong.
 Of the 46 such studies in which a dietary vitamin C index was calculated, 33 found statistically significant protection, with high intake conferring approximately a twofold protective effect compared with low intake.
 Of 29 additional studies that assessed fruit intake, 21 found significant protection.
 For cancers of the esophagus, larynx, oral cavity, and pancreas, evidence for a protective effect of vitamin C or some component in fruit is strong and consistent.
 For cancers of the stomach, rectum, breast, and cervix there is also strong evidence.
 Several recent lung cancer studies found significant protective effects of vitamin C or of foods that are better sources of vitamin C than of beta-carotene.
 It is likely that ascorbic acid, carotenoids, and other factors in fruits and vegetables act jointly.
 Increased consumption of fruits and vegetables in general should be encouraged.
",3
335,"Vitamin E and cancer prevention.
 Some animal experiments and human studies suggest that vitamin E may protect against cancer.
 Serum alpha-tocopherol concentration was studied for its prediction of cancer in a cohort of 36,265 adults in Finland.
 During a mean follow-up of 8 y, cancer was diagnosed in 766 persons.
 The levels of serum alpha-tocopherol were determined from stored serum samples (at -20 degrees C) taken from these cancer patients and from 1419 matched control subjects.
 Individuals with a low level of alpha-tocopherol had about a 1.5-fold risk of cancer compared with those with a higher level.
 The strength of the association between serum alpha-tocopherol level and cancer risk varied for different cancer sites and was strongest for some gastrointestinal cancers and for the combined group of cancers unrelated to smoking.
 The association was strongest among nonsmoking men and among women with low levels of serum selenium.
 The findings agree with the hypothesis that dietary vitamin E in some circumstances protects against cancer.
",3
336,"Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis.
 N-nitroso compounds (NOC) are strongly implicated in the causation of cancer of the stomach and it has been suggested that ascorbic acid might reduce the risk of gastric cancer by preventing their formation within gastric juice.
 However, until recently there have been no measurements of gastric juice ascorbic acid concentrations.
 We have measured both gastric juice ascorbic and total vitamin C (ascorbic acid and dehydroascorbic acid).
 Our findings suggest that ascorbic acid is secreted into the gastric lumen so that gastric juice concentrations are often greater than those in plasma.
 Gastric pathology affects this secretion, leading to values in gastric juice that are lower than plasma levels.
 Stimulation of gastric secretion does not raise vitamin C concentrations in individuals whose values are initially low.
 The role of ascorbic acid in preventing formation of NOC and protecting against gastric cancer is discussed in the light of these findings.
",3
337,"Interaction of chloramphenicol and metabolites with colony stimulating factors: possible role in chloramphenicol-induced bone marrow injury.
 We have recently demonstrated that two chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria, dehydro-CAP (DH-CAP) and nitrophenylaminopropane (NPAP), are much more cytotoxic to bone marrow in vitro than CAP itself.
 Since colony stimulating factors (CSFs) play an essential role in hematopoietic cell growth, toxicity from CAP metabolites could also involve interaction with CSF or CSF-producing cells.
 In the present study, we found that increasing concentrations of rhGM-CSF or rhG-CSF completely reversed the inhibitory effect of CAP (2 x 10(-4) M) on human CFU-GM growth and on the growth of KG-1 cells.
 GM-CSF also reversed the inhibitory effect of CAP on HL-60 cells.
 Inhibition by DH-CAP (50% at 5 x 10(-7) M), nitroso-CAP (NO-CAP) (60% at 5 x 10(-6) M) and NPAP (35% at 10(-5) M) was not affected by either CSF.
 In addition to their inhibitory effect on cell growth, DH-CAP (5 x 10(-6) M) and NO-CAP (5 x 10(-6) M) inhibited CSF production by buffy coat cells 50-70% without affecting cell viability.
 Neither CAP nor NPAP inhibited CSF production.
 It is suggested that the dual toxic-inhibitory effect of some intestinal metabolites of CAP such as DH-CAP on hematopoietic cell growth on the one hand, and on CSF production on the other, renders them very potent as potential mediators of CAP induced aplastic anemia.
",3
338,"Kaposi's sarcoma involvement of the bone marrow.
 Kaposi's sarcoma (KS) is a predominantly cutaneous malignancy with several clinical variants.
 Extracutaneous sites of involvement are uncommon in all disease variants except epidemic KS (human immunodeficiency virus related) and the African lymphadenopathic variant.
 Extracutaneous KS usually involves the lymph nodes, gastrointestinal tract, and respiratory tract.
 The authors report the first description of a patient with classic KS to have bone marrow involvement.
 Two additional patients with KS variants and bone marrow involvement have been described.
 Bone marrow tumor invasion should be considered in patients with KS and hematologic abnormalities.
",3
339,"Ethanol causes accelerated G1 arrest in differentiating HL-60 cells.
 The effects of clinically relevant ethanol concentrations on myeloid differentiation in the HL-60 cell promyelocytic leukemia line have been studied.
 The exposure of noninduced stem cells to 60 mM ethanol results in an increase in G1 cells, but there is no increase in superoxide production or expression of the Mo1 antigen.
 When HL-60 cells are induced to differentiate along the myeloid line with dimethylsulfoxide (DMSO) or retinoic acid (RA), there is a shift to smaller cell size, an increase in G1 cells and acquisition of the ability to produce superoxide as reported previously by several authors.
 When ethanol is present during differentiation, there are further increases in G1 cells, and increases in the percentage of cells which produce superoxide and express Mo1, and decreases in mean cell size and total growth during the incubation period.
 Regrowth experiments after periods of differentiation indicate that the increased G1 arrest seen in the presence of ethanol represents terminal commitment if inducer is present, but in the absence of inducer the increased G1 percentage is readily reversible.
 Examination of RNA content by flow cytometry reveals a decrease in both the peak and mean G1 RNA content during DMSO or RA induced differentiation.
 These decreases are accentuated by the presence of ethanol, resulting in a higher G1A/G1B ratio than in nonexposed cells.
 These findings indicate that ethanol enhances G1 growth arrest in HL-60 cells exposed to myeloid inducers.
 Partial differentiation occurs during this process, resulting in terminally arrested cells, some of which have undergone fewer postinduction cell divisions than normal and may not be fully competent.
",3
340,"Magnetic resonance imaging and computed tomography in pediatric head and neck masses.
 Fifty-three magnetic resonance imaging (MRI) and 25 computed tomography (CT) studies of 53 head and neck masses in pediatric patients were reviewed retrospectively.
 All lesions had pathologic proof except for 2 metastatic and 2 recurrent lesions, which only had prior pathologic confirmation at their primary sites.
 These included 12 malignant tumors, 23 benign tumors, 6 inflammatory masses, and 12 congenital lesions.
 The MRI performance ranged predominantly from good to excellent in detection of the lesion and the extent of involvement and in contrast to the surrounding tissue; when CT comparison was available, MRI proved to be equal to or better than it in detection of these factors and in preoperative diagnosis.
 Our results suggest that MRI should be the method of choice for the initial evaluation of the pediatric head and neck region, especially in those patients requiring multiple examinations.
 However, CT and MRI should be used conjunctively in complicated cases, especially those possibly involving lesions with calcifications or bony involvement.
",3
341,"Hemangioma of the temporalis muscle.
 A rare case of an intramuscular hemangioma of the temporalis muscle is reported.
 The clinical examination, carotid arteriogram, computed tomographic scan, and aspiration cytology suggested the vascular nature of the tumor, but an exact diagnosis could only be made after histopathologic examination.
 Temporary occlusion of the ipsilateral external carotid artery and subperiosteal dissection permitted complete, wide excision without much bleeding.
",3
342,"Synthesis of type I collagen in healing wounds in humans.
 To quantify wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube for 7 postoperative days and their concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured with specific radioimmunoassays.
 The mean concentration of PICP in would fluid on day 1 was 207 +/- 92 (SD) micrograms/L, and on day 2 908 +/- 469 micrograms/L (p less than 0.001, signed rank test).
 On day 7, the mean concentration reached was 380 times higher than that of day 1 (79,330 +/- 54,151 micrograms/L).
 Only one peak of PICP antigenicity, corresponding to the intact propeptide as set free during synthesis of type I procollagen, was detected on Sephacryl S-300 gel filtration analysis of wound fluid samples.
 The mean concentration of PIIINP was 70 +/- 61 micrograms/L on day 1, 86 +/- 88 micrograms/L on day 2, and 180 +/- 129 micrograms/L on day 3 (p less than 0.001 when compared with day 1).
 Finally on day 7, a 250-fold concentration (17,812 +/- 9839 micrograms/L), compared with day 1, was reached.
 Methods described in the present paper allow separate and repetitive quantification of the synthesis of both type I and type III procollagen during human wound healing.
",3
343,"Rectus abdominis muscle flap with microvascular anastomoses for repair of recurrent sarcoma.
 After radical resection of a recurrent leiomyosarcoma, the thoracic wall was stabilized with a Gore-Tex graft.
 The skin and soft tissue defect was repaired with a large rectus abdominis flap in which the circulation was secured by end-to-end microvascular anastomosis of the inferior epigastric artery to the internal mammary artery, which had to be cut during tumor removal.
",3
344,"The impact of physician compliance on screening mammography for older women.
 Screening mammography is underutilized, even for women older than 50 years for whom there is a general consensus that regular annual screening is appropriate and necessary.
 To evaluate reasons for this underutilization, we studied a random sample of 517 women in Los Angeles, Calif who were older than 50 years.
 All women were found to be underscreened, especially women older than 65 years.
 For example, approximately 35% of women 50 to 64 years old and 47% of women aged 65 years and older never had had even one mammogram.
 Analyses revealed that the most important factor that predicted whether a women ever had had a mammogram was whether her physician had talked to her about mammography.
 Women were between four and 12 times more likely, depending on their age group, to have had a mammogram at some time if their physicians discussed it with them.
 The discussions did not need to be lengthy or complex.
 These results indicate that physicians need to know that discussing screening mammography with their patients has a major impact on breast cancer screening behaviors.
",3
345,"The relationship of Papanicolaou testing and contacts with the medical care system to stage at diagnosis of cervical cancer.
 The relationship of Papanicolaou (Pap) testing and physician visits to stage at diagnosis of cervical cancer was assessed by interviews with 149 women with invasive cervical cancer and 214 women with in situ cervical cancer.
 A significantly smaller percent of study subjects with invasive disease than in situ disease had at least one Pap test in the 3 years prior to diagnosis (age- and race-adjusted odds ratio: 3.38).
 The two groups did not differ in visits to a physician for other reasons during this period.
 Pap testing decreased with increasing age for both groups, but not physician visits.
 While 65% percent of the subjects with invasive disease aged between 65 and 79 years had never had a Pap test until diagnosis, 88% had seen a physician in the preceding 3 years.
 Women with regional or distant invasive disease were least likely to have had Pap tests, and, within this group, those aged between 35 and 64 years were also least likely to have seen a physician.
 Strategies for early detection must reflect missed opportunities and the need to bring those not receiving care into the system.
",3
346,"Decreased mortality in users of estrogen replacement therapy 
 In a prospective study of 8881 postmenopausal female residents of a retirement community in southern California, we evaluated in detail the relationship between estrogen use and overall mortality.
 After 7 1/2 years of follow-up, there had been 1447 deaths.
 Women with a history of estrogen use had 20% lower age-adjusted, all-cause mortality than lifetime nonusers (95% confidence interval, 0.70 to 0.87).
 Mortality decreased with increasing duration of use and was lower among current users than among women who used estrogens only in the distant past.
 Current users with more than 15 years of estrogen use had a 40% reduction in their overall mortality.
 Among oral estrogen users, relative risks of death could not be distinguished by specific dosages of the oral estrogen taken for the longest time.
 Women who had used estrogen replacement therapy had a reduced mortality from all categories of acute and chronic arteriosclerotic disease and cerebrovascular disease.
 This group of women had a reduced mortality from cancer, although this reduction was not statistically significant.
 The mortality from all remaining causes combined was the same in estrogen users and lifetime nonusers.
",3
347,"Combined hepatic and vena caval resection with autogenous caval graft replacement.
 Right-sided and caudate hepatic lobectomy with resection of the retrohepatic vena cava were performed in a 34-year-old woman with recurrent adrenal carcinoma.
 The vena cava was replaced with a graft constructed from autogenous superficial femoral vein.
 Included herein is a review of the literature detailing the three previously reported cases of combined hepatic and caval resection; to our knowledge, there are no prior reports of the use of an autogenous vein graft in this setting.
 With surgical and anesthetic techniques, including total vascular exclusion of the liver and venovenous bypass, methods that were developed in large part through experience in liver transplantation, this type of surgery can be performed with a high rate of success.
",3
348,"Photodynamic therapy to treat tumors of the extrahepatic biliary ducts. A case report.
 The poor survival rate of patients with extrahepatic bile duct tumors is well documented.
 Over the course of 4 years, we treated a white woman with diabetes diagnosed with histologically proven adenocarcinoma of the common bile duct with six injections of dihematoporphyrin ether followed by seven photodynamic therapy treatments to the biliary duct.
 As of July 1989, the patient was still alive, was not jaundiced, and had a Karnofsky performance status of 70.
 No changes occurred in any blood chemistry value from the time of injection to the time of photodynamic therapy.
 Of the transient elevations of some blood chemistry values and the white blood cell count, which occurred within 24 to 48 hours after photodynamic therapy, only those of alanine aminotransferase, aspartate aminotransferase, and amylase were significant.
",3
349,"Pigmented spindle cell naevus.
 We report 22 cases of pigmented spindle cell naevus (PSCN).
 The usual appearance of these naevi is that of a heavily pigmented papule found mostly on the legs of young patients.
 Histologically, PSCN was characterized by symmetrical proliferation of spindle-shaped pigmented melanocytes grouped in large junctional nests.
 Pagetoid spread of single cells in the overlying epidermis was frequently found.
 In our opinion, PSCN is a distinctive benign acquired melanocytic naevus that in the past has been frequently misdiagnosed as atypical Spitz naevi or malignant melanoma.
",3
350,"Factor XIIIa in nodular malignant melanoma and Spitz naevi.
 The distribution of factor XIIIa-positive dermal dendritic cells was studied in a series of nodular malignant melanomas and compared with that seen in Spitz naevi.
 Two patterns of distribution were recognizable: (a) diffusely spread through the tumour and (b) located mainly at the periphery of the tumour.
 These did not correlate with the diagnosis of melanoma or Spitz naevus and the distribution appeared to be a function of growth pattern of the tumour.
 The diffuse pattern was the most common regardless of diagnosis and the distribution of factor XIIIa-positive cells is the same in malignant melanoma and Spitz naevi.
",3
351,"Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells.
 The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the growth of multiple myeloma (MM) was investigated in 21 patients with MM.
 In 17 patients with proliferating myeloma cells in vivo, recombinant GM-CSF significantly increased the endogenous-IL-6-mediated spontaneous myeloma cell proliferation occurring in 5-day cultures of tumor cells in vitro (P less than .01).
 Furthermore, GM-CSF was detected in 5-day culture supernatants of myeloma bone marrow cells.
 This endogenous GM-CSF was produced by the myeloma bone marrow microenvironment but not by myeloma cells and contributed to the spontaneous myeloma-cell proliferation observed in 5-day cultures.
 In fact, this proliferation was partially blocked (67%) by anti-GM-CSF monoclonal antibodies.
 The stimulatory effect of rGM-CSF was mediated through IL-6 because it was abrogated by anti-IL-6 monoclonal antibodies.
 rGM-CSF did not reproducibly increase the endogenous IL-6 production in short-term cultures of bone marrow cells of MM patients.
 Using an IL-6-dependent myeloma cell line (XG-1 cell line), rGM-CSF was shown to act directly on myeloma cells stimulating by twofold their IL-6 responsiveness.
 rGM-CSF did not induce any IL-6 production in XG-1 cells, nor was it able to sustain their growth alone.
 Although no detectable GM-CSF levels were found in the peripheral or bone marrow blood of MM patients, it is possible that GM-CSF, produced locally by the tumoral environment, enhances the IL-6 responsiveness of myeloma cells in vivo in a way similar to that reported here in vitro.
",3
352,"Retroviral transformation of cerebral microvascular endothelial cells: macrophage-like and microvascular endothelial cell properties.
 We report that L-cell-conditioned medium (LCM) transforms porcine cerebral microvascular (PCMV) endothelial cells into cells with macrophage-like properties.
 LCM is known to contain both cytokine(s) and the L-cell virus, a murine retrovirus found in the L929 cell and LCM.
 Our evidence suggests that both LCM cytokine(s) and the L-cell virus are involved in this PCMV endothelial cell transformation.
 Criteria for transformation include focus formation, decreased serum requirements for growth, changes in morphology including nonadherence, propagation in suspension culture, and a decreased growth response to stimulation with a known endothelial cell mitogen.
 Macrophage-like characteristics of this transformed cell, designated as RVTE, include pinocytosis of low-density lipoprotein, Fc receptor-mediated phagocytosis, phagocytosis of bacteria and zymosan, the expression of macrophage enzyme markers, and constitutive production of colony-stimulating factor 1.
 However, the transformed cell retains several properties of the nontransformed cell including the expression of FVIII:RAg and in vitro self-organization into capillary-like structures.
 Cloning of RVTE cells clearly shows that both macrophage-like and cerebral microvascular endothelial cell properties are present in the same cell.
 During self-organization, nontransformed cells express morphologic and functional characteristics classically associated with the macrophage.
 These findings suggest that some brain capillary pathophysiologies could involve macrophage-like cerebral microvascular endothelial cells.
 Furthermore, the ""reticuloendothelial"" phenotypic repertoire expressed by this transformed cerebral microvascular endothelial cell may show that the cerebral capillary endothelial cell in vivo is derived from a hematopoietic and/or phagocytic precursor.
",3
353,"Consistent involvement of the bcr gene by 9;22 breakpoints in pediatric acute leukemias.
 To investigate the relationship of bcr-abl fusion mRNAs with childhood acute lymphoblastic leukemias (ALL), we examined 27 pediatric Philadelphia chromosome (Ph1)-positive acute leukemias using a reverse polymerase chain reaction (PCR) procedure.
 In cells from 24 leukemias, single bcr-abl PCR products were detected that corresponded to breakpoints in the minor breakpoint cluster region (mbcr in intron 1 of the bcr gene) associated with production of the P190 fusion protein.
 Cells from the three remaining leukemias contained breakpoints in the major breakpoint cluster region (Mbcr) as shown by PCR and Southern blot analyses.
 These three leukemias also contained low levels of the mbcr PCR product that may have resulted from alternative splicing of the bcr-abl precursor RNA.
 A screen of 35 additional leukemias from patients who failed therapy before day 180 (induction failures or early relapses) found one case with unsuccessful cytogenetics to express Mbcr-abl RNA.
 All four children with Mbcr breakpoints had white blood cell levels in excess of 250,000 at presentation (compared with 2 of 24 with mbcr breakpoints) and two had hematologic and clinical features suggestive of chronic myelogenous leukemias (CML) in lymphoid blast crisis.
 Our results indicate that in Ph1-positive pediatric leukemias, all 9;22 breakpoints occur in one of the two known breakpoint cluster regions in the bcr gene on chromosome 22.
 The reverse PCR reliably detected all patients with cytogenetic t(9;22) and is capable of detecting additional Ph1-positive leukemias that are missed by standard cytogenetics.
 Furthermore, the Mbcr-type breakpoint, associated with production of p210, can be seen in childhood leukemias presenting either as clinical ALL or as apparent lymphoid blast crisis of CML, suggesting that t(9;22) breakpoint locations do not exclusively determine the biologic and clinical features of pediatric Ph1-positive ALL.
",3
354,"Synergistic inhibition by verapamil and quinine of P-glycoprotein-mediated multidrug resistance in a human myeloma cell line model.
 In an effort to develop a clinically useful approach to overcoming P-glycoprotein-mediated multidrug resistance (MDR1), we evaluated combined chemosensitization with verapamil and quinine in a multidrug-resistant (MDR) human myeloma cell line model.
 In clonogenic assay, verapamil was used at concentrations from 0.1 to 1.0 micrograms/mL, bracketing the plasma levels achieved by oral administration and high-dose intravenous (IV) infusion, respectively.
 The dose of quinine was held constant at 1.0 micrograms/mL, a plasma concentration readily achieved by oral administration.
 At each dose level of verapamil tested, the combination with quinine proved more effective than either drug individually in reversing resistance to doxorubicin and vinblastine and synergistic chemosensitizing interaction was observed.
 Verapamil at 0.1 microgram/mL combined with quinine was capable of restoring sensitivity to doxorubicin fully and reduced resistance to vinblastine as effectively as verapamil alone at 1.0 micrograms/mL.
 Furthermore, the combination of 1.0 mumol verapamil with 10 mumols quinine increased accumulation and retention of anthracycline in the resistant cells to a greater extent than did either drug individually (P less than .001) and inhibited drug efflux as effectively as verapamil alone at 10 mumols.
 Our findings suggest that combined chemosensitization with verapamil and quinine may prove useful for overcoming MDR1 in patients with drug-refractory B-cell neoplasms such as multiple myeloma or non-Hodgkin's lymphomas.
",3
355,"Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia.
 Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone.
 Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell pool in the majority of patients with ANLL.
 The agents were tested singly or sequentially, with a 1-hour incubation of the drugs preceding complement-mediated lysis using MY9.
 VP16 combined with Ara C killed up to 3.9 +/- 0.3 and 5.11 +/- 0.4 logs of the human ANLL cell lines HL60 and K562 at drug concentrations that killed only 1.2 +/- 0.1 logs of normal committed granulocyte/macrophage stem cells (CFU-GM).
 Adding a single exposure of the MY9 and complement (C') to the drug-treated cells, greater than 5.4 logs of HL60 were killed.
 Similar to other pharmacologic agents, no differential kill for clonagenic leukemic cells (colony-forming unit-leukemia; CFU-L) from patients with ANLL was seen for drug only treated blasts versus normal CFU-granulocyte-macrophage (CFU-GM), with less than 1 log CFU-L kill at drug concentrations that spared 1 log of CFU-GM.
 Similarly, only 1.1 +/- 0.3 logs of ANLL CFU-L were eliminated using MY9 and C'.
 However, with the sequential VP16/Ara C----MY9 + C' treatment, synergy was demonstrated and 2.6 +/- 0.3 logs of CFU-L were eliminated.
 Because CD33 is also found on the normal CFU-GM pool, two-stage long-term BM cultures were performed to determine pluripotent stem cell elimination by the drug/MoAb purging combination.
 No difference of CFU-GM or BFU-E production at 4 to 6 weeks of culture for VP16/Ara C, MY9 + C', or VP16/AraC----My9 + C' treated cells was seen compared with untreated controls indicating sparing of early progenitor cells.
 Sequential ex vivo treatment of human ANLL CFU-L with VP16/Ara C followed by complement-mediated lysis using MY9 synergistically kills CFU-L while sparing early normal hematopoietic progenitor cells, and thus may be a more effective way to purge BM than either alone.
",3
356,"Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients.
 Optimum methods of harvesting circulating hematopoietic progenitors for autologous transplantation to support myeloablative cancer therapy are still uncertain, mostly because of the lack of an assay for marrow-repopulating stem cells.
 The CFU-GM assay, the commonly used indirect indicator of the quality of the graft, is poorly standardized and provides results evaluable only retrospectively.
 Based on the knowledge that hematopoietic progenitors express CD34 and CD33 differentiation antigens, we developed a dual-color direct immunofluorescence flow cytometry assay with the aim of replacing the CFU-GM assay advantageously.
 For this purpose, we applied both assays to 157 blood samples obtained daily throughout 20 different recoveries from pancytopenia induced by high-dose cyclophosphamide or etoposide cancer therapy with or without recombinant human GM colony-stimulating factor (rhGM-CSF).
 The appearance of CD34+ cells in the circulation indicated that hematopoietic progenitors had increased to more than 500 CFU-GM/mL, a level clinically adequate for large-scale harvest by leukapheresis.
 Total CD34+ cells correlated well with CFU-GM (r = .89), and data could be fitted by a linear regression line described by the equation y = 388.3 + 64.0x, where y = CFU-GM/mL and x = CD34+ cells per microliter.
 Moreover, in a series of six patients treated with myeloablative chemoradiotherapy, early hematopoietic recovery of marrow functions was predicted more accurately by the number of transplanted CD34+/CD33+ cells than by either total nucleated cells, CFU-GM, CD34+/CD33- cells, or CD34-/CD33+ cells.
 Data presented in this article favor clinical use of the CD34/CD33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation and contribute to better understanding of the role played by circulating hematopoietic progenitor cell subsets in marrow recovery after myeloablative cancer therapy.
",3
357,"Variability in DNA measurements in multiple tumor samples of human colonic carcinoma.
 The DNA ploidy and cell-cycle distribution of three separate fresh tissue samples of 60 colorectal adenocarcinomas were analyzed by flow cytometry.
 DNA ploidy was concordant among the three samples in 38 cases (63.3%).
 In the remaining 22 cases (36.6%), the DNA histograms of two of the three multiple samples were similar; however, the ploidy of the third sample was discordant.
 No relationship was observed between Dukes' stage and histologic grade with concordance or discordance among samples.
 Thus, in about one third of the colonic carcinomas, a single sample showing either a diploid or diploid-cycling DNA histogram would not detect aneuploid DNA patterns.
 Comparison of scrapes and fine-needle aspirates of tumors as alternative sampling methods of tumors for DNA ploidy analysis indicated a strong association with the tumor ploidy (84% and 96%, respectively) only when the ploidy of the multiple samples was concordant.
 In about 25% of the cases, tumor scrapes and fine-needle aspirates did not correlate with the ""most abnormal"" ploidy observed in one of the three tissue samples.
 The data suggest that single or even double tissue samples may not show aneuploid DNA patterns in a substantial proportion of colorectal cancers.
",3
358,"Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity.
 Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose).
 The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers.
 All four parameters were significantly elevated in oral PC patients compared with controls.
 The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers.
 A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC.
 Increasing levels of all the biomarkers were found with progression of the malignant disease.
 Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients.
 The patients with metastases had higher levels of the biomarkers than the patients with primary OC.
 However, elevations only in LSA levels were statistically significant.
 These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC.
 In addition to their value in early detection, they can also help in staging of the disease.
",3
359,"A prospective randomized comparison of protracted infusional 5-fluorouracil with or without weekly bolus cisplatin in metastatic colorectal carcinoma. A Mid-Atlantic Oncology Program study.
 One hundred eighty-four patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to assess the value of weekly cisplatin (20 mg/m2) when added to a protracted schedule of 5-fluorouracil (5-FU) infusion (PIF) at 300 mg/m2/d for 10 weeks of every 12 weeks.
 The liver was the primary indicator lesion in approximately 75% of the study group.
 All tumor measurements required radiographic confirmation.
 The response rate in the PIF alone arm was 35% (29 of 83; 95% confidence interval [CI], 25% to 46%) compared with 33% (28 of 85; 95% CI, 23% to 44%) for the arm in which weekly cisplatin was added to PIF.
 The median survival times were 11.8 and 11.2 months in the two groups.
 Weekly cisplatin does not appear to add to the effectiveness of PIF in colorectal carcinoma.
",3
360,"Prognostic value of histopathology in Ewing's sarcoma. Long-term follow-up of distal extremity primary tumors.
 The pathologic material from 56 patients diagnosed initially as Ewing's sarcoma of the distal extremity and treated on National Cancer Institute protocols between 1968 and 1984 was reviewed and correlated with clinical outcome.
 Histologically, the tumors were categorized, based on recent pathologic criteria, into three diagnostic groups: (1) typical Ewing's sarcoma, (2) atypical Ewing's sarcoma, and (3) other (predominantly peripheral neuroepithelioma [PN]).
 Thirty-two patients (57%) had typical Ewing's, 13 (23%) were atypical, and 11 (20%) were in the ""other"" diagnostic category (seven [13%] PN, two primitive rhabdomyosarcoma, one primitive sarcoma of bone, and one synovial cell sarcoma).
 No cases of metastatic neuroblastoma, osteosarcoma, or lymphoma were found.
 Forty-five patients had localized disease at diagnosis; 11 had metastases.
 Patients with typical Ewing's sarcoma were less likely to have metastatic disease at the time of diagnosis.
 Only two of 32 patients with typical Ewing's sarcoma had metastases compared with nine of 24 patients in the two other groups.
 The pattern of relapse was also different in these other groups compared with typical Ewing's patients; five patients developed lymph node metastases and two patients developed brain metastases.
 Although the presence of metastatic disease at diagnosis was a strong negative prognostic factor, our histologic grouping was independently prognostic of clinical outcome in patients with localized disease.
 Patients with typical osseous Ewing's sarcoma had an improved overall survival (P2 = 0.03) and patients with other tumors (neither typical nor atypical Ewing's sarcoma) had a poorer disease-free survival (P2 = 0.02).
 Since no generally accepted histopathologic prognostic criteria exist for Ewing's sarcoma, the potential value of our proposed classification should be evaluated in a larger retrospective and a prospective study.
",3
361,"Prognostic factors in yolk sac tumors of the ovary. A clinicopathologic analysis of 29 cases.
 Twenty-nine ovarian cancer patients with yolk sac tumors and germ cell tumors with yolk sac tissue as a component of their disease (16 endodermal sinus tumor, 11 mixed germ cell tumors, one embryonal carcinoma, and one polyembryoma) were treated with cytoreductive surgery and combination chemotherapy.
 Prognostic factors were investigated in this group.
 Patients with Stage I disease had a more favorable prognosis (P less than 0.003) than those with Stages II and IV disease.
 The difference in prognosis was significant in cases where residual tumor was absent (P less than 0.003) and in cases where ascites was either absent or less than 100 ml in volume (P less than 0.05).
 Endodermal sinus tumor with either an intestinal (P less than 0.05) or microcystic pattern (P less than 0.01) was more common in survivors than in those who died.
 The age, preoperative serum alpha-fetoprotein level, maximum tumor size, and tumor weight had no significant correlation with prognosis.
 In advanced cases, chemotherapy regimens including cisplatin gave better results than those containing vincristine, dactinomycin, and cyclophosphamide (P less than 0.05).
 The optimal treatment of yolk sac tumors or tumors with yolk sac tissue as a component of the ovary is discussed in light of these results.
",3
362,"Bone sarcomas as second malignant neoplasms following childhood cancer.
 This study explores the relationship between histologic variants of bone sarcomas and previous therapy in patients in whom an unrelated malignant neoplasm had been diagnosed during childhood.
 Sarcomas of bone were the most common second malignant neoplasm (SMN) reported to the Late Effects Study Group, a 13-institution consortium consisting of pediatric oncology centers from western Europe, Canada, and the United States.
 The authors attempted to relate the histologic subtypes of the 91 bone tumors to clinical factors such as previous therapy and genetic predisposition because morphologic variants have been shown to have biologic significance in other tumors and may have etiologic import.
 The literature concerning the subtypes of bone tumors, clinical and experimental, is also reviewed.
 The authors also investigated the effect of several factors on the time interval from the first diagnosis to the SMN (i.e., the bone sarcoma).
 Anthracyclines significantly shortened the interval by about 3 years.
 The primary diagnosis also significantly affected the interval, with leukemia/lymphomas having the shortest interval and retinoblastoma the longest.
 The authors could not demonstrate any significant relationship between morphologic characteristics of the osteosarcoma and predisposing conditions.
 However, lesions diagnosed as chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in patients who had received radiation therapy to the site in which the SMN developed.
",3
363,"A Southwest Oncology Group study on the use of a human tumor cloning assay for predicting response in patients with ovarian cancer.
 A total of 211 patients with epithelial ovarian cancer (168 with tumors refractory to prior chemotherapy and 43 with no prior chemotherapy) from 33 different Southwest Oncology Group institutions had their tumors sampled and specimens shipped to two central laboratories for drug-sensitivity testing in a human tumor cloning assay.
 The 168 patients with a prior history of chemotherapy failure (median of four prior chemotherapeutic agents) were treated with the most effective agent(s) found in the cloning assay (23 patients), and those patients whose tumors did not form colonies in vitro or did not manifest any sensitivity to agent(s) were treated with a clinician's choice of agent(s) (101 patients).
 The remaining 44 of the 168 patients were not treated with chemotherapy because of deteriorating performance status or early death.
 The complete and partial response rate in patients treated according to assay results was 28% versus 11% for the patients treated according to clinician's choice (P = 0.03).
 There was no statistically significant difference in survival between the two options (6.25 versus 7 months, respectively).
 The 43 patients with no history of prior chemotherapy were all treated with standard combination chemotherapy, and their clinical response was compared with their in vitro sensitivity to the same agents.
 Overall there was a 100% true-positive rate and 100% true-negative rate for the seven evaluable patients.
 From these data the authors conclude that use of the human tumor cloning assay may increase the response rate but not the survival for selected patients with advanced chemotherapy-refractory ovarian cancer.
 The study is weakened, however, by the many steps of patient selection necessitated by inadequate tumor colony formation in vitro and the inability to treat all patients (because of early death or a rapid decline in performance status).
 The assay does appear to be worthy of additional study for predicting response to combination chemotherapy in patients without a prior history of chemotherapy.
 Finally the use of central chemosensitivity testing laboratories is feasible for testing in vitro predictive assays in a cooperative group setting.
",3
364,"Achievement of life goals by adult survivors of modern treatment for childhood cancer.
 To assess the impact of the diagnosis and modern treatment of childhood cancer on achievement of adult goals, the authors evaluated employment, health and life insurance coverage, marriage, divorce, and reproduction in 227 former pediatric cancer patients.
 Each area was evaluated in relation to a common set of disease and demographic factors that included age at follow-up, age at diagnosis, gender, marital status, history of disease recurrence, and diagnosis.
 Patients were younger than 20 years of age at diagnosis, and their diagnoses were made between January 1, 1960, and December 31, 1984.
 The median age at diagnosis was 11.4 years, and the median age at follow-up was 26.6 years.
 The percentage of unemployed male respondents did not differ from population norms.
 The percentage of unemployed female respondents, however, was slightly higher than that of the United States population.
 Approximately 11% of the survivors reported some form of employment-related discrimination, a level significantly lower than that of prior reports.
 Company-offered health insurance was provided to 92.4% of full-time and 90.0% of part-time employed respondents.
 Life insurance was purchased by 60% of full-time employed men and 55% of women.
 These percentages were lower than those reported for the United States population.
 Twenty-four percent of those with life insurance had difficulty obtaining it.
 Fifty-eight percent of the subjects were married or lived as married.
 The percentages of married men and women were significantly lower than United States norms.
 Twenty percent of those who were married or lived as married have divorced or separated or no longer live as married.
 Women aged 20 to 24 years were less likely to marry, and women aged 35 to 44 years had a significantly higher frequency of divorce than similarly aged United States women.
 In general, the history of childhood cancer did not influence the decision to marry or live as married but was occasionally (20%) important in the decision to dissolve a marital relationship.
 Many former patients indicated that their diagnosis and treatment for childhood cancer influenced their decision to have children.
 The current study suggests that most former pediatric cancer patients achieve adult life goals.
 Additional research is necessary to define those populations at greatest risk of failure to achieve these goals.
",3
365,"Prolonged response to carboplatin in an infant with brain stem glioma.
 Adults and children with brain stem gliomas have a mean survival time of 15 months after radiation therapy (XRT).
 Infants with this tumor present additional complexities for treatment because of possible neurotoxicity of the radiation to the developing brain.
 We report a 15-month-old child with biopsy-proven brain stem glioma with clinical and radiographic evidence of disease progression.
 She was treated with 24 monthly courses of carboplatin without radiation therapy and has had a 39+ month response.
 The clinical response started after 3 months and the radiographic evidence was documented at 10 months by magnetic resonance imaging.
 The toxicity was minimal.
 Longitudinal neuropsychological assessment demonstrated continued improvement at 36 months post diagnosis but with some motor functioning below expected age levels.
 Cervico-medullary astrocytoma in a young patient may be the appropriate clinical setting for future trials of chemotherapy without XRT.
",3
366,"Postoperative follow-up of patients with early breast cancer. Patterns of care among clinical oncologists and a review of the literature.
 Eighty clinical oncologists in the southeastern United States were surveyed to determine their strategies for follow-up care after primary treatment of early-stage breast cancer.
 The frequency of use of the history and physical examination, complete blood count, liver function tests, carcinoembryonic antigen levels, chest x-ray, skeletal survey, bone scan, liver scan, and mammogram for observing hypothetical low- and high-risk patients was assessed.
 Yearly mammograms were recommended by more than 95% of respondents.
 History and physical examination were the modalities used most often, whereas periodic bone and liver scans were used only in a minority of patients.
 A review of the literature supported the strategy of the respondents in this survey and further underscored the cost-effectiveness of the history and physical examination in detecting recurrence during follow-up.
 Based on this survey and supporting literature, recommendations for reasonable yet cost-conscious follow-up are presented.
",3
367,"Imaging of a parapharyngeal hemangiopericytoma. Radioimmunoscintigraphy (SPECT) with indium-111-labeled anti-CEA antibody, and comparison to digital subtraction angiography, computed tomography, and immunohistochemistry.
 A 27-year-old male patient with a parapharyngeal hemangiopericytoma was investigated radiologically with orthopantomography, computed tomography, and digital subtraction angiography before the operation.
 Because a malignancy was suspected, the patient was imaged with gamma camera using radiolabeled monoclonal anticarcinoembryonal antigen antibody including single photon emission computed tomography.
 The radioantibody accumulated strongly into the neoplasm.
 Tumor to background ratio was 2.2.
 Samples of the excised tumor were stained immunohistochemically for desmin, vimentin, muscle actin, cytokeratin, CEA (carcinoembryonic antigen), and factor VIII.
 They showed that the antibody uptake was of unspecific nature and not due to CEA expression in the tumor.
",3
368,"Results of treating ductal carcinoma in situ of the breast with conservative surgery and radiation therapy.
 To determine the frequency, pattern, and time course of tumor recurrence in the breast, the outcome of 38 women with ductal carcinoma in situ (DCIS) treated with conservative surgery and radiation therapy between 1976 and 1985 was studied.
 Surgery typically consisted of local excision without evaluation of the microscopic margins of resection.
 The median radiation dose to the tumor site was 6400 cGy.
 With a median follow-up time of 81 months, eight patients (21%) have experienced a recurrence in the breast.
 The time course to recurrence was protracted in some cases, with failures occurring at 17, 27, 43, 63, 71, 83, 92, and 104 months.
 The 5-year and 8-year actuarial rates of tumor recurrence in the breast were 8% and 27%, respectively.
 Seven patients had a recurrence at or near the primary tumor site, four with invasive carcinoma, and one had an invasive recurrence at a site elsewhere in the breast.
 No clinical or pathologic factor was significantly associated with an increased risk of recurrence, but the number of patients in the study population was small.
 The authors reached the following conclusions for patients with DCIS treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation: (1) recurrence in the breast may be seen in at least one fifth of the patients; (2) recurrence typically occurs at or near the primary site; and (3) recurrence can occur long after treatment.
 Careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy.
",3
369,"The interferon system in carcinoma of the cervix. Effect of radiation and chemotherapy.
 Thirteen patients with advanced carcinoma of the cervix were studied for parameters of the interferon system compared with 40 age-matched and sex-matched controls.
 All patients had measurable serum interferon levels; controls did not.
 All patients had non-antibody-type interferon-inhibitory activity, and controls had none.
 Interferon-synthesizing potential was higher in controls than in patients.
 After successful radiation and chemotherapy, these parameters normalized in the patients.
 No change was seen in one patient who did not respond to therapy.
",3
370,"Immunohistologic detection of the epidermal growth factor receptor in human esophageal squamous cell carcinoma.
 Epidermal growth factor receptor (EGF-R) expression was studied immunohistologically in 38 patients with esophageal squamous cell carcinoma.
 The EGF-R was faintly expressed in basal and parabasal layers of normal esophageal epithelia and in cancer nests of 20 patients; it was strongly expressed in all areas of dysplastic epithelia and in cancer nests of 18 patients.
 The patients with strongly expressed EGF-R had lymph node metastases more frequently, and their prognosis was poorer than those with faintly expressed EGF-R.
 The EGF-R expression showed a mosaic pattern in 17 patients and a diffuse pattern in 21 patients.
 The patients with a mosaic pattern had lymph node metastases more frequently and a worse prognosis than those with a diffuse pattern.
 Expression of EGF-R in metastatic lymph nodes was similar to that in strongly expressing areas of primary cancers with a mosaic pattern.
 Thus EGF-R expression may be an important indicator for malignancies of esophageal squamous cell carcinomas because primary cancer cells with strongly expressed EGF-R metastasize to lymph nodes more frequently.
",3
371,"The value of immunohistochemistry for collagen IV expression in colorectal carcinomas.
 The Dukes' classification has well-established prognostic value in colorectal cancer patients.
 Yet, in each Dukes' class, the survival of individual patients may vary considerably.
 Recent studies show prognostic significance of genetic alterations in colorectal carcinoma.
 However, the importance of tumor stromal components noted in the surrounding tissue may have been overlooked by the methods used.
 Therefore, in a longitudinal study of 154 patients with colorectal cancer operated on between 1967 and 1974, the authors determined the influence on prognosis of lymphocytic infiltration and expression of collagen type IV in tumor stroma.
 Also, age, sex, Dukes' classification, grade of tumor differentiation, vasoinvasion, and the number of positive lymph nodes were analyzed.
 Follow-up was at least 15 years.
 Lymphocytic infiltration and collagen IV expression were scored as mild, moderate, or severe.
 Survival was analyzed by a Cox proportional-hazards model.
 The density of lymphocytic invasion showed no significant influence on survival.
 Collagen IV expression analyzed as a single variable was significantly (P = 0.038) related to better prognosis in colorectal cancer patients.
 By multi-variate analysis collagen IV expression showed a trend toward better prognosis that was not statistically significant (P = 0.12).
 Dukes' classification (P less than 0.001), the presence of vasoinvasion (P = 0.009), and lymph node status (P = 0.04) significantly influenced survival.
 In conclusion immunohistochemistry for collagen IV is an important additional staining technique with prognostic value.
 In addition, collagen IV immunostaining facilitates recognition of vascular invasion by highlighting the basement membrane of vessels.
",3
372,"A phase II trial of carboplatin and vinblastine in the treatment of advanced squamous cell carcinoma of the esophagus.
 Cisplatin-containing regimens are active in the treatment of esophageal cancer, with response rates of 25% to 35% in advanced disease.
 Carboplatin is less toxic than cisplatin; as a single agent, several responses were seen against esophageal tumors.
 To better define the role of carboplatin in esophageal cancer, the authors treated 19 chemotherapy-naive patients with advanced squamous cell carcinoma of the esophagus with carboplatin and vinblastine.
 Carboplatin (450 mg/m2 intravenously [IV] on days 1, 29, 57, and every 6 weeks thereafter) was given with vinblastine (5 mg/m2 IV on day 1 and then every 2 weeks).
 No major responses were seen.
 No significant renal toxicity and only mild gastrointestinal toxicity (emesis, diarrhea) were observed.
 Hematologic toxicity was more severe in patients with prior radiation therapy (RT), with three of six patients with prior RT exhibiting Grade 4 hematologic toxicity.
 Although generally less toxic than cisplatin-containing regimens, carboplatin and vinblastine is also less active in the treatment of squamous cell carcinoma of the esophagus.
 Hematologic toxicity with this regimen was severe in patients who had received prior RT.
",3
373,"A phase II multi-institutional trial of low-dose N-(phosphonacetyl)-L-aspartate and high-dose 5-fluorouracil as a short-term infusion in the treatment of adenocarcinoma of the pancreas. A Southwest Oncology Group study.
 Adenocarcinoma of the pancreas is a highly lethal malignancy and chemotherapy has had little impact on the natural history of this disease.
 PALA, used to potentiate 5-fluorouracil (5-FU), has been shown to have synergy in vivo and in vitro.
 Twenty-seven patients were treated with an intravenous push dose of PALA (250 mg/m2) followed 24 hours later with a 24-hour infusion of 5-FU (2600 mg/m2).
 This regimen was repeated weekly.
 There was one partial response of 21 eligible patients with an estimated response rate of 5%.
 Toxicity was severe with one toxic death and four patients experiencing Grade 4 toxicity.
 5-Fluorouracil and PALA, given in the schedule described, do not appear to be effective against adenocarcinoma of the pancreas.
",3
374,"A dose-intensive regimen of 5-fluorouracil for the treatment of metastatic colorectal carcinoma.
 5-Fluorouracil (5-FU) was delivered in a dose-intensive schedule to 23 patients with metastatic or unresectable colorectal carcinoma.
 The schedule consisted of bolus single-dose 5-FU therapy 400 to 500 mg followed by 4-day infusion of 5-FU, 600 to 800 mg/m2/day, followed by a 17-day to 24-day infusion of 200 to 250 mg/m2/day.
 Partial remissions were seen in 22% of all eligible patients.
 Significant toxicity, including mucositis, diarrhea, and hand-foot syndrome, necessitated dose reductions in most patients.
 The authors conclude that 5-FU given in this moderately intensive schedule is associated with a moderate level of response, as easily achieved with more conventional schedules or with 5-FU-leucovorin combinations.
 Tumor responsiveness to dose intensive 5-FU regimens may be limited.
",3
375,"Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival.
 Between January 1986 and September 1988, 75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB-III) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM).
 Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR).
 Pretreatment characteristics were analyzed for response to NAC.
 Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall.
 None of the biological parameters studied was related to chemoresponsiveness.
 Patients achieving CR or PR had a significantly improved 3-year survival rate compared with those who did not respond.
 After NAC, radical surgery was possible in all responding patients.
 The median number of lymph nodes removed was 60.
 A lower than expected incidence of lymph node metastases was detected.
 None of the clinical and pathologic features considered was significantly correlated with the lymph node status.
 Twelve of the 62 operated patients had disease recurrence.
 Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence.
 A 3-year, disease-free survival of 89%, 73%, and 43% for Stage IB-IIA, IIB, and III, respectively, was found.
 Among the operated patients these rates increased to 100%, 81%, and 66% for Stage IB-IIA, IIB, and III, respectively.
 A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress.
",3
376,"Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion.
 From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC).
 Two hundred seventy-five patients were included.
 Okuda's staging system was employed.
 Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2).
 Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2).
 As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3).
 Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy.
 Treatment method was the most important factor.
 Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3.
 Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement.
",3
377,"Second cancer after radiation therapy for cancer of the uterine cervix.
 Radiation-induced cancers after radiation therapy for cancer of the uterine cervix were investigated on 11,855 patients including 5725 patients treated with radiation therapy alone, 1969 postoperative radiation therapy and 4161 surgery alone.
 The observed-to-expected ratios of the second primary cancer was 0.933 for the patients with radiation therapy alone and 1.074 for the patients with postoperative radiation therapy, respectively.
 No significant increase was observed in the risk of second primary cancers when all sites were combined.
 However, assessing on site by site basis, significant excess was noted for the rectum cancer, leukemia, and bladder cancer for the radiation therapy group but not for the surgery group.
 A significant excess of lung cancer was observed in both radiation therapy and surgery groups, which was attributed to some other causative factors.
 Radiation-induced cancers were suggested to develop apparently in organs involved in the irradiated field.
",3
378,"Evaluation of a simple line width test involving magnetic resonance spectroscopy of plasma in carcinoma of the ovary.
 Magnetic resonance spectroscopic (MRS) measurement of human plasma has been reported as a generally applicable marker for malignancy: patients with malignancy had a MRS line width significantly different from patients with benign diseases or healthy controls.
 The authors investigated the value of this test in 213 women with ovarian carcinoma, benign pelvic masses, benign nongynecologic diseases, and healthy controls.
 The MRS measurements were performed on plasma samples at 21 degrees C or 27 degrees C.
 The line width parameters were obtained by averaging the width at half the height of the methyl and methylene peaks on the resonance spectra.
 At 27 degrees C using 33 Hz as the threshold for an abnormal result, there was a significant correlation between the result of the test and the presence or absence of malignancy.
 However, the study demonstrates that the specificity (0.44) and positive predictive value (0.42) are too low for the test to be useful in the management of patients with carcinoma of the ovary.
 At 21 degrees C no correlation between the results of the test and the clinical status of women with carcinoma of the ovary were observed.
 In 47 patients the test did not predict preoperatively the benign or malignant nature of a pelvic mass.
",3
379,"Ki-67 immunostaining in human breast tumors and its relationship to prognosis.
 Ki-67 labeling was quantified in 37 nonmalignant breast tissues and in 63 breast carcinomas by counting ten random high-power fields each in three section planes (RC) or by evaluation of the area with the highest labeling density (HDC).
 Both procedures proved to be highly correlated (rs = 0.94).
 Ki-67-positive fractions of the nonmalignant tissues (mean, 2.1% for RC and 4.1% for HDC) were significantly lower as compared with the carcinomas (mean, 14.5% for RC and 17.5% for HDC).
 In carcinomas the Ki-67 labeling was significantly associated with pT stage, axillary lymph node status, and tumor grading and inversely related to progesterone receptor status.
 Using the medians of both counting methods (12% for RC and 17% for HDC) as cutoff points, significantly different curves for overall and disease-free survival (median follow-up, 37 months) were obtained.
 However, Cox multivariate analysis failed to demonstrate an independent effect of Ki-67 labeling.
 In contrast, Ki-67 reactivity seems to be of independent prognostic value if a higher cutoff level was selected.
",3
380,"A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan.
 In Japan, hepatocellular carcinoma (HCC) is one of the most prevalent cancers, with a reported fatality rate showing a consistent and significant increase in the last decade.
 At most, only 25% of HCC cases are positive for the hepatitis B surface antigen (HBsAg).
 To investigate a potential role for hepatitis C virus (HCV) in the development of HCC, sera from 105 HBsAg-negative HCC patients were collected from five districts of Japan and assayed for antibody to HCV antigen (HCVAb).
 A large number of these patients (76.2%) were found to be positive for the HCVAb in comparison with the reported prevalence in sera from blood donors (1.1%).
 A history of blood transfusion was found in 39.6% of the cases positive for HCVAb, which was significantly different to the lower rate (4.7%) observed in HCC patients who were both positive for HBsAg and negative for HCVAb (P less than 0.001).
",3
381,"Non-Hodgkin's lymphoma of the brain after Hodgkin's disease. An immunohistochemical study.
 Non-Hodgkin's lymphoma (NHL) of the central nervous system (CNS) is a rarely reported complication of Hodgkin's disease (HD).
 Two patients with NHL of the brain after HD were studied by histologic and immunohistochemical methods.
 Both patients were in the second decade, had been treated with radiation and chemotherapy, had experienced a relapse of HD before development of NHL, had no evidence of HD at the time of diagnosis of NHL, and died within 1 year of diagnosis.
 Both brain neoplasms were large cell immunoblastic lymphomas of B-cell lineage.
 Patients with HD appear to be at increased risk for NHL of the CNS, which may have a poor prognosis.
",3
382,"DNA and RNA flow cytometric study in multiple myeloma. Clinical correlations.
 Flow cytometric studies of cellular DNA and RNA content using the acridine-orange technique were conducted in 81 patients with multiple myeloma (MM).
 All patients were treated with the M-2 protocol and clinical response was evaluated according to the criteria of the Chronic Leukemia-Myeloma Task Force.
 Aneuploid DNA stemlines were found in 38.2% of untreated patients with a median DNA index (DNA-I) of 1.15 in marrow aspirates and 1.22 in biopsy specimens.
 The median percentage of cells with abnormal DNA content was 31.5 (aspirates) and 35 (biopsy specimens) and a positive correlation with the percentage of bone marrow plasma cells was observed.
 Significantly higher proliferation (S-phase) was found in marrow biopsy specimens as compared with marrow aspirates.
 Significantly higher RNA content (RNA index [RNA-I]) was observed in aneuploid versus diploid patients in biopsy material.
 There was no difference in response to the Memorial Hospital M-2 protocol between diploid and aneuploid patients.
 In patients with DNA-I greater than 1.15 remission duration was shorter as compared with DNA-I less than or equal to 1.15.
 Furthermore, no difference in cellular RNA content was noted between responders and nonresponders.
 This study demonstrates no correlation between cellular RNA content and response, as previously described for patients treated with vincristine, Adriamycin, and dexamethasone (VAD), but DNA aneuploidy appears to be an adverse prognostic factor in MM patients treated with the M-2 protocol.
 It also demonstrates that prognostic models for MM are not universal but depend on the chemotherapeutic regimen used.
",3
383,"An immunohistochemical evaluation of progesterone receptor in frozen sections, paraffin sections, and cytologic imprints of breast carcinomas.
 Two monoclonal antibodies to progesterone receptor (PR), JZB39 and KD68, were used for the immunocytochemical visualization of PR in different kinds of breast cancer specimens including (1) cryostat sections of tumors frozen at -80 degrees C; (2) paraffin sections of tumors fixed in formalin or in Bouin's fixative for varying periods of time at room temperature or at 4 degrees C; and (3) imprints and cryostat sections prepared from the tissue used for frozen section diagnosis and stored at -80 degrees C after fixation in Zamboni's solution.
 Sections of conventionally frozen specimens as well as imprints and cryostat sections stored for varying periods of time were stained with the peroxidase-antiperoxidase technique, whereas the avidin-biotin technique was used for paraffin sections.
 In all types of specimens the PR immunostaining was localized to the nuclei of carcinoma cells and displayed considerable heterogeneity both in intensity and in distribution of positive cells.
 Close correspondence was found between the different immunohistochemical techniques as well as between immunostaining and steroid-binding assays.
 PR staining was more frequently positive in well-differentiated than in moderately or poorly differentiated carcinomas, whereas no meaningful correlation was found between PR staining and extent of the disease.
 Similar results were obtained with the immunostaining of estrogen receptor in the same material using monoclonal antibodies H222 and D75P3 gamma.
 Thus, by choosing the technique that best suits the type of specimen available, it is possible to obtain valid information on the receptor status of any breast carcinoma, regardless of its size and clinical presentation.
",3
384,"A comparative study of histopathology, hormone receptors, peanut lectin binding, Ki-67 immunostaining, and nucleolar organizer region-associated proteins in human breast cancer.
 The current study was performed on 71 cases of human female breast cancer and compares the results of five morphologic methods developed for the detection of estrogen receptors (ER), progesterone receptors (PgR), lectin Peanut agglutinin (PNA) binding sites, monoclonal antibody Ki-67 immunoreactivity, and the mean number of argyrophilic nucleolar organizer regions (Ag-NOR).
 All the parameters were evaluated on serial cryostat sections representative of a closely related, if not identical, neoplastic population.
 A significant positive correlation was found between the occurrence of estrogen, progesterone, and peanut receptors and between Ki-67 immunoreactivity, mean number of NOR, and mitotic index.
 Furthermore, ER, PgR, and PNA receptors showed a significant, inverse correlation with Ki-67 immunoreactivity, mitotic index, and mean number of Ag-NOR.
 These results provide further data that support the hypothesis that (1) progesterone and PNA receptors are estrogen-induced and indicate a metabolic response of the target cells to functioning estrogen receptors; (2) the mean number of NOR reflects the cell kinetics of the tumor; and (3) metabolic differentiation of neoplastic cells is inversely correlated to the proliferation index.
",3
385,"Nucleolar organizer regions in precancerous and cancerous lesions of the bronchus.
 Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NOR) were studied in paraffin sections of five specimens of normal bronchial epithelium, eight of atypical squamous metaplasia, five of carcinoma in situ, and seven of microinvasive squamous cell carcinoma.
 The mean number of Ag-NOR in the nucleus were normal epithelium 1.2 +/- 0.1 (mean +/- SD), atypical squamous metaplasia (borderline lesion) 2.2 +/- 0.5, carcinoma in situ 3.8 +/- 0.6, and microinvasive squamous cell carcinoma 4.8 +/- 1.1.
 There was a highly significant difference between the Ag-NOR numbers in the atypical squamous metaplasia and those in the carcinoma in situ (P less than 0.01).
 The Ag-NOR staining is a useful technique for the differential diagnosis of difficult borderline lesions in the bronchial epithelium.
",3
386,"Insulin secretion and action in patients with pancreatic cancer.
 The authors investigated insulin secretory capacity and insulin action in 11 preoperative patients with pancreatic carcinoma and 15 age-matched and weight-matched healthy subjects (C).
 Five patients were classified as diabetic (D), two as impaired glucose tolerant (IGT), and four as nondiabetic (ND).
 Postabsorptive serum insulin levels (mean +/- SE, in uU/ml) in D (12 +/- 2), IGT (17 +/- 7), and ND (10 +/- 2) were comparable.
 After administration of 100 g of oral glucose, peak insulin achieved in D (60 +/- 11) was lower than in IGT (101 +/- 26) and ND (83 +/- 20), whereas peak insulin levels in IGT and ND were significantly (P less than 0.05) higher than in C (45 +/- 6).
 Comparable insulin response to nonglucose stimuli was documented in all subjects using the slow arginine infusion test with mean serum insulin of 27 +/- 4 in D, 28 +/- 6 in IGT, 34 +/- 10 in ND, and 32 +/- 5 in C.
 In six patients (P) and six controls, insulin action was assessed by the euglycemic hyperinsulinemic clamp technique, with glucose turnover rates estimated by [3-3H]glucose infusion.
 Steady-state plasma glucose concentrations were maintained at 92 +/- 3 (P) and 91 +/- 1 mg/dl (C).
 After insulin infusion at the rate of 1.0 mU/kg/min, comparable high physiologic insulin levels were observed in P (73 to 104 uU/ml) and in C (81 to 103 uU/ml).
 Postabsorptive rates of endogenous glucose appearance (Ra) were higher in P (2.86 to 3.02 mg/kg/min) than in C (1.50 to 2.80 mg/kg/min).
 At high physiologic insulin concentrations, negative Ra values were documented in all subjects, and complete suppression of Ra was assumed.
 Total body glucose use (M) was consistently lower in P (3.90 to 6.40 mg/kg/min) than in C (6.98 to 10.40 mg/kg/min), consistent with a state of insulin resistance.
 Patients with pancreatic cancer manifest insulin resistance by virtue of a decrease in total body glucose use (M) and decreased insulin response to glucose due to either inherent beta cell dysfunction or decreased islet cell mass.
 The latter is not identifiable by histologic morphology.
",3
387,"Pancreatic mucinous cystadenocarcinoma with pseudosarcomatous mural nodules. A report of a case with immunohistochemical study.
 A case of pancreatic mucinous cystadenocarcinoma (PMC) with two pseudosarcomatous mural nodules (PMN) is described.
 These nodules have not been previously described in this type of tumor.
 In ovarian mucinous tumors (OMT), similar nodules have been reported, the nature of which has been discussed in detail.
 Here the similarity between the tumor described here and ovarian tumors is stressed.
 The immunohistochemical study carried out disclosed in the nodules strong positive staining for vimentin and moderate positivity for keratin and epithelial membrane antigen.
 These findings, along with histologic details, favor the epithelial nature of the nodules.
 It was concluded that the nodules are foci of anaplastic carcinoma with high proliferative cell rate, which could explain the coexpression of vimentin and keratin.
",3
388,"Prognostic implications of tumor diameter in carcinoma of the head of the pancreas.
 Two hundred twenty patients with a carcinoma in the head of the pancreas were divided into three tumor diameter groups: group 1, 0.5 to 4.4 cm (n = 72); group 2, 4.5 to 6.0 cm (n = 77); and group 3, 6.1 to 15.0 cm (n = 71).
 For these tumor diameter groups a six-fold eliminatory curability analysis was performed.
 Of the patients with liver metastases in group 1 the last patient had died at 10 months and in groups 2 and 3 no patients were alive at 18 months after the start of complaints.
 Patients with extrahepatic metastases did not survive 12 months in group 1, 16 months in group 2, and 25 months in group 3.
 The 6% actuarial survival rate for inoperable patients was reached in group 1 after 17 months, in group 2 after 36 months, and in group 3 after 27 months after the start of complaints.
 For groups 1 through 3 in curable, but not curatively operated patients, the respective 0% actuarial survival rate was reached at 24 months, 23 months, and 14 months.
 The 0% actuarial survival rate in patients with irresectable vessel invasion was reached in group 1 at 33 months, in group 2 at 23 months, and in group 3 at 25 months.
 The 0% actuarial survival rate in patients with an irresectable tumor was reached at 33 months, 31 months, and 27 months after the start of complaints in groups 1, 2, and 3, respectively.
 The 0% actuarial survival rate in curatively operated patients was reached in group 3 after 26 months and in group 2 after 29 months.
 In group 1 25% of the patients were alive at 36 months after the start of complaints.
 Small tumors were associated with the greatest chance of curative operation and on average had the longest survival.
 However, small tumors with liver or other metastases carried a worse prognosis than large tumors with liver or other metastases.
 If tumors were found not to be resectable at the time of operation, the size of the tumor did not appear to affect survival.
",3
389,"Response rates in relapsed Wilms' tumor. A need for new effective agents.
 Three hundred eighty-one children with Wilms' tumor were treated in the United Kingdom Children's Cancer Study Group WT1 Study (1982 to 1986).
 Seventy-one patients had relapses during or after treatment with surgery and chemotherapy, and radiation therapy, depending on stage and histologic characteristics.
 Forty-nine patients were evaluable for disease response to second-line chemotherapy alone.
 Evaluation of response to chemotherapy was impossible in the remaining patients because either surgery or radiation therapy was used at the time of relapse.
 With second-line combination chemotherapy (which included ifosfamide, etoposide/VM26, cisplatin/carboplatin, bleomycin, melphalan, and Thiotepa [Lederle Laboratories, Pearl River, NY]), there were five complete responses and 12 partial responses.
 In patients with favorable histologic findings, six of nine with Stage I, five of ten with Stage II, none of 11 with Stage III, three of 16 with Stage IV, and one of five with Stage V disease survived.
 Two survivors were treated with chemotherapy alone; the others received combined treatment with chemotherapy, radiation therapy, and/or surgery.
 For those with unfavorable histologic findings of any stage, only two of 20 survived.
 The authors conclude that, even for patients with localized disease with favorable histologic findings, the ""salvage"" rate is little more than 50%, and for all other stages and histologic findings the likelihood of cure after relapse is remote.
 There is clearly a need for additional effective chemotherapeutic agents for these patients.
",3
390,"Primary treatment of large and massive adult sarcomas with iododeoxyuridine and aggressive hyperfractionated irradiation.
 For a decade, the authors have experimented with treatment for unresectable adult soft tissue and bony sarcomas.
 Over the last 6 years, they have combined hyperfractionated radiation therapy and intravenous iododeoxyuridine as a radiosensitizer, in regimens designed to minimize toxicity and permit delivery of aggressive radiation therapy.
 Patients with solitary lesions and those with metastasis (38%) were treated in the hope of both potential cure in some and durable palliation in others.
 The most formidable of these cancers have been those that are large or massive, often requiring five or more fields and extensive treatment planning.
 The authors report results from 36 patients with large unresectable sarcomas (tumors ranging from 5 to 35 cm; average 14 cm) treated with hyperfractionated radiation therapy, with a minimum follow-up of 1 year, follow-up of 4 or more years (in 50%), or follow-up until death.
 Overall local control has been 60%, with control of 66% of lesions from 5 to 9 cm, 63% of those from 10 to 14 cm, 63% of those from 15 to 19 cm, and 57% of those greater than 20 to 40 cm.
 Morbidity has been modest.
 This experience compares favorably with the authors' earlier trials with misonidazole, and toxicity has been reduced considerably.
",3
391,"Ultrasound and ultrasound-guided fine needle aspiration biopsy of supraclavicular lymph nodes in patients with esophageal carcinoma.
 The use of ultrasound combined with ultrasound-guided fine-needle aspiration biopsy (UGFAB) of supraclavicular lymph nodes in the pretreatment staging of 37 patients with squamous cell carcinoma of the esophagus is described.
 All patients underwent computed tomography (CT) scans of the chest and the abdomen and ultrasound of the abdomen and supraclavicular regions.
 Supraclavicular lymph node metastases (Stage IV disease according to the tumor nodes metastasis [TNM] classification) were cytologically diagnosed in seven (18.9%) of the 37 patients.
 In two of these patients, no other metastases were found.
 In the other five patients, UGFAB replaced more invasive diagnostic procedures.
 Due to their superficial location, ultrasound and UGFAB of the supraclavicular lymph nodes was relatively simple to perform, and contributed to an improved staging of squamous cell carcinoma of the esophagus.
",3
392,"Altered protein tyrosine kinase levels in human colon carcinoma.
 To further understand the molecular mechanisms and the biological indicators of colonic tumorigenesis, the authors examined tyrosine kinase activity in the cytosol and in the particulate fraction of the homogenates of specimens from 20 human colonic carcinomas and compared them with the adjacent normal mucosal tissues.
 Total protein tyrosine kinase activity could be precisely detected using miniphosphocellulose column purification and a synthetic peptide, Glu-asparagine (Asp)-alanine (Ala)-Glu-tyrosine (Tyr)-Ala-Ala-arginine (Arg)-Arg-Arg-glycine (Gly) (E11-G1), as an artificial substrate.
 Tyrosine kinase activity of colonic carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity in the particulate fraction was elevated with respect to protein concentration.
 The average specific activity ratios were 1.95 +/- 0.27 (normal cytosolic/carcinoma cytosolic) and 0.57 +/- 0.01 (normal particulate/carcinoma particulate) for tyrosine kinase activity.
 Cellular distribution (% cytosol) of tyrosine kinase activity in normal mucosa and in carcinoma varied from 21.0% to 91.2% and from 7.0% to 61.4%, respectively.
 In nearly all cases the percentage of cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal tissues.
 There was no difference due to histologic type or the presence of adenomatous components.
 A significant decrease of cytosolic tyrosine kinases was correlated with Dukes' Stage A.
 With advancing Dukes' stage, the average specific activity ratios (normal cytosol/carcinoma cytosol) were decreased.
 This study indicates that colonic carcinogenesis might be associated with alterations in cellular levels of tyrosine kinase activity and that the average specific activity ratio (normal cytosol/carcinoma cytosol) had a possible correlation with colonic tumor growth.
",3
393,"Watch and wait after careful surgical treatment and staging in well-differentiated early ovarian cancer.
 Patients with well-differentiated epithelial ovarian cancer Stages Ia, Ib, Ic, and IIa (FIGO 1976) were observed after surgical treatment without adjuvant therapy.
 Careful surgical staging was required, and the extent of the staging procedure was assessed in each individual patient.
 There were 107 patients entered in the study by nine Dutch oncology centers.
 Of these 107, 21 did not fulfill all of the inlet criteria of the study and were excluded.
 Central pathologic review was performed in the remaining 86 cases, revealing that there was borderline tumor in seven patients, moderately or poorly differentiated tumor in nine patients, and tumor of nonepithelial histologic cell type in one patient.
 In two cases, no material for histologic review was available.
 After exclusion of these 19 cases, 67 patients were further analyzed.
 None of these 67 patients was lost during the follow-up period that ranged from 19 to 99 months (mean, 50 months).
 Tumor recurrence was found in four patients after 11, 25, 34, and 34 months of follow-up, all of whom died shortly after diagnosis of the recurrence without satisfactory response to secondary treatment.
 For the patients who underwent the most extensive staging procedure, disease-free 5-year survival was 100%.
 For the patients who were inaccurately staged, disease-free 5-year survival was 88%.
 It was concluded that well-differentiated early stage (Ia-IIa) ovarian cancer carries an excellent prognosis after surgical treatment and complete surgical staging, with the possible exception of patients with Stage Ic disease with malignant peritoneal washings.
 Furthermore, it was considered that the application of more objective and consistent ways of assessing tumor grade should be encouraged.
 Surgical staging should be regarded as the golden standard in defining subsets of low-risk patients and should be included and clearly defined in future trials on early ovarian cancer.
",3
394,"Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas.
 Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells.
 Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure.
 H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., spread of the tumors.
 However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy.
 These findings support the view that features relating to the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors, and that loss of H-antigen expression is related to the stage of tumor and invasion of carcinoma cells.
",3
395,"Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases.
 Five intraductal papillary neoplasms of the pancreas were analyzed for the presence of the Ras gene mutations.
 Three (60%) of the five neoplasms showed point mutations at K-ras codon 12.
 This incidence of the mutations was rather low compared with that found with ordinary pancreatic adenocarcinoma.
 The presence of the mutations did not correlate with the severity of cellular atypia, but was apparently related to the size of the tumor.
 The two neoplasms that had no mutations were smaller than the others that had mutations.
 The analysis suggested that Ras gene mutation is not the first genetic alteration of tumor progression, but that it occurs during the development of neoplasms of the pancreas.
",3
396,"Osteosarcoma in young children.
 The clinicopathologic features of osteosarcoma in 12 children younger than 16 years of age treated at The Children's Hospital and Dana-Farber Cancer Institute, Boston, during a 70-year time period are presented.
 Only one of six children treated before 1972 is a long-term survivor.
 Four of six children (67%) treated after 1972 are disease-free with an average follow-up of 8.8 years.
 The year 1972 marked the onset of use of effective chemotherapy in osteosarcoma, namely, high-dose methotrexate and leucovorin rescue.
 It would appear that the pathologic features and behavior of osteosarcoma in young children is similar to that of osteosarcoma in older children and adolescents.
 A combination of complete (wide) surgical resection or amputation and aggressive chemotherapy offers the best chance of long-term survival.
",3
397,"Fine-needle aspiration in hepatocellular carcinoma. Combined cytologic and histologic approach.
 Cytologic features of fine-needle aspiration (FNA) of hepatocellular carcinoma (HCC) have not been well documented.
 Most previous reports described only the the morphologic features of the tumor cells without considering the sinusoidal stroma.
 Cytohistologic correlation on tissue from the same aspirate has rarely been done.
 This report describes the cytologic patterns of 50 cases of HCC in terms of histologic pattern observed in cell blocks prepared from the same aspiration specimen and classified according to the World Health Organization (WHO) classification.
 Tumors were classified according to the predominant pattern.
 Thirty-two cases gave the trabecular pattern.
 Smears could be subdivided into a central-sinusoidal pattern (23 cases) and a peripheral-sinusoidal pattern (nine cases).
 One case gave the pseudoglandular pattern.
 Seventeen cases gave the compact pattern with inconspicuous sinusoids.
 In all cases sinusoids were easily recognized in cell block sections.
 Other cytologic features such as intranuclear cytoplasmic inclusions, eosinophilic globules, and bile secretion could be seen in both smears and cell blocks.
 Mallory's hyalin and ground glass inclusions were only recognized in cell blocks.
 More attention should be paid to the sinusoidal stroma for diagnosis of HCC in FNA; cell blocks should be more widely utilized to this effect; cytologic patterns could be classified according to the WHO histologic classification.
",3
398,"Clinical presentation, treatment, and outcome of trilateral retinoblastoma.
 In this report, three new cases of trilateral retinoblastoma are presented.
 The clinical presentation, treatment, and outcome of the patients are described and compared with those of 32 cases that have been previously reported in the literature.
 A positive family history was obtained in 68% of the patients.
 The mean age at diagnosis of bilateral retinoblastoma was 7.2 months.
 The mean age at diagnosis of trilateral disease was 39.7 months, resulting in a mean latent interval of 32.6 months.
 The mean time from diagnosis of trilateral retinoblastoma to death was 6.6 months, and all patients died with spinal metastases.
 The patients who received no therapy survived an average of 1.3 months after the diagnosis of trilateral disease.
 The patients who received any form of definitive therapy survived 9.7 months.
 Five patients who had complete or dramatic response to therapy by computed tomography scans had local intracranial tumor present at autopsy.
 Therefore, more aggressive local therapy may be warranted.
",3
399,"Factors related to and consequences of weight loss in patients with stomach cancer. The Norwegian Multicenter experience. Norwegian Stomach Cancer Trial.
 Of 1165 patients with stomach cancer included in a national, prospective multicenter study with 51 surgical units participating, information about weight loss before diagnosis was available for 855 patients (73%).
 Median weight loss was 5 kg; 259 patients (31%) experienced no weight loss.
 By logistic regression analysis the authors found that weight loss increased with age and advancing stages of disease (TNM Stage I-IV), with decreasing Karnofsky index, in Lauren's diffuse versus intestinal tumor type, and with tumors located at the cardia/esophagus.
 Increasing weight loss reduced the resectability rate significantly, but no association between weight loss and postoperative complication rate was found.
 The odds ratio for postoperative mortality was 2.5 to 1 for the weight loss group 5 to 10kg versus 0 kg.
 In conclusion, weight loss reflects a less favorable tumor status.
 Weight loss did not increase postoperative morbidity but did lead Weight to a higher death rate after surgery.
",3
400,"Zinc and copper in breast cancer. A joint study in northern Italy and southern France.
 The relationship between breast cancer and two trace elements, zinc (Zn) and copper (Cu), was investigated by means of an hospital based case-control study at Milan (Italy) and Montpellier (France).
 Variables concerning dietary intake of Zn and Cu (in Milan) and their blood levels (both in Milan and Montpellier) were measured.
 Dietary intake, evaluated through a questionnaire of the dietary history type, and blood levels of Zn and Cu were measured in 261 cases and 261 controls.
 Cu blood level showed a contradictory tendency in the two samples (higher in controls in Milan, higher in cases in Montpellier), which tended to lessen after adjustment for related variables.
 No odds ratios (OR) in the different quantiles, nor X2 for trend reached statistical significance.
 A sharp difference was evidenced on the opposite with regard to Zn blood values in cases and controls.
 In both samples Zn mean values are significantly higher in cases than in controls, and the difference remains significant in the two samples even after adjustment for related variables.
 The pooled OR computed from the two samples, after adjustment for known risk factors and related variables, reaches in the fourth quartile a value of 9.5 (CI: 4.9-18.2).
 Dietary intake of the two minerals (measured only in Milan sample) showed no difference between cases and controls, but a stronger relationship between dietary and blood Zn was evidenced in cases with respect to controls.
 The authors suggest that the higher Zn level in cases might be related with an higher incorporation of Zn in cancer cases and that the same mineral might play a possible role in tumor growth promotion.
",3
401,"Type II oestrogen binding sites in human colorectal carcinoma.
 Seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors.
 The tumours specifically bound oestradiol.
 This binding almost exclusively resulted from the presence of high numbers of type II oestrogen binding sites.
 Oestrogen receptors were absent or present at very low concentrations.
 Immunohistochemical investigation of nuclear oestrogen receptors gave negative results.
 This indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type II oestrogen binding sites.
 The presence of specific type II oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma.
",3
402,"Improved silver staining of nucleolar organiser regions in paraffin wax sections using an inverted incubation technique [published erratum appears in J Clin Pathol 1991 Jun;44(6):528]
 A new simple modification to the silver staining of nucleolar organiser regions (AgNORs) was devised which, by performing the incubation with the slide inverted, results in minimal undesirable background staining, a persistent problem.
 Inverted incubation is facilitated by the use of a commercially available plastic coverplate.
 This technique has several additional advantages over other published staining protocols.
 In particular, the method is straightforward, fast, and maintains a high degree of contrast between the background and the AgNORs.
",3
403,"Neuromesenchymal hamartoma of the small bowel.
 We present the case of a long small bowel stricture with pathological features similar to those described as ""neuromuscular and vascular hamartoma,"" showing in addition extensive fatty submucosal infiltration and fibrous intramural nodules.
 In the controversy about the nature of this disorder, we consider it a separate entity.
 Taking into account that other mesenchymal tissues than the originally described can participate, we propose the alternative term of ""neuromesenchymal hamartoma"" of the small bowel.
",3
404,"Pharyngeal adenocarcinoma with intestinal features.
 A high grade adenocarcinoma arising primarily in the pharynx of a 67-year-old man is presented.
 A CT-scan revealed a tumour mass growing in the pharynx, largely affecting parapharyngeal soft tissues.
 Lymph node metastases were found at clinical presentation.
 Both morphological and immunohistochemical studies displayed similar features to those of intestinal origin.
 To our knowledge, no previous examples of such neoplasm have been reported at this site.
 Its possible histogenetical origin is discussed.
",3
405,"Cystic hygroma: massive recurrence in adult life.
 Cystic hygroma is considered a disease of childhood.
 It may appear for the first time in adult life but recurrence by that stage is rare and may present difficulties in diagnosis due to previous treatment.
 The authors present a case where early pharmacological intervention may have prevented a potentially life threatening situation.
 The world literature is also reviewed.
",3
406,"Papillary adenocarcinoma of the middle ear.
 A case of papillary adenocarcinoma of the middle ear is presented.
 The patient had an unusually short history of otalgia, aural discharge and facial palsy, and, at presentation the tumour was too large for surgical resection to be a feasible option.
 The management of this rare tumour is discussed and the relevant literature reviewed.
",3
407,"Trends in female breast cancer in Connecticut and the United States.
 Trends for female breast cancer were examined by age, period and cohort for the years 1950-1984 in U.S.
 mortality.
 Connecticut mortality and Connecticut incidence.
 Birth cohort patterns were evident for all three sets of data.
 The results confirm a continuing increase in invasive breast cancer by providing evidence of a strong birth cohort pattern, over a time series of 90 years of birth cohorts.
 This trend appears to be real for the most part because of the cohort patterns and because there is minimal underdetection in data obtained by autopsy and blind biopsy.
 Secondly, when cohort modeling is applied to breast cancer mortality, there is an indication of a modest decline in recent breast cancer mortality (in the face of an apparent long-term increase), which suggests that control of breast cancer mortality may have developed in recent decades, perhaps through earlier detection and improved treatment.
 Finally, in contrast with a prior report, there is little evidence for a clinically important difference in time trend between pre- and postmenopausal breast cancer.
",3
408,"Recent life change and large bowel cancer. Data from the Melbourne Colorectal Cancer Study.
 In a large, population based, epidemiological study of colorectal cancer, The Melbourne Colorectal Cancer Study, several etiological factors were investigated.
 Persons' recent life changes, as well as the degree of upset they experienced as a result of these changes, were included.
 Interviews with 715 histologically confirmed new cases of colorectal cancer occurring over a 12-month period in Melbourne, Australia, and with 727 age and sex matched community controls were conducted.
 As one of the methods of assessing any effect of recall bias, 179 hospital controls were also investigated.
 Major illness or death of a family member, major family problems and major work problems were found to be significantly more common for cases over the 5 years preceding diagnosis compared to controls.
 Cases also reported being significantly more upset with their recent life changes than did controls.
 No significant differences in results were found between males and females, or between colon cancer and rectal cancer patients.
 Although the possibility of recall bias, was not completely controlled for in this study, it was probably not an important factor in explaining case-control differences.
 Recent life changes, and their perceptions, may have significance in the development of large bowel cancer.
",3
409,"Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer 
 Indium-111-antimyosin (111In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2).
 Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR).
 Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25.
 Left ventricular ejection fraction (EF) was determined before and after chemotherapy.
 Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01].
 HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05).
 Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients.
 Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy.
",3
410,"Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma.
 Indium-111- (111In) labeled murine monoclonal antibodies ZCE 025 (against carcinoembryonic antigen) and CYT-103 MAb B72.3 (against tumor-associated glycoprotein - 72) have been used to image patients with colorectal cancers with encouraging results.
 The objectives of this study were to assess the frequency and causes of 111In MAb localization in tumor-free, benign tissues.
 Thus, scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with 111In-ZCE 025 (n = 37) or 111In-CYT-103 (n = 38) were reviewed in conjunction with operative and histopathology reports.
 Localization in non-tumored tissues was seen in 10.8% and 13.1%, respectively, of patients receiving ZCE 025 and CYT-103.
 The most common sites involved were: degenerative joint disease, abdominal aneurysms, postoperative bowel adhesions, and local inflammatory changes secondary to surgery or external irradiation.
 Review of patients' medical history and results of concurrent diagnostic modalities is likely to lessen the false-positive rate of 111In-labeled MAb scan interpretation.
",3
411,"6-[18F]fluoro-L-fucose: a possible tracer for assessing glycoconjugate synthesis in tumors with positron emission tomography.
 The potential of 6-[18F]fluoro-L-fucose (6-[18F]FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated.
 Using the tissue sampling method with five tumor models, different time-radioactivity profiles were found: a nearly constant level in Lewis lung carcinoma (3LL) and different clearance patterns in others.
 Rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas.
 Metabolic studies and the L-fucose loading effects on the tissue uptake proved the tracer to be a biochemically active L-fucose analog.
 Imaging of the intracranial rat glioma and 3LL in lungs or hepatomas in mice by autoradiography (ARG) and intramuscular VX-2 carcinoma in rabbits by PET was demonstrated.
 Using double-radionuclide ARG, similar distribution images of 6-[18F]FFuc and 14C-L-fucose but different tumor-to-liver uptake ratios were found.
 A metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model.
",3
412,"SPECT imaging of pediatric brain tumor with hexakis (methoxyisobutylisonitrile) technetium (I).
 Technetium-99m-Hexamibi [Hexakis (methoxyisobutylisonitrile) technetium (i)] was developed as a myocardial perfusion agent with biologic properties similar to those of thallium-201 (201TI).
 As 201TI has recently been observed to be of value for the diagnosis of brain tumors when used in conjunction with single-photon emission computed tomography (SPECT) imaging technology, the possibility that the biologic similarity of the two radiopharmaceuticals extended to their affinity for tumors was tested.
 A 5-yr-old female patient with a brain stem astrocytoma showed marked focal uptake of 99mTc-Hexamibi at the site of tumor recurrence as defined by biopsy and prior 201TI/SPECT study.
 Tumor-to-normal cortex radioactivity ratios for the 99mTc-Hexamibi/SPECT study were 132:1 and the spatial resolution of the 99mTc-Hexamibi images was high.
 This observation suggests that 99mTc-Hexamibi merits further study as a potential agent for SPECT imaging of human brain tumors.
",3
413,"Beta camera for static and dynamic imaging of charged-particle emitting radionuclides in biologic samples.
 A detection system based on microchannel plates has been constructed to image charged particles emitted by radionuclides in biomedical samples.
 This technique has significant advantages over conventional film autoradiography for investigating the distribution of radiolabeled compounds: shorter acquisition times due to the high sensitivity, easier sample handling, direct quantification and the ability to perform dynamic studies.
 The detector performance shows a spatial resolution of 0.9 mm for carbon-14 (14C) (0.156 MeV), good linearity and homogeneity.
 The noise level is below 50/(cm2.sec).
 Successful imaging with this system has been performed with beta-emitters 14C, sulfur-35 (35S), iodine-131 (131I), yttrium-90 (90Y), and positron emitters gallium-68 (68Ga), and fluorine-18 (18F).
 Dynamic studies of axonal transport of 35S-methionine in a nerve, and static images of 90Y-labeled monoclonal antibodies in slices of tumors are presented.
 The system shows promise for rapid quantitative imaging of charged-particle emitting radionuclides in small biologic samples.
",3
414,"Modified anterior compartment resection.
 In the majority of patients with soft tissue sarcomas of the anterior compartment of the thigh, it is possible to preserve a small portion of the quadriceps with intact nerve supply without compromising on the radicality of the procedure or the local control rate.
 The distal one-third of the vastus medialis can usually be spared with a long, slender branch providing its innervation.
 Dissection of the femoral nerve below the inguinal ligament and its branch(es) to an uninvolved area of the quadricepts the farthest from the location of the tumor is essential.
 This modified anterior compartment resection improves dramatically the function of the extremity.
",3
415,"Granular cell neoplasm of the extrahepatic biliary tree: morphological, ultrastructural, and immunohistochemical study and review of the literature.
 A recent case of a biliary granular cell tumor of the cystic duct prompted a literature review and an extensive pathological examination of the tumor in question.
 A total of 44 cases have been described mostly in black females.
 Most cases present with biliary symptoms, and simple surgical resection allows complete control of this benign condition.
 Granular cell tumors are most likely derived from neural crest cells.
",3
416,"Bilateral malignant phyllodes tumours.
 We report a rare example of bilateral primary malignant phyllodes tumours.
 The diagnosis was supported by the identification of a benign epithelial element in each lesion.
 The case illustrates the typical dimorphic features of malignant phyllodes tumours.
 A contralateral tumour should not be regarded as metastatic without histological confirmation.
",3
417,"Migration stimulating activity in serum of breast cancer patients.
 An assay to measure the ability to stimulate migration of fibroblasts into collagen gel was carried out on serum from treated and untreated breast cancer patients and from healthy controls.
 Migration stimulating activity was found in the serum of 10 (83%) of 12 untreated breast cancer patients immediately before surgical resection of the primary tumour and in 9 (75%) of them 4 days after resection; in 13 (93%) of 14 patients 1-13 years after tumour resection who had received adjuvant treatment; and in 2 (10%) of 20 healthy women matched for age.
 The migration stimulating activity in cancer patients' serum was indistinguishable from the migration stimulating factor produced in vitro by fetal and cancer patient skin fibroblasts in its behaviour in various biochemical fractionation procedures.
 The presence of this activity in the serum of treated breast cancer patients clearly distinguishes it from other oncofetal proteins, which all seem to be produced by tumours.
",3
418,"The axilla: not a no-go zone 
 Many surgeons, particularly in the UK, give inadequate primary treatment to patients with operable breast cancer.
 For spurious reasons they regard axillary clearance as unnecessarily extensive surgery and rely instead upon total mastectomy or tumour excision and node sampling, with or without postoperative radiotherapy.
 But it is now clear that relapse-free and overall survival can be improved by appropriate adjuvant therapy.
 Thus inadequate exploration of the axilla is doubly unjustified.
 Not only is there the obvious risk of failure to remove nodes that contain metastases--so that some patients are deprived of cure by primary treatment--but the extent of tumour spread will be inadequately assessed in many more patients, with the risk that they may not receive appropriate adjuvant treatment.
",3
419,"Prothymosin alpha antisense oligomers inhibit myeloma cell division.
 The function of prothymosin alpha has been investigated by using four different antisense oligodeoxyribonucleotides directed at selected regions of its mRNA.
 In every case, when synchronized human myeloma cells were released from stationary phase by incubation in fresh medium containing antisense oligomers, cell division was prevented or inhibited; sense oligomers and random antisense oligomers had no effect.
 A detailed analysis of synchronized cell populations indicated that sense-treated and untreated cells divided approximately 17 hr after growth initiation, whereas cells incubated with antisense oligomer 183, a 16-mer targeted 5 bases downstream of the initiation codon, entered mitosis approximately one cell division late.
 The failure to divide correlated directly with a deficit in prothymosin alpha and with the continued presence of intact intracellular antisense oligomers over a period of at least 24 hr.
 Because antisense oligomers had no effect either on the timing of the induction of prothymosin alpha mRNA upon growth stimulation or on mRNA levels seen throughout the cell cycle, we concluded that antisense DNA caused specific hybrid arrest of translation.
 Our data suggest that prothymosin alpha is required for cell division.
 However, there is no evidence that prothymosin alpha directly regulates mitosis.
",3
420,"Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel.
 Regulation of insulin secretion involves the coordinated control of ion channels in the beta-cell membrane.
 We have isolated and characterized cDNA and genomic clones encoding a voltage-dependent K+ channel isoform expressed in human islets and in a human insulinoma.
 This K+ channel isoform, designated hPCN1, with a deduced amino acid sequence of 613 residues (Mr = 67,097), is related to the Shaker family of Drosophila K+ channels.
 hPCN1 is homologous to two other human K+ channel isoforms we have isolated, hPCN2 and hPCN3, with 55% and 65% amino acid sequence identity, respectively.
 The electrophysiological characteristics of hPCN1 were determined after microinjection of synthetic RNA into Xenopus oocytes.
 Two-microelectrode voltage-clamp recordings of oocytes injected with hPCN1 RNA revealed a voltage-dependent outward K+ current that inactivated slowly with time.
 Outward currents were inhibited by 4-aminopyridine with a Ki less than 0.10 mM and were relatively insensitive to tetraethylammonium ion or Ba2+.
 A delayed rectifier K+ channel such as hPCN1 could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion.
",3
421,"Dimerization of mammalian progesterone receptors occurs in the absence of DNA and is related to the release of the 90-kDa heat shock protein.
 In this study we have demonstrated that dimerization of mammalian progesterone receptors (PR) occurs in the absence of DNA.
 A specific immune coisolation assay was performed on extracts of T-47D human breast cancer cells with a monoclonal antibody specific for the full-length B form of progesterone receptor (PR-B).
 This resulted in coisolation of significant amounts of truncated form-A receptors (PR-A), indicating the presence of stable PR-A.PR-B dimers in solution.
 A positive correlation was observed between the ability of different receptor forms to oligomerize in solution and their ability to bind to specific DNA sequences.
 The ability to form stable PR-A.PR-B oligomers in the absence of DNA was also found to correlate with release of 90-kDa heat shock protein (hsp90) from the unactivated PR complex.
 These results support the hypothesis that dimerization in the absence of DNA is an important mechanism controlling receptor DNA-binding function and that hsp90 release may be a key step regulating dimerization.
 This suggests that hsp90 may function to repress DNA-binding activity indirectly by blocking receptor dimerization.
",3
422,"Pancreatic tumor pathogenesis reflects the causative genetic lesion.
 Transgenic mice in which c-myc expression is targeted to pancreatic acinar cells develop mixed acinar/ductal pancreatic adenocarcinomas between 2 and 7 months of age.
 This contrasts with the effect on pancreas of the simian virus 40 tumor antigen or activated ras, which in adult mice causes lesions composed exclusively of acinar-like cells.
 Furthermore, during an early stage of myc-induced pathology, transformed acinar-derived cells appear within islets, suggesting that islet hormones may influence the progression of these exocrine pancreatic tumors.
 These findings demonstrate that the initial oncogenic alteration can influence the pattern of subsequent tumor pathogenesis and, given that human exocrine pancreatic tumors are predominantly ductal adenocarcinomas, support the suggestion that transformed acinar cells may contribute to the genesis of this serious disease in man.
",3
423,"Williams' vulvovaginoplasty after supralevator total pelvic exenteration.
 Seven patients had delayed Williams' vulvovaginoplasty after supralevator total pelvic exenteration.
 Of the three patients who died of carcinoma of the cervix (at 2, 5, and 15 months after vulvovaginoplasty), the first died before having a chance to attempt intercourse, but the other two had reported intercourse on at least two occasions after the reconstruction.
 One of the patients described the experiences as neither pleasant nor unpleasant but stated that her husband seemed satisfied.
 The other patient described the experience as satisfactory to both herself and her husband.
 The remaining four patients are alive with no evidence of recurrent disease at 28, 42, 56, and 106 months after operation.
 Two of these patients have reported entirely satisfactory sexual relations approximating pre-exenteration frequency, but the remaining two have not had sexual relations since surgery.
 Both give the main reason for this as lack of opportunity.
 The Williams' vulvovaginoplasty appears to be a reasonable alternative for vaginal reconstruction in patients who will have and especially who have had exenteration.
 To improve results, other methods of vaginal reconstruction should continue to be evaluated.
",3
424,"Roentgenographic evaluation of the augmented breast.
 We performed a retrospective study to determine the sensitivity of mammography in detecting breast cancer arising in women with augmented breasts.
 Of eight women with breast implants in whom breast cancer developed, six had mammograms before biopsy.
 Only two of the six cancers were identified mammographically (sensitivity = 33%), and one of these two was seen only in retrospect.
 In both cases, the mammographic findings suggested a benign rather than a malignant process.
 All eight women had a palpable mass and early disease, and all are clinically disease-free at present.
 The sensitivity of mammography in detecting palpable cancers in a control group of women without implants was 92% (118 of 128).
 For tumors of 2 cm or less, the sensitivity was 88% (58 of 66).
 These results suggest that the sensitivity of mammography in detecting breast cancer is decreased when implants are present.
 Further investigations are needed to determine the effects of prostheses on mammographic evaluations.
",3
425,"Scoring system for the preoperative evaluation of metastatic spine tumor prognosis.
 An assessment system for the prognosis of metastatic spine tumors was evaluated for 64 cases who had undergone surgery.
 Six parameters were employed in the assessment system: 1) the general condition, 2) the number of extraspinal bone metastases, 3) the number of metastases in the vertebral body, 4) metastases to the major internal organs (lungs, liver, kidneys, and brain), 5) the primary site of the cancer, and 6) the severity of spinal cord palsy.
 Each parameter ranged from 0 to 2 points.
 The total score obtained for each patient can be correlated with the prognosis, while being valuable in predicting it.
 However, the prognosis could not be predicted from a single parameter.
 In conclusion, an excisional operation should be performed on those cases who scored above 9 points, while a palliative operation is indicated for those who scored under 5 points.
",3
426,"Total sacrectomy and reconstruction for huge sacral tumors.
 The authors carried out successful total sacrectomy in three cases, two with giant cell tumors and one with a chordoma.
 The anterior and posterior approach is feasible for resecting huge sacral tumors en bloc, but it is important to reconstruct the continuity between the pelvic ring and spinal column using spinal instrumentation and sacral rods or AO plates.
 As total sacrectomy is a large-scale, time-consuming, and collaborative operation, two or three teams should be used in relays.
 Both pelvic and spinal surgical techniques are required.
 Post-operatively the patient can stand within 3 to 6 months and well-planned rehabilitation allows ambulation.
 In spite of the serious structural and neurologic damage caused, total sacrectomy can be rewarding procedure in terms of improved morbidity and mortality.
",3
427,"Infiltration of the lower respiratory tract by helper/inducer T lymphocytes in HTLV-1-associated adult T-cell leukemia/lymphoma.
 The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL), a disorder in which peripheral blood and multiple organs are infiltrated by malignantly transformed T lymphocytes.
 We investigated the nature of pulmonary disease in a patient with serologic evidence of HTLV-1 infection.
 In this case, endobronchial biopsy specimens showed infiltration of the bronchial mucosa by pleomorphic cells exhibiting a high degree of nuclear irregularity.
 These cells were morphologically identical in appearance to malignant cells found in peripheral blood and infiltrating the dermis, expressed the OKT4/Leu3 phenotype and the receptor for interleukin 2, and, by analogy to gene rearrangement studies on leukemic blood cells, were monoclonal in origin.
 However, in situ hybridization of endobronchial biopsy specimens with full-length HTLV-1 probes failed to detect retroviral RNA or proviral DNA.
 These studies indicate that T lymphocytic involvement of the lower respiratory tract in HTLV-1-associated ATLL is characterized by expression of a malignant phenotype despite the inability to document actual cellular infection with this retrovirus by a molecular hybridization technique.
",3
428,"The diagnosis of ovarian cancer by pathologists: how often do diagnoses by contributing pathologists agree with a panel of gynecologic pathologists?
 The Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study of ovarian, breast, and endometrial cancer in women 20 to 54 years of age, permitted the diagnoses of contributing pathologists to be compared with those of a panel of three gynecologic pathologists.
 A diagnosis of ovarian cancer was made by contributing pathologists on 477 subjects.
 Agreement between the two groups of pathologists was 97% for primary epithelial ovarian cancer and 89% for primary nonepithelial ovarian malignancies.
 Agreement on diagnosis of major cellular subtypes of ovarian malignancy ranged between 73% for endometrioid cancer and 100% for clear cell carcinomas.
 We conclude that the diagnosis of pathologic features of primary ovarian cancer is highly predictable.
 Nonetheless, diagnosis by histologic type varies sufficiently that a review process should be considered for clinical or investigative decisions involving specific histologic diagnoses of ovarian cancer.
",3
429,"Dissection of the cardinal ligament in radical hysterectomy for cervical cancer with emphasis on the lateral ligament.
 Surgical experience with carcinomas of the uterus and rectum has provided new insights into the surgical anatomy of a lamina, which separates the paravesical space from the pararectal space.
 It has been proved that each of the lamina consists of the cardinal and lateral ligaments and pelvic splanchnic nerves, descending in the following order.
 The cardinal and lateral ligaments, as a connective stalk, insert into the lateral walls of the uterus and rectum extending from the inner aspect of the pelvic wall.
 Clarification of this structural relationship led to the development of a new procedure for the dissection of the cardinal ligament in radical hysterectomy, while still preserving the lateral ligament.
 This facilitated systematic dissection of the cardinal and uterosacral ligaments with posterior manipulation, leading to a reduction in blood loss and to prevention of brisk bleeding from the venous plexuses.
",3
430,"The elusive colonic malignancy. A need for definitive preoperative localization.
 Colonoscopy with biopsy is the standard of practice for the diagnosis of colonic malignancies.
 Unfortunately, the inability of endoscopy to obtain precise distance measurements from the anal verge can make localization of lesions at operation difficult.
 For this reason, preoperative barium enema or intraoperative colonoscopy have been advocated to further pinpoint the sites of those lesions not thought to be easily located at operation.
 Five patients are presented in whom malignant lesions of the colon were diagnosed and verified histologically, but were later undetectable at operation or subsequent colonoscopic examinations.
 Four of these patients underwent laparotomy and three received colon resections.
 None of these patients' tumors were identified during intraoperative colonoscopy, in the resected bowel on pathologic examination, or on follow-up colonoscopy.
 A fifth patient is presented who spontaneously passed a polyp containing invasive adenocarcinoma, but multiple colonoscopic examinations have failed to identify the site of the lesion.
 To date, none of these tumors have recurred with periods of follow-up ranging from 6 months to 2 years.
 These patients demonstrate a poorly documented and little understood aspect of the behavior of colonic malignancies, i.e., the ability to spontaneously regress or slough from the bowel wall.
 Based on these instances, localization of potentially malignant colon lesions is recommended with submucosal dye injections at initial endoscopy or with colonoscopy in the operating room immediately prior to operation.
",3
431,"The pathology of nonpalpable breast cancer.
 A principal goal of mammographic screening is the early detection of breast cancer.
 We reviewed records of 125 women who were referred because of nonpalpable, suspicious abnormalities on mammogram, which subsequently proved to be cancer, requiring mammographic localization biopsy and subsequent surgery for therapy.
 We found that 72 (57.6%) had invasive tumors, 15 (12%) showed evidence of microinvasion and 38 (30.4%) were noninvasive.
 A total of 115 patients had lymphadenectomy as part of their definitive surgery.
 Nine (12.7%) of the patients with infiltrating tumors had between one and 10 malignant nodes on histologic section.
 None of the patients with noninvasive or microinvasive tumors were found to have involved nodes.
 The mammographic abnormalities which led to biopsy in our series were: calcifications in 74 (59.2%) patients, mass lesions in 39 (31.2%), mass lesions with calcifications in 11 (8.8%), and asymmetry in one (0.8%).
 Of the nine patients with nodal metastases, seven (77.8%) had a mass with or without calcifications as the indication for biopsy.
 Increasing tumor size was found to correlate with invasive tumors on histopathologic examination and the incidence of lymph node metastases.
 Thirty-seven (54.4%) of the patients with infiltrating tumors had a tumor size greater than 1 cm.
 Further, seven (77.8%) of the nine lymph node positive patients had tumors between 1 and 3 cm in size.
 Of note, however, is that two (22.2%) patients with microscopic tumors had involved nodes.
 The 4-year actuarial survival in patients with infiltrating tumors was 85.2 per cent, while that for patients with noninvasive or microinvasive tumors was 100 per cent (median follow-up of 20 months).
",3
432,"Intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor causes a cutaneous eruption 
 The intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor to three patients with leukemia who were receiving marrow aplasia-inducing chemotherapy resulted in the development of wide-spread erythematous macules and papules.
 The course of the eruption paralleled the time of infusion of the granulocyte-macrophage colony-stimulating factor.
 Skin biopsy specimens taken from two of the eruptions displayed characteristic changes consisting of a variable mixture of granulocytes and lymphocytes, increased number and size of dermal macrophages, mild to moderate epidermal exocytosis, intercellular edema, and rare dyskeratotic keratinocytes.
 Immunophenotypic analysis of one specimen was notable for keratinocyte intercellular adhesion molecule-1 expression.
 Administration of the recombinant human cytokine in pharmacologic doses is postulated to induce changes in the immunologic status of the skin, resulting in the expression of a cutaneous eruption.
",3
433,"Intraepithelial anchoring fibril components.
 Cultured human keratinocytes and cultured human cervical carcinoma cells (ME-180) contained intracellular pools of antigens that reacted with the anchoring fibril antibodies AF1 and AF2.
 In keratinocytes, these antigens formed a basement membrane-like structure near the apical portions of the cells.
 Using flow cytometric techniques, pretreatment of the ME-180 cells with acetone revealed large intracellular pools of antigen.
 The intracellular epitope was calcium sensitive.
 Some forms of recessive dystrophic epidermolysis bullosa have retention of intracellular portions of the anchoring fibril suggesting a relation of the intracellular anchoring fibril antigens to that disease.
",3
434,"Familial multiple desmoplastic trichoepitheliomas.
 A kindred with familial multiple desmoplastic trichoepitheliomas is described.
 Desmoplastic trichoepitheliomas should be added to the group of lesions that indicate an inherited pattern when they occur as multiple primary tumors.
 The implications for nosologic status and treatment of desmoplastic trichoepitheliomas are considered.
",3
435,"In vivo ultraviolet irradiation of human skin results in profound perturbation of the immune system. Relevance to ultraviolet-induced skin cancer [published erratum appears in Arch Dermatol 1991 Sep;127(9):1368]
 Ultraviolet exposure of human skin deletes the function of antigen-presenting Langerhans cells normally resident within the epidermis.
 Langerhans cells are capable of activating T-lymphocytes by presenting antigens (such as nickel or tumor antigens) to T-lymphocytes.
 Such activated T-lymphocytes may be involved in the development of contact dermatitis and the immune surveillance of immunogenic skin cancers.
 Deletion of the function of Langerhans cells does not result in abrogated epidermal antigen presentation since ultraviolet irradiation simultaneously induces the appearance of another epidermal antigen-presenting cell population that is distinct from the Langerhans cell population and seems to induce suppression of the immune response.
 Suppression of the immune response following ultraviolet irradiation in murine models is critical for growth of immunogenic ultraviolet-induced skin neoplasm.
 Thus, ultraviolet irradiation of human skin may facilitate the growth of human neoplasms, and the spreading of skin-associated infections due to induction of suppressor T cells.
",3
436,"Drug response of head and neck tumors in native-state histoculture.
 We describe a chemosensitivity testing of head and neck tumors, in which a native-state histoculture, ie, a three-dimensional culture system that maintains important in vivo properties, including tissue architecture, was used.
 Fifteen specimens of head and neck tumors were evaluated for sensitivity to the following drugs: cisplatin (DDP) at concentrations of 1.5, 15, and 37.5 micrograms/mL; fluorouracil at concentrations of 4.0, 40, and 100 micrograms/mL; and combinations of cisplatin and fluorouracil in corresponding doses.
 Growth and measurement of drug responses were successfully completed in 10 specimens (five others were contaminated, four of them prior to instituting rigorous antibiotic washes).
 The results indicated cisplatin sensitivity in five of 10 patients; fluorouracil sensitivity in four of 10 patients; and fluorouracil-cisplatin sensitivity in seven of eight patients.
 Our preliminary results indicate that the native-state histoculture technique is feasible to test chemosensitivity of head and neck tumors.
",3
437,"Progress and challenges in psychosocial and behavioral research in cancer in the twentieth century.
 Research in the psychosocial and behavioral aspects of cancer has shown steady growth since the 1950s, and its course of development has paralleled the history of medical techniques in treating cancer.
 Table 1 outlines this parallel evolution from the 1850s to the 1960s.
 The roles of the American Cancer Society and the National Cancer Institute (NCI) in spearheading and nurturing research in this area are documented.
 Interest in psychooncologic questions can be traced back for centuries to the search for etiologic factors and psychologic variables that would explain individual vulnerability to cancer.
 The first psychologic studies of cancer patients were reported in 1951 and 1952 from the Massachusetts General Hospital and Memorial Sloan-Kettering Cancer Center, respectively.
 The 1970s saw new interest in psychosocial and behavioral research with many issues being addressed for the first time: better care of the terminally ill through more humanistic approaches including better means of pain control; ethical concerns related to patient rights and their status as subjects in experimental protocols; trying to measure quality of life for cancer patients on protocols; seeing the need for multidisciplinary collaborative groups to make up for the absence of formal training in this area; and the need to design valid, accurate measuring scales specific to the symptomology of patients with cancer.
 Table 4 outlines how the 1980s gave increasing recognition and support to the psychosocial dimensions of cancer.
 This period produced a series of key conferences that examined a broad research and education perspective and produced recommendations that remain a benchmark in regard to instrumentation, conceptual models, pitfalls of psychosocial research, training, and education, and the organization of research efforts.
 New precision has been added to the field in the past 6 years: studies measuring concurrent psychologic, endocrine, and immune function; use of statistical modeling to incorporate quality of life data as a correction factor in survival data (TWiST and QALY); and broadened definitions of medical outcome to include functional status, thus allowing advances in psychiatric measurements to help answer questions in cancer.
 The challenges for the 1990s are identified in a summary in Table 9.
 Especially noteworthy is the observation that the comprehensive research needed today cannot be carried out by any one discipline alone.
 New approaches call for areas of the social sciences formerly inactive in cancer research (e.g., anthropology) to contribute the tools and expertise required to address the problems.
",3
438,"Social environment and social support.
 Research on the relevance of social support to cancer has been plentiful since the first American Cancer Society workshop on methodological issues in behavioral and psychosocial science.
 Nonetheless, critical shortcomings continue to characterize the attempt empirically to establish such things as the extent to which social support predicts adjustment to cancer diagnosis and treatment.
 Prominent among these is the failure to adequately address large elements of the social structure, such as social class and urbanization, and to investigate how they shape the well being of persons with or at risk for cancer and their caregivers.
 We recommend that more psychosocial research on the link between social support and cancer be conducted within populations beset by poverty and without adequate access to health care.
 Funding is needed for the training and maintenance of multidisciplinary and multicultural teams of researchers working within community-based organizations and hospitals serving the underserved.
",3
439,"Social support and the cancer patient. Implications for future research and clinical care.
 This review assesses past progress, current practices, and future needs in research and clinical practice involving the social support needs of cancer patients.
 A review is given of the various conceptualizations of the social support/stress paradigm and of the state of the art of measuring social support.
 Then the current work in the field of social support and cancer is considered and an argument is made for the use of social support measures, which are relevant to the experiences of the cancer patient.
 Potential adaptations of an existing instrument (the Duke-UNC Functional Social Support Scale) are demonstrated, and a taxonomy of stages of cancer that would require additional types of social support measures and interventions is outlined.
 Interventions are discussed in terms of the traditional support groups as well as interventions by the oncologist and primary care physician.
 An argument is made for the inclusion of quality of life or functional measures as outcomes in clinical trials and the care of the cancer patient.
 Finally, the need to address the existential, philosophic, or religious issues surrounding cancer and its treatment is discussed.
",3
440,"Needs and recommendations for behavior research in the prevention and early detection of cancer.
 Because life-style patterns affect many cancer risks, research on health-risk behavior and behavior change is critical to cancer prevention.
 This report recommends priorities for the next decade of psychosocial research on cancer prevention and detection.
 The leading priority for future research is to fill gaps in basic knowledge left by the rush to intervention and outcome studies.
 Such research must be theoretically driven and should aim to develop broad principles applicable to diverse health behaviors.
 Studies that include relevant process data on various stages of behavior change are considered more desirable than simple outcome studies.
 Epidemiologic investigations should be expanded to include measures of relevant behaviors, so that their impact on clinical outcomes might be established.
 More research is needed on lay perception of health risks and on individual and health-system barriers to effective cancer prevention and detection.
 Studies that address the needs of minority and underprivileged populations are crucial.
 Funding agencies' narrow categorical mandates impede interdisciplinary research on multiple risk factors and their interactions; these boundaries must be relaxed to promote such approaches.
 Funding agencies should also consider basic research as a long-term investment towards the development of effective interventions.
",3
441,"Epidemiologic perspectives on life-style modification and health promotion in cancer research.
 The clinical, patient-oriented focus of medicine and psychology is contrasted with the epidemiologic (public health) approach in assessing the role of life-style factors and health promotion in cancer research.
 The unifying host-agent-environment epidemiologic paradigm is applied to contemporary cancer prevention issues, principally smoking cessation and dietary modification, to demonstrate differences in inferences, prevention strategies, and research opportunities.
 An integration of population-based approaches with the dynamics of patient behavior and risks for cancer is especially salient when considering the role of psychosocial stress and personal and social resources.
 The social epidemiologic perspective, the study of the psychosocial determinants of physical health status, offers one approach for resolving the outlined differences in perspectives and is particularly relevant for understanding the etiology of life-style behaviors and how they might be altered.
",3
442,"Psychoneuroimmunology. Implications for oncology?
 Accumulating evidence indicates that the central nervous system (CNS) may regulate the activity of the immune system.
 Although the overall significance of the immune system in cancer remains controversial, psychosocial influences on immune function could potentially provide a mechanism to account for some of the reports of an association between psychosocial factors and cancer prognosis.
",3
443,"Scientific inquiry in childhood cancer psychosocial research. Theoretical, conceptual, and methodologic issues in the investigation and behavioral treatment of procedure-related distress.
 This paper discusses the current status of scientific inquiry in childhood cancer psychosocial research.
 The investigation and behavioral treatment of procedure-related distress serves as a model for illustrating and outlining some of the theoretical, conceptual, and methodologic issues and problems that exist in the area of childhood cancer psychosocial research.
 Specifically, issues related to the process of scientific inquiry, theoretical/conceptual modeling, measurement and assessment, and behavioral treatment strategies are discussed.
 Examples of how these issues have been addressed in our investigations of procedure-related distress are presented and recommendations for facilitating growth and development in the field of childhood cancer psychosocial research are offered.
",3
444,"Quality of life research in oncology. Past achievements and future priorities.
 The status of quality of life research in oncology is assessed, and priorities for future research with regard to conceptual and theoretical developments, focus and content of research, research designs and practical strategies for research implementation, and transferring information to clinical practice and medical policy decision-making are identified.
 There is general agreement that quality of life is a subjective and multidimensional construct, yet comprehensive theoretical models have not been developed and applied fully.
 We recommend that future research be based on conceptual models that explicate the interrelationships among quality of life domains throughout the stages of cancer care.
 These models, and the longitudinal research that follows from them, should attend specifically to cross-class and cross-cultural issues to avoid overgeneralization from theory and research that are based largely on the views of the majority culture.
 We encourage the inclusion of this theory-based quality of life assessment as a standard component of clinical trials.
 Success in this endeavor will require additional standardization of quality of life measures for use across a range of cancer patient populations, including the development of age-specific norms and instruments designed to assess the entire family system.
",3
445,"Methodologic issues in assessing the quality of life of cancer patients.
 Although quality of life assessments have been employed successfully in descriptive and evaluative studies in oncology, their use in cancer clinical trials has, to date, been limited.
 A range of issues have impeded the conduct of clinical trial-based quality of life investigations.
 These include: the absence of theoretical models to guide the development of quality of life measures; over-reliance on ad hoc approaches to quality of life assessment; and insufficient attention to the practical constraints operating in clinical research settings.
 Of primary importance is the need to develop multidimensional quality of life instruments that are brief and psychometrically robust.
 It is suggested that future work on instrument development focus on refining currently available generic or cancer-specific measures, and on developing new diagnostic-specific questionnaire modules.
 This psychometric work should be guided by appropriate theoretical models of the relationship among health-related quality of life domains.
 Although it is widely accepted that the patient represents the most appropriate source of quality of life data, it is suggested that efforts also be directed toward improving the validity and reliability of physician-generated assessments of patients' performance status and of treatment toxicities, and toward determining the feasibility of employing family members as proxy raters of the psychologic and social health status of patients who are unwilling or unable to provide such information.
 Additional attention should be paid to the many logistical problems that arise in clinical trial-based quality of life investigations.
 In particular, research designs and data collection procedures should be selected that minimize patient, medical staff, and institutional burden.
",3
446,"Quality-of-life-adjusted survival for comparing cancer treatments. A commentary on TWiST and Q-TWiST.
 In chronic disease situations where treatment comparisons favor no particular therapy, or where definitive outcome requires a considerable follow-up period, it is useful to have additional and perhaps intermediate endpoints of relevant clinical significance to compare treatments.
 One such endpoint is Time Without Symptoms and Toxicity (TWiST) which, together with Q-TWiST, attempts to address the quality of life of patients receiving the competing regimens.
 This paper provides a commentary on these techniques with an emphasis on the problems inherent in implementing Q-TWiST, a measure that attempts to incorporate patient value preferences into TWiST.
 It is argued that while Q-TWiST is intuitively appealing in the clinical setting, there are formidable design and psychometric hurdles that must be overcome to fully operationalize the concept.
",3
447,"Progress in psychosocial and behavioral cancer research. The need for enabling strategies.
 A major component of the Second Workshop on Methodology in Behavioral and Psychosocial Cancer Research was a discussion of enabling strategies, that is, strategies by which future goals and needs in the area of psychosocial and behavioral oncology might be accomplished.
 This report describes and comments on the discussion that took place at a special plenary session at which representatives from four funding agencies, the American Cancer Society, National Cancer Institute, National Institute of Mental Health, and National Science Foundation, presented their views and their agencies' programs for promoting research in psychosocial and behavioral oncology.
 It is concluded that much progress has been made in the field and that strategies are in place for ensuring continued progress.
 However, suggestions are also made for new strategies that might accelerate and broaden that progress.
",3
448,"Behavioral and psychosocial cancer research. Building on the past, preparing for the future.
 This report identifies five general conclusions that emerged from the Second Workshop on Methodology in Behavioral and Psychosocial Cancer Research.
 These conclusions address diverse topics, including a focus on areas other than methodology; an emphasis on the transfer of technology and knowledge to applied settings; a recognition of the role of basic behavioral research in answering clinical questions; the need to recognize and strengthen ties between the field of behavioral and psychosocial oncology and the basic behavioral and social science fields from which it emerged; and the importance of additional research on minorities and other special populations.
 It is suggested that meeting the challenges posed in each of these five areas is critical to continued progress in the field.
",3
449,"Fertility-sparing treatment of patients with ovarian cancer.
 The variety of malignant neoplasms produced by the ovary are legion.
 Each must be considered individually in the young woman with early disease who wishes to preserve her childbearing capability.
 The risks of conservative surgery are often low, and the patient can be so advised.
 Careful monitoring of this group of patients is essential regardless of the approach.
",3
450,"Chromogranin A: posttranslational modifications in secretory granules.
 The primary structure of chromogranin A indicates multiple domains which might be subject to posttranslational modification.
 We explored chromogranin A's proteolytic cleavage, glycosylation, and possible intermolecular disulfide links, using biochemical and cell biological approaches.
 Anti-chromogranin A region-specific immunoblots on chromaffin granules suggested bidirectional endoproteolytic cleavage of chromogranin A; control experiments ruled out artifactual cleavage during granule isolation or lysis.
 Isolation of chromogranin A-derived peptides by gel filtration chromatography or sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by N-terminal amino acid sequencing, established several cleavage sites, including at least two at dibasic sites.
 Secretion of chromogranin A from bovine chromaffin cells did not initiate further cleavage, nor did prolonged exposure of secreted chromogranins to the secretory cells.
 The chromogranin A cleavage pattern was qualitatively similar in other neuroendocrine tissues, though cleavage was more complete in adrenal medullary than in anterior pituitary hormone storage vesicles, and N-terminal fragments of 45 and 55 kilodaltons were more prominent in the hypothalamus.
 A similar cleavage pattern was seen in human pheochromocytoma granules, as judged by chromogranin A region-specific immunoblots, fragment isolation by SDS-PAGE, and microsequencing.
 The presence of full-length chromogranin A as the core protein of a chromaffin granule soluble proteoglycan was suggested in bovine (but not human) chromaffin granules by glycoprotein staining, chondroitinase ABC digestion, chemical deglycosylation, and region-specific immunoblotting.
 Human (but not bovine) chromogranin A displayed intermolecular disulfide crosslinks on SDS-PAGE gels and immunoblotting.
 These results document diverse structural paths that the chromogranin A molecule may take in endocrine secretory cells after its translation.
",3
451,"Comparison of FRTL-5 cell growth in vitro with that of xenotransplanted cells and the thyroid of the recipient mouse.
 The present work was designed to compare in vitro cell growth kinetics with in vivo growth under conditions as similar as possible using labeling with [3H]thymidine.
 To this purpose, FRTL-5 cells were cultured as monolayers and as three-dimensional spheroids embedded in collagen gels and transplanted simultaneously into nude mice treated with perchlorate and a low iodine diet.
 The growth of the transplants was compared to that of the thyroids in host mice.
 In the intact thyroid, the fraction of [3H]thymidine-labeled follicular cells (FLC; 24-h labeling) increased sluggishly to a maximum of 10% after 3 weeks of goitrogen exposure, with a subsequent autoregulatory decrease to 3% at 7 weeks.
 A 4-fold higher FLC was found in six adenomas, indicating focal failure of growth-restraining mechanisms.
 In nonconfluent monolayer cultures the FLC was as high as 90%, even within large individual clusters where cells are in tight mutual contact.
 Solid, highly cellular grafts growing from transplanted monodispersed cells showed an average FLC of 20%, which is 5 times higher than the FLC in the identically stimulated mouse thyroid.
 In collagen-embedded cells, forming three-dimensional spheroids, the mean FLC decreased from 70% at 1 week in vitro (40% in vivo) to 20% at 3 weeks both in vitro and in vivo, suggesting effective auto-regulation of excessive growth in both conditions.
 However, these FLC were again much higher than the 3% FLC in simultaneously assessed host thyroids.
 The difference remained throughout the 45-day period studied.
 We conclude that FRTL-5 cells growing as monolayers and as three-dimensional spheroids in vitro or after xenotransplantation in vivo invariably show much higher proliferation rates under comparable environmental conditions than the normal follicular epithelium in the thyroids of host mice.
 The one exception is the confluent monolayer with near-zero growth, while densely packed three-dimensional transplants still grow intensively.
 Although growth-retarding cell to cell interactions are also clearly operative in growing FRTL-5 cells, they are less effective than those dampening the replication rate of the thyrocytes within the monolayer hull of normal follicles.
 A local failure of these mechanisms, allowing growth rates comparable to those of grafted FRTL-5 cells results in adenoma formation in normal thyroids.
 These observations call for caution in the transfer of in vitro growth studies with FRTL-5 cells to in vivo conditions prevailing in the normal thyroid.
",3
452,"Regulation of pancreastatin release from a human pancreatic carcinoid cell line in vitro.
 The objective of these experiments was to investigate the influence of activation of three second messenger systems (protein kinase-C, adenylate cyclase-cAMP, and calcium mobilization) on the secretion of pancreastatin (PST) and chromogranin-A (CGA) by a human pancreatic carcinoid cell line (BON) in tissue culture.
 Stimulation of protein kinase-C by a phorbol ester (0.025-7.5 microM) caused a significant dose-related release of PST (186 +/- 22-4271 +/- 228% over controls).
 Treatment of BON cells with graded doses of 8-bromo-cAMP (0.14-3.0 mM) and isobutylmethylxanthine (IBMX; 0.01-1.0 mM) also stimulated a dose-related release of PST (107 +/- 22-284 +/- 28 and 16 +/- 12-1076 +/- 100% over controls, respectively).
 Incubation of BON cells with ionomycin (0.134-13.4 microM) increased the release of PST (102 +/- 15-554 +/- 21% over controls) in a dose-related manner.
 A combination of IBMX and ionomycin resulted in an additive effect, whereas treatment with a phorbol ester plus IBMX resulted in a synergistic effect on PST release.
 Pretreatment of BON cells with monensin, an agent that prevents processing of precursors to smaller peptides, significantly decreased PST, but not CGA, secretion in response to phorbol ester or ionomycin.
 These findings indicate that protein kinase-C, cAMP, and Ca2+ mobilization participate in CGA and PST secretion.
 Although the observation that secretions of PST and CGA in response to theophylline are quantitatively associated, the absence of a quantitative relationship in the release patterns of PST and CGA in response to phorbol ester and ionomycin do not support a simple precursor-product relationship between CGA and PST.
 The monensin experiments are consistent with the notion that PST is derived from CGA in BON cells.
",3
453,"Regulation of the truncation of luteinizing hormone receptors at the plasma membrane is different in rat and mouse Leydig cells.
 Regulation of the truncation of LH receptors was investigated in two types of mouse tumor Leydig cells (MA10 and MLTC-1), rat testis Leydig cells (RTL), and a rat tumor Leydig cell (R2C).
 Receptor numbers were measured by binding [125I]hCG to the cells cultured in monolayers.
 Addition of 3.3 nM LH for 2 h at 34 C had no detectable effect on binding sites in RTL or R2C cells, but in MA10 and MLTC-1 cells it caused a loss in binding sites.
 The effect on MA10 and MLTC-1 cells could be mimicked by inhibiting receptor internalization with 5 mM NaN3 and prevented by the addition of protease inhibitors.
 Incubating RTL and R2C cells with protease inhibitors caused a 2- to 3-fold increase in binding sites and a 2- to 3-fold increase in LH (0.033 and 0.33 nM)-stimulated cAMP production.
 When RTL and MA10 cells were incubated in the presence of [125I]hCG, a radioactive protein complex with an approximate mol wt of 80,000-90,000 was released into the incubation medium.
 We conclude that LH receptors are regulated by proteolysis at the plasma membrane in both mouse and rat Leydig cells.
 Furthermore, truncation of the LH receptor in the mouse Leydig cells is involved in down-regulation, whereas in the rat it is a continuous process.
",3
454,"Breast cancer screening in older women: practices and barriers reported by primary care physicians.
 Annual mammography, in combination with clinical breast examinations, can reduce mortality from breast cancer.
 However, surveys of both patients and physicians suggest that mammography is underutilized.
 This study examined whether physicians' reported breast cancer screening practices and barriers to mammography varied with patients' age.
 Data from 576 primary care physicians (internal medicine, family/general practice, and obstetrics/gynecology) who participated in a mailed statewide survey were analyzed.
 Physicians reported screening elderly women significantly less often than younger women, regardless of family history of breast cancer.
 With the exception of medical specialty, physicians' demographic and practice characteristics were not associated with reported screening practices.
 However, physicians' knowledge and beliefs about breast cancer in older women were associated with reported screening practices.
 When analyzing barriers to ordering mammography, cost to the patient was viewed as a barrier for women of all ages, and pain was viewed as a greater barrier for younger women; otherwise, physicians consistently believed that their elderly patients faced considerably more barriers compared with younger women.
 Further investigation is required to examine why primary care physicians report age-related differences in both breast screening and barriers to mammography.
",3
455,"The role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. I. Induction of regulatory macrophages in normal mice by the in vivo administration of rGM-CSF.
 Using a dimethylbenzanthracene-induced immunogenic nonmetastatic murine mammary adenocarcinoma in BALB/c mice, our previous work has shown that splenocytes from tumor bearers have reduced responses to both mitogens and Ag including tumor-associated Ag.
 NK and cytotoxic T cell activities are also reduced in splenocytes of tumor bearers.
 Mac-1+2+ macrophages induced in mammary tumor bearers are capable of down-regulating lymphocyte responses to mitogens and tumor-associated Ag by cell to cell contact interaction and increased PGE2 production.
 We have found that the tumor constitutively releases a granulocyte-macrophage (GM)-CSF-like factor in vivo and in vitro, which may be responsible for the systemic increase in cells of the macrophage lineage in tumor-bearing mice.
 A tumor cell line established from the in vivo tumor expresses and releases GM-CSF as shown by Northern and Western blot analyses.
 Daily i.p.
 injections for 3 wk of 10,000 U of rGM-CSF into normal mice induces hemopoietic and immunologic alterations similar to those observed in tumor bearers.
 Mac-1+ and/or Mac-2+ macrophages can also be detected in the spleens and bone marrow of the mice treated with rGM-CSF.
 Additionally, splenocytes from rGM-CSF-treated mice have reduced responses to mitogens and their peritoneal exudate cells can cause in vitro down-regulation of proliferative responses of lymphocytes from normal mice.
 The suppression can be partially reversed by the addition of indomethacin to the cultures suggesting that PGE2 may contribute to the effect.
 rGM-CSF enhances the in vitro release of PGE2 by the spleen, bone marrow, and peritoneal cells of normal mice.
 These data indicate that the high levels of GM-CSF constitutively produced by the tumor may be responsible for the hemopoietic changes and immunologic alterations observed in tumor-bearing mice.
",3
456,"Insulin-like growth factors are mitogenic for human keratinocytes and a squamous cell carcinoma.
 Normal adult human keratinocytes in monolayer culture and SCL-1, a skin-derived squamous-cell carcinoma cell line, were investigated for the expression of receptors for insulin-like growth factors (IGF) and insulin.
 As demonstrated by affinity crosslinking, radiolabeled IGF-1, IGF-2, and insulin bound specifically to both cell types.
 Each cell expressed type I IGF receptors, with affinity for IGF-1 greater than IGF-2 much greater than insulin.
 Insulin receptors, with highest affinity for insulin, were also present on both cells.
 However, keratinocytes and SCL-1 cells differed in 125I-IGF-2 binding.
 125I-IGF-2-bound to both type I and type II IGF receptors in normal keratinocytes, but bound predominantly to membrane-associated IGF binding proteins in SCL-1.
 IGF-1 was slightly more potent than IGF-2 in stimulating growth of both keratinocytes and SCL-1 cells.
 In keratinocytes, concentrations of IGF-1 ranging from 5-100 ng/ml, and of IGF-2 from 50-100 ng/ml, resulted in a significant increase in cell number.
 At the maximum dose of 100 ng/ml, either IGF-1 or IGF-2 caused a 2.3-times increase in cell number.
 In SCL-1 cells, IGF-1 was more potent than IGF-2 or insulin at lower concentrations, but either IGF-1 or IGF-2 at the maximal concentration of 333 ng/ml stimulated a 4.7-times increase in thymidine incorporation.
 The stimulatory effect of insulin in SCL-1 was 10-50 times less potent than that of the IGF.
 The effect of either IGF on SCL-1 was completely inhibited by the type I IGF receptor antibody alpha IR-3, suggesting that both IGFs are mitogenic through the type I IGF receptor.
 Insulin action was partially blocked by alpha IR-3, suggesting that insulin can act through both the insulin and type I IGF receptors.
 It thus appears that IGF-1 and IGF-2 are mitogens for normal and transformed human keratinocytes and that their actions are primarily mediated through the type I IGF receptor, whereas insulin is a mitogen through both the IGF-1 receptor and the insulin receptor.
",3
457,"Inositol phosphate formation in the human squamous cell carcinoma line SCC-12 F: studies with bradykinin, the calcium ionophore A23187, and sodium fluoride.
 The phospholipase C (PLC)-mediated hydrolysis of membrane phosphoinositides is an important signal transduction pathway coupled to the cell-surface receptors for several hormones and growth factors.
 In addition, PLC activity can be modulated by changes in intracellular calcium and activation of GTP binding proteins.
 In this report, differential activation of PLC in the human keratinocyte cell line SCC-12F was studied as judged by specific patterns of inositol phosphate formation.
 Several hormones and growth factors previously shown to stimulate PLC in a variety of cell types were screened for activity in SCC-12F cells.
 Only bradykinin was active, stimulating the PLC-dependent generation of inositol (1,4,5) triphosphate (Ins(1,4,5)P3).
 Ins(1,4,5)P3 was rapidly metabolized to inositol(1,4)biphosphate (Ins(1,4)P2) and inositol(1,3,4,5)tetrakisphosphate (Ins(1,3,4,5)P4), and subsequently degraded to inositol monophosphates.
 The response elicited by bradykinin was concentration dependent (EC50 value of 50 nM), suggesting involvement of a specific bradykinin receptor.
 Treatment of these cells with the calcium ionophore A23187 appeared to result in the direct formation of Ins(1,4)P2 without Ins(1,4,5)P3 as precursor.
 Treatment of the cells with AIF4-, a putative activator of GTP binding proteins, resulted in the generation of inositol monophosphates as the major metabolites in the absence of detectable Ins(1,4,5)P3 formation.
 Taken together, these observations suggest that the PLC complex present in SCC-12F cells can be differentially activated to yield either Ins(1,4,5)P3, Ins(1,4)P2, or InsP.
 The observed effects may be due to a direct PLC-dependent hydrolysis of the appropriate membrane phosphoinositide.
",3
458,"Thyroid cancer.
 There have been important recent advances in our understanding of the biologic nature of thyroid cancer and in the early diagnosis of the disease.
 Despite these advances, there is still considerable controversy over the management of thyroid cancer, including the extent of surgery, the indications for the use of iodine-131, the effectiveness of thyroid-stimulating hormone suppression, and the prediction of outcome.
 In this review, the current status of the diagnosis and management of the various types of thyroid cancer are carefully reviewed and extensively documented.
",3
459,"Hepatic dynamic sequential CT: section enhancement profiles with a bolus of ionic and nonionic contrast agents.
 The enhancement characteristics in different portions of the liver during dynamic sequential bolus computed tomography (CT) with iodinated contrast material (DSBCT) were prospectively evaluated in 75 patients by using iothalamate meglumine, iopamidol, and iohexol (25 patients received each agent).
 After baseline noncontrast CT was performed, DSBCT was performed with a 180-mL intravenous bolus administered at 2 mL/sec.
 Scanning was started 25 seconds after the bolus was initiated, by using a 3-second scan time and rapid cephalocaudal table incrementation, yielding contiguous 8-mm-thick sections at a rate of nine sections per minute.
 On postcontrast images, peak enhancement was 115% for iopamidol and 117% for iohexol, both of which were superior to iothalamate meglumine at 95% (P less than .05).
 After peaking, enhancement then decreased for all three contrast agents, although the decline was more precipitous for iothalamate meglumine.
 Enhancement on the more caudal sections with both iopamidol and iohexol was superior to that with iothalamate meglumine (P less than .05).
 The data suggest that the enhancement characteristics for the two nonionic agents may be more optimal for detection of focal hepatic lesions than the ionic agent.
",3
460,"Linkage of early-onset familial breast cancer to chromosome 17q21.
 Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited.
 Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population.
 Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease.
 Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease.
 Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.
",3
461,"Detection of Ki-67 proliferation rate in breast cancer. Correlation with clinical and pathologic features.
 In situ determination of proliferative activity was performed on 203 breast cancers by use of Ki-67 monoclonal antibody and immunohistochemical methods.
 Tumor proliferation rate was analyzed and correlated to tumor size and nodal status.
 The relationship between Ki-67 proliferative activity and nuclear estrogen receptor content was also investigated on adjacent tissue sections.
 Ki-67 values ranged from 1 to 75%, with a median value of 10%.
 Premenopausal patients had greater Ki-67 values (median value, 14.1%) than postmenopausal ones (median value, 9.8%).
 The authors observed no correlation with lymph nodal involvement, whereas a statistically significant relationship with tumor size was found (P less than 0.01).
 An inverse correlation (Spearman's coefficient = -0.56; P less than 0.001) was seen between Ki-67 values and nuclear estrogen receptor content.
 These results, similar to those reported for other kinetic measurements, suggest that in situ detection of Ki-67 proliferation rate is a useful method for obtaining cell cycle information.
 Follow-up studies will be needed to assess an eventual prognostic relevance.
",3
462,"Fluorescent cytochemical detection of estrogen and progesterone receptors in breast fine-needle aspirates.
 Estrogen and progesterone receptors were studied in fine-needle aspiration biopsy specimens of 56 patients with primary, recurrent, or metastatic breast carcinoma.
 The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum albumin fluorescein isothiocyanate (FITC-BSA estradiol) and hydroxyprogesterone hemisuccinate bovine serum albumin tetramethyl rhodamine isothiocyanate (TMRITC-BSA progesterone), were used in the fluorescent cytochemical method.
 The findings obtained from the aspirated cells with the use of the fluorescent cytochemical technique were compared with results obtained from the cell population of the same tumor after removal with the use of both the fluorescent cytochemical technique and the biochemical dextran-coated charcoal (DCC) assay.
 For the needle aspirates, there was 89% concordance for estrogen receptor and 86% concordance for progesterone receptor between biochemical and cytochemical results.
 A high degree of correlation was also demonstrated between fine-needle aspirates and imprint preparations with the use of the cytochemical technique.
 This study suggests that the fluorescent cytochemical technique is an effective tool in assessment of estrogen and progesterone receptor content in fine-needle aspirates of primary and metastatic breast cancer.
 The fluorescent cytochemical technique can be performed easily at community hospitals and is well suited for specimens of insufficient size for biochemical assay.
",3
463,"Evaluation of in vitro bromodeoxyuridine labeling of breast carcinomas with the use of a commercial kit.
 The prognostic significance of S-phase fraction analyses of breast carcinomas has been reported by several investigators.
 The Cell Proliferation Kit (Amersham Corporation, Arlington Heights, IL), which uses in vitro bromodeoxyuridine (BRDU) labeling to evaluate cell cycle kinetics without a flow cytometer or radioisotopes, simplifies this assay for the clinical-based laboratory by providing standardized reagents and recommended methods.
 This study was performed to determine whether data derived from its use were comparable to published S-phase data from the use of thymidine labeling, BRDU, or other methods on breast carcinomas.
 Primary infiltrating ductal carcinomas (n = 142) and primary lobular carcinomas (n = 6) showed mean and median BRDU labeling of 4.63% and 3%, 1.3% and 1%, respectively, with a range of 0-28%.
 Benign lesions always had less than 3% BRDU uptake (n = 21).
 Estrogen receptor (ER) and progesterone receptor (PR) status correlated with BRDU labeling (P less than 0.05), with the highest S-phase fractions in ER- and PR-negative tumors.
 Correlations between BRDU uptake and histologic tumor type or size were observed.
 Significant correlations between BRDU uptake and lymph node status, patient age, or histologic tumor grade were not observed.
 S-phase studies of breast carcinomas using other techniques have shown similar data, therefore, the Cell Proliferation Kit appears to be a practical and useful method for in vitro S-phase analysis that allows concomitant histologic examination of the same tumor tissue sample.
",3
464,"Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques.
 In this study, double-labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens (BGA) that are differentiation antigens in the normal colon, and BGA that are sequential moieties in the same synthetic pathway.
 Paired-wise Sialylated-Le(a)/Le(y) and H-2/Le(y) was studied.
 The Sialylated-Le(a) and Le(y) are synthesized from type 1 and type 2 backbones, respectively.
 In the normal colon, the Le(y) and Sialylated-Le(a) are expressed by cells at the base and surface of the crypt, respectively, representing undifferentiated and differentiated enterocytes.
 The H-2 is considered oncofetal in nature, and is considered to be the immediate precursor in the synthesis of Le(y).
 In individual cancers.
 Sialylated-Lea and Le(y) were detected in different cancer cells within the same malignant glands, separately in different glands, and in different subcellular compartments of the same cell.
 Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of cancers expressing both these BGA.
 In 50% of the cancers, the H-2 and Le(y) also were expressed separately in different malignant glands within individual tumors.
 These findings indicate that, in colorectal cancers, differentiation antigens (Sialylated Le(a) and Le(y)) are expressed by different individual cells within the same malignant gland somewhat, recapitulating the normal colon crypt.
 Antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments.
 Precursor accumulation is common in cancers, and antigens in the same synthetic pathway are coexpressed in the same cell.
 The expression of H-2 and Le(y) in different glands (lack of coexpression) may be explained possibly by aberrant synthesis of Le(y) by an alternate pathway.
",3
465,"Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells.
 Vascular permeability factor (VPF), a tumor-secreted heparin-binding protein (Mr approximately 38,000), is responsible for increased vessel permeability and fluid accumulation associated with tumor growth.
 Vascular permeability factor also promotes the growth of human umbilical vein endothelial cells (EC) and bovine pulmonary ECs in vitro.
 It is shown for the first time that guinea pig VPF (half-maximal and maximal dose approximately 0.4 and 22 pmol/l (picomolar), respectively), as well as human VPF, are potent stimuli for human ECs resulting in [Ca2+]i increases (maximal three- to fourfold) and inositol triphosphate (IP3) formation.
 Unlike the maximal responses to thrombin and histamine, the [Ca2+]i response to a maximal VPF dose was preceded by a characteristic 10- to 15-second delay.
 Guinea pig VPF also selectively increased [Ca2+]i in cultured aortic and pulmonary artery ECs, but not aortic smooth muscle cells, human fibroblasts, or neutrophils.
 Affinity-purified rabbit antibody (raised to a synthetic peptide representing VPF N-terminal amino acids 1 to 24) adsorbed all vessel permeability-increasing activity, EC growth-promoting activity, and specifically all activity responsible for increasing EC [Ca2+]i.
 Similar to other mediators that increase [Ca2+]i in cultured ECs, VPF also induced a 200% increase in von Willebrand factor release.
 Together these data indicate that VPF acts directly on ECs and that rapid cellular events in its in vivo/in vitro actions are likely to involve phospholipase C activation, [Ca2+]i increase, and von Willebrand factor release.
",3
466,"Immunoreactivity and receptor expression of insulinlike growth factor I and insulin in human adrenal tumors. An immunohistochemical study of 94 cases.
 Using immunoperoxidase methods, 94 human adrenal tumors were examined for evidence of immunoreactivity and receptor expression of insulinlike growth factor I (IGF-I) and insulin.
 The frequency of IGF-I in adrenocortical carcinomas was significantly higher than that in adenomas of the adrenal glands.
 The adrenocortical carcinomas showed strong intensity of staining for IGF-I, IGF-I receptors, and insulin receptors.
 A significant correlation between immunoreactivity and receptor expression of both IGF-I and insulin was found only in the adrenocortical carcinomas.
 The adrenocortical adenomas with Cushing's syndrome and pheochromocytomas, more than adrenocortical adenomas with Conn's syndrome, also stained strongly for insulin receptors.
 Thus the IGF-I and insulin probably play a role in the growth of adrenocortical carcinoma tissues, possibly through autocrine mechanisms.
 The expression of insulin receptors in adrenocortical adenomas in the presence of Cushing's syndrome and pheochromocytomas may be associated with functions.
",3
467,"A critical analysis of the largest reported mass fecal occult blood screening program in the United States.
 Fecal occult blood testing for the detection of colon cancer remains controversial.
 We performed a mass screening program from January 24, 1988, to February 19, 1988, with intensive media promotion, including 121 minutes of televised air time.
 A total of 5,000 primary practitioners were notified by mail.
 Hemoccult-II tests were distributed to 156,000 individuals; 55,051 (35%) were returned.
 Ninety-five percent of the respondents were informed of the program by television.
 A total of 3,375 persons (6%) tested positive for fecal occult blood; of these, 2,469 (73%) informed the center that they saw their physician to initiate a work-up.
 Information from physicians regarding work-ups was returned on only 1,356 (55%) patients.
 Diagnostic tests numbered 2,227 (1.6 tests per patient).
 However, 5% had no testing, 16% had a repeat Hemoccult only, and 35% had neither a barium enema nor colonoscopy performed.
 Thirty-six colorectal cancers and 212 polyps were identified.
 The predictive value (i.e., number of cancers per number of patients who tested positive) increased directly by decade.
 Thirty-three of 36 patients (92%) with cancer underwent either a barium enema or colonoscopy versus only 185 of 438 (42%) patients with a ""negative"" work-up.
 Cancers found were carcinoma in situ in 10 patients (29%), Dukes A in 12 (35%), Dukes B in 4 (12%), and Dukes C in 8 (24%); distant metastases were not found in any participant.
 Thirty-six percent of the tumors were located in either the right or transverse colon.
 We conclude that: (1) Screening identified early cancers.
 All were potentially curable and 64% were limited to the bowel wall.
 (2) Massive Hemoccult distribution was possible over a short interval, but patient and physician compliance was disturbingly low.
 (3) Total colonic evaluation is mandatory, since at least 36% of tumors were beyond the reach of the flexible sigmoidoscope.
 (4) Many work-ups were unnecessary (repeat Hemoccults) or inadequate, indicating a need for physician education.
",3
468,"Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer.
 Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies.
 The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months.
 The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival.
 Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival.
 The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05).
 Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05).
 The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion).
 However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival.
",3
469,"Implications of peritoneal cytology for staging of early pancreatic cancer.
 Cytologic examination of peritoneal washings was performed in 40 patients with pancreatic ductal adenocarcinoma (35 head, 5 body) whose tumors had been selected as potentially resectable by computed tomographic (CT) findings.
 Saline (100 mL) was instilled and aspirated at laparoscopy in 27 patients and at laparotomy in 13.
 Malignant cells were found in the peritoneal washings in 12 of 40 patients (30%): 29% in cancers of the pancreatic head versus 40% in the body; 33% at laparoscopy versus 23% at laparotomy; and in 4 of 8 patients with ascites versus 8 of 32 without ascites.
 The cytology was positive in 6 of 8 patients (75%) who had a prior percutaneous needle biopsy versus 6 of 32 (19%) of those who did not (p less than 0.01).
 Liver metastases were found in six patients, all with negative cytology.
 One of 10 pancreatic head cancers with positive cytology was resectable versus 13 of 25 with negative cytology (p less than 0.05).
 Survival was significantly longer in patients with negative cytology.
 We conclude that (1) pancreatic cancer sheds malignant cells into the peritoneum early and commonly; (2) laparoscopic lavage is an effective means of cytologic study; (3) ascites is not a precondition for cytologic study, nor does its presence necessarily imply carcinomatosis; (4) intraperitoneal spread of cancer cells may be promoted by tumor biopsy; (5) cytologic findings provide an additional index of resectability; and (6) cytologic findings appear to correlate with duration of survival.
 This study shows that even ""localized"" pancreatic cancer is often not contained and suggests caution with biopsy of potentially curable lesions.
",3
470,"Expression of ABH blood group antigens, Ulex europaeus agglutinin I, and type IV collagen in the sinusoids of hepatocellular carcinoma.
 The expression of blood group antigens (A, B, H, Lewis(a) and Lewis(b)), Ulex europaeus agglutinin I (UEA-I), factor VIII-related antigen, and type IV collagen on the sinusoids was examined immunohistochemically in 15 cases of hepatocellular carcinomas (HCC), 11 cases of cirrhosis, 12 cases of chronic active hepatitis, and in a control sample of 16 normal livers.
 Sinusoidal endothelial cells of HCC characteristically showed a diffuse and strong immunoreactivity to ABH blood group antigens in the specimen with a comparable ABO blood group.
 The sinusoidal endothelial cells were also diffusely and strongly positive for UEA-I receptors.
 In contrast, in cirrhosis and chronic active hepatitis a few sinusoidal endothelial cells were positive for ABH blood group antigens and UEA-I receptors.
 In normal livers, only a few sinusoidal endothelial cells were positive for ABH blood group antigens and UEA-1 receptors.
 Tests for factor VIII-related antigen and Lewis blood group antigens were almost negative on sinusoidal endothelial cells.
 Although type IV collagen was distributed diffusely in the space of Disse in these four groups, its expression was strongest in HCC.
 Blood vessels of portal tracts and fibrous septa were positive for ABH blood group antigens, UEA-1 receptors, factor VIII-related antigen, and type IV collagen, but negative for Lewis blood group antigens.
 These findings suggest that some sinusoidal endothelial cells undergo ""capillarization"" in cirrhosis and chronic active hepatitis, and that the majority of sinusoidal endothelial cells of HCC have phenotypic characteristics of capillaries.
",3
471,"Pleomorphic (anaplastic) neuroblastoma in nude mice.
 Two pleomorphic (anaplastic) neuroblastomas, from two children aged 1 and 6 years, were transplanted into nude mice.
 Two noteworthy observations were made.
 In one case, the transplanted tumor gave rise to a soft-tissue sarcoma.
 Moreover, in both cases hepatic metastases were associated with a striking modification of murine hepatocytes, resulting in hyperchromatic and dysplastic nuclei.
 The latter finding was particularly evident in the hepatic areas surrounding all metastases of pleomorphic (anaplastic) neuroblastoma cells.
",3
472,"Glomus tumor of the coccyx. A curable cause of coccygodynia.
 A 30-year-old woman presented with recurrent severe coccygodynia.
 She underwent exploration for a possible pilonidal sinus and was found to have a precoccygeal glomus tumor that also involved bony trabeculae of the coccyx.
 To our knowledge, a glomus tumor involving the coccygeal bone has not been previously documented.
 In view of the relief of this patient's pain following the surgical excision of coccyx and tumor, a causal role is suggested.
",3
473,"Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla.
 We present a rare case of carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the left maxilla that developed in a 63-year-old Japanese man.
 The tumor recurred repeatedly despite multiple surgical removals, radiotherapy, and chemotherapy and led to progressive cachexia; the patient died after 3.8 years of hospitalization.
 Histopathologic examination revealed that the recurrent tumor was carcinosarcoma, which had progressed from malignant ameloblastoma with fibroma.
 An autopsy confirmed the diagnosis of malignant mixed tumor with lung metastasis of malignant ameloblastoma and fibrosarcoma.
",3
474,"Response by women aged 65-79 to invitation for screening for breast cancer by mammography: a pilot study [published erratum appears in BMJ 1991 Jul 27;303(6796):234] 
 OBJECTIVE--To determine whether there is sufficient benefit to be gained by offering screening for breast cancer with mammography to women aged 65-79, who are not normally invited for screening.
 DESIGN--Pilot study of women eligible for screening but not for personal invitation.
 The results of this study were compared with the results of routinely screened younger women (aged 50-64) from the same general practice.
 SETTING--One group general practice in south Manchester.
 PATIENTS--The 631 women aged 65-79 on the practice list.
 A total of 42 (7%) were excluded by the general practitioner, and 22 (4%) invitation letters were returned by the post office.
 MAIN OUTCOME MEASURES--Response rates to invitation for screening assessed by three indices: crude population coverage ratio, crude invited population coverage ratio, and corrected invited population coverage ratio.
 RESULTS--344 Patients aged 65-79 (61% of those invited, excluding those who could not be traced) were screened compared with 77% of women aged 50-64.
 The three response indices were higher for younger women than older: crude population coverage ratio = 66.5%, crude invited population coverage ratio = 69.3%, corrected invited population coverage ratio = 76.8% for women aged 50-64, compared with 54.5%, 58.4%, and 60.7% respectively for women aged 65-79.
 All four biopsies done in the older women gave positive results, giving a cancer detection rate of 11.6/1000 compared with 4.1/1000 among younger women.
 CONCLUSIONS--These results show that there is a potential for high attendance at routine screening by older women if they are invited in the same way as younger women.
 If these results are found elsewhere the costs and benefits of screening older women should be reassessed.
",3
475,"Recreational sun exposure in Puerto Rico: trends and cancer risk awareness.
 Persons who sunbathe or engage in other activities at the beach are exposed to large amounts of UV radiation.
 Four hundred seven adults who visited the beaches of Puerto Rico were surveyed to determine their knowledge about the risks of sun exposure and to evaluate sunscreen use.
 The group consisted of 195 year-round Puerto Rican residents and 212 tourists.
 Ninety-five percent believed that the sun can cause skin cancer, although only half of the subset who lived all year in Puerto Rico believed that they personally received enough exposure to be at risk.
 The majority of the group (83%) understood the meaning of the sun protection factor numbers, although 35% used either nothing or a nonscreening oil.
 Half of Puerto Rican residents rarely or never used sunscreen protection while sunbathing.
 When sunscreen was used, the most important factor sought was given as sun protection factor (64%), followed by a perceived ability to aid in tanning (26%).
",3
476,"Cutaneous angiolipoleiomyoma.
 We describe eight cases of cutaneous angiolipoleiomyoma, a rare tumor previously reported only once under the term cutaneous angiomyolipoma.
 Clinically, the tumors were acquired, solitary, asymptomatic nodules that were always acral in location.
 Patients' ages ranged from 33 to 77 years (median 52.6 years); the male/female ratio was 7:1.
 Signs of tuberous sclerosis or renal angiomyolipoma were absent in all cases.
 Histologically, the tumors were subcutaneous, well circumscribed, and composed of smooth muscle, vascular spaces, connective tissue, and mature fat.
 In some tumors the fat was the predominant component, and in others smooth muscle predominated.
 Elastic tissue stains revealed that some blood vessels had developed an elastic lamina whereas other blood vessels lacked it.
 Additional histologic features occasionally observed included vascular thrombi, glomus bodies, and focal mucin deposition.
",3
477,"The risk of developing subsequent nonmelanoma skin cancers.
 Data from the Southeast Arizona Skin Cancer Registry collected during 1985 through June 1988 were used in this study.
 Patients who had a nonmelanoma skin cancer (basal cell or squamous cell carcinoma) removed in 1985 were observed until subsequent nonmelanoma skin cancers developed or until June 30, 1988.
 Twelve categories of nonmelanoma skin cancers were developed on the basis of the type of first nonmelanoma skin cancer and type of second, third, and fourth nonmelanoma skin cancers.
 Analyses showed the highest risk of a subsequent nonmelanoma skin cancer developing was within 1 year (36.39%), the rate of developing another nonmelanoma skin cancer depended on type (squamous cell carcinoma, 100%; basal cell carcinoma, 44.23% to 83.65%), and total risk decreased during the 1277 days of the study.
",3
478,"Histologic pattern analysis of basal cell carcinoma. Study of a series of 1039 consecutive neoplasms.
 This study attempts to define histologic patterns in 1039 consecutive cases of basal cell carcinoma and to correlate these patterns with adequacy of margins of surgical excision.
 Five major histologic patterns were identified: nodular, 218 cases (21%); superficial, 181 cases (17%); micronodular, 151 cases (15%); infiltrative, 77 cases (7%); and morpheic, 11 cases (1%).
 A mixed pattern (two or more major histologic patterns) was present in 401 cases (38.5%).
 Our study indicates that nodular and superficial basal cell carcinomas can be completely removed by simple surgical excision in a high percentage of cases (93.6% and 96.4%, respectively) whereas the micronodular, infiltrative, and morpheic basal cell carcinomas have a higher incidence of positive tumor margins (18.6%, 26.5%, and 33.3%, respectively) after excision.
 Mixed patterns that consisted of combinations of the nodular, micronodular, or infiltrative types exhibited a behavior similar to the pattern that resulted in a greater chance of incomplete surgical removal.
",3
479,"Treatment of port-wine stains during childhood with the flashlamp-pumped pulsed dye laser.
 Seventy-three patients between the ages of 3 months to 14 years (average age 6 years 2 months) with port-wine stains were treated with the flashlamp-pumped pulsed dye laser.
 More than 75% lightening was achieved with an average of 2.5 treatments in 33 patients (45%), 50% to 74% lightening after an average of 1.7 treatments in 31 (42%), 26% to 49% lightening after 2 treatments in 5 (7%), and less than 25% lightening after 1 treatment in 4 (5%).
 The overall average lightening after one treatment was 53%.
 The percentage of lightening increased as the number of treatments increased.
 Three patients had 100% clearance of the port-wine stain.
 Patients aged between 3 months and 6 years (44 patients) had a better response after the first treatment (55% lightening) than did patients aged between 7 and 14 years (29 patients with a 48% lightening; p = 0.027).
 Complications included cutaneous depressions in four patients, hyperpigmentation in 16 patients, and hypopigmentation in three patients.
 All complications were transient and disappeared completely.
",3
480,"Induction of DNA fragmentation in chronic B-lymphocytic leukemia cells.
 Chronic lymphocytic leukemia of B cell type (B-CLL) is a neoplastic disorder characterized by the accumulation of small resting lymphocytes in the periphery.
 The phenotype of these cells suggests that they are ""frozen"" at an early stage of maturation.
 Glucocorticoid hormones are commonly used to treat patients with B-CLL, resulting in a reduction in the peripheral lymphocyte count by an undefined mechanism.
 Here we report that glucocorticoids stimulate DNA fragmentation characteristic of a suicide process known as apoptosis or programmed cell death (PCD) in suspensions of cells from patients with B-CLL.
 The effects can be mimicked by Ca2+ ionophore and involve a sustained increase in the cytosolic Ca2+ concentration.
 Specific antibodies binding to membrane-associated IgM on the leukemic cells can also induce PCD by a similar mechanism.
 Phorbol esters block DNA fragmentation and cell killing in response to all of the agents, suggesting that activation of protein kinase C desensitizes the cells to PCD.
 Targeting the B-CLL cells with antibodies that induce an unbalanced, sustained Ca2+ increase may therefore represent a rational strategy for the destruction of leukemic cells.
",3
481,"Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state.
 The present study investigates the nature of humoral component(s) generated in tumor-bearing hosts to induce immune dysfunction of T cells.
 Cell-free ascitic fluid and culture supernatant (SN) were obtained from the ascites and cultures allowing MH134 hepatoma cells to grow.
 These ascites and SN samples were tested for their abilities to influence the generation of CTL responses to TNP and alloantigens.
 The generation of the anti-TNP CTL responses that require self H-2-restricted CD4+ Th cells was markedly suppressed by addition of the ascites or SN under conditions in which these samples did not inhibit anti-allo CTL responses capable of using alternate pathways of allo-restricted CD4+ and CD8+ Th.
 The activation of CD8+ CTL precursors and CTL activity were also resistant to the ascites or SN.
 The ascites- or SN-induced suppressive effect to which CD4+ Th were most susceptible was found to be mediated by transforming growth factor-beta (TGF-beta) activity, because: 1) the TGF-beta activity was detected in the MH134 ascites and culture SN; 2) the suppression of CD4+ Th function required for anti-TNP CTL responses was almost completely prevented by addition of anti-TGF-beta antibody to cultures and; 3) rTGF-beta also induced similar patterns of immunosuppression to those observed by ascites or SN.
 These results indicate that TGF-beta produced by tumor cells induces deleterious effects on T cell, especially on the CD4+ Th subset, and provide an explanation for the molecular mechanism underlying the previously observed CD4+ Th-selective suppression in the tumor-bearing state.
",3
482,"Expression of VHIII-associated cross-reactive idiotype on human B lymphocytes. Association with staphylococcal protein A binding and Staphylococcus aureus Cowan I stimulation.
 It has been demonstrated that staphylococcal protein A (SPA) has an ""alternative"" binding site with specificity for human Ig H chain V region of the VHIII subgroup.
 Because the major mitogenic component of Staphylococcus aureus Cowan I (SAC) is SPA, it is possible that SAC stimulates a subpopulation of B cells expressing Ig of the VHIII H chain subgroup.
 In the present study, we have investigated further the relationship between SPA binding and the expression of VHI- or VHIII-associated cross-reactive idiotype (CRI) on the surface of tonsillar B lymphocytes enriched for the expression or nonexpression of the CRI, and we examined the Ig secreted by cell lines established from these populations of B cells by EBV transformation.
 The VHIII CRI (D12)-enriched population yielded 21 cell lines, with 67% of them secreting SPA-reactive Ig; in contrast, only 6% (1 of 16) of VHI CRI-expressing lines secreted SPA-reactive Ig.
 The CRI-negative B cell population yielded 54 cell lines, of which 20% secreted SPA-reactive Ig, as might be anticipated because a majority of VHIII Ig+ B cells will be CRI-.
 SAC stimulation of CRI+ and CRI- populations showed preferential stimulation of the D12 population.
 These data support the proposal that SAC stimulation of human B cells is mediated through binding of SPA by its alternative binding site to IgV regions of the VHIII subgroup.
",3
483,"Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma 
 Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma.
 To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course).
 Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease.
 The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3).
 Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%).
 Three patients declined surgical reassessment.
 Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm.
 There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules.
 IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease.
",3
484,"Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial.
 Malignant pleural effusions are a common and significant problem in patients with advanced malignancies.
 Pleurodesis with tetracycline or other sclerosing agents is the usual treatment for malignant pleural effusions.
 In contrast to this approach, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the effusion.
 Intracavitary cisplatin-based chemotherapy, which is cytotoxic rather than sclerosing, has proven safe and effective via the intraperitoneal route in ovarian cancer and malignant mesothelioma.
 There has been little previous experience, however, with intrapleural cisplatin-based chemotherapy.
 As part of a planned series of trials in malignant mesothelioma, the Lung Cancer Study Group first evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors.
 From April 1986 to November 1987, 46 patients with cytologically proven, symptomatic, and previously untreated malignant pleural effusions were entered on study.
 A single dose of cisplatin 100 mg/m2 plus cytarabine 1,200 mg was instilled into the pleural space via a chest tube, which was then immediately removed.
 Patients were evaluated for toxicity and response at 24 hours; 1, 2, and 3 weeks; and then monthly.
 No recurrence of the effusion was considered a complete response (CR).
 Partial response (PR) was defined as a 75% or greater decrease in the amount of the effusion on serial chest radiographs.
 One patient experienced reversible grade 4 renal toxicity, four patients had grade 3 hematologic toxicity, and five patients had grade 3 cardiopulmonary toxicity.
 The overall response rate (CR plus PR) at 3 weeks was 49% (18 of 37 patients).
 The median length of response was 9 months for a CR and 5.1 months for a PR.
 The outcome of this trial was sufficiently encouraging that this regimen has been incorporated into subsequent trials for malignant pleural mesothelioma.
",3
485,"When is a prognostic factor useful? A guide for the perplexed.
 Traditionally, a number of variables have been used to predict outcome in patients with early-stage breast cancer.
 These tests are simple to perform and relatively inexpensive.
 Recently, a number of new factors, eg, tumor proliferative index, nuclear DNA content, and amplification or overexpression of growth-promoting genes or oncogenes have been identified as potential predictors of outcome in patients with breast cancer.
 There is now increasing pressure to introduce such tests into routine clinical practice.
 How does a clinical practitioner identify which test, or group of tests, best predicts adverse outcome and whether any more clinically useful information is provided than with the use of more traditional factors alone? The aim of a prognostic test in breast cancer is to predict which patients are destined to develop a recurrence of cancer and those who are not.
 The prognostic usefulness of a test can be expressed in terms of relative risk (RR), which is the ratio of the risk of breast cancer recurrence in patients who test positive to the risk in those who test negative.
 Methodologic guidelines that should be satisfied by a study evaluating the predictive ability of a test include the following: (1) Was an inception cohort assembled? (2) Was the referral pattern described? (3) Were laboratory and clinical outcomes assessed in a blinded fashion? (4) Was complete follow-up achieved? (5) Was adjustment for extraneous prognostic factors carried out? (6) Were appropriate statistical methods used? An approach is suggested to help the clinician choose the test, or combination of tests, likely to discriminate between ""high-"" and ""low-risk"" patients in his/her own practice.
 The decision regarding what particular threshold value (risk) defined by a prognostic test (or series of tests) warrants adjuvant therapy for an individual patient is a complex one but should be based on a clear presentation of the risks and benefits to the patient.
",3
486,"L-methionine uptake by human cerebral cortex: maturation from infancy to old age 
 Age-associated changes in amino acid transport from blood to normal frontal cortex were studied using positron emission tomography (PET).
 Seventeen patients, 1.8-71 yr, were injected intravenously with tracer doses of [11C] L-methionine and a baseline PET scan was obtained.
 To assess competitive inhibition of [11C]L-methionine uptake, patients received either oral L-phenylalanine or an i.v.
 infusion of amino acids 1 hr before a second PET study.
 Uptake of [11C]L-methionine by frontal cortex decreased seven-fold between 1.8 and 71 yr (r = -0.71; p less than 0.05).
 Blood-to-brain transfer of [11C]L-methionine, at 4.5 yr, exceeded mean adult values by more than five-fold.
 Competitive inhibition reduced L-methionine uptake in all patients older than 4.6 yr.
 These developmental changes parallel findings in animals.
 The neutral amino acid transport system may modulate human brain amino acid levels to meet changing developmental metabolic needs.
",3
487,"Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma 
 In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs.
 With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples.
 Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index).
 The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation.
 The end point was defined as either local/regional recurrence or metastasis.
 Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02).
 Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.
",3
488,"Phase I clinical and pharmacokinetic trial of flavone acetic acid.
 Flavone acetic acid is a synthetic benzopyrone derivative with an unknown mechanism of action.
 Thirty-eight patients (30 men and 8 women) were treated once a week for 4 weeks every 5 weeks with doses of flavone acetic acid ranging from 0.33 to 12.5 g/m2.
 At doses less than or equal to 3.9 g/m2, the drug was administered intravenously over 1 hour; at doses greater than or equal to 5.28 g/m2, the infusion period was lengthened to 6 hours.
 Treatment of all patients included hydration before and after treatment and alkalization to maintain urine pH at greater than or equal to 6.5.
 A dose-limiting toxic effect was hypotension at 10 g/m2.
 Pharmacokinetic studies revealed linear behavior in the eight patients studied, beginning at 3.9 g/m2.
 Peak plasma levels ranged from 125 to 630 micrograms/mL, with a mean terminal half-life of 22.4 hours.
 Immunologic monitoring was performed in three patients at 10 g/m2.
 A transient increase in CD16- and/or Leu-19-positive cells was noted in all three patients.
 In one patient, this increase correlated with a 10-fold increase in K562 cell killing.
 There were no objective tumor responses seen in this trial.
 The recommended phase II dose on this schedule is 8 g/m2.
 Further studies to elucidate the drug's mechanism of action and to define its immunologic properties are recommended.
",3
489,"Tumor suppressor genes: new prospects for cancer research.
 Cancer is thought to arise from the accumulation of several genetic mutations in a single cell.
 Until recently, the only tumorigenic mutations that have been studied in detail are those that activate oncogenes.
 The discovery of tumor suppressor genes, for which inactivating mutations elicit tumorigenesis, has added a new dimension to our understanding of neoplasia.
 The retinoblastoma susceptibility gene RB is the prototype tumor suppressor gene and has been shown to suppress the transformed phenotype for several different cancers.
 Additional studies have revealed other tumor suppressor genes that may operate in a variety of tissues through a variety of mechanisms.
 These mechanisms may regulate the choice between cellular proliferation and differentiation and appear to involve such processes as the initiation of DNA replication, regulation of expression of certain genes, intercellular communication and adhesion, and the transduction of external signals to intracellular effectors.
 The elucidation of these mechanisms will enhance our understanding of both oncogenesis and the fundamental operations of the cell.
",3
490,"Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations 
 Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or stress-response protein (srp-27) was evaluated in human breast carcinomas and established breast cancer cell lines.
 Results obtained by Northern and Western blot analyses and immunohistochemical methods were concordant.
 Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas (with median patient follow-up of 8 years) was performed.
 Twenty-six percent of lymph node-negative and 45% of lymph node-positive tumors were overexpressors.
 Univariate analysis demonstrated significant correlations between srp-27 overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease-free survival period (but not a shorter overall survival) for the study population as a whole.
 Regression tree analysis showed that srp-27 expression was an independent prognostic indicator for disease-free survival only in patients with one to three positive lymph nodes.
 The Cox proportional hazards model confirmed the independent prognostic significance of nodal involvement, T stage, and ER content but failed to recognize srp-27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole.
 The observed associations between srp-27 overexpression and more aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas.
",3
491,"Therapeutic advantage of hypoxic cells in tumors: a theoretical study 
 The presence of hypoxic cells in solid tumors has long been considered a problem in cancer treatment, particularly for radiation therapy but also for treatment with some anticancer drugs.
 Three general strategies are being actively explored to overcome the problem: oxygenating the tumor, sensitizing the hypoxic cells to radiation (or chemotherapy), or killing the hypoxic cells (with a hypoxic cell cytotoxin).
 In the present study, we have examined the impact of each of these three strategies on a standard radiation therapy regimen (30 doses of 2 Gy), using either of two major assumptions: full reoxygenation or no reoxygenation of the tumor cells.
 We demonstrate that a hypoxic cell cytotoxin can produce a level of tumor cell killing higher (by several orders of magnitude) than that produced by full oxygenation of a tumor or by use of an optimum hypoxic cell radiosensitizer, provided the cytotoxin kills more than approximately 50% of the hypoxic cells each time it is given.
 The only assumption that makes a difference is whether reoxygenation occurs: In the worst case (ie, no reoxygenation), the hypoxic cell cytotoxin performs only as well as an optimum radiosensitizer.
 The analysis shows that hypoxic cells in tumors can be a major therapeutic advantage.
 Therefore, we recommend that research efforts be concentrated on development of superior hypoxic cell cytotoxins rather than improved hypoxic cell radiosensitizers and that, in parallel, emphasis be placed on development of agents to increase hypoxia.
",3
492,"Diffusion and binding of monoclonal antibody TNT-1 in multicellular tumor spheroids.
 Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were established to investigate the uptake and clearance kinetics of TNT-1, a monoclonal antibody that targets necrotic cells of tumors.
 Our data reveal that there was rapid uptake of TNT-1 and its F(ab')2 fragment in both spheroid models, whereas an antibody of irrelevant specificity, Lym-1, and its F(ab')2 fragment bound poorly to the spheroids.
 Unlike previously reported monoclonal antibodies to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased over time without saturation in tumor spheroids and 2) an unexpected uptake by a subpopulation of cells in the viable outer rim of the spheroids.
 These preclinical studies provide important information concerning the therapeutic potential of TNT monoclonal antibodies for the treatment of cancer and micrometastases.
",3
493,"Longitudinal study of women with negative cervical smears according to endocervical status 
 A longitudinal study of 20,222 women who received negative cervical smear reports in 1987 showed that the incidence of definite or equivocal cervical intraepithelial neoplasia (CIN) was not significantly different between those whose first smear lacked an endocervical component and those whose smear included an endocervical component.
 The incidence of definite cytological evidence of CIN was significantly lower in women whose first smear did not include an endocervical component.
 It is concluded that women whose smears are reported as negative but lack an endocervical component should not be rescreened any earlier than women with negative smears that include an endocervical component.
",3
494,"Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of pheochromocytoma.
 Chromogranin A, co-stored and co-released with catecholamines from adrenal medullary and sympathetic neuronal vesicles, is elevated in the plasma of patients with pheochromocytoma.
 The usefulness of the hormone in the differential diagnosis of hypertension is examined.
 An elevated level of chromogranin A had comparable diagnostic sensitivity (83%, 24/29) to, but greater diagnostic specificity (96%, 86/90) than the level of plasma catecholamines when subjects with pheochromocytoma (n = 29) were evaluated in comparison to several reference groups, including normotensive controls (n = 49), subjects with essential hypertension (n = 28), subjects with renovascular hypertension (n = 5), and subjects with primary aldosteronism (n = 3).
 Subjects with signs or symptoms suggesting pheochromocytoma, but in whom the diagnosis was ultimately ruled out (n = 5) had normal plasma levels of chromogranin A.
 A modest rise in chromogranin A in those with essential hypertension, and correlation of chromogranin A with diastolic blood pressure in normotensive patients and patients with essential hypertension did not impair the diagnostic usefulness of chromogranin A for pheochromocytoma.
 Renal failure was associated with an elevated plasma chromogranin A independently of blood pressure.
 Plasma chromogranin A correlated with tumor mass, tumor chromogranin A content, tumor norepinephrine content, and urinary vanillylmandelic acid excretion; it did not correlate with plasma or urinary catecholamines, nor with blood pressure in patients with pheochromocytoma.
 Plasma chromogranin A levels did not differ in subjects with pheochromocytoma when stratified by age, sex, tumor location, or tumor pathology.
 Several drugs used in the diagnosis or treatment of pheochromocytoma (clonidine, metoprolol, phentolamine, and tyramine) had little effect on plasma chromogranin A concentration.
 Within the pheochromocytoma, chromogranin A was localized along with catecholamines to the soluble core of chromaffin granules, where it accounted for 18 +/- 5% of vesicle soluble protein.
 We conclude that 1) chromogranin A emerges along with catecholamines from pheochromocytoma chromaffin granules; 2) plasma chromogranin A is a sensitive and specific diagnostic tool in evaluation of actual or suspected pheochromocytoma; 3) plasma chromogranin A predicts pheochromocytoma tumor size and overall catecholamine production; and 4) drugs commonly employed in the diagnosis or treatment of pheochromocytoma have little effect on plasma chromogranin A level, preserving the usefulness of chromogranin A in evaluating pheochromocytoma.
 Thus, measurement of chromogranin A provides a useful adjunct to the diagnosis of pheochromocytoma.
",3
495,"A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience.
 Pheochromocytoma is an unusual but potentially devastating tumor.
 Although a high index of suspicion is necessary, the likelihood of a pheochromocytoma is lower in the absence of the typical symptoms and findings.
 Nonetheless, screening must be broadened to include patients with a lower risk of the disease, such as those with resistant or labile hypertension who are minimally symptomatic.
 Extensive diagnostic evaluations should be reserved for those whose clinical or laboratory findings are more suggestive.
 Symptoms in a group of patients in whom a pheochromocytoma was seriously considered but excluded overlap symptoms in patients with a pheochromocytoma.
 Certain symptoms are useful: flushing to suggest a non-pheochromocytoma illness; visual symptoms, flank pain, and pallor to suggest that a pheochromocytoma is more likely.
 Combinations of symptoms can be of value: 2 or more symptoms from the triad of headache, palpitations, and diaphoresis were present in the majority of pheochromocytoma patients, but in a smaller number of non-pheochromocytoma patients.
 The presence of the entire triad is more specific, but less sensitive.
 New hypertension, or hypertension associated with unexplained orthostatic hypotension, are suggestive of an underlying pheochromocytoma.
 Twenty-four-hour urine studies are consistently abnormal in patients with a pheochromocytoma, but are also elevated in a significant proportion of non-pheochromocytoma patients.
 Values greater then 1.5-2-fold above the upper limit of normal are very suggestive that a pheochromocytoma is present, and warrant a more intensive subsequent evaluation.
 Imaging studies are reliable in the diagnosis of pheochromocytoma, and can help to confirm or exclude the disease.
 Patients with a higher clinical likelihood and any elevated urinary testing, or with a lower clinical likelihood and persistently and/or significantly elevated urinary testing, should have imaging studies performed.
 This combination of clinical screening, 24-hour urinary testing, and imaging studies is a useful and reliable approach to patients suspected of harboring a pheochromocytoma.
",3
496,"Myeloma manifesting as a large jugular tumor: case report.
 The authors report a case of cranial plasmacytoma with multiple myelomas and palsy of the lower cranial nerves.
 The osteolytic lesion adjacent to the jugular foramen was demonstrated by an angiogram to be exceedingly hypervascular, with arteriovenous shunting resembling that seen in paragangliomas.
 Forty-five cases of cranial and intracranial plasmacytoma from the literature were reviewed.
 The findings indicate that a cranial plasmacytoma commonly appears to be a hypervascular tumor, whereas most dural tumors or intraparenchymal tumors have poor vascularity.
",3
497,"Prognostic factors in stage IB squamous cervical cancer patients with low risk for recurrence.
 About one-half of cervical cancer patients whose tumors recur after radical surgery have negative lymph nodes and clear resection margins.
 We evaluated 95 patients with squamous cell tumors who underwent radical hysterectomy and pelvic lymphadenectomy between January 1975 and December 1985 and who were thought to be at low risk for recurrence to see whether other clinical or histopathologic factors were predictive of tumor recurrence.
 Detailed retrospective record review and complete pathology review were accomplished for each case.
 The 5-year actuarial survival rate was 89%.
 Nine patients developed recurrent disease (9.5%), of whom eight died.
 Several clinical features were evaluated as possible prognostic factors: patient age (P = .26), patient race (P = .60), cervical diameter (P = .24), extent of gross cervical involvement (P = .36), and presence of contact bleeding (P = .82).
 Histopathologic features were examined: depth of invasion (P = .31), number of mitoses (P = .42), character of the tumor-stromal border (P = .15), histologic differentiation (P = .02), lymph-vascular space invasion (P = .56), and width of tumor (P = .23).
 Depth of invasion did correlate with increasing tumor width (P less than .001).
 Once node- and margin-positive patients are excluded, differentiation may be the only feature useful in identifying patients at risk for recurrence.
 Because almost one-half of our patients had poorly differentiated tumors, sole use of this feature as a criterion for adjuvant therapy would have resulted in overtreatment of low-risk patients.
",3
498,"Familial ovarian cancer in Israeli Jewish women.
 Among 310 women with ovarian cancer of epithelial origin, eight ovarian cancer-prone families were identified, accounting for 24 cases.
 Five first-degree relatives underwent prophylactic oophorectomy, and early ovarian carcinoma was diagnosed in one of them.
 Familial aggregation of ovarian cancer occurs in the Israeli Jewish population.
",3
499,"Cone cerclage in pregnancy.
 We report a technique of cone cerclage and the results and outcome in 17 patients who required a diagnostic cone biopsy in pregnancy.
 The mean age of the patients was 30.6 years (range 21-41).
 The mean gestational age was 18.8 weeks (range 10-32) at the time of the procedure.
 There were no major complications and hemorrhage was not a significant problem.
 There were no second-trimester abortions.
 Two patients required beta-sympathomimetics to suppress uterine activity for longer than 24 hours after the procedure.
 Six patients had invasive carcinoma, nine had cervical intraepithelial neoplasia (CIN) III, and two had CIN II.
 In 14 cases, the endocervical and ectocervical margins were negative; two patients with CIN and one with multifocal microinvasion had positive margins.
 Cone cerclage is a safe and easy method for performing diagnostic cervical conization during pregnancy.
",3
500,"Queuine, a tRNA anticodon wobble base, maintains the proliferative and pluripotent potential of HL-60 cells in the presence of the differentiating agent 6-thioguanine.
 6-Thioguanine (6-TG)-induced differentiation of hypoxanthine phosphoribosyltransferase (IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8)-deficient HL-60 cells is characterized by 2 days of growth, after which morphological differentiation proceeds.
 Addition of the tRNA wobble base queuine, in the presence of 6-TG, maintains the proliferative capability of the cells.
 The ability of 6-TG to induce differentiation correlates with c-myc mRNA down-regulation, but queuine has no effect on this parameter.
 Treatment with 6-TG for 2-3 days commits HL-60 cells to granulocytic differentiation, and, once committed, these cells do not respond to the monocytic inducer phorbol 12-myristate 13-acetate.
 Nonetheless, when cells are treated with queuine and 6-TG, they maintain the promyelocytic morphology and are capable of being induced down the monocytic pathway by phorbol 12-myristate 13-acetate as indicated by stabilization of c-fms mRNA and cell adherence.
 In the absence of queuine, phorbol 12-myristate 13-acetate is incapable of inducing monocytic markers in the 6-TG-treated cells.
 The data presented indicate that 6-TG-induced differentiation of HL-60 cells is a tRNA-facilitated event and that the tRNA wobble base queuine is capable of maintaining both the proliferative and pluripotent potential of the cells.
",3
501,"Metastatic melanoma to the facial nerve.
 Isolated metastatic malignant melanoma to the facial nerve has never been reported.
 This presentation illustrates a primary melanoma of the helix of the ear that was treated by excisional biopsy and then wedge resection in 1983.
 The primary melanoma was Clark's level IV and 1.3 mm in thickness.
 In 1985, a facial paresis slowly developed.
 There was no gross evidence of recurrent melanoma in the ear or neck, but CT scan showed a mass in the region of the stylo mastoid foramen.
 A reoperation of the primary site revealed metastatic melanoma in the facial nerve, expanding it to approximately 10 times its normal size.
 A composite resection was done for the melanoma, and the paralyzed face was immediately rehabilitated by a masseter muscle transfer.
 The patient received 6000 rads to this area postoperatively and has remained free of disease to date, having returned to his profession as a dentist.
 A detailed study of all the specimens indicated that this represented a primary metastasis to the facial nerve.
",3
502,"An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing's syndrome by clinical features, biochemical tests and radiological findings.
 The efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent Cushing's syndrome was studied, based on findings in 23 patients with verified Cushing's disease and seven patients with the ectopic ACTH syndrome.
 Clinical features strongly favouring the ectopic type were male sex and history for less than 18 months.
 Basal biochemical features strongly indicating the ectopic syndrome included plasma K+ less than 3.0 mmol/l and HCO3 greater than 30 mmol/l; serum cortisol at 9 a.m.
 or midnight of greater than 800 nmol/l; urine free cortisol greater than 1300 nmol/24 hours; plasma ACTH greater than 100 ng/l.
 In the high-dose dexamethasone suppression test, suppression by less than 50 per cent of 9 a.m.
 serum cortisol, urine free cortisol or 17-oxogenic steroids was usually indicative of an ectopic source of ACTH.
 A mean suppressed value of greater than 450 nmol/l for the 9 a.m.
 and midnight cortisol combined occurred in all of those with the ectopic syndrome, but in none of the 23 patients with Cushing's disease.
 For urine free cortisol, a mean suppressed value of less than 1000 nmol/24 hours was found in all patients with Cushing's disease, but in none of those in the ectopic group.
 In the metyrapone test, there was an increase of less than or equal to 3-fold in 11-deoxycortisol at 24 hours in patients with ectopic ACTH; the increase was greater than 3-fold in all but one of the patients with Cushing's disease.
 Failure to respond to either dexamethasone or metyrapone was found in only one of the patients with Cushing's disease (Patient 16); in the ectopic group, all patients except Patient D failed to respond to either test.
 It is concluded that patients presenting with clinically obvious Cushing's syndrome along with measurable plasma ACTH can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic ACTH.
",3
503,"Genetic mechanisms of tumor suppression by the human p53 gene.
 Mutations of the gene encoding p53, a 53-kilodalton cellular protein, are found frequently in human tumor cells, suggesting a crucial role for this gene in human oncogenesis.
 To model the stepwise mutation or loss of both p53 alleles during tumorigenesis, a human osteosarcoma cell line, Saos-2, was used that completely lacked endogenous p53.
 Single copies of exogenous p53 genes were then introduced by infecting cells with recombinant retroviruses containing either point-mutated or wild-type versions of the p53 cDNA sequence.
 Expression of wild-type p53 suppressed the neoplastic phenotype of Saos-2 cells, whereas expression of mutated p53 conferred a limited growth advantage to cells in the absence of wild-type p53.
 Wild-type p53 was phenotypically dominant to mutated p53 in a two-allele configuration.
 These results suggest that, as with the retinoblastoma gene, mutation of both alleles of the p53 gene is essential for its role in oncogenesis.
",3
504,"Reoperation for colorectal carcinoma.
 In the management of the patient with intra-abdominal recurrence of colorectal carcinoma, surgery remains the primary mode of therapy when cure or significant palliation is anticipated.
 Appreciation of the importance of close follow-up after primary resection coupled with improved diagnostic modalities has allowed the surgeon not only to detect earlier recurrence but also to select the patients most likely to benefit from resection of recurrent disease.
 Improved surgical techniques with resultant decreases in the rates of morbidity and mortality have allowed safe hepatic resection of metastatic disease.
 In selected patients, this procedure produces 5-year survival rates approaching 50%.
 Although a clear consensus has not been reached, most studies agree that positive prognostic indicators include absence of extrahepatic disease, a small number of intrahepatic lesions, a low CEA level, and a better Dukes stage of the primary.
 Likewise, in the patient with recurrent disease locally, surgery provides the only means of cure and also plays a significant role in palliation.
 Aggressive resection with generous surgical margins in patients with contained disease may yield 5-year survival rates approaching 35%.
 In patients with unresectable disease and even in those with carcinomatosis, palliation can be obtained by surgical therapy.
 Judgment is necessary in treating these patients both preoperatively and intraoperatively.
 Surgical intervention for obstruction, perforation, or other anatomic or physiological compromise is often indicated and can improve the quality of life of the patient with intra-abdominal recurrence.
",3
505,"The Merkel cell and associated neoplasms in the eyelids and periocular region.
 Merkel cells are clear oval cells in the epidermis and outer root sheaths of hair follicles, which are probably of epithelial origin, share ultrastructural features with neuroendocrine cells, and are found in association with touch receptors.
 In the eyelid, they occur singly in the epidermis and external root sheaths of hairs and eyelashes, and in specialized touch spots alternating with eyelashes.
 Their typical electron microscopical and antigenic features include dense-core granules, intranuclear rodlets, spinous processes, and a positive reaction for specific cytokeratins, epithelial membrane antigen, neuron-specific enolase, chromogranin and synaptophysin.
 Merkel cell carcinoma probably develops from precursor cells which give rise to keratinocytes and Merkel cells, and nearly one out of ten Merkel cell carcinomas occur in the eyelid and periocular region.
 They tend to be bulging lesions near the lid margin of elderly patients, reddish in color, and erythematous with telangiectatic vessels.
 The diagnosis is based on the frequent presence of neurofilaments and paranuclear aggregates of intermediate filaments in addition to features typical of normal Merkel cells.
 The tumor often mimics lymphoma or undifferentiated carcinoma and frequently invades lymphatic vessels.
 One third of Merkel cell carcinomas recur, almost two thirds give rise to regional node metastases, and up to one half metastasize widely and result in death.
 Initial treatment should be prompt and aggressive, with wide resection and routine postoperative irradiation.
 Although metastatic lesions often respond to radiation therapy and cytostatic drugs, these treatments are mainly of palliative value.
",3
506,"Surgical strategy for early gastric cancer.
 The diagnostic and therapeutic options in early gastric cancer are reviewed.
 In Japan, the rate of detection of early gastric cancers has increased so that minute gastric cancers can now be identified as a result of advances in diagnostic methods.
 The results of histopathological staging of a large number of resected specimens have led to three surgical options based on size and depth of the primary lesion, namely classical R2 resection, radical resection with limited lymphadenectomy and endoscopic surgery.
",3
507,"Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.
 A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported.
 In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration.
 Twenty-seven patients had a limited resection of their cancer.
 After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups.
 Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract.
 In 30 patients treatment was discontinued because of recurrent disease.
 The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.
",3
508,"Value of retesting subjects with a positive Hemoccult in screening for colorectal cancer.
 Within a prospective randomized screening study for early detection of colorectal cancer with rehydrated Hemoccult II test, the possibility of increasing the specificity of the test by retesting patients with an initially positive Hemoccult II test was investigated.
 Of those offered the test 3561 (62.6 per cent) returned it and it was positive in 210 cases (5.9 per cent).
 The repeat test was performed by 184 patients and was positive in 68 (1.9 per cent).
 All those with a positive initial test had rectosigmoidoscopy to 60 cm and a double contrast enema.
 A carcinoma was found in one in seven patients with a positive retest but in only one in 100 patients with a negative retest (P less than 0.001).
 The specificity of the test was, therefore, increased from 95 per cent to 98 per cent and the sensitivity was unchanged.
 Rescreening was offered at a later date and increased numbers were available: 7147 patients returned the test and 369 (5.2 per cent) were positive.
 The test was repeated in 360 patients and 118 (1.7 per cent) were positive.
 A colorectal neoplasm was found in one in three of those with a positive repeat test, compared with one in seven of those with a negative repeat test.
 In conclusion, screening for early detection of colorectal cancer with a rehydrated Hemoccult II test may be followed by investigation of only those patients with a positive retest.
 Such a procedure will reduce the work-load by 60 per cent without reducing sensitivity.
",3
509,"Epidermal growth factor receptor expression in colorectal cancer.
 Epidermal growth factor (EGF) receptor expression was estimated in 50 invasive human colorectal cancers using immunohistochemistry and the degree of expression was quantified from integrated optical density measurements on the stained sections.
 All tumours stained positively, but Dukes' C tumours exhibited significantly higher levels of receptor than either Dukes' A or B tumours.
 In addition, histologically high grade cancers expressed receptors more strongly than those of low grade.
 It is concluded that a high EGF receptor concentration is associated with poor prognostic factors in colorectal malignancy.
",3
510,"Levamisole and 5-fluorouracil therapy for resected colon cancer: a new indication.
 OBJECTIVE: To evaluate the benefits and risks of postoperative treatment with levamisole plus 5-fluorouracil (5-FU) in patients with colon cancer.
 DESIGN: Computerized searches of MEDLINE and CANCERLIT were performed, and the reference list of each retrieved article was checked.
 Only randomized trials of therapy with levamisole alone or combined with 5-FU for colon cancer without distant metastases were included.
 The studies were then evaluated with the use of four criteria.
 RESULTS: We reviewed six randomized trials, of which three satisfied our criteria.
 Two studies demonstrated a significant improvement in the survival rate with levamisole plus 5-FU among patients with colon cancer and pathologically confirmed metastases to adjacent lymph nodes (Dukes' stage C).
 A subgroup analysis in another study demonstrated a similar benefit.
 The toxic effects of the drugs were generally mild.
 The three other studies showed no difference in survival rates between the treatment groups; however, the samples were too small to detect a clinically or statistically important difference.
 CONCLUSIONS: Because many patients with colon cancer will suffer a relapse we recommend that they be offered the opportunity to participate in clinical trials of adjuvant therapy.
 For those with stage C disease not entering a clinical trial levamisole plus 5-FU is appropriate adjuvant therapy.
",3
511,"Retinoid modulation of insulin-like growth factor-binding proteins and inhibition of breast carcinoma proliferation.
 Retinoids induce cellular differentiation and inhibit cellular proliferation.
 Proliferation of human breast carcinoma cells in vitro is markedly inhibited by these compounds.
 On the other hand, insulin-like growth factors (IGFs) and their receptors seem to be involved in the growth of certain breast carcinoma cells by autocrine or paracrine effects.
 Since the effects of both IGF-I and IGF-II may be modulated by specific binding proteins (IGF-BPs) we examined the possibility that one mechanism by which retinoic acid may inhibit cancer growth is by an alteration in these BPs, thereby blocking IGF's growth effect.
 Retinoic acid (RA; 1 microM) completely blocked the effect of IGF-I (50 ng/ml) on enhancing proliferation of MCF-7 cells in culture.
 This effect of RA was not associated with any significant change in specific IGF-I-binding sites on these cells.
 RA induced a 3-fold increase in IGF-binding activity in conditioned medium, measured using a polyethylene glycol-immunoglobulin precipitation assay and a charcoal absorption assay.
 This increase was associated with the appearance of 42- and 46-kDa IGF-BPs on ligand blotting.
 The effect of RA on these IGF-BPs was time and concentration dependent.
 In contrast, during some experiments the 27- and 36-kDa BPs actually decreased.
 These findings support the hypothesis that RA may inhibit the growth of certain breast carcinoma cells by increasing the secretion of certain IGF-BPs, which could directly modulate the growth effect of IGFs.
",3
512,"Evaluation of the serum level of immunosuppressive substance in oral cancer patients.
 The serum level of immunosuppressive substance (IS) was studied in 40 patients with primary oral cancer and in 79 patients without cancer.
 Its usefulness was evaluated as a parameter for monitoring therapy as well as recurrence of the tumors.
 Mean values for serum IS in patients with cancer and patients without were 687 +/- 284 micrograms/mL and 464 +/- 153 micrograms/mL, respectively.
 Normal healthy controls had a mean value of 431 +/- 105 micrograms/mL, with the cutoff value set at 641 micrograms/mL (mean +2 SD).
 Patients without cancer who had a severe infectious disease showed conspicuously high serum IS levels, and these values were closely correlated with their C-reactive protein values.
 The positive rate of IS increased in all patients with oral cancer was 58%.
 The mean level of serum IS in cancer patients was significantly higher than that of the controls (P less than .01), and the level was found to be more elevated as the stage of the disease advanced (stage I to III, 48%; stage IV, 68%).
 Histologic analysis of the tumor cells in patients with squamous cell carcinoma (SCC) showed that the mean serum IS level of those who had poorly differentiated SCC was much higher (937 +/- 181 micrograms/mL) than that of patients with well-differentiated SCC (616 +/- 159 micrograms/mL).
 Patients who had recurrent or metastatic cancer, or those who died from the cancer exhibited marked elevation of the serum IS levels, whereas patients who remained free of cancer in the follow-up period showed significantly lower serum IS levels.
 The rise and fall of the serum IS level was closely correlated with the disease progression and/or remission.
 These data strongly suggest that serum IS is a useful parameter for monitoring the disease stage as well as the effect of therapy on patients with oral cancer.
",3
513,"Literacy and laryngectomy: how should one treat head and neck cancer in patients who cannot read or write?
 The entire population of otolaryngologists and radiation oncologists (N = 192) in active practice in the state of North Carolina were surveyed to assess their level of awareness of illiteracy among adults in the United States and to determine whether these physicians consider illiteracy in the treatment decision process for patients with head and neck cancer.
 Excluding respondents who did not treat patients with head and neck cancer and physicians practicing outside of the state of North Carolina, the response rate was 115 of 182, or 63%.
 Only 26% of respondents were able to estimate correctly the prevalence of illiteracy in the US adult population.
 Forty-one percent of respondents, however, stated that they did consider their patient's ability to read and/or write before making treatment recommendations for head and neck cancer.
 This survey and accompanying literature review suggest that physicians perceive illiteracy as a problem that may have a significant impact on patients with head and neck cancer, but lack the data needed to enable them to quantify the effect of illiteracy on treatment outcome.
 The study reported is the first step in examining ways in which illiteracy might negatively affect patient outcomes.
",3
514,"Paratesticular myxoma: an unusual benign intrascrotal neoplasm.
 We have presented a case of paratesticular myxoma and have described the clinical history, findings on light microscopy and immunohistochemistry, and possible pathogenesis.
 Although primary paratesticular myxoma is a rare lesion, it should be considered in the differential diagnosis of intrascrotal mesenchymal tumors.
",3
515,"Astroblastoma: electron microscopy and immunohistochemical findings: case report.
 The clinical, histological, immunohistochemical, and electron microscopic features of a cerebral astroblastoma are reported.
 The patient is a young woman with a superficial parietal tumor.
 Macroscopic findings include a well-delineated superficial nodule with a hard central core.
 Histological study disclosed a predominantly papillary tumor with hyalinized vessels.
 Tumor cells were scarcely positive with immunohistochemical stain for glial fibrillary acidic protein, extensive and diffusely positive with vimentin and neuron-specific enolase, and intensely positive with S-100 and epithelial membrane antigen in the papillary areas.
 Ultrastructural study showed abundant intermediate filaments forming bundles in tumoral cytoplasms, membrane junctions, and external laminae when cells were in contact with collagen fibers.
 Based on immunohistochemical and ultrastructural characteristics, we believe that the filaments seen in tumor cells are mainly vimentin filaments.
 These peculiar immunohistochemical patterns in a glioma may aid in the histological diagnosis of this rare tumor type.
",3
516,"Intramedullary spinal cord germinoma: case report.
 A case of intramedullary spinal cord germinoma within the conus medullaris, with lumbago and pain in the lower extremities, is presented.
 The intramedullary spinal cord germinoma was determined by a biopsy specimen.
 After local irradiation of 50 Gy, the tumor markedly decreased in size and clinical symptoms disappeared.
",3
517,"Ganglioneuroma of the spinal cord.
 This report describes a 2-year-old boy who harbored an intramedullary ganglioneuroma involving almost the entire length of the spinal cord.
 The terminology, pathology, and neurobiological behavior of this tumor is discussed.
",3
518,"Mammography and early breast cancer detection.
 Screening mammography has been shown to reduce breast cancer mortality.
 Both film-screen mammography and xeromammography are highly sensitive and specific.
 Mammography accreditation programs assure physicians and patients that a facility provides mammography of the highest quality, using the lowest possible radiation dose.
 Mammographic signs of early cancer include a small mass, calcifications, architectural distortion and a neodensity.
 Dense tissue may result in a false-negative examination even when a cancer is palpable, with adverse effects if biopsy is delayed.
",3
519,"Carcinoma of the ductus choledochus.
 A retrospective review of patients treated for carcinoma of the common bile duct has demonstrated improvement in diagnostic capabilities, leading to earlier management by resectional therapy.
 The ability to resect these tumors is directly translatable to improved long-term survival.
 Efforts to obtain proof of malignancy prior to resection are often frustrated by the inability to obtain adequate representative tissue for frozen section.
 Choledochoscopic biopsies and incisional biopsies have given the highest yield of positive diagnoses.
 In experienced hands, a program of fewer preoperative tests with emphasis on early operation, diagnosis, and definitive treatment may be more cost-effective in the management of patients with common bile duct cancer.
",3
520,"The effects of midazolam on cerebral blood flow and oxygen consumption. Interaction with nitrous oxide in patients undergoing craniotomy for supratentorial cerebral tumours.
 Cerebral blood flow and the cerebral metabolic rate of oxygen were measured in 30 patients during craniotomy for supratentorial cerebral tumours by a modification of the Kety-Schmidt technique using Xenon 133 intravenously.
 Anaesthesia was induced with midazolam 0.3 mg/kg, fentanyl and pancuronium, and maintained with midazolam as a continuous infusion, fentanyl, pancuronium and nitrous oxide in oxygen or oxygen in air.
 The concentration of midazolam in the blood of 10 patients was about 300 ng/litre during two measurements; the patients' lungs were ventilated with N2O in oxygen.
 The concentration of midazolam in the blood of another 10 patients was doubled to about 600 ng/litre during the second flow measurement; the patients' lungs were ventilated with N2O/O2.
 The concentration of midazolam in the blood of the third group of 10 patients was doubled to 600 ng/litre during the second flow measurement; the patients' lungs were ventilated with oxygen in air.
 No relationship was found between the dose of midazolam and cerebral blood flow or oxygen consumption.
 Nitrous oxide in combination with midazolam also had no effect on these variables.
",3
521,"Capillary hemangiomas and treatment with the flash lamp-pumped pulsed dye laser 
 Strawberry, or capillary, hemangiomas are common vascular neoplasms, with an incidence of approximately 2.6% in neonates.
 They usually develop in the first few weeks of life, so that between 1 month and 1 year the incidence rises to between 8.7% and 10.1%.
 These lesions may grow quite large in the first year of life, and they may ulcerate or obstruct a vital organ or function.
 The great majority will spontaneously regress after the first year of life.
 Parents are often alarmed at the sight of these hemangiomas and need reassurance that the great majority will regress spontaneously.
 Treatments such as cryosurgery, irradiation, radium instillation, corticosteroid therapy, or surgical excision are often ineffective or cause significant morbidity.
 We describe 10 children with capillary hemangiomas treated with the flash lamp-pumped pulsed dye laser.
 The patients ranged in age from 7 weeks to 5.5 years at the beginning of laser therapy.
 The patients underwent 3.1 +/- 1 (mean +/- SD) laser treatments, with a mean regression of the lesions of 69.9% +/- 4.5%.
 All patients demonstrated some diminution in the size and color of their hemangiomas after the treatments, and there were no ill effects, such as ulceration, hemorrhage, infection, or scarring.
 There was no evidence of hyperpigmentation or hypopigmentation.
 Pulsed dye laser therapy should be considered as an option in the treatment of capillary hemangiomas, preferably prior to their full evolution.
 It is also a useful therapeutic approach in those hemangiomas that are slow to regress in older children.
",3
522,"Effectiveness of radiotherapy with radical neck dissection in cancers of the head and neck.
 A retrospective analysis of 457 radical neck dissections performed over a 30-year period for cancers of the oral cavity, pharynx, and larynx was carried out.
 Two hundred thirteen patients underwent radiotherapy to the primary cancer site and/or to the neck.
 Of these, 164 underwent perioperative adjuvant radiotherapy and 24 underwent definitive radiation for cure and were followed up by salvage surgery.
 Thus, 188 patients received radiotherapy for nonrecurrent disease.
 Twenty-five additional patients underwent radiation for surgical failure following radical neck dissection.
 The goal of the study was to determine whether radiotherapy altered the course or end result of the disease.
 The T and N stage at onset of disease was similar for the radiotherapy and nonradiotherapy groups.
 Preoperative radiotherapy was effective in down staging the disease at the primary site and, to a lesser extent, in the lymph nodes, but had limited impact on survival.
 Failure to control the disease in the neck occurred in 60 (32%) of the 188 patients who received radiotherapy for primary disease; recurrence rates were lower in the combined therapy group than in the surgical group of patients with N2 and N3 stages of disease.
 The 3-year disease-free survival was 45%; this was no better than the 63% survival rate in patients who did not receive radiotherapy, although survival was better in the combined therapy group for patients with N3 stage of disease.
 The worst results were in those patients who were irradiated for surgical failure (14% survival); the 24 patients who required salvage radical neck dissection following failure of definitive radiotherapy for cure had a 42% survival.
",3
523,"Juvenile (embryonal and alveolar) rhabdomyosarcoma of the head and neck in adults. A clinical, pathologic, and immunohistochemical study of 12 cases.
 Sites in the head and neck region (orbit, nasopharynx, nasal cavity, etc.) are among the most frequent locations for juvenile (embryonal and alveolar) rhabdomyosarcomas in patients younger than 15 years; however, comparable neoplasms in adults are very uncommon.
 A clinicopathologic and immunohistochemical study of 12 juvenile rhabdomyosarcomas in patients between the ages of 18 and 36 years is presented.
 There was a female:male ratio of 2:1.
 The orbit with or without contiguous paranasal sinus involvement, nasal cavity, sphenoid sinus, middle ear, and soft tissues of the neck and preauricular region were the primary sites.
 Seven tumors involved a parameningeal site and eight cases were alveolar rhabdomyosarcomas which together contributed to the adverse outcome.
 Only two patients were long-term, disease-free survivors.
 Six patients have died of tumor and two others are alive with persistent disease.
 Immunohistochemical study in 11 cases demonstrated reactivity for vimentin and muscle-specific actin (HHF-35) and desmin in ten cases.
 Juvenile rhabdomyosarcoma rarely presents in the head and neck of adults but should be considered in the differential diagnosis of a small cell neoplasm in patients during the third and fourth decades of life.
",3
524,"A comparative analysis of three different techniques for the detection of breast cancer cells in bone marrow.
 Three different methods, morphologic, immunocytochemic, and fluorescence activated cell sorter (FC) analysis, were compared with respect to their efficiency in detecting breast cancer cells in bone marrow.
 In the first series of experiments, the three techniques were compared using bone marrow cells artificially mixed with a known amount of breast cancer cells, whereas in a second series bone marrow from breast cancer patients with bone metastases were used.
 The following results were obtained: When mixtures of the first series were analyzed, FC analysis detected from 1% to 10% of breast cancer cells in bone marrow (0.2% was a border line value), the morphologic method detected from 0.05% to 10%, and the immunocytochemic method, which was clearly superior, detected breast cancer cells in all mixtures (from 0.00025% to 10%).
 It was noted that, with both the morphologic and immunocytochemic methods, the percentage of breast cancer cells detected was 2 to 360 times higher than the percentage of added cells, and enrichment was inversely proportional to the percentage of added cells.
 This result could be a result of different separation of cells during centrifugation due to the different density of breast cancer cells.
 The superiority of the immunocytochemic method was confirmed in the second series of experiments.
",3
525,"Microinvasive carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics Stage IA).
 In 1985 the International Federation of Gynecology and Obstetrics (FIGO) subdivided Stage IA cervical cancer and specified metric criteria to demarcate Stage IA from Stage IB.
 Early stromal invasion (Stage IA1) denotes the first invasive protrusions of a carcinoma in situ into the stroma.
 Microcarcinomas (Stage IA2) are small cancers a number of orders of magnitude larger than Stage IA1 lesions and with a maximum depth of invasion of 5 mm and a maximum horizontal spread of 7 mm; larger lesions are classified as Stage IB.
 This study reviews 486 patients previously classified as having Stage IA disease.
 This yielded 344 Stage IA1 and 101 Stage IA2 lesions; 41 cancers were reclassified as Stage IB.
 Three hundred nine, 89, and 38 patients were followed for greater than or equal to 5 years.
 One (0.3%) patient with Stage IA1 disease re-presented with Stage IIB disease 12 years after conization.
 Five (5.6%) patients with Stage IA2 lesions developed invasive recurrences; three died.
 None of the 38 patients reclassified as having a Stage IB lesion, including 16 who were treated conservatively, developed a recurrence.
 The FIGO classification is not a guideline for treatment.
 Stage IA1 lesions can be treated conservatively, but treatment in Stage IA2 must be individualized.
 Risk factors such as vascular space involvement and confluency are of high sensitivity but low specificity.
",3
526,"Leiomyosarcoma of bone. A clinicopathologic, immunohistochemical, and ultrastructural study of five cases.
 The authors identified five leiomyosarcomas (LMS) in a review of 13 nonmatrix-producing spindle cell sarcomas of bone.
 Only two were initially recognized as LMS; the others had been diagnosed as malignant fibrous histiocytoma (two) and fibrosarcoma (one).
 The patients, four of whom were women, ranged in age from 32 to 70 years.
 Sites included proximal humerus (two), distal femur (two), and rib (one).
 All tumors presented with clinical and radiographic features consistent with a diagnosis of primary bone neoplasms, although one probably represented a solitary metastasis from a primary uterine LMS.
 Radiographs showed lytic bone destruction with a moth-eaten appearance, and three cases had soft tissue extension.
 Histologically, all tumors showed broad, interlacing fascicles of spindle cells with pleomorphic nuclei, frequent mitoses, and necrosis.
 Two cases had a focal storiform pattern and bizarre multinucleated cells, and two other cases had focally prominent osteoclast-like giant cells.
 Extensive immunoreactivity for muscle actin was seen in all cases and for desmin in three.
 In each case, electron microscopy showed definite smooth muscle differentiation including cytoplasmic filaments with densities.
 At this writing, two patients are free of disease (including the patient with a presumed metastasis), one is alive with locally recurrent disease, and two are dead of disease.
 Experience suggests that LMS of bone is a distinct clinicopathologic entity that may be more common than previously recognized.
 Application of immunohistochemistry and electron microscopy to nonmatrix-producing bone sarcomas should facilitate diagnosis of additional cases.
",3
527,"Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study.
 Of 2947 children with acute lymphocytic leukemia (ALL), treated during three consecutive studies of the Pediatric Oncology Group (1974-1986), 52 (1.8%) had Down's Syndrome (DS).
 Comparison of clinical and laboratory characteristics showed no significant differences in leukocyte count, racial distribution, sex ratio, platelet count, incidence of mediastinal mass, lymphadenopathy or hepatosplenomegaly, or percentage of blood or bone marrow blasts for children with ALL with or without Down's Syndrome (DS-ALL or NDS-ALL, respectively).
 However, children with DS-ALL were slightly older at the time of presentation and had higher hemoglobin values.
 The relative frequency of each major immunophenotype (early pre-B, pre-B, T, or B) was also comparable for patients with or without DS.
 For this report, treatment regimens were categorized as either conventional (no consolidation therapy) or intensive.
 Cox regression analysis revealed that the presence of DS, a higher leukocyte count, black race, or age older than 10 years was independently associated with a poorer event-free survival (EFS) for children treated with conventional chemotherapy.
 However, for the cohort of children who received intensive chemotherapy, DS was no longer an independent risk factor.
 In fact, event-free survival (EFS) was markedly improved to a level comparable with that observed in the children diagnosed as having NDS-ALL.
 On the other hand, serious toxicity, requiring interruption of treatment, was significantly more frequent in the intensively treated children with DS compared with similarly treated patients with NDS-ALL, although deaths resulting from toxicity occurred infrequently.
",3
528,"Psychosocial adjustment in women with breast cancer.
 There is a plethora of studies investigating psychosocial adjustment in women with breast cancer, its correlates, clinical course, and prognosis.
 These studies have been conducted with varying degrees of methodologic rigor.
 An assessment has been made of the quality of this existing evidence to identify from the best evidence the factors which predict the adjustment status of women with breast cancer.
 Studies have been reviewed, using methodologic standards for the critical appraisal of studies on prognosis, developed by Sackett and colleagues in the Department of Clinical Epidemiology and Biostatistics at McMaster University (Hamilton, Ontario, Canada).
 Few of the studies investigating psychosocial adjustment of women with breast cancer meet all of the criteria for reviewing studies of clinical course and prognosis.
 This review focuses the direction and methodologic rigor required in future investigations.
 In particular, studies are needed that employ prospective designs and that deliberately measure or control for the extraneous prognostic variables that may affect adjustment.
 Future investigations need to incorporate adequate precision in measurement so that measures of the psychosocial variables are objective, reliable, and valid.
",3
529,"Prognosis of pregnancy-associated breast cancer.
 The survival of patients with pregnancy-associated (PA) breast cancer is difficult to predict for two reasons: The combination is very rare, and the natural history of breast cancer that is not associated with pregnancy is intricate and varies among individuals.
 Valid data collection and analysis is problematic given that studies gather patients over many years.
 The charts of 56 women with Stages I, II, and III breast cancer, who were pregnant or within 1 year postpartum at the time of breast cancer diagnosis between 1960 and 1980, were analyzed.
 Patients with PA breast cancer were compared to nonpregnant women of comparable ages, who were treated at the same hospital, by the same physicians, and during the same period.
 Four patients were lost before 5-year follow-up, and one patient before 10-year follow-up.
 These five patients had distant metastases at the time they were lost to follow-up, and are considered to have died within that time.
 Across stages, patients with PA breast cancer have survival not significantly different from those patients with non-pregnancy-associated (non-PA) breast cancer.
",3
530,"Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer. An updated analysis.
 A randomized trial was performed to determine if therapy with tamoxifen (TAM) plus fluoxymesterone (FLU) was more efficacious than TAM alone for postmenopausal women with metastatic breast cancer.
 Patients failing TAM could subsequently receive FLU.
 The dose of both drugs was 10 mg orally twice daily.
 Objective responses were seen in 50 of 119 (42%) TAM patients and 64 of 119 (54%) TAM plus FLU patients (two-sided P = 0.07).
 Time to disease progression was better for TAM plus FLU (medians: 11.6 versus 6.5 months; Cox model, P = 0.03).
 Duration of response and survival were similar in the two treatment arms.
 Among 97 patients with estrogen receptor (ER) of 10 or greater and 65 years of age or older, there were highly significant advantages for treatment with TAM plus FLU in both response rate and time to progression.
 Of particular note is that in this patient group TAM plus FLU showed a survival advantage (Cox model, P = 0.05).
 Although these data require confirmation in a prospective randomized trial, they suggest that there is a substantive therapeutic advantage for TAM plus FLU over TAM alone in elderly women with ER of 10 fmol or greater.
",3
531,"Sphincter preservation in rectal cancer by local excision and postoperative radiation therapy.
 The authors report the preliminary results of 14 patients with localized, mobile, resectable rectal cancer treated with local excision and postoperative radiation therapy (RT).
 All had negative surgical resection margins and two received 5-fluorouracil (5-FU).
 The median follow-up was 29 months (4-43 months).
 The 3-year actuarial survival was 88%.
 The incidence of local failure was 7% (only site of failure) and 21% (component of failure).
 The incidence of local failure increased with T stage (T1, 0/3 [0%]; T2, 1/7 [14%]; and T3, 2/4 [50%]) and tumor size (greater than 3 cm, 33%, versus less than or equal to 3 cm, 0%).
 Three patients developed local failure at 6, 15, and 21 months.
 Three underwent a salvage abdominoperineal resection and were locally controlled at 2 and 28 months following salvage surgery.
 One patient underwent an abdominoperineal resection for a clinically presumed local failure; however, no tumor was found in the specimen.
 Therefore, the 13 patients who either were initially locally controlled or underwent salvage or nonsalvage surgery had no evidence of disease in the pelvis at the time of last follow-up.
 Local excision and postoperative RT may be an alternative to standard surgery in selected cases.
 However, additional follow-up and more experience are needed in order to determine if this approach will ultimately have local control and survival rates similar to those of a low anterior resection or an abdominoperineal resection.
",3
532,"Flow cytometric DNA analysis of hepatocellular carcinoma.
 The prognostic value of nuclear DNA content was studied retrospectively using flow cytometry in 203 cases of resected hepatocellular carcinoma.
 The occurrence of DNA aneuploidy, which was detected in 50% of patients, correlated significantly with tumor size and the presence of vascular invasion or intrahepatic metastasis.
 Overall, patients with DNA aneuploid tumors had a significantly worse prognosis than those with DNA diploid tumors (P less than 0.001) and, also in subdivided groups by tumor size (P less than 0.01).
 Among DNA aneuploid patients, the survival times were significantly shorter for patients with a low DNA index (less than 1.5) than for those with a high DNA index (greater than or equal to 1.5) (P less than 0.05).
 In a Cox multivariate analysis, nuclear DNA content provided significant prognostic value (P = 0.008), as did vascular invasion (P = 0.001) and intrahepatic metastasis (P = 0.005).
 These results indicated that nuclear DNA content has an important prognostic value in hepatocellular carcinoma.
",3
533,"Predictors of physician nonadherence to chemotherapy regimens.
 Physician nonadherence to cancer treatment regimens may diminish treatment efficacy and compromise clinical research.
 The influence of clinical, demographic, and psychosocial patient characteristics on physician adherence to breast cancer chemotherapy was investigated, as was the role of the clinician's attitudes concerning the chemotherapy.
 One hundred seven women recently diagnosed with breast cancer were followed for 26 weeks of treatment.
 Fifty-six (52%) of the patients experienced unjustified modification for at least one chemotherapeutic agent.
 Stepwise multiple regression revealed independent contributions of increased patient age, treatment setting (clinic versus academic or community private practice), and stage of disease to physician nonadherence.
 Regimen complexity, delay in seeking treatment, and presence of psychiatric disorder did not contribute, in general, to unjustified regimen modifications.
 Patient psychological and psychiatric factors, however, did influence prescribing behavior for vincristine.
 Physician awareness of factors contributing to unnecessary treatment modifications may reduce the frequency of such behaviors.
",3
534,"Complete remission in refractory anaplastic adult Wilms' tumor treated with cisplatin and etoposide.
 A 61-year-old woman underwent a left radical nephrectomy for Stage II anaplastic Wilm's tumor.
 She received no adjuvant therapy.
 One year later computerized tomography (CT) of the abdomen revealed a mass in the left renal fossa and retroperitoneal adenopathy.
 A CT-guided needle biopsy was nondiagnostic.
 The patient had progressive disease after treatment with dactinomycin, doxorubicin, and vincristine, but achieved a complete response after treatment with cisplatin and etoposide.
 The therapy of Wilms' tumor in adults is discussed.
",3
535,"Expression of class I and II human leukocyte antigens by thyrocytes and lymphocytic infiltration on human thyroid tumors. An immunofluorescence study.
 Surgical thyroid sections from 30 papillary carcinomas (PC), six medullary carcinomas (MC), three anaplastic carcinomas (AC), two follicular carcinomas (FC), and 16 adenomas (AD) were examined with an indirect immunofluorescence technique employing different monoclonal antibodies to evaluate the expression of human leukocyte antigen (HLA)-A, B, C (Class I) and DR, DP, DQ (Class II) by thyrocytes, together with the phenotype and distribution of inflammatory cells.
 Ten PC and four FC were also investigated for the presence of intercellular adhesion molecule-1 (ICAM-1).
 In situ deposits of immunocomplexes and circulating thyroid autoantibodies were also evaluated.
 An increased expression of Class I antigens was found in all PC and FC, in 33% of MC and AC, and in 31% of AD.
 An anomalous expression of Class II antigens was observed in 70% of PC, in 50% of FC, in 33% of AC, in 19% of AD, and in none of the MC.
 Expression of DP or DQ was revealed only in a portion of the DR-positive glands.
 A reduction of microsomal autoantigen expression was found.
 No ICAM-1-positive thyrocytes were detected.
 A moderate T-lymphocytic infiltrate was noticed only in PC, where it was correlated with DR and DP and/or DQ coexpression.
 B-cells and natural killer cells were virtually absent.
 The authors speculate that the weak Class II antigens expression, together with the partial or complete loss in microsomal autoantigen and the absence of ICAM-1 by thyrocytes, may account for the limited engagement of immunocompetent cells observed in thyroid tumors.
",3
536,"Advances in medical imaging for cancer diagnosis and treatment.
 Over the last several decades, significant ""new eyes"" have been developed that improve the diagnosis, treatment, planning, and monitoring of human cancer: computer tomography (CT), magnetic resonance imaging (MRI) and spectroscopy (MRS), single photon emission computed tomography (SPECT), and positron emission tomography (PET).
 Innovative advances in both morphologic and functional imaging have led to a dramatic improvement in our ability to diagnose and monitor human cancer.
 Frequently, anatomic detail can be demonstrated in ways that exceed views at surgery, and functional biochemical imaging is being used to show the metabolic activity and receptor status of normal and pathologic states.
 In vivo functional and biochemical studies differentiate normal from neoplastic or nonviable tissue, and make it possible to measure progression or regression of the disease.
 Because physiologic changes often precede morphologic findings in many disease processes, the use of in vivo biochemical probes can demonstrate disease before anatomic abnormalities become evident.
 Gross changes in anatomy are no longer adequate endpoints for therapy protocols.
 Today, using physiologic imaging, we can evaluate the response to treatment within hours of administration of therapy.
 Adjuvant metabolic tumor imaging studies provide complimentary information to morphologic evaluation of human cancers that will ultimately lead to better patient care.
",3
537,"The natural history of colorectal cancer. Opportunities for intervention.
 There is now a better understanding of the natural history of colorectal cancer, which has provided a basis for intervention to influence outcome.
 The possible interventions include earlier detection of colorectal cancer, removal of premalignant adenomas, demonstration of the mucosal field defect that precedes neoplasia to evaluate baseline risk and its change with dietary modification, and identification of inherited and dietary risk factors.
 Five controlled trials evaluating early detection of colorectal cancer with fecal occult blood testing have enrolled more than 309,000 patients.
 Early stage cancers with improved survival has been observed, but data on mortality reduction have not as yet been reported.
 Studies of patients with adenomas have demonstrated high synchronous and metachronous rates as a basis for complete colon evaluation initially and a surveillance follow-up program.
 Hyperproliferation and lack of normal differentiation have been observed as a field defect in the colon preceding neoplasia.
 Inherited factors have recently been shown to be important in a larger proportion of individuals destined to develop colorectal adenomas and cancer.
 These observations of the natural history of colorectal cancer have provided new opportunities for the application of radiologic and endoscopic techniques in diagnosis and surveillance; each examination has its merit.
 Further research is needed to answer many critical questions that have been raised regarding the impact of these interventions.
",3
538,"Imaging techniques in the diagnosis of carcinoma of the colon.
 The variability in the published results for colonoscopy and barium enema examinations is confusing.
 With both, optimum results are dependent on meticulous preparation, technical excellence, and operator proficiency.
 It is a mistake to place colonoscopy and the barium enema in competitive positions; the two methods ideally complement one another in the evaluation of high risk individuals, including those with positive Hemoccult tests.
 The exclusion of significant pathology by the double-contrast enema can be relied on and is less costly to the patient.
 Detection of abnormalities by a barium enema should, when necessary, be followed by colonoscopic verification and/or biopsy.
 When used in this sequence, the procedures provide a cost-effective approach to the early detection and control of cancer; it is estimated that observance of the ACS guidelines can reduce mortality rates by 30%.
",3
539,"Imaging bone tumors in the 1990s.
 Progress in bone tumor management has occurred as a result of cooperation among surgeons, oncologists, pathologists, and radiologists.
 During the 1990s radiologists will contribute to care of patients with bone tumors in major ways.
 Tumor detection and preliminary diagnosis will be accomplished by radiography.
 Tumor local extent will be assessed by magnetic resonance imaging (MRI) and to a lesser degree by computed tomography (CT).
 Distant spread of malignancy will be documented by radionuclide scintigraphy (skeleton) and by CT (lungs).
 The combined estimate of local extent and distant spread will assure adequate staging before definitive management decisions.
 Preoperative closed percutaneous biopsy for histologic diagnosis will be accomplished on an outpatient basis under fluoroscopic or CT guidance.
 Arteriography will be employed for delivery of local chemotherapy.
 Some combination of arteriography, MRI, and MR spectroscopy will be used to evaluate tumor response.
 After limb-salvage surgery, MRI will sequentially assess the tumor bed; bone scintigraphy and CT will detect skeletal and pulmonary metastases.
 The radiologist's role will undergo continuous redefinition.
",3
540,"Primary neoplasms of the hollow organs of the gastrointestinal tract. Staging and follow-up.
 The number of imaging modalities available to stage and follow-up patients with primary neoplasms of the gastrointestinal (GI) tract continues to increase.
 Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasonography are useful techniques for both staging and follow-up.
 For staging, CT is most frequently used for the detection of liver metastases and is increasingly used as a substitute for the chest radiograph in the detection of lung metastases.
 CT is still the imaging test of choice for the preoperative staging of esophageal carcinoma.
 CT is less helpful in staging the patient with gastric carcinoma or colorectal carcinoma.
 The current usefulness of MRI in the staging of GI tract malignancies is limited by the lack of an adequate oral intraluminal contrast agent and degradation of images due to motion.
 Sonography, especially the new technique of endoscopic ultrasound, is promising for the detection of local invasion from GI tract malignancies.
 CT is used in the follow-up of patients with tumors of the GI tract to detect liver, adrenal, and nodal metastases as well as local recurrence because of the ability of CT to detect extraluminal masses.
 CT of the pelvis has been recommended as a routine follow-up procedure in patients who have undergone abdominal-peroneal resection.
 Both CT and MRI can be used to detect local recurrence, but suffer from the inability to differentiate scar from recurrent tumor.
 The initial hope that MRI would be capable of differentiating postoperative scar tissue from recurrent tumor has not been realized.
 Therefore, with positive CT or MRI findings, occasionally a percutaneous biopsy will be required to confirm local recurrence.
",3
541,"Liver tumor imaging.
 Liver tumor imaging is the paradigm of the dilemma of diagnostic decision-making in the current era of abundant high technology.
 In part, this is a reflection of the multiplicity of imaging techniques now in wide use worldwide.
 These include ultrasound (US), radionuclide scintigraphy (RNS), computed tomography (CT), magnetic resonance imaging (MRI), and techniques especially designed for staging the extent of known liver cancer, such as computed tomography during arterial portography (CTAP) and intraoperative ultrasound (IOUS).
 Most authorities concede that CT scanning is the single test most closely fitting the designation ""gold standard"" for liver tumor imaging, although MRI, a less mature technique, is already preferred by some.
 Local factors profoundly influence the selection and sequence of imaging studies, including available equipment, radiologic skills, institutional interests, and especially the specific clinical circumstances of the patient.
 Thus, diagnostic algorithms or decision trees for sequential imaging workup of liver tumor suspects tend to be somewhat institution specific.
",3
542,"Staging and follow-up of breast cancer patients.
 Staging systems for breast cancer, unlike those of neoplasms in distant or recessed sites, allowed for the early development of clinical staging evaluation.
 It was established that clinical assessment of the breast lesion was often wrong compared with the pathologic examination (benign vs.
 malignant); clinical measurement of the tumor in centimeters was often larger than histologic size; and clinical assessment of axillary nodes (clear or metastatic) was incorrect in about 30% of cases.
 Although both clinical and pathologic staging provide effective discriminants for prognosis of treated patients, prognosis is more accurately determined by the pathologic stage.
 The single most important prognostic indicator is the axillary nodal status, and when positive, the number of positive nodes.
 The American Joint Committee on Cancer and the Union International Contra Cancer have agreed on a TNM staging for breast carcinoma, and this is the preferable staging system.
 Follow-up of treated patients is of most value in detecting local recurrence on the chest wall (after mastectomy) or in the irradiated breast (after lumpectomy), and also in early detection of contralateral breast cancer.
 Physical examination and periodic mammography are most useful.
 There is a tendency to overinvestigate asymptomatic patients (with bone scans, blood tests, etc.), but this has been correctly criticized in recent years.
",3
543,"Primary neoplasms of the central nervous system in children.
 Modern diagnostic imaging techniques are able to detect primary neoplasms of the central nervous system (CNS) in children safely and accurately but with less specificity as to cell type or degree of malignancy.
 These neoplasms, often peculiar in cell type and size, mediated by hydrocephalus in their clinical presentation, demand careful and often extensive imaging techniques best to evaluate their geography and character.
 Added to these basic observations, determination of the neoplasm from surrounding edema, detection of possible spread, and evaluation of residual or recurrent neoplasm are prime responsibilities of the pediatric neuroradiologist toward the child, neurosurgeon, and oncologist.
",3
544,"Magnetic resonance imaging in the evaluation of spinal tumors.
 Magnetic resonance imaging (MRI), which has recently begun to replace myelography, postmyelography computed tomography (CT), and to some extent, bone scans, has become the procedure of choice in the evaluation of spinal tumors; the applications of MRI in this role are reviewed.
 In the extradural space, MRI is the most sensitive technique for the detection of tumors in the vertebral bodies.
 At the same time, it provides superb delineation of suspected thecal sac impingement.
 In the intradural extramedullary space, MRI is generally as accurate as myelography and postmyelography CT while being noninvasive.
 Finally, in the intramedullary space, MRI is unquestionably the procedure of choice in the evaluation of suspected cord tumors.
 In general, MRI has become the best initial procedure in the evaluation of suspected tumors of the spine, regardless of the space in which they may lie; frequently, it is the only required examination.
",3
545,"Radioimmunology. Imaging and therapy.
 Targeting of radioactivity to tumors using antitumor antibodies is evolving from a laboratory curiosity toward a practical diagnostic and therapeutic technique that promises widespread benefits for many common human cancers.
 The development of the hybridoma technique by Kohler and Milstein for producing monoclonal antibodies is probably the single most important contribution to the development of this field.
 A large array of monoclonal antibodies against many human tumors have been created and labeled with a variety of radioisotopes; 110 clinical trials have been identified from the literature between the interval of 1978 to the present.
 These studies are beginning to form the basis for certain conclusions regarding likely benefits for certain combinations of antitumor antibodies and isotopes in specific instances of clinical management in patients with malignant neoplasms.
 For example, in melanoma, lymphoma, neuroblastoma, and colorectal malignancies, radiolabeled antibodies have demonstrated occult tumors, which could not be disclosed with conventional methodologies.
 Radioimmunotherapy of malignant lymphoma is achieving durable remissions in patients who have failed conventional forms of therapy.
 For the most part, these advances have been achieved through intelligent application of known principles of immunochemistry, imaging physics, and tumor immunology.
 Progress has been slow but steady.
 In a few instances, the term ""magic bullet"" is warranted in describing the targeting of a particular radiolabeled antibody to a human tumor.
 I-131, 3-F8, an IgG3 against the GD2 antigen of neuroblastoma, which was introduced by Cheung, and In-111 T-101, against the CD5 antigen of T-cells, which was developed by Royston, stand out because of the consistency and high concentration of radioactive targeting to human tumors in clinical trials.
 If certain technical innovations fulfill their initial promise, the future will be bright for radioimmunologic methods of diagnosis and therapy.
 Genetic engineering will permit the development of ""humanized"" antibodies with biologic properties that favor tumor localization.
 New chemical approaches will broaden the range of isotopes available as diagnostic and therapeutic radiolabels.
 Application of modern imaging methodologies, such as positron emission tomography (PET), will detect more lesions of smaller size and permit quantitative imaging for dosimetry considerations.
 Greater speed and ease of use of computerized work stations will lead to the broader application of fusion imaging in which radioantibody images will be viewed simultaneously with TCT or MRI for better anatomic correlation of abnormal sites of antigen-reactive tumor deposits.
",3
546,"Single photon emission computed tomography and positron emission tomography in cancer imaging.
 Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are now being used to improve the information available from radioisotopic imaging of patients with cancer.
 These nuclear medicine techniques offer the potential for studying regional function and biochemistry by using radiolabeled substrates.
 The chemical changes of malignancy precede anatomic changes, and PET and/or SPECT may detect these changes before anatomic changes have occurred.
 The superiority of SPECT compared with planar imaging has been demonstrated for cardiac and brain imaging.
 Radiopharmaceuticals containing technetium 99 m (99mTc) are best suited for SPECT imaging because large amounts of radioactivity are administered and the collimator-camera systems are optimized for the 140 keV photons of 99mTc.
 The current interest in imaging cancer with SPECT relates to the use of gallium 67 citrate and monoclonal antibodies labeled with iodine 123 or indium 111.
 SPECT can image these radioisotopes, but the advantages compared with planar imaging have not been clearly defined.
 Furthermore, the ability to quantitate the distribution of single photon emitters other than 99mTc has not been demonstrated.
 New SPECT systems with three heads or rings of detectors offer promise for improved, quantitative imaging.
 PET has the capability of imaging tracers with the biologically important elements C-11, N-13, O-15, and F-18 used for positron labeling.
 These radioisotopes have short half-lives and require a cyclotron close to the PET facility.
 The most prominently used radiopharmaceutical for PET is F-18 fluorodeoxyglucose (FDG).
 PET studies with FDG in patients with primary brain tumors have demonstrated the ability to determine the degree of malignancy, to differentiate necrosis from recurrent tumor after radiation therapy or chemotherapy, and to predict prognosis.
 Other metabolic functions of cancer have been studied, including amino acid accumulation, thymidine uptake, oxygen utilization, intermediary metabolism, and receptor status.
 PET has the potential to make a major impact on the characterization of a malignancy and the effect of therapy.
",3
547,"New directions in medical imaging of cancer. Magnetic resonance methods and single photon emission computed tomography.
 Magnetic resonance methods and single photon emission computed tomography (SPECT) are developing technologies that provide both functional and anatomic information.
 Their role in the diagnosis and monitoring of cancer is the subject of current clinical research.
 Magnetic resonance imaging (MRI) delineates organs and tissue heterogeneities using differences in the relaxation parameters of water and fat protons; both protons and other nuclei can be imaged or studied by magnetic resonance spectroscopy (MRS) to provide information on the state of naturally occurring or infused molecules.
 SPECT quantifies the distribution of radiolabeled agents in tissues and organs; labeled monoclonal antibodies provide highly specific imaging of tumors.
 Spatial resolution is the limiting technologic factor.
 Proton MRI provides the highest current resolution, better than 1 mm in vivo in deep tissues, whereas the resolution of MRS and SPECT is limited to several cubic centimeters.
 Recent advances in these technologies have significantly increased their specificity and ability to detect small, deep lesions.
",3
548,"Imaging of adult central nervous system primary malignant gliomas. Staging and follow-up.
 A classification and staging system for primary adult gliomas was proposed.
 This system uses the high signal intensity found on proton density or T2-weighted magnetic resonance (MR) scans at the site of the tumor and surrounding edema (including infiltrating tumor).
",3
549,"Proliferation and DNA ploidy in malignant breast tumors in relation to early oral contraceptive use and early abortions.
 In 175 premenopausal breast cancer patients, a history of oral contraceptive (OC) use before 20 years of age was significantly associated with higher tumor cell proliferative activity, as indicated by a higher S-phase fraction (SPF), and a higher fraction of DNA aneuploid tumors, compared with later or never users (P = 0.05 and p = 0.01, respectively).
 The higher SPF among early OC users was apparent in patients with aneuploid tumors but not in patients with euploid tumors.
 Abortions (spontaneous or induced) before the first full-term pregnancy also were associated with a higher SPF compared with other young patients with breast cancer (P = 0.03).
 Adjusting for parity and abortions or OC use, respectively, an early OC use was associated with a 43% higher SPF and early abortions were associated with 49% higher SPF.
 Younger patients had a higher SPF and a higher frequency of aneuploid tumors, but this was found to be because the users of OC had a lower median age at diagnosis.
 Among never users, no significant age relationship was seen for SPF or the frequency of aneuploidy.
 For the DNA analyses there is a selection of patients with breast cancer with larger tumors, and therefore the conclusions drawn in this article may not be generalizable to patients with smaller primary tumors, e.g., cases diagnosed at breast cancer screening.
 The higher tumor proliferative activity and frequency of aneuploidy in early OC users are in line with previously reported findings of worse prognostic indicators and a worse survival in early users of OC compared with other young women with breast cancer.
",3
550,"Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin.
 Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma.
 Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy.
 Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days.
 After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions).
 The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%).
 Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients.
 The median survival time was 11.5 months, with 15% of the patients alive at 2 years.
 The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression.
 There was no episode of life-threatening toxicity.
 Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients.
 The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.
",3
551,"Serum tumor markers and patient allocation to good-risk and poor-risk clinical trials in patients with germ cell tumors.
 The allocation of patients with advanced germ cell tumors (GCT) to different treatment programs based on clinical characteristics is standard in the design of clinical trials today.
 Studies have shown that substantial differences exist between entry criteria and that these differences could influence the outcome of clinical trials.
 The factors contributing to these differences are not clear due to patient selection biases.
 Two hundred five unselected and consecutive patients allocated to and treated in good-risk and poor-risk treatment programs at Memorial Sloan-Kettering Cancer Center (MSKCC) were reassigned risk status by the Indiana University (IU) Classification.
 The results were compared with those of the Southeastern Cancer Study Group (SECSG).
 The results using both criteria indicated substantial agreement in total end results and the identification of good-risk patients.
 The results in poor-risk patients differed substantially, with 39 patients (19%) classified as poor-risk by MSKCC criteria and 66 (32%) by Indiana criteria.
 The major discrepancy occurred in IU Stage 7, in which 26 of 32 patients (81%) achieved a complete response.
 The major factor contributing to this difference in risk assignment was the use of serum tumor markers.
 Serum tumor markers must be incorporated into risk assignment criteria for GCT clinical trials to minimize the number of good-risk GCT patients in poor-risk trials.
",3
552,"Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989).
 Twenty-eight of 124 (23%) advanced germ cell tumor (GCT) patients who were treated on four successive platin-based induction regimens and who failed to achieve a durable complete response (CR) remain alive (median follow-up, 50 months).
 An analysis of prognostic factors for response and survival was conducted on the 94 patients who received salvage chemotherapy.
 Survival and/or response to salvage therapy were significantly enhanced for patients with a prior CR to induction chemotherapy, treatment with a cisplatin-based salvage regimen, a testis primary site, a normal serum human chorionic gonadotropin level, a normal serum lactate dehydrogenase level, one site of metastasis, and an Indiana Class of 6 or less.
 Patients with a prior incomplete response (IR) had a particularly poor prognosis (P = 0.00007) with only 4 of 52 (9%) patients alive (median follow-up, 37 months) compared with 15 of 42 (36%) patients with a prior best response of a CR (median follow-up, 35 months).
 The poor survival of patients who fail to achieve a durable CR to induction chemotherapy warrants the continued investigation of new salvage therapy.
 The identification of prognostic features may direct salvage therapy and aid in the interpretation of clinical trials of salvage regimens.
",3
553,"The prognostic value of image analysis in ovarian cancer.
 Histologic grading is very important for treatment decisions in ovarian cancer.
 All grading systems contain a significant subjective component, which could be reduced by including objective measurements into the diagnostic decision.
 Image analysis was used to determine nuclear area and ploidy distributions in 42 patients with epithelial ovarian cancer, and the results were related to tumor grade and clinical outcome.
 The mean nuclear area, mean optical density, number of hyperploid cells, and the standard deviation between measurements were significantly higher in Grade 2 and 3 tumors compared with Grade 1 tumors, in rapidly progressive tumors compared with less aggressive malignancies, and in recurrent tumors compared with primary lesions.
 The number of nuclei with very high DNA content was found to be of prognostic importance.
 Image analysis thus provides additional prognostic information in epithelial ovarian cancer.
",3
554,"Resection of the primary liver cancer of the hepatic hilus.
 Primary liver cancer (PLC) of the hepatic hilus was designated as a tumor situated at the main branch of the portal vein or pedicle of the hepatic veins in contact with the intrahepatic vena cava.
 That is, the main tumor located at segment I, IV, V, or VIII and concentrating on the central part of the liver was called ""the central type of PLC,"" which differed from a tumor located at segment II, III, VI, or VII; the latter was called ""the peripheral type of PLC."" Surgical treatment of the PLC has been significantly improved in the past two decades, but the resection of the central type of PLC is difficult and hazardous.
 This institution admitted 903 PLC from January 1970 to April 1988, of which 118 cases were the central type; 65 cases were resected successfully, a resectability of 55.1%.
 One patient died from sepsis within 1 month of operation (mortality 1.53%).
 The modes of operation for the different segments are described, and suggestions for improvements are presented.
 The survival rates were compared with a similar number of patients with the peripheral type of tumor in the same period and treated by the same surgeons.
 The results show noticeable differences.
 The one-year, three-year, and five-year survival rates after resection were 70.9%, 43.2%, and 39.2% in the central type of PLC; they were 98.3%, 85.0%, and 76.4% in the peripheral type of PLC (P less than 0.001).
 Further discussion of improvements in surgical techniques and mental awareness are suggested.
",3
555,"Structural and functional integrity of ovarian tumor tissue obtained by ultrasonic aspiration.
 For patients with ovarian epithelial cancer, survival increases when residual disease approaches zero after surgical removal of the tumor.
 A previous study using the Cavitron Ultrasonic Surgical Aspirator (CUSA) (Cavitron Lasersonic Corp., Stamford, CT) showed the successful removal of ovarian tumors from areas often considered unresectable: the diaphragm, spleen, stomach, and small bowel.
 However, the CUSA has not yet been approved by the Food and Drug Administration for gynecologic surgery except on an experimental basis.
 This study was designed to test whether ultrasonic irradiation produced by the CUSA caused alterations in cell structure or physiology of gynecologic tissue in adjacent areas.
 Paired tumor samples, unirradiated and irradiated, were obtained from ten patients, and portions were sent for pathologic structural evaluation and physiologic tissue culture evaluation.
 Histologic sections, stained with hematoxylin and eosin, showed that CUSA irradiation produced only minor tissue distortion as observed under the light microscope.
 A correct diagnosis would have been made in all cases had only tissue fragments obtained from the CUSA specimen trap been stained.
 For nine of ten patients, initial tumor cell viability was similar in the two specimen types.
 Flow cytometric DNA analysis confirmed that surgical methods produced matched samples.
 Cells that survived high-frequency ultrasound appeared functionally intact.
 For five of eight patients, the cells from the CUSA specimen traps survived and/or divided to a greater extent than those from the knife-dissected tumors.
 Cells from both surgical routes attained a similar number of passages in culture.
 It seems reasonable to extrapolate these in vitro observations with pelvic tumor tissues to normal surrounding tissue left in situ.
 Thus pelvic tissue is believed to be uninjured by CUSA ultrasonic irradiation.
",3
556,"The expression of progesterone receptors coincides with an arrest of DNA synthesis in human breast cancer.
 Two main models to account for the heterogeneous expression of estrogen receptors (ER) and progesterone receptors (PR) in human breast cancer have been proposed: the clonal model and the stem cell model.
 The authors previously provided evidence supporting the stem cell model since it was found that most of the proliferating cells in ER-positive (ER+) human breast cancer lack ER and that the ER-negative (ER-) and ER+ subpopulations are interrelated.
 The authors have analyzed in eighteen ER+/PR+ primary breast tumors the simultaneous expression of ER or PR (by immunohistochemistry) and DNA synthesis (by autoradiography) after 30 minutes of 3H-thymidine incorporation.
 The authors demonstrated that: (1) the average numbers of ER+ and PR+ cells were similar (36.8 +/- 10.7% and 39.3 +/- 17.6%, respectively); (2) The thymidine-labeling indexes of the ER+, ER-, PR+, and PR- subpopulations were 0.53 +/- 0.69%, 0.74 +/- 0.49%, 0.21 +/- 0.21 and 0.94 +/- 0.54%, respectively; and (3) 75.2% of the DNA-synthesizing cells were ER-, and 88.8% of them were PR-.
 The authors conclude that the cellular subpopulations expressing ER and PR were not identical, and the expression of PR was associated with a lower rate of cellular proliferation than was ER expression.
",3
557,"Amplification of oncogenes in mammary carcinoma shown by fine-needle biopsy.
 A procedure that measures the amplification of oncogenes in human cancer cells is described.
 The cells were obtained by fine-needle biopsy to allow repeated sampling from individual metastases.
 A drawback was the low number of cells obtained, but this could be overcome by using a slot-blot hybridization technique to measure gene amplification.
 Two patients with mammary cancer (primary tumors or metastases), analyzed for the levels of amplification of the oncogene erb-B2, are described in detail.
 This technique is suitable for analyzing alterations occurring during cancer progression and for identifying subgroups of mammary cancer with different characteristics.
",3
558,"Predicting recurrence time of esophageal carcinoma through assessment of histologic factors and DNA ploidy.
 Cytophotometric analysis of nuclear DNA content was done in 128 patients with squamous cell carcinoma of the esophagus.
 The relationship among histopathologic features, DNA distribution pattern, and survival time was investigated from the standpoint of recurrence.
 Of 128 patients, 77 (60.1%) died of recurrence within 2 years after surgery: 16 (12.5%) from 2 to 5 years and two (1.6%) over 5 years.
 The rate of death of recurrence within 2 years was higher in patients with T4 or N1 than T1, T2, and T3 or N0 (P less than 0.01).
 Survivors over 5 years more frequently possessed type II DNA pattern than types III and IV (P less than 0.05).
 The rate of death of recurrence within 2 years was 34.4% in type II, which was lower than the 59.6% rate in type III (P less than 0.05) and the 76.6% rate in type IV (P less than 0.01).
 Survivors from 2 to 5 years were higher in type III than in type IV (P less than 0.05), and recurrence over 5 years was found only in type II.
 This inclination was more apparent in those with curative resection.
 In the patients with type II, careful follow-up may be needed over 5 years for late recurrence.
 However, in those with type IV, no recurrence over 2 years could be regarded as healed because most of their recurrences occur within 2 years.
 These findings suggest that the growth rate of esophageal carcinoma should reflect DNA aneuploidy, and the DNA analysis of esophageal carcinoma should be a valuable parameter for postoperative follow-up planning.
",3
559,"Serial immunocytologic analysis of blood for tumor cells in two patients with neuroblastoma.
 Tumor surveillance tests are used to determine whether malignant cells are responsive or resistant to therapeutic regimens.
 For patients with neuroblastoma, conventional methods of surveillance are not sensitive enough.
 Because tumor cells are shed into the circulation, immunocytologic analysis of blood may function as a sensitive monitoring system.
 In this study, five blood samples were obtained from two patients with disseminated neuroblastoma at diagnosis and during therapy.
 These samples were analyzed with monoclonal antibodies and immunoperoxidase staining to determine whether circulating neuroblasts were present.
 In both patients, the presence or absence of circulating neuroblasts yielded information that was more sensitive than that from conventional tests.
 The authors conclude that immunocytologic analysis of blood should be included with conventional monitoring methods for surveillance of patients with disseminated neuroblastoma.
",3
560,"A recurrent pelvic desmoid tumor successfully treated with tamoxifen.
 A case of recurrent retroperitoneal desmoid tumor successfully treated with tamoxifen (Nolvadex tablets, ICI Pharma, Division of ICI Americas, Wilmington, DE) is reported.
 The patient presented late in her second pregnancy with a large retroperitoneal pelvic desmoid tumor that was treated with surgical excision and megestrol acetate.
 When the tumor recurred 12 months later, it was again treated with surgery, this time followed by radiation therapy.
 The desmoid tumor quickly recurred.
 The patient was then treated with tamoxifen, resulting in a complete tumor regression that has remained stable for 27 months.
 Tamoxifen should be considered as first-line therapy in recurrent desmoid tumors.
",3
561,"Rural-urban differences in stage at diagnosis. Possible relationship to cancer screening.
 Stage at diagnosis was examined for various malignancies identifiable through screening to determine whether rural-urban differences exist in Georgia.
 Data were obtained from a population-based cancer registry which registers all incident cancers among residents of metropolitan Atlanta and ten neighboring rural counties.
 Black and white patients with a first primary invasive malignancy newly diagnosed between 1978 and 1985 were included in this study.
 Residents of the rural area were twice as likely to have unstaged cancers (18.3%) as were urban residents (9.6%).
 Among patients with known stage at diagnosis, rural patients tended to have more advanced disease than urban patients.
 The relative excess of nonlocalized malignancies in rural Georgia was 21% for whites and 37% for blacks.
 The rural excess of nonlocalized prostate cancer among blacks was especially pronounced.
 Differences in access to or utilization of early detection methods may contribute to the rural-urban differential in the extent of disease at diagnosis.
",3
562,"Detection by CT during arterial portography of colorectal cancer metastases to liver.
 A prospective evaluation of the accuracy of real-time ultrasonography (US), computed tomography (CT), infusion hepatic angiography (IHA), and computed tomography during arterial portography (CT-AP) was performed on 65 resected liver metastases of colorectal cancers.
 The total detection rate was 58.5 percent for US, 56.3 percent for CT, 55.4 percent for IHA, and 86.2 percent for CT-AP.
 The sensitivity of 29 lesions with diameters of smaller than 1 cm was 65.5 percent for CT-AP, CT found only two, and both US and IHA localized no more than three.
 The smallest lesions detectable by CT-AP were as small as 0.4 cm in diameter.
 CT-AP proved most useful in detecting the liver metastases, and the use of this technique is recommended for preoperative planning of hepatectomy on patients with liver metastases.
",3
563,"Intraepithelial bodies in colorectal adenomas: Leuchtenberger bodies revisited.
 The presence of intraepithelial inclusion bodies (Leuchtenberger bodies) was recorded in rectal or colonic specimens from 130 patients.
 Large to moderate number of intraepithelial bodies were recorded in 81.8 percent of 55 colorectal adenomas from patients with familial adenomatous polyposis (FAP).
 Conversely, none of the 55 non-FAP adenomas or of the 20 specimens with ulcerative colitis (10 with dysplasia) had similar amounts of intraepithelial granules.
 Feulgen studies demonstrated that the granules contain DNA and are probably nuclear fragments of destroyed lymphocytes.
 Although the pathogenesis of this phenomenon remains obscure, it appears that the presence of large to moderate number of intraepithelial bodies in colorectal adenomas should strongly raise the suspicion of FAP.
",3
564,"Subsite distribution and incidence of colorectal cancer in New Zealand, 1974-1983.
 The purpose of this study was to examine changes in subsite distribution and incidence of colorectal cancer within different age groups.
 Registration of colorectal cancer by the National Cancer Registry of New Zealand approached 100 percent by 1974.
 The present study was based on 15,395 individuals aged 25 years and over and registered for colorectal cancer between 1974 and 1983.
 Subsite distribution (right colon, left colon, rectum) for different age groups (25-49, 50-69, 70+ years) was significantly skewed, with an excess of right colonic cancer in individuals aged 25-49 years and 70+ years.
 This right colonic excess was accompanied by a relative reduction in left colonic cancer.
 Age adjusted incidence rates for the periods 1974-78 and 1979-83 were compared and stratified by age group and subsite.
 Incidence rates increased in all subsites in individuals aged 50+ years.
 This was particularly evident for right sided cancer in the elderly of both sexes.
 There was a marked reduction in the incidence of left colonic cancer and rectal cancer in individuals under 50 years.
 In contrast, the incidence of right colonic cancer remained relatively stable in young individuals.
 Time trend studies indicate that the skewed subsite distribution of large bowel cancer in different age groups may increase with time and is probably due to varying etiological factors acting on different cohorts.
",3
565,"Colorectal cancer: differences between community and geographically distant patients seen at an urban medical center.
 Many studies in clinical oncology rely on hospital-derived patients.
 Hospitals vary in the proportions of patients from the local catchment area vs.
 those from more distant places, of whom a larger proportion are presumably referrals.
 To study the differences between these two types of patients, we analyzed 1,245 colorectal cancer patients seen at a large urban medical center over a seven-year period.
 Three hundred ninety-eight patients were from the local community (32 percent), 489 were from the extended community (39.3 percent), and 358 from more distant communities (28.8 percent).
 The patients from the local community tended to be older and from minority ethnic groups.
 In addition, the local community patients were more likely to have advanced disease at the time of presentation.
 The grade of the tumor and its site distribution within the large bowel were similar for the three groups.
 After adjusting for age, sex, race, and stage of disease, the survival was somewhat better for the distant community patients as compared with the local and extended communities (P less than 0.02).
 Overall, in our patient population, the distant patients tended to have more favorable socioeconomic factors and less advanced disease, and these differences may account, in large part, for a better prognosis for these patients.
 Particularly in large cooperative trials, studies may need to take into account the respective proportions of local community and geographically distant patients in analyzing and generalizing treatment outcomes.
",3
566,"Intra-abdominal desmoid tumors in familial polyposis coli: a case report of tumor regression by prednisolone therapy.
 A case of intra-abdominal desmoid tumors in familial polyposis coli (FPC), which regressed and disappeared by prednisolone treatment, is reported.
 A 37-year-old Japanese man with abdominal lumps was admitted to our hospital.
 He had had proctocolectomy two years before because of FPC with rectal cancer.
 At laparotomy, tumors were present in the abdominal wall, mesentery, and retroperitoneum.
 Only a small part of the tumors was resected and diagnosed microscopically to be desmoid tumors.
 With prednisolone administration (20 to 5 mg/day) subjective symptoms were ameliorated and desmoid tumors slowly regressed.
 Bilateral hydronephrosis continued and resulted in ""retroperitoneal fibrosis."" To our knowledge, this case is the first well-documented case of retroperitoneal fibrosis in a patient with FPC.
 The characteristics of the desmoid tumor in familial polyposis coli or in Gardner's syndrome and the methods for its management are discussed.
",3
567,"Polycystic ovary syndrome and bulimia.
 One hundred fifty-three patients classified as suffering from polycystic ovarian syndrome (PCOS) and 109 patients who were suffering from a clear organic disorder or endocrinopathy received the bulimia investigation test (Edinburgh) (BITE) questionnaire for abnormal eating behaviors.
 Patients with PCOS showed a significant increase in their mean BITE score for approximately a third had abnormal eating patterns, and 6% have scores suggestive of clinical bulimia compared with only 1% of women in the group with organic endocrinopathies.
 The work suggests that women with PCOS should be screened for abnormal eating behaviors and raises the possibility that treatment by psychological means should be considered when abnormal eating behaviors are present.
",3
568,"Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors.
 Endoscopic biopsy specimens and surgically resected specimens in a collective series of 78 Japanese patients with ampullary tumor were retrospectively reviewed to investigate the clinical implications of endoscopic biopsy.
 Endoscopic biopsy specimens were classified into five groups based on the degree of epithelial atypia: group 1 (no atypia), group 2 (mild atypia), group 3 (moderate atypia or adenoma), group 4 (severe atypia or carcinoma in situ), and group 5 (invasive carcinoma).
 Final diagnosis of the 78 resected ampullary tumors was adenoma in five cases, carcinoma in 27 cases, and both adenoma and carcinoma in 46 cases.
 Biopsy accuracy of carcinoma (group 4 or 5) was 70% (51 of 73) overall in 73 carcinoma cases.
 Biopsy accuracy was 50% (7 of 14) in the intramural protruding type, 64% (21 of 33) in the exposed protruding type, and 88% (23 of 26) in the ulcerating type.
 The diagnostic accuracy of adenoma (group 3) was 80% (4 of 5) in five cases of ampullary adenoma.
 In 18 (25%) of the 73 carcinoma cases, biopsy diagnosis was adenoma (group 3), whereas carcinoma was found in the deeper layers of surgically resected specimens.
 Biopsy diagnosis of adenoma does not rule out the possibility of deeper carcinoma in ampullary tumors.
",3
569,"Evaluation of endosonography in TN staging of oesophageal cancer.
 Strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis.
 Resection, the only curative treatment, is confined to early tumour stages.
 Tumours with local infiltration are usually unresectable and require palliative treatment.
 Computed tomography has been widely used for preoperative staging but often fails to define this correctly.
 Endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours.
 In a comparative prospective study, 52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement.
 Thirty seven of these patients underwent operation, resection, or dissection and entered the study.
 The intraoperative findings or the histopathological assessment, or both, were taken as a reference.
 For all TN stages of oesophageal tumours, correct preoperative staging was accomplished by endoscopic ultrasound in 89% for T stage and 69% for N stage compared with 51% and 51% respectively by computed tomography (highly significant using Fisher's exact test).
 This study shows that endoscopic ultrasound is useful in preoperative TN staging of tumours of the oesophagus.
",3
570,"Chondrosarcoma of the soft tissues. Two different sub-groups.
 Chondrosarcomas arising from soft tissues are rare.
 Two different varieties are described, myxoid and mesenchymal.
 We have collected nine cases of the tumour, five myxoid and four mesenchymal, from a review of 513 cases of chondrosarcoma seen between 1904 and 1988.
 We report the principal clinical, radiographical and histological differences between the two varieties and discuss their surgical treatment and prognosis.
",3
571,"Determination of plasma calcitonin gene-related peptide concentrations by a new immunochemiluminometric assay in normal persons and patients with medullary thyroid carcinoma and other neuroendocrine tumors.
 There is doubt about concentrations of circulating calcitonin gene-related peptide (CGRP) and the value of plasma CGRP measurements in the detection and follow-up of medullary thyroid carcinoma (MTC).
 Thus, we developed an immunochemiluminometric sandwich assay for CGRP using antibodies purified from a polyclonal antiserum against human CGRP.
 The assay was sensitive (limit of detection, 0.4 pmol/L; multiply by 3.7892 to derive nanograms per L) and highly specific [no cross-reaction with human calcitonin (CT)].
 Normal plasma CGRP values ranged from less than 0.4 to 4.5 pmol/L (median, 0.8; n = 31), with 61% having detectable levels.
 Values in samples from patients with MTC were elevated: unoperated patients (n = 10), 4.7-137 pmol/L (median, 7.1); and operated patients with gross persistent or recurrent tumor (n = 14), 4.7-171 pmol/L (median, 23.2).
 In contrast, CGRP values were normal in 78% of nine postoperative patients with elevated CT, but no detectable tumor (range, less than 0.4 to 6.3 pmol/L; median, 1.6).
 CGRP levels increased after pentagastrin injection in MTC patients, but less than did CT values.
 Cultured MTC cells in vitro secreted large amounts of CGRP, and rat nerve root ganglia, human osteoblasts, and microvessel endothelial cells secreted lesser amounts.
 We conclude that CGRP circulates in normal plasma, but at very low levels.
 Plasma CGRP concentrations are frequently high in patients with MTC, but primarily in those with gross tumor or metastases.
 Plasma CT assay is the preferable test for MTC, but CGRP assay deserves prospective study for a possible role in predicting gross metastasis.
",3
572,"Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma.
 The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months.
 Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases.
 The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi).
 The absorbed cumulative dose in tumors ranged from 12-155 Gy.
 A beneficial effect of the treatment was observed in 9 patients (60%).
 No complete remission of the disease was observed.
 Seven patients died during the study, among whom 4 never responded to the treatment.
 Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months.
 Among these patients, 4 relapsed, and 3 died within 3 months.
 Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months.
 All patients with a hormonal response had objective improvement in clinical status and blood pressure.
 There was no clear-cut relationship between the cumulative dose and the responses.
 The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued.
 This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.
",3
573,"Quantitation of G0 and G1 phase cells in primary carcinomas. Antibody to M1 subunit of ribonucleotide reductase shows G1 phase restriction point block.
 Human cancers have an apparent low growth fraction, the bulk of cells presumed to being out of cycle in a G0 quiescent state due to the inability in the past to distinguish G0 from G1 cells.
 The allosteric M1 subunit of ribonucleotide reductase (M1-RR) is constitutively expressed by cycling cells (i.e., G1, S, G2-M).
 It is acquired during transition from G0 to G1, lost during exit to G0 and thus distinguishes G0 from G1 cells.
 To estimate the proportion of G0 and G1 cells in primary human breast (n = 5) and colorectal (n = 12) adenocarcinomas, we used both analytical DNA flow cytometry (ADFC) and immunoperoxidase staining of sections with the monoclonal antibody to M1-RR (MAb M1-RR).
 ADFC of fresh tumors revealed a low percentage of cells in the S phase (4.0 +/- 3.4%) but immunoperoxidase staining for M1-RR revealed an unexpectedly high proportion of positive cells (52.4 +/- 12.7%) in the G1, S, G2-M phases indicating a high G1 content of primary human tumors.
 Thus, human cancers are blocked in transition in G1 and are not predominantly in a G0 or quiescent differentiated state.
 This block was interpreted to mean that human cancers are responding to putative regulatory events at a restriction point in the G1 phase, such as relative growth factor deficiency, density inhibition, antiproliferative cytokines, or gene products.
 Using flow cytometry for both DNA and M1-RR content we found that human colon cancer cell lines arrest in the G1 but not G0 phase upon serum deprivation or density inhibition.
 Similarly, human breast cancer cell lines are arrested in G1 but not G0 phase by medroxyprogesterone acetate (MPA) or tamoxifen exposure.
 These findings match our in situ observations, and support the concept of a restriction point block in primary human tumors.
",3
574,"Insulin-like growth factor II-mediated proliferation of human neuroblastoma.
 Neuroblastoma is an embryonal tumor that typically arises in cells of the developing adrenal medulla.
 IGF-II mRNA is expressed at high levels in the adrenal cortex before birth but it is not detectable until after birth in the adrenal medulla.
 Neuroblastoma cell lines corresponding to early adrenal medullary precursors did not express IGF-II, although all three cell lines we tested were growth stimulated by IGF-II.
 Cell lines corresponding to more mature adrenal medullary cells expressed IGF-II, and one, SK-N-AS, grows by an IGF-II autocrine mechanism (J.
 Clin.
 Invest.
 84:829-839) El-Badry, Romanus, Helman, Cooper, Rechler, and Israel.
 1989.
 An examination of human neuroblastoma tumor tissues for IGF-II gene expression using in situ hybridization histochemistry revealed that IGF-II is expressed by tumor cells in only 5 of 21 neuroblastomas, but is detectable in cells of nonmalignant tissues including adrenal cortical cells, stromal fibroblasts, and eosinophils in all 21 tumors.
 These findings indicate that IGF-II may function as an autocrine growth factor for some neuroblastomas and as a paracrine growth factor for others.
 They suggest that the growth regulatory pathways utilized by neuroblastoma mimic those used in the precursor cell type from which individual tumors arise.
",3
575,"Patterns of epidermal growth factor receptors in basal and squamous cell carcinoma.
 The presence of immunoreactive epidermal growth factor receptors in human skin tumors was investigated using the indirect immunoperoxidase technique.
 Sixteen basal cell carcinomas and 11 squamous cell carcinomas were evaluated.
 All of the specimens studied were receptor positive.
 In 70% of the specimens there was prominent staining of the cell membranes.
 In 54% of the nodular basal cell carcinoma specimens there was increased staining at the periphery of the tumor cell masses.
",3
576,"Basal cell carcinoma recurring after radiotherapy: a unique, difficult treatment subclass of recurrent basal cell carcinoma.
 Twenty-seven basal cell carcinomas (BCCs) recurring following radiation therapy alone or in addition to other treatment modalities were treated with Mohs micrographic surgery (MMS) from 1983 to 1989.
 Mean tumor size was 2.1 cm.
 Of the tumors, 70.4% arose in the mid-face region, 55.6% had undergone multiple previous treatment modalities.
 The present recurrence rate is 7.4% (mean follow-up: 25 months).
 Basal cell carcinoma recurring following radiotherapy deserves special subclassification among recurrent BCC.
 It is very difficult to eradicate, with high recurrence rates following standard surgical excision or further radiotherapy.
 Tumors are usually large, aggressive, and invasive.
 Most arise in the cosmetically crucial mid-face region, where extension into subcutaneous tissue planes is common.
 Mohs surgery, with its inherent abilities to examine all margins, map tumor extension, and conserve tissue, is uniquely suited to treatment of these difficult tumors.
",3
577,"The medical necessity of evaluation and treatment of port-wine stains.
 New lasers and improved laser delivery systems have allowed for the safe and effective treatment of port-wine stains in patients of all ages.
 The satisfactory results obtained by laser treatment have increased the number of patients seeking consultation regarding their birthmarks.
 It is imperative that physicians recognize the various medical syndromes and problems associated with port-wine stains.
 A review of 415 patients with facial port-wine stains has revealed hypertrophy and/or nodularity in 65% of patients by the fifth decade of life, which increases significantly the morbidity of these lesions.
 It is believed that laser treatment will minimize the medical and psychologic complications that result from the natural evolution of port-wine stains.
",3
578,"Retroviral transduction of protein kinase C-gamma into cytotoxic T lymphocyte clones leads to immortalization with retention of specific function.
 The molecular pathways that are responsible for delivering the proliferative signals from the cell surface to the nucleus in T lymphocytes are still unresolved, but recent data implicates protein kinase C (PKC) involvement in the TCR signaling pathway.
 To further address the role of PKC in T cell activation, the effects of high level expression of the PKC-gamma isoenzyme in murine CTL clones were examined.
 Unlike the parental cells that required periodic Ag stimulation for cell activation and growth, cells expressing a retrovirally transduced PKC-gamma gene propagated in culture independent of the need for Ag stimulation, although maintaining identical functional specificity to the parental CTL.
 Constitutive PKC-gamma expression may therefore mimic physiologic PKC activation, thereby abrogating the requirement for TCR-Ag interaction in T cell activation.
",3
579,"Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor.
 Recently purified and molecularly cloned monocyte chemotactic and activating factor (MCAF) may play a major role in recruiting and activating monocytes in the inflammatory process.
 We examined the effects of a potent anti-inflammatory agent, dexamethasone (DXS), on the production of this factor.
 Over a wide range of concentrations (10(-5) to 10(-8) M), DXS inhibited the production of MCAF at the mRNA and protein level in a human fibrosarcoma cell line, which was stimulated with either IL-1 or TNF-alpha.
 We examined the turn-over of synthesized MCAF mRNA that showed DXS decreased the stability of MCAF mRNA.
 Furthermore, the addition of actinomycin D and cycloheximide abolished this effect of DXS, indicating that de novo mRNA and protein synthesis were required for this process.
 In addition, a nuclear run-off analysis revealed that DXS also inhibited the transcription of IL-1- or TNF-activated MCAF genes.
 Therefore, both the destabilization of MCAF mRNA and the inhibition of transcription of the gene contribute to the decrease in the MCAF mRNA steady state level by DXS.
",3
580,"DNA sequences 3' of the Ig H chain cluster rearrange in mouse B cell lines.
 A mouse myeloma cell line MPC11 (IgG2b, kappa) and variants derived from it have been used to study DNA rearrangements that occur at the Ig H chain locus.
 One variant, F5.5, has acquired both VH gene and C epsilon gene rearrangements.
 Through genomic Southern blot analysis initially directed to mapping the C epsilon gene rearrangement, we observed that the VH region rearrangement was linked, through an inversion event, to sequences that originate 3' of the CH cluster, i.e., 3' of the C alpha gene.
 Subsequent studies have shown that DNA rearrangements within the region 3' of the C alpha gene are detected in several other mouse myeloma and hybridoma cell lines and are not associated with the expression of specific isotypes.
",3
581,"Examination of HTLV-I integration in the skin lesions of various types of adult T-cell leukemia (ATL): independence of cutaneous-type ATL confirmed by Southern blot analysis.
 The various clinical features of adult T-cell leukemia/lymphoma (ATL) are frequently accompanied by skin eruptions.
 Recently, a cutaneous type of ATL has been proposed by clinical studies.
 We analyzed the viral integration of human T-cell leukemia virus-I (HTLV-I) and monoclonal rearrangement of T-cell receptor (TCR) gene in blood lymphocytes and the cutaneous infiltrated cells of nine ATL patients with various clinical features and skin eruptions.
 We classified them by the results of Southern blot analysis and propose a cutaneous-type ATL accordingly.
 In two of them, we could detect the monoclonal integration of HTLV-I and T-cell monoclonality only in the skin but not in the peripheral lymphocytes.
 We also demonstrated the time course study in one patient.
 Clinicians should be aware of the HTLV-I positive cutaneous T cell lymphoma that can be named cutaneous-type ATL.
 Examination of viral integration and T-cell monoclonality in skin lesions is required to make an exact diagnosis of cutaneous ATL.
",3
582,"Immunolocation of TNF-alpha/cachectin in human melanoma cells: studies on co-cultivated malignant melanoma.
 We have investigated the ability of metastatic cells to produce the macrophage cytokine, TNF-alpha/cachectin, as these cells have macrophage-like properties such as infiltration and migration.
 We looked for TNF-alpha/cachectin in three tumor cell lines derived from human malignant melanomas and six co-cultivated malignant melanomas derived, in vitro, from these three cell lines plus angioma fibroblasts.
 Immunohistochemistry with an anti-TNF-alpha/cachectin monoclonal antibody showed that TNF-alpha/cachectin was produced by two of the three parent melanoma cell lines.
 All the tumor cells in both the co-cultivated malignant melanomas and their in vitro tumorous nodules produced TNF-alpha/cachectin, even those derived from the melanoma cell line, which originally did not.
 The results clearly show that TNF-alpha/cachectin can be produced by non-hematopoietic tumor cells.
 A co-cultivated tumor model prepared from other types of human tumor cell lines promises to provide a useful tool for exploring the relationship between TNF-alpha/cachectin and oncogenesis.
",3
583,"Immunohistochemical alterations in basement membrane components of squamous cell carcinoma.
 To investigate alterations in the basement membrane (BM) in squamous cell carcinoma (SCC), we investigated 20 tumors.
 Four had the cytologic characteristics of Bowen's disease (SCC-BD) and 16 did not have them (SCC-NB).
 Tumors were studied immunohistochemically by double immunofluorescent staining by using mouse monoclonal antibodies to the core protein of heparan sulfate proteoglycan (HSPG) and chondroitin 6-sulfate glycosaminoglycan (Ch6S) as well as rabbit antiserum to laminin (LN) and type IV collagen (C-4).
 In well-differentiated and highly keratinized SCC-NB, LN, C-4, and HSPG could be detected in the tumor nest BM and showed no loss of continuity, but they were largely lost in poorly differentiated and poorly keratinized SCC-NB.
 This suggests that poorly differentiated SCC-NB cause greater enzymatic degradation of BM components than well-differentiated SCC-NB.
 Ch6S was detected in parts of the BM of SCC-BD, but it was absent in all SCC-NB examined.
 It appears that SCC-NB have lost the ability to synthesize Ch6S, and that SCC-BD degrade Ch6S although they continue to produce it.
 Thus, it appears that in SCC the BM is qualitatively different from that of normal epidermis, and that SCC-BD can be distinguished from SCC-NB by the Ch6S content of the BM.
",3
584,"Identification of a melanoma progression antigen as integrin VLA-2.
 The expression of the integrin receptors VLA-1, -2, -3, and -6 was studied in normal cultured melanocytes and in five melanoma cell lines.
 Normal melanocytes synthesized VLA-3, but did not reveal detectable levels of VLA-1, -2, and -6.
 All melanoma cell lines, however, expressed VLA-2, -3, and -6.
 VLA-1 was synthesized by two of five melanoma lines.
 In parallel, we had analyzed the expression of four previously characterized melanoma cell surface antigens.
 One of them (antigen A.1.43), which is associated with tumor progression of human melanoma, revealed a striking similarity to VLA-2.
 In sequential immunoprecipitation experiments, we show that A.1.43 is identical with the integrin VLA-2, a cell surface receptor for collagen, laminin, and fibronectin.
",3
585,"Reproducibility of image interpretation in immunoscintigraphy performed with indium-111- and iodine-131-labeled OC125 F(ab')2 antibody injected into the same patients.
 An important criterion for the clinical use of a new imaging technique is the correct reproducibility of interpretation.
 Forty-six paired immunoscintigraphic examinations were performed on 43 patients with suspected ovarian carcinoma recurrence using F(ab')2 fragments of OC125 antibody labeled first with indium-111 and then with iodine-131.
 Planar scintigraphy (PS) and emission computed tomography (ECT) images were interpreted blindly and separately by three observers, and reproducibility was evaluated by a kappa concordance index.
 Intra- and interobserver reproducibility were generally satisfactory (kappa values of 0.6 and 0.7, respectively).
 Binomial analysis of kappa values for ECT showed the superiority of indium-111 for intraobserver (p = 0.035) and interobserver (p = 0.0039) study.
 However, for PS there was no significant difference in reproducibility with the two radionuclides.
",3
586,"Relationship of uptake of technetium-99m(Sn)-N-pyridoxyl-5-methyltryptophan by hepatocellular carcinoma to prognosis 
 The relationship of technetium-99m(Sn)-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) uptake by hepatic tumors to survival was studied in 162 cases of hepatocellular carcinoma (HCC).
 The median survival of 82 patients in whom hepatic tumors showed increased uptake in delayed 99mTc-PMT imaging was 1013 days, which was significantly longer than the survival time of 398.5 days of 80 patients in whom hepatic tumors did not show increased uptake of radioactivity (p less than 0.002).
 The relationship between the ability of hepatic tumors to take up 99mTc-PMT and survival was also analyzed in patients with HCC showing filling defects in 99mTc-colloid liver images and, in relation to the therapy, serum values of bilirubin and alpha-fetoprotein.
 Results indicated that the degree of 99mTc-PMT uptake by hepatic tumors is closely correlated with the prognosis of patients with HCC.
",3
587,"Comparison of 1073 MBq and 3700 MBq iodine-131 in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid cancer.
 In a randomized prospective study, we compared the efficacy of low dose (1073 MBq) and high dose (3700 MBq) iodine-131 administration in postoperative ablation of residual functioning thyroid tissue in 63 patients with differentiated thyroid cancer.
 We were unable to demonstrate any difference between the low- and the high-dose of radioactive iodine in scintigraphic ablation of remnant tissue.
 In 81% (21/26) of the patients, 1073 MBq ablated after the first dose, 77% (21/26 + 3/5 = 24/31) after the first plus second dose, and 69% (24/31 + 0/4 = 24/35) after the first, second, and third dose.
 Radioiodine (3700 MBq) ablated in 84%, 73%, and 69% of the patients after respectively 1., 1.
 plus 2., and 1.
 plus 2.
 plus 3.
 dose.
 Forty percent of the patients ablated with the low dose and 44% ablated with the high dose had elevated thyroglobulin levels at the time of complete scintigraphic ablation.
 In conclusion, we did not find any difference between 3700 MBq and 1073 MBq iodine-131 as regard to number of doses needed for complete scintigraphic ablation of residual functioning thyroid tissue.
",3
588,"Extracranial metastatic glioblastoma: appearance on thallium-201-chloride/technetium-99m-HMPAO SPECT images.
 Sequential thallium-201-chloride and technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) images were obtained in a patient with extracranial metastatic glioblastoma multiforme.
 Thallium-201 uptake was high (three times the scalp background) in all pathologically confirmed extracranial metastases and moderate (1.6 times scalp background) intracranially, where most biopsy specimens showed gliosis with scattered atypical astrocytes.
 Technetium-99m-HMPAO uptake was decreased intracranially in the right frontal and parietal lobes which had been irradiated.
 It was also decreased in one well-encapsulated scalp lesion and high in another scalp mass with less defined borders.
 Possible mechanisms of tumor uptake of these agents are reviewed.
",3
589,"Technetium-99m-methylene diphosphonate (MDP) uptake in a sympathetic effusion: an index of malignancy and a review of the literature.
 We report a patient with a sympathetic pleural effusion secondary to T-cell lymphoma that accumulated the bone imaging agent, Technetium-99m-methylene diphosphonate (99mTc-MDP).
 This case is significant in that malignant cells were not present on three cytologic examinations of the pleural fluid or multiple pleural biopsies.
 We also present a review of the published literature on pleural effusions that accumulate bone tracers.
 We conclude that pleural effusions that accumulate 99mTc-MDP should be considered malignant or secondary to a malignancy and further work-up is essential even if the cytologic exam of the pleural fluid is unremarkable.
",3
590,"HTLV-I-associated leukemia/lymphoma in south Florida.
 We report here 10 cases of adult T-cell leukemia/lymphoma (ATL) seen in South Florida between February 1988 and July 1989.
 All were seropositive for human T-lymphotropic virus type I (HTLV-I) and seronegative for human immunodeficiency virus type 1 (HIV-1).
 DNA extracted from tumor biopsies/peripheral blood lymphocytes of nine patients was shown by the polymerase chain reaction (PCR) to contain HTLV-I proviral DNA.
 Blot hybridization of DNA extracted from seven patients with an HTLV-I cDNA probe revealed a monoclonal pattern of proviral integration consistent with a diagnosis of ATL.
 Eight of the 10 patients were women.
 Six patients were from Haiti, three from Jamaica, and one from the Bahamas.
 All patients had very aggressive non-Hodgkin's lymphoma.
 Two patients presented with sinus and retro-orbital involvement; another had gastric lymphoma that perforated.
 Nine patients developed hypercalcemia.
 Eight patients died within 1 year of diagnosis.
 Two were lost to follow-up.
 During the course of this study, 66 new cases of non-Hodgkin's lymphoma were diagnosed at this hospital.
 Ten of these cases were ATL.
 The prevalence of HTLV-I-related lymphoma in this sample was 15%.
 Since tissue from all patients was not available for HTLV-I screening, however, it is possible that other cases of ATL went undetected.
 We conclude from this initial survey that a retroviral etiology should be considered in patients from populations known to be at risk for HTLV-I infection who present with non-Hodgkin's lymphoma.
",3
591,"Comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer.
 In ongoing reviews of 339 patients with surgically treated primary squamous cell carcinoma, there were 19 (5.6%) with concurrent gastric cancer and 11 (3.2%) with head and neck cancer.
 The incidences of intra-esophageal multiple occurrence of esophageal cancer are 27.3% and 26.3% in those with associated head and neck cancer and gastric cancer, respectively, and higher than 7.1% in those without such a concurrent cancer.
 There was no difference in the clinicopathological characteristics of those with concurrent head and neck and gastric cancers, except for the higher incidence of metachronous occurrence in the former.
 These findings suggest that, in cases of esophageal cancer associated with concurrent head and neck cancer and gastric cancer, intraesophageal multiplicity of the esophageal carcinoma is frequent and that preoperative serial evaluations is most important to design treatment and estimate the prognosis.
",3
592,"Activation and in vitro expansion of tumor-reactive T lymphocytes from lymph nodes draining human primary breast cancers.
 The feasibility of in vitro activation of lymphocytes from the draining lymph nodes (DLN) of breast cancer patients was examined.
 Lymphocytes isolated from 48 DLN from 12 patients were examined for their proliferative responses to rIL-2, autologous tumor cells, or rIL-2 plus tumor cells.
 Three general patterns of cellular responses were observed.
 Cells from some DLN (17%) were unresponsive to any stimuli.
 Lymphocytes from 52% of the DLN responded moderately to rIL-2 alone.
 The combination of rIL-2 and tumor antigen had a synergistic effect on the proliferation of cells from 31% of the DLN assayed.
 Phorbol dibutyrate and ionomycin plus rIL-2 stimulated expansion of DLN lymphocytes by up to 850-fold after 35 days.
 These expanded cell populations, as well as those stimulated with antigen plus rIL-2, were predominantly CD3+ and CD16- cells, varying in proportions of CD4+ and CD8+ subsets.
 Both populations were cytotoxic against autologous tumor, MCF-7, and K562 target cells.
",3
593,"Neuroendocrine carcinoid tumours of the breast: a variant of carcinoma with neuroendocrine differentiation.
 Carcinoid tumours most frequently develop in the gastrointestinal tract but have been described in many organs of the body.
 In 1977 the first cases were reported in the mamma, followed by descriptions of argyrophilic carcinoid-like, neuroendocrine mammary tumours by many investigators who performed immunohistochemical and ultrastructural examinations.
 The existence of true carcinoids in the mamma is still a controversial issue.
 Eight mammary neoplasms with monomorphous cytonuclear features, five of the small cell carcinoid-like variety and three composed of larger cells, were examined by immunohistochemical and ultrastructural examination.
 We believe this kind of tumours are ductal or lobular carcinomas with focal or more extensive neuroendocrine features and are the result of a dual differentiation of neoplastic precursor stem cells along epithelial and endocrine lines.
 Consequently, we consider that treatment of such cases should not be different from that of the ordinary type of mammary carcinomas.
",3
594,"Characterization and histopathological correlation of cytosol proteins of benign and malignant breast tumors.
 Significant differences in cytosol protein level exist between normal/benign and cancerous breast tissues.
 There is a positive correlation between the cytosol protein level and histological grade of carcinoma.
 Well-differentiated carcinoma have a lower value of cytosol protein than poorly differentiated carcinoma.
 In slab gel electrophoregrams, the total numbers of bands are almost identical in normal, benign, and malignant conditions.
 In addition, 37 Kd protein band is consistently present in malignant cases and always absent in normal or benign cases.
 More extensive biophysical examination of this band may provide further insight into the protein alterations in cancer cells at the molecular level.
",3
595,"Lactation following conservation surgery and radiotherapy for breast cancer.
 A 38-year-old woman with early stage invasive breast cancer was treated with wide excision of the tumor, axillary lymph node dissection, and breast irradiation.
 Three years later, she gave birth to a normal baby.
 She attempted breast feeding and had full lactation from the untreated breast.
 The irradiated breast underwent only minor changes during pregnancy and postpartum but produced small amounts of colostrum and milk for 2 weeks postpartum.
 There are only a few reports of lactation after breast irradiation.
 These cases are reviewed, and possible factors affecting breast function after radiotherapy are discussed.
 Because of scant information available regarding its safety for the infant, nursing from the irradiated breast is not recommended.
",3
596,"Subrenal capsule assay as a chemosensitivity test for primary esophageal squamous cell carcinoma.
 The efficiency of the subrenal capsule assay (SRCA) was studied with fresh tissue of esophageal squamous cell carcinoma.
 The day-to-day changes in 10 carcinoma cases were evaluated for 9 days.
 The cancer cells continued to proliferate from the 3rd to the 7th day after the implantation and then decreased.
 The host reaction was recognized histologically from the 3rd or 4th day to the 9th day.
 However, the immune reaction did not significantly influence the evaluation of SRCA until the 7th day.
 The immunohistochemical staining with anti-bromodeoxyuridine monoclonal antibody revealed the existence of cancer cells at the DNA synthesizing stage (S stage) in the graft until the 7th day.
 In chemosensitivity test by SRCA, 21 patients were studied, and all were evaluable.
 5-FU administration produced a response in 8/21 cases (38.1%), VDS in 8/21 (38.1%), and CDDP in 3/21 (14.3%).
 Used in combination, CDDP + VDS was effective in 7/18 cases (38.9%) and CDDP + BLM in 6/18 cases (33.3%).
",3
597,"Squamous carcinoma of the distal esophagus: a survival study.
 A survival study for squamous carcinomas of the distal esophagus treated by the Southern California Permanente Medical Group in the interval of 1954 to 1988 was undertaken.
 We found radiation therapy and surgery equally efficacious in terms of cure for patients without distant disease and performance status sufficient to tolerate treatment.
 We did not find survival benefit for patients treated with palliative surgery, and plan less invasive endoscopic means along with chemotherapy and radiation for palliation, reserving surgery for special circumstances.
",3
598,"Lymphoscintigraphy with 123I-labelled epidermal growth factor 
 We have used 123I-labelled epidermal growth factor (EGF) scans to study 14 patients with advanced cervical cancer.
 Abnormal lymph node imaging was seen most clearly 6-8 h after the injection and revealed abnormal uptake by pelvic lymph nodes in 11 patients.
 4 of these 11 had abnormal computerised tomographic and ultrasound scans; in the other 7 conventional radiology did not confirm the presence of disease.
",3
599,"Imaging modalities in recurrent head and neck tumors.
 Patients with recurrent neoplasms of the head and neck present perplexing management problems, and accurate preoperative assessment of their disease is crucial.
 Thirty-eight patients with suspected recurrent neoplasms comprise this study: 30 had computed tomography scans, 4 had magnetic resonance images, and 4 patients underwent both computed tomography and magnetic resonance imaging to assess the anatomical extent of pathology in 34 malignant and 4 benign tumors.
 Contrast enhancement was essential for detecting disease on computed tomography scan.
 Differentiation of recurrent tumor was more difficult when the patient had undergone radiation.
 Magnetic resonance imaging demonstrated superior visibility in recurrent parotid and paranasal sinus neoplasm, but was less helpful in laryngeal and pharyngeal recurrences.
 Computed tomography demonstration of a mass with infiltration of normal fat or tissue planes or lymphadenopathy correlated highly with recurrent disease.
 Imaging techniques and fine points for determining recurrent neoplasms are presented.
",3
600,"The use of bromodeoxyuridine cytokinetic studies as a prognostic indicator of cancer of the head and neck.
 Traditional measures of head and neck tumors often fail to predict patient outcome or clinical course, particularly in nonadvanced disease.
 This problem of unpredictable tumor behavior has been one focus of cell proliferation studies.
 Such studies, however, have been limited by difficult methodology.
 A newer method of quantifying tumor cell proliferation using bromodeoxyuridine is applicable for head and neck squamous cell carcinomas, as shown in the present study.
 The relative ease with which cell proliferation can be evaluated using this technique will allow large numbers of head and neck tumors to be studied, enabling correlations with tumor behavior to be made.
",3
601,"Introduction to limb-salvage surgery for sarcomas.
 This article provides a history of limb-salvage surgery and definitions of terms used to describe aspects of the procedure.
 Staging is also discussed.
",3
602,"Limb salvage in pediatric surgery. The use of the expandable prosthesis.
 Limb sparing in growing children has proved to be very effective from an oncologic perspective, with good, long-term acceptance by the patients.
 As in the adult, when performed by experienced surgeons, limb sparing neither compromises the survival rate nor significantly increases the local recurrence rate, compared with cross-bone amputation.
 Discussions include patient evaluation, surgical options, materials and methods, and results.
",3
603,"Resection and reconstruction for bone tumors in the proximal tibia.
 The proximal tibia is a common site for both benign and malignant tumors.
 This article reviews pertinent anatomy, clinical presentation, and staging methods for tumors of this area.
 Discussion is given to various methods of resection and reconstruction with useful guidelines for procedure selection.
 The use of allografts for reconstruction is discussed in depth.
",3
604,"Endoprosthetic reconstruction after bone tumor resections of the proximal tibia.
 The advent of successful adjuvant chemotherapy and radiation therapy protocols for primary malignant tumors and the development of custom-designed metallic endoprostheses has now made possible a successful limb salvage procedure for malignancies of the proximal tibia.
 Use of the transposed medial gastrocnemius flap, as proposed by Dr.
 Jean Duboussett of Paris, has been critical to the soft-tissue reconstruction that routinely permits an excellent active and passive range of motion for these patients.
 This article describes the operative techniques and technical considerations necessary for a successful proximal tibial endoprosthesis reconstruction.
",3
605,"Resection and reconstruction for soft-tissue sarcomas of the extremity.
 Soft-tissue sarcomas are uncommon malignant tumors, and when a diagnosis is made early, the patient has up to an 80% chance of surviving.
 In treating soft-tissue sarcomas, the goal of the surgeon is the prolongation of patient survival, the total eradication of local disease, and the minimization of functional deficits.
 In addition to treatment, this article discusses evaluation, histology, and staging.
",3
606,"Allograft reconstructions of the shoulder after bone tumor resections.
 Large skeletal defects resulting from tumor resections about the shoulder create reconstructive challenges for the orthopedic surgeon.
 Bone allografts offer several advantages compared with other reconstructive techniques, and functional outcomes are generally satisfactory.
 They may be used either as osteoarticular grafts, intercalated segments to create an arthrodesis, or in combination with standard proximal humerus metallic implants.
 Patient expectations and specific oncologic factors must be considered when selecting the optimal method of reconstruction.
",3
607,"Resections and reconstructions for tumors of the distal radius.
 The primary objective in surgical management of the patient with a distal radius tumor is control of the disease.
 Accurate staging and diagnostic methods applied preoperatively will predict not only the amount of resection necessary to obtain adequate tumor margins, but also the amount of remaining bone and soft tissues to assist reconstruction.
 With this information, a method of reconstruction can be chosen that provides the patient optimal long-term function and stability with predictable results and the fewest potential complications.
",3
608,"Tumors of the shoulder girdle. Technique of resection and description of a surgical classification.
 Limb-sparing surgery is safe and reliable for most bone and soft-tissue tumors of the shoulder girdle.
 Eighty to ninety percent of patients with high-grade sarcomas of the shoulder can be safely treated by the various surgical techniques described.
 Attention must be paid to appropriate patient selection, preoperative staging, and planning.
 In addition, careful skeletal and muscular reconstruction of the surgical defect is necessary for a successful outcome.
 A new, universal, classification schemata (types I-VI) of shoulder girdle resections has been developed.
 This classification system is based on the bones resected, the status of the abductor mechanism, and the relationship to the glenohumeral joint.
 This system permits easy description and comparison of the various limb-sparing procedures performed.
",3
609,"cDNA cloning and sequencing of human fibrillarin, a conserved nucleolar protein recognized by autoimmune antisera.
 We have isolated a 1.1-kilobase cDNA clone that encodes human fibrillarin by screening a hepatoma library in parallel with DNA probes derived from the fibrillarin genes of Saccharomyces cerevisiae (NOP1) and Xenopus laevis.
 RNA blot analysis indicates that the corresponding mRNA is approximately 1300 nucleotides in length.
 Human fibrillarin expressed in vitro migrates on SDS gels as a 36-kDa protein that is specifically immunoprecipitated by antisera from humans with scleroderma autoimmune disease.
 Human fibrillarin contains an amino-terminal repetitive domain approximately 75-80 amino acids in length that is rich in glycine and arginine residues and is similar to amino-terminal domains in the yeast and Xenopus fibrillarins.
 The occurrence of a putative RNA-binding domain and an RNP consensus sequence within the protein is consistent with the association of fibrillarin with small nucleolar RNAs.
 Protein sequence alignments show that 67% of amino acids from human fibrillarin are identical to those in yeast fibrillarin and that 81% are identical to those in Xenopus fibrillarin.
 This identity suggests the evolutionary conservation of an important function early in the pathway for ribosome biosynthesis.
",3
610,"Free radical-derived quinone methide mediates skin tumor promotion by butylated hydroxytoluene hydroperoxide: expanded role for electrophiles in multistage carcinogenesis.
 Free radical derivatives of peroxides, hydroperoxides, and anthrones are thought to mediate tumor promotion by these compounds.
 Further, the promoting activity of phorbol esters is attributed, in part, to their ability to stimulate the cellular generation of oxygen radicals.
 A hydroperoxide metabolite of butylated hydroxytoluene, 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHTOOH), has previously been shown to be a tumor promoter in mouse skin.
 BHTOOH is extensively metabolized by murine keratinocytes to several radical species.
 The primary radical generated from BHTOOH is a phenoxyl radical that can disproportionate to form butylated hydroxytoluene quinone methide, a reactive electrophile.
 Since electrophilic species have not been previously postulated to mediate tumor promotion, the present study was undertaken to examine the role of this electrophile in the promoting activity of BHTOOH.
 The biological activities of two chemical analogs of BHTOOH, 4-trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH, were compared with that of the parent compound.
 4-Trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH have a reduced ability or inability, respectively, to form a quinone methide; however, like the parent compound, they both generate a phenoxyl radical when incubated with keratinocyte cytosol.
 The potency of BHTOOH, 4-trideuteromethyl-BHTOOH, and 4-tert-butyl-BHTOOH as inducers of ornithine decarboxylase, a marker of tumor promotion, was commensurate with their capacity for generating butylated hydroxytoluene quinone methide.
 These initial results were confirmed in a two-stage tumor promotion protocol in female SENCAR mice.
 Together, these data indicate that a quinone methide is mediating tumor promotion by BHTOOH, providing direct evidence that an electrophilic intermediate can elicit this stage of carcinogenesis.
",3
611,"Survival after groin dissection for malignant melanoma.
 Groin dissection was performed in 158 patients with malignant melanoma (superficial dissection, 76 patients; radical dissection, 82 patients).
 Of 63 patients with palpable nodes, 57 patients (90%) had histologic involvement.
 Of 93 patients with nonpalpable nodes, 31 patients (33%) had histologically positive nodes.
 The 5-year survival rate for patients with histologically negative nodes (n = 69) was 77%; the 5-year survival rate for patients with histologically positive nodes (n = 89) was 43%.
 The respective 5-year disease-free survival rates were 72% and 34%.
 Of 57 patients with palpable, positive inguinal nodes, 21 patients (37%) had involvement of the deep nodes.
 Of 31 patients with nonpalpable, histologic involvement of the inguinal nodes, six patients (19%) had or developed involvement of the deep nodes.
 One of two patients with uncertain clinical status of the nodes preoperatively had positive deep nodes.
 In prophylactic node dissection, frozen section of the inguinal group of the nodes does not provide a reliable method, because of sampling errors, in determining microscopic involvement of the nodes and in deciding whether a superficial or radical groin dissection is to be done.
 For patients with positive nodes the 5-year survival rate was 48% when only the inguinal group was involved and was 28% when both inguinal and deep nodes were involved; the respective 5-year disease-free survival rates were 39% and 20%.
 Survival after therapeutic groin dissection may partly depend on the thoroughness of the procedure.
 Patients who have positive, deep nodes and who are undergoing an incontinuity dissection of the inguinal, iliac, and obturator nodes have an appreciable 5-year survival rate.
",3
612,"The role of resection in the management of melanoma metastatic to the adrenal gland.
 Melanoma metastatic to the adrenal gland diagnosed before death was exceedingly rare before the development of computed tomographic (CT) scanning.
 The records of 28 patients with melanoma metastatic to the adrenal gland seen since 1975 were reviewed.
 Eighteen patients were men and 10 were women.
 Twenty-three patients had unilateral disease.
 Four patients were diagnosed only at autopsy, leaving 24 for analysis of treatment and survival.
 Twenty-one patients had received specific active immunotherapy, four had received chemotherapy (dacarbazine, lomustin, bleomycin, and vincristine), and three had received both before the diagnosis of their adrenal disease.
 Adrenal metastases were diagnosed by CT scanning in 14 patients with symptoms, 10 (91%) of whom had pain.
 Ten patients were diagnosed by CT before entry into a chemotherapy protocol.
 Of eight patients who underwent resection of all known disease, five underwent unilateral adrenalectomy, two underwent unilateral adrenalectomy and bowel resection, and one underwent bilateral adrenalectomy.
 Two patients underwent partial resection of large unilateral tumors.
 Fourteen patients with adrenal metastases and disease elsewhere were initiated or continued with chemotherapy or were treated symptomatically.
 Mean survival in the group that underwent resection for cure was 59 months (3 to 112 months), whereas survival in the group with unresectable tumors was 15 months (1.5 to 132 months).
 Four of eight patients who underwent resection for cure lived more than 5 years after detection of adrenal metastasis, whereas in only one of 14 patients with unresectable tumors was the same true.
 Patients with metastatic melanoma localized to one or both adrenal glands may benefit from early detection and surgical intervention.
",3
613,"Evaluation of preoperative computed tomography in gastric malignancy.
 Ninety patients with gastric malignancy underwent computed tomography (CT) before surgery.
 The CT findings regarding neoplastic invasion of adjacent organs and metastasis or enlarged lymph nodes were compared with the findings at laparotomy (85 cases) or autopsy (5 cases), thus permitting evaluation of the diagnostic accuracy of CT and its usefulness for predicting resectability.
 When present, neoplastic invasion of adjacent organs was overestimated or underestimated by CT in 21 cases.
 Invasion of adjacent organs according to CT was false positive in 17 cases and false negative in 11 cases.
 When liver metastasis or enlarged regional or distant lymph nodes were present, CT overestimated or underestimated their extent in 17 cases, and the diagnosis was false positive in one case and false negative in 33 cases.
 The positive and negative predictive values of CT concerning resectability of the tumor were 81% and 64%, respectively.
 Routine preoperative CT in gastric malignancy is concluded to be of limited value and surgical exploration, when feasible, remains the method of choice.
",3
614,"A hepatoblastoma originating in the caudate lobe radically resected with the inferior vena cava.
 Complete resection of a rare hepatoblastoma in the caudate lobe, involving the inferior vena cava (IVC), is reported.
 After systemic chemotherapy, a 5-year-old child underwent exploratory laparotomy at another hospital, but resection was not attempted because the tumor in the caudate lobe had extensively invaded the retrohepatic IVC.
 However, because not only the lack of distant metastases but also the establishment of extrahepatic collaterals were confirmed by imaging, we thought it was possible to radically resect the tumor.
 We successfully performed an extended left hepatic lobectomy including total excision of the caudate lobe and the involved portion of the IVC.
 Although we did not reconstruct the IVC, no clinical manifestations arising from caval congestion were seen.
 The serum alpha-fetoprotein value declined below the normal limit.
 Our experience with this case has introduced a radical resectability for hepatic malignancy in the caudate lobe, even if it has extended into the IVC.
",3
615,"Partial and total penectomy for cancer.
 Squamous carcinoma of the penis remains an uncommon tumor in the United States.
 In the properly selected patient, partial or total penectomy performed with an understanding of the salient surgical anatomy results in adequate local control of these cancers with excellent functional and cosmetic results.
",3
616,"Primary hepatic carcinoid tumor. An electron microscopic and immunohistochemical study.
 A case of primary carcinoid tumor of the liver with striking morphologic and electron microscopic features is reported.
 Conventional histologic examination showed a prominent paranuclear clear zone in numerous tumor cells.
 By electron microscopic examination, this clear zone corresponded to a paranuclear mass of intermediate filaments admixed with neurosecretory granules and other cytoplasmic organelles.
",3
617,"Secretin provocation test in the diagnosis of Zollinger-Ellison syndrome.
 The secretin stimulation test has become the preferred provocative test in suspected cases of Zollinger-Ellison syndrome.
 A pure secretin preparation, a gastrin-specific radioimmunoassay, and an appropriate sampling sequence are important for the proper interpretation of this test.
 Gastric acid analysis is necessary in the assessment of hypergastrinemia to confirm acid hypersecretion and exclude achlorhydria.
 When properly performed and interpreted, the secretin provocation test offers a safe, expeditious, and reliable means of evaluating patients with hypergastrinemia.
",3
618,"DNA flow cytometry of colorectal carcinoma: correlation of DNA stemlines with other prognostic indices.
 DNA flow cytometry (FCM) was performed on paraffin-embedded tissue blocks of 38 surgically resected colorectal carcinomas (CRC).
 Forty-seven percent of tumors exhibited aneuploidy and 53% were diploid.
 Seventy-two percent of patients in the aneuploid but only 35% in the diploid group were alive after a mean follow-up of 30.7 and 28.8 months (p = 0.01), and 5-yr survival of 56.7% and 11.7%, respectively (p less than 0.05).
 The site of tumor location, Dukes' stage, and serum CEA level did not predict a certain DNA stemline.
 However, irrespective of the ploidy pattern, a serum CEA level greater than 5.0 was associated with a higher mortality and poor 5-yr survival (p less than 0.005).
 Similarly, advanced Dukes' stage was associated with higher mortality (p less than 0.05).
 Forty-six percent of the patients with lesions that were Dukes' B2 or advanced stage received adjuvant therapy.
 Eighty-five percent of this subgroup of patients died; 18% of these patients had aneuploid tumors.
 The role of FCM in the assessment of prognosis of CRC deserves further clinical evaluation in a randomized control trial.
",3
619,"Magnetic resonance imaging of small hepatocellular carcinoma.
 Thirty-eight patients with small hepatocellular carcinomas (HCCs), size less than 20 mm, initially detected by ultrasound (US) and histologically confirmed, were examined by magnetic resonance (MR) imaging, computed tomographic (CT) scan, and angiography.
 MR imaging demonstrated HCC nodules in nine (75.0%) of 12 patients with tumors less than 10 mm in diameter and in 22 (84.6%) of 26 patients with tumors 10-20 mm in diameter.
 In total, HCC nodules were detected in 31 of 38 patients (81.6%) by MR imaging.
 On the other hand, HCC lesions were found on CT scan in 14 of 26 patients (53.8%) and in 27 of 35 patients (77.1%) by angiography.
 With MR imaging, HCC nodules were demonstrated in 21 of 31 patients on both T1 and T2 weighted images, and 13 of 21 patients (61.9%) were shown to have low intensity areas or iso intensity areas on T1 weighted image, whereas the other eight patients (38.1%) were shown to have high intensity areas.
 All 21 patients were shown to have high intensity areas on T2 weighted image.
 Among 15 resected cases, four patients had a high intensity area on T1 weighted image, and a significant fatty change was noted in HCC nodules by histological study of the resected specimen.
 We suggest that MR imaging is a useful diagnostic imaging modality, even in small HCC of less than 20 mm.
",3
620,"Intrahepatic lymphatics opacified during hepatic arteriography in a patient with hepatocellular carcinoma.
 Extrahepatic lymph node metastases are not uncommon in advanced cases of hepatocellular carcinoma (HCC).
 This is the account of a HCC case in which intrahepatic lymphatics running toward the hepatic hilus were clearly opacified during hepatic arteriography.
 The patient was treated by hepatic artery embolization followed by selective embolization of the portal branches, but lymph node metastases at the hepatic hilus were later found during follow-up.
 The clinical course of this case suggests that the communication between the tumor and the lymphatics was responsible for the lymph node metastasis.
",3
621,"Inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia.
 A patient with inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia (M4) is reported.
 He had spiking fever, epigastralgia, and elevated levels of serum C-reactive protein (CRP) and alkaline phosphatase (ALP).
 Ultrasonography showed a hypoechoic mass in the liver, and ultrasonically guided fine needle aspiration biopsy of the mass revealed that it was composed of fibrous connective tissue infiltrated with plasma cells, eosinophils, and neutrophils.
 Accordingly, a diagnosis of inflammatory pseudotumor of the liver was made.
 Marked reduction in the size of the lesion and a decrease of the levels of the CRP and ALP occurred without specific treatment.
 We emphasize the importance of ultrasonically guided aspiration biopsy in diagnosis of inflammatory pseudotumor of the liver without the need for surgery.
",3
622,"Endodermal sinus tumor of the ovary during pregnancy: a case report.
 Serum alpha-fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24-year-old female in week 17 of pregnancy.
 After surgery, chemotherapy was postponed.
 In week 28 levels of serum alpha-fetoprotein increased, but delivery was delayed until 33 weeks' gestation.
 After delivery, the patient received four chemotherapy courses (cisplatin, etoposide, and bleomycin).
 Mother (24 months after last chemotherapy) and child are doing well.
",3
623,"Laparoscopic pelvic lymphadenectomy in the staging of early carcinoma of the cervix.
 Laparoscopic pelvic lymphadenectomy was performed in 39 patients.
 An incision of the peritoneum between the round and infundibulo-pelvic ligament on each side gave access to the retroperitoneal space.
 Subsequently, laparoscopic surgery allowed precise dissection of external and internal iliac vessels, umbilical artery, and obturator nerve.
 The peritoneum was left open, and the lymph was drained into the peritoneal cavity.
 No lymphocele was observed.
 Three to 22 (mean, 8.7) nodes were removed, and there was no significant morbidity.
 Sensitivity and specificity were 100% in this preliminary experience.
 It is thus possible to remove the first-line regional lymph nodes of the cervix for pathologic examination.
 Because ""skip"" metastases are quite rare in early cervical carcinoma, the risk of missing a positive node is low.
 Brachytherapy alone, vaginal surgery, or, in microinvasive carcinoma, conization alone can be applied safely without the need of a staging laparotomy in cases with negative nodes.
",3
624,"The value of squamous cell carcinoma antigen in patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.
 Serum levels of squamous cell carcinoma antigen were measured in 688 samples from 119 patients with cervical cancer.
 Ninety-seven patients had primary tumors and 22 had recurrent disease.
 Serum samples were obtained before each cycle of chemotherapy, before surgery, at least 4 weeks after surgery, and at 2- to 3-month intervals during follow-up from 78 of the patients with locally advanced cervical cancer who were receiving neoadjuvant chemotherapy.
 Squamous cell carcinoma antigen serum levels were elevated (greater than 2.5 ng/ml) in 71% of the patients with primary tumors and in 77% of the patients with recurrent carcinomas.
 The percentage of positivity increased significantly with stage (p = 0.03) and was higher in squamous cell tumors than in adenocarcinomas (p less than 0.001).
 Pretreatment squamous cell carcinoma antigen levels were not predictive of neoadjuvant chemotherapy response; however, the serial measurement during chemotherapy showed a good correlation with clinical response.
 In the patients who had surgery, squamous cell carcinoma antigen positivity did not correlate to pathologic findings (lymph node status, cervical and parametrial infiltration).
 Disease-free survival was significantly longer in patients with squamous cell carcinoma antigen pretreatment values that were lower than 5 ng/ml, compared with patients with marker higher than 5 ng/ml (p less than 0.01).
 Abnormal squamous cell carcinoma antigen serum levels preceded the clinical detection of recurrence in eight of 11 patients with a median lead time of 5 months.
",3
625,"Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer.
 Previous studies in breast and bladder cancer have suggested that epidermal growth factor receptor is expressed by only a proportion of cancers and is associated with poor clinical outcome.
 We used a monoclonal antibody specifically reactive with the extracellular domain of the epidermal growth factor receptor to localize this receptor immunohistochemically in frozen sections of normal ovary and epithelial ovarian cancer.
 Normal ovarian epithelium was found to express epidermal growth factor receptor in all cases.
 Among 87 ovarian cancers, however, 23% did not express immunohistochemically detectable receptor.
 Epidermal growth factor receptor expression was not related to histologic grade or stage, but was associated with poor survival (p less than 0.05).
 The median length of survival of patients with tumors that did not express epidermal growth factor receptor was 40 months compared with 26 months in patients with tumors that did express epidermal growth factor receptor.
 As in breast and bladder cancer, expression of epidermal growth factor receptor in ovarian cancer appears to be a poor prognostic factor.
",3
626,"Detection of loss of heterozygosity in formalin-fixed paraffin-embedded tumor specimens by the polymerase chain reaction.
 A polymerase chain reaction-based procedure was used for the detection of DNA length polymorphisms generated by naturally occurring genetic deletions or insertions of known sequence.
 This method consists of a simple one-step assay that does not require any restriction enzyme analysis or Southern blot hybridization, allowing identification in ethidium bromide-stained gels.
 The procedure described here was used to detect loss of heterozygosity at various loci, including the Hbb beta-globin gene cluster, in chemically induced mouse skin tumors, using a variety of tissue preparations, including microdissection of formalin-fixed, paraffin-embedded specimens, short-term cultures, and fluorescence-activated cell sorting of epithelial populations.
 This approach may be useful in detecting tumor-specific reduction to homozygosity at polymorphic chromosomal loci, allowing the mapping of putative tumor-suppressor loci involved in carcinogenesis.
",3
627,"Characterization of preneoplastic and neoplastic lesions in the rat pancreas.
 Nodules of acinar cells with increased proliferative potential develop in the pancreas of carcinogen-treated rats and in untreated aged rats.
 Large nodules are classed as adenomas.
 Phenotypic and genotypic characteristics of nodule cells were compared with normal pancreas and transplantable acinar cell carcinomas by several methods.
 Nuclei of acinar cells from normal pancreas, adenomas, and three carcinomas in situ had normal diploid DNA content as determined by flow cytometry.
 One of two primary carcinomas had a hypodiploid DNA content.
 Two of three transplantable carcinomas were aneuploid with a DNA content in the tetraploid range.
 Explants from nodules and adenomas failed to grow in soft agar, whereas several carcinomas were positive in this assay.
 A primary carcinoma was serially transplanted, but transplantation of nodules or adenomas failed.
 Transfection of DNA from carcinomas in situ yielded a higher frequency of NIH 3T3 transformants than DNA from adenomas.
 DNAs from the transformants did not contain ras sequences.
 These studies indicate that cells from nodules and adenomas have low growth potential and lack critical phenotypic and genotypic characteristics of transformed malignant cells that were present in some primary and transplanted carcinomas.
",3
628,"Induction of different morphologic features of malignant melanoma and pigmented lesions after transformation of murine melanocytes with bFGF-cDNA and H-ras, myc, neu, and E1a oncogenes.
 Malignant melanomas show a remarkable degree of heterogeneity because of different morphologic features, biologic behavior, and prognosis.
 In this communication, the authors attempted to correlate morphologic heterogeneity of melanomas with transformation by different activated oncogenes; they studied the histologic features of melanocytic lesions induced by murine melanocytes transformed by basic fibroblast growth factor (b-FGF-cDNA) or H-ras, neu, myc, and E1a oncogenes, and the lesions were compared with those observed in human pathology.
 Tumors formed after grafting onto syngenic mice or subcutaneous injections in nude mice were studied.
 In syngenic mice, benign melanocytic lesions reminiscent of intradermal nevus were observed with melanocytes transformed with b-FGF-cDNA, and myc and E1a oncogenes.
 Benign lesions were also formed by neu-transformed melanocytes when they were grafted concomitantly with keratinocytes, whereas malignant tumors were formed by the same cells when grafted alone or together with fibroblasts.
 In contrast, H-ras melanocytes always formed malignant tumors.
 In nude mice, b-FGF-transformed melanocytes induced benign lesions, whereas transformed melanocytes by the other oncogenes formed malignant tumors with distinctive and homogeneous morphologic features that depended on the transforming oncogene.
 Melanomas with either epithelioid cell, spindle cell, small round cell, and anaplastic cell growth patterns could be distinguished after transformation with H-ras, neu, E1a, and myc oncogenes, respectively.
 These various histologic types are analogous to those that may be observed in human melanomas, even within the same tumor.
 These studies suggest a possible molecular mechanism for tumor heterogeneity in which distinct oncogenes or oncogenelike activities can be activated in different tumors or discrete parts of the same tumor.
",3
629,"Treatment of angiomas with sclerosing injection of hydroxypolyethoxydodecan.
 The authors discuss the indications for hydroxypolyethoxydodecan in the sclerosing treatment of angiomas, with particular reference to cavernous, venous, and evolutive angiomas (ie, immature angiomas that fail to involute by eight to ten months).
 Moreover, the sclerosing agent may be employed, in connection with embolization and subsequent surgery, in arteriovenous angiomas with a relevant cutaneous-subcutaneous development.
 The authors have successfully used the ""interstitial"" sclerosing technique, according to Andrews' method.
 This technique involves interstitial injections to obtain the sclerosis of the thin threads of fibrous tissue stroma between the blood vessels.
 The sclerosing therapy may cause the complete regression of ""low flow"" angiomas or, at least, a partial reduction that simplifies the ensuing surgical excision.
 In the case of partial regression of the angioma obtained with the sclerosing therapy, the surgery of the remaining angioma causes a lesser degree of bleeding (especially in areas that do not particularly lend themselves to surgical exploration, ie, the oral cavity); an increased reliability in the radicality of the intervention (due also to the reduced size of the lesion); and better results from an aesthetic-functional point of view.
",3
630,"Intraoperative pancreatic fine needle aspiration biopsy. Results in 166 patients.
 Intraoperative fine needle aspiration biopsy (NAB) of undiagnosed pancreatic masses was studied in 166 patients over a 17-year period.
 The cytologic diagnoses were correlated with histologic specimens, autopsy results, or clinical follow-up (benign disease was documented if the patient was alive without malignancy at least 2 years after laparotomy).
 Aspirates were interpreted as benign, suspicious, malignant, or unsatisfactory.
 Malignant disease was the final diagnosis in 109 patients; the cytology was concordant in 101 and was interpreted as suspicious in four.
 Four patients with benign cytology later proved to have malignant disease--a false-negative rate of 2.5 per cent.
 A total of 57 patients had benign disease; 51 of these had benign cytology.
 The remaining patients had ""unsatisfactory"" cytology reports.
 A 93 per cent sensitivity, 100 per cent specificity, and 0 per cent complication rate are reported.
 There were no false-positive cytology reports.
 Complications are rare and represent case reports, thus, additional sampling is at minimal risk.
 Intraoperative pancreatic NAB is a safe, easy, more accurate biopsy technique than historical wedge or core needle biopsies.
 It is the biopsy method of choice for pancreatic masses found at laparotomy.
",3
631,"Surgical voice restoration with the Blom-Singer prosthesis following laryngopharyngoesophagectomy and pharyngogastric anastomosis.
 Surgical voice restoration using the Blom-Singer technique is a well-established procedure in patients who have undergone simple laryngectomy.
 Operations for hypopharyngeal carcinoma are more extensive and require reconstruction using regional skin or myocutaneous flaps, or reanastomosis with colon, jejunum, or stomach.
 We report the use of the Blom-Singer prosthesis in four patients who had undergone pharyngogastric repair following laryngopharyngoesophagectomy and who had failed to achieve a satisfactory voice.
 All patients initially developed good speech using the prosthesis.
 Two patients subsequently had their prostheses removed: one because of recurrent malignant disease and one because the procedure had not significantly altered the quality of the voice.
 The remaining two patients have continued to use the device at 2 and 5 years after insertion with good voice production.
",3
632,"Selenium in forage crops and cancer mortality in U.S. counties.
 The potential protective effect of selenium status on the risk of developing cancer has been examined in animal and epidemiologic studies.
 This ecological study investigated the association between U.S.
 county forage selenium status and site- and sex-specific county cancer mortality rates (1950-1969) using weighted least squares regression.
 Consistent, significant (p less than .01) inverse associations were observed for cancers of the lung, rectum, bladder, esophagus, and cervix in a model limited to rural counties and for cancers of the lung, breast, rectum, bladder, esophagus, and corpus uteri in a model of all counties.
 No consistent significant positive associations were observed in the rural county models.
 This remarkable degree of consistency for the inverse associations strengthens the likelihood of a causal relationship between low selenium status and an increased risk of cancer mortality.
",3
633,"Rapid analysis of carcinoembryonic antigen levels in gallbladder bile. Identification of patients at high risk of colorectal liver metastasis 
 Recently it was found that immunoanalysis of carcinoembryonic antigen (CEA) levels in gallbladder bile may be a sensitive method to detect colorectal liver metastases in humans.
 Methods used in the past for the detection of CEA in various body fluids were cumbersome and time consuming, requiring acid extraction, extensive dialysis, and column purification.
 Single-step, solid-phase radioimmunoassays, designed specifically for serum CEA analysis, were developed commercially to replace these methods.
 Parameters and methodology necessary to adapt these kits for Parameters and methodology necessary to adapt these kits for use with gallbladder bile are presented here.
 A combination of pretreatment procedures for bile, before radioimmunoassay, permit rapid, reproducible, and accurate measurement of CEA levels in gallbladder bile.
",3
634,"Liver transplantation for hepatoblastoma. The American experience.
 The current role of liver transplantation in treating malignant tumors of the liver is uncertain, except for select histologic types.
 Pooled data on the results of liver transplantation in 12 children with hepatoblastoma is presented here.
 One half of the children are alive 24 to 70 (44 +/- 19) months after transplantation with no evidence of recurrence.
 Three patients (25%) died of tumor recurrence and three (25%) died of other causes.
 Unifocal and intrahepatic tumors were associated with better prognosis compared to the multifocal tumors and tumors with extrahepatic spread (p = 0.04 and 0.13).
 Microscopically vascular invasion and the predominance of embryonal and/or anaplastic epithelium were associated with a poor prognosis compared to the tumors with no vascular invasion and with predominantly fetal epithelium (p = 0.08 and 0.1).
 It is concluded that continued efforts to treat unresectable hepatoblastomas by liver transplantation is justified and the role of adjuvant chemotherapy in improving the results needs to be better defined.
",3
635,"A population-based study of functional status and social support networks of elderly patients newly diagnosed with cancer.
 We assessed the functional status and social support networks of 799 men and women aged 65 years or older newly diagnosed with cancer and living in six New Mexico counties.
 Functional limitations included depending on others for transportation (33%) and mental incompetence or poor recent memory (42%).
 The percentage of patients with functional limitation increased sharply with increasing age.
 In a substantial number of patients there was also evidence for poor social support networks; 26.5% of subjects lived alone and 38.9% had no children living in the vicinity.
 In a multiple logistic regression analysis, the predictors of having a poor social support network included non-Hispanic white ethnicity, advanced age, low income, and being a recent migrant to the area.
 Subjects with functional limitations were more likely to have poor social support networks than subjects without such limitations.
 The deleterious combination of impaired functional status and a limited social support network may explain why elderly cancer patients are at increased risk for not receiving appropriate therapy.
 Given the potential complexities involving the evaluation and appropriate treatment of cancer, care must be taken to adequately assess functional status and support mechanisms of older patients, and to provide adequate support to ensure compliance with treatment.
",3
636,"Recurrent pigmented melanocytic nevus. A benign lesion, not to be mistaken for malignant melanoma.
 Melanocytic nevi that recur after incomplete removal are pigmented lesions that may clinically and pathologically simulate malignant melanoma in situ.
 Five examples of recurrent pigmented melanocytic nevus, with emphasis on light microscopic and immunohistochemical findings, are reported herein.
 Prominent HMB-45 staining in these nevi may cause further confusion in differentiating them from malignant melanoma.
 The differential diagnosis of recurrent pigmented melanocytic nevi is discussed, with particular emphasis on distinguishing these lesions from malignant melanoma.
 Our immunohistochemical observations indicate that the recurrences most likely develop as a result of proliferation of melanocytes remaining in the epidermis and/or adnexae following incomplete removal.
 The approach and management of recurrent nevi are also discussed.
",3
637,"Secretory carcinoma of the breast.
 Most studies of secretory carcinoma of the breast have been single case reports or separate analyses of the problem in either children or adults.
 We studied 10 female patients, aged 5 to 87 years.
 Most patients presented with a palpable mass, often near the areola.
 Five of six tumors were estrogen receptor negative; three analyzed for progesterone receptor were positive.
 Histologic patterns present in varying proportions were ""classic"" secretory carcinoma with microacini, abundant secretion with papillary features, and with prominent solid and papillary apocrine features.
 The tumors had strong reactivity for alpha-lactalbumin, S100, and carcinoembryonic antigen (polyclonal) and were negative for gross cystic disease fluid protein and anti-carcinoembryonic antigen (monoclonal).
 Six patients had mastectomy; four had local excision; none had axillary nodal metastases initially.
 With follow-up of 3 to 72 months (mean, 47 months; median, 48 months), two patients treated by local excision had local recurrences, one patient had axillary nodal metastases.
 All patients are alive.
 Comparison of patients under and over 30 years of age revealed one important difference: younger patients had a longer interval between detection and biopsy-30 vs 2 months.
 Treatment recommendations are initial wide excision or quadrantectomy with low axillary dissection in most cases and, in premenarchal patients, strong effort to preserve the breast bud without jeopardizing local control.
",3
638,"Intraluminal crystalloids in struma ovarii. Immunohistochemical, DNA flow cytometric, and ultrastructural study.
 We recently encountered a unique case of follicular variant of papillary carcinoma arising in struma ovarii that contained numerous intrafollicular crystalloids.
 There was no evidence of capsular or vascular invasion or metastases, though the DNA content of the papillary carcinoma was aneuploid.
 In contrast, diploid DNA was manifested in the histologically benign thyroid tissue.
 The nature of the crystalloids and the significance of aneuploid DNA content are discussed.
",3
639,"The tall cell variant of papillary carcinoma of the thyroid gland. Comparison with the common form of papillary carcinoma by DNA and morphometric analysis.
 The tall cell variant of papillary carcinoma of the thyroid manifests a more aggressive behavior than the usual form of papillary carcinoma of the thyroid.
 Morphometric analysis of nuclear features and DNA analysis may yield information predictive of aggressive behavior.
 Accordingly, the DNA content and morphometric features of the neoplastic cells of the tall cell variant were measured and compared with measurements obtained from neoplastic cells of the usual form of papillary carcinoma.
 Six of the 11 tall cell neoplasms were aneuploid, as were four of the eight usual papillary neoplasms.
 Although benign cells were separated from malignant cells in each case, differences between tall and usual papillary carcinoma cells were not observed regarding DNA content, chromatin texture, or nuclear size and shape.
 Differences in the clinical behavior of these neoplasms will likely need to be explained on the basis of other characteristics.
",3
640,"Squamous cell carcinoma in situ arising in an ovarian mature cystic teratoma. Report of one case with histopathologic, cytogenetic, and flow cytometric DNA content analysis.
 A squamous cell carcinoma in situ arose in an ovarian mature teratoma (ie, dermoid cyst) in a 62-year-old woman.
 Flow cytometric DNA content analysis of paraffin-embedded in situ carcinoma showed a normal DNA content with moderate to high proliferative activity (S-phase fraction estimate, 16% to 18%).
 Cytogenetic analysis of the in situ cancer and the benign cystic portion of the tumor revealed a 46,XX karyotype.
 In addition, the benign cystic portion of the tumor revealed homozygous chromosomal heteromorphisms, compared with heterozygous markers found in peripheral blood lymphocytes.
 These results show that this squamous cell carcinoma in situ was euploid and suggest that the mature cystic teratoma was derived from a single germ cell after meiosis I.
",3
641,"Extramammary Paget's disease of the bronchial epithelium.
 We report the first case, to our knowledge, of extramammary Paget's disease of the bronchial epithelium.
 The tumor displayed Paget's cells scattered within the bronchial epithelium in most of the lesion, but infiltrating into the bronchial submucosa and pulmonary parenchyma with microglandular and papillary patterns in some area.
 In addition to the histologic findings of coexistence with adenocarcinomatous components, in situ involvement into bronchial glands and ducts by Paget's cells was observed, suggesting that extramammary Paget's disease of the bronchial epithelium may be a variant of pulmonary adenocarcinoma, which is associated with bronchial glands.
",3
642,"An adult with common acute lymphoblastic leukaemia (C-ALL) presenting with skin infiltration.
 A 22-year-old man presented with multiple raised erythematous skin lesions, pyrexia and epistaxis.
 A diagnosis of common acute lymphoblastic leukaemia (C-ALL) was made by morphological, cytochemical, immunological and cytogenetic examination of peripheral blood and bone marrow.
 Biopsy of the skin revealed leukaemic infiltration by similar cells.
",3
643,"Monoclonal antibody-purged autologous bone marrow transplantation therapy for multiple myeloma.
 Eleven patients with plasma cell dyscrasias underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow transplantation (ABMT).
 The majority of patients had advanced Durie-Salmon stage myeloma at diagnosis, all were pretreated with chemotherapy, and six had received prior radiotherapy.
 At the time of ABMT, all patients demonstrated good performance status with Karnofsky score of 80% or greater and had less than 10% marrow tumor cells.
 Eight patients had residual monoclonal marrow plasma cells and 10 patients had paraprotein.
 Following high-dose melphalan and total body irradiation (TBI) there were seven complete responses, three partial responses, and one toxic death.
 Granulocytes greater than 500/mm3 were noted at a median of 21 (range 12 to 46) days posttransplant (PT) and untransfused platelets greater than 20,000/mm3 were noted at a median of 23 (12 to 53) days PT in 10 of the 11 patients.
 Natural killer cells and cytotoxic/suppressor T cells predominated early PT, with return of B cells at 3 months PT and normalization of T4:T8 ratio at 1 year PT.
 Less than 5% polyclonal marrow plasma cells were noted in all patients after transplant.
 Three of the seven complete responders have had return of paraprotein, two with myeloma, and have subsequently responded to alpha 2 interferon therapy.
 Eight patients are alive at 18.9 (8.9 to 43.1) months PT and four remain disease-free at 12.3, 17.5, 18.9, and 29 months PT.
 This preliminary study confirms that high-dose melphalan and TBI can achieve high response rates without unexpected toxicity in patients who have sensitive disease, and that MoAb-based purging techniques do not inhibit engraftment.
 Although the follow-up is short- and long-term outcome to be determined, relapses post-ABMT in these heavily pretreated patients suggest that ABMT or alternative treatment strategies should be evaluated earlier in the disease course.
",3
644,"The beta globin 3' enhancer element confers regulated expression on the human gamma globin gene in the human embryonic-fetal erythroleukemia cell line K562.
 We have constructed fusion genes comprised of gamma and beta globin elements and globin sequences linked to neomycin resistance (neoR) genes to define the cis acting sequences responsible for developmental stage-specific expression and induction of fetal globin genes in embryonic-fetal erythroleukemia K562 cells.
 The results indicate that the gamma promoter is required for proper initiation of transcription.
 However, the accumulation of gamma globin transcripts in response to hemin induction requires the additional presence of either gamma intervening sequence 2 or the 3' enhancer element of the beta globin gene.
 Thus, the gamma promoter may provide the elements for developmental stage-specific gene expression during fetal life.
 By contrast, the beta 3' enhancer is erythroid-specific but not developmental stage- or gene-specific.
",3
645,"Detection of residual leukemia after bone marrow transplant for chronic myeloid leukemia: role of polymerase chain reaction in predicting relapse.
 We used the polymerase chain reaction (PCR) to detect residual leukemia-specific mRNA in blood and marrow from 37 patients in complete hematologic and cytogenetic remission after allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML).
 Our two-step PCR method involved the use of ""nested primers"" in the second step and could detect one K562 cell diluted into 10(5) normal cells.
 Elaborate measures were taken to exclude false-positive and false-negative results.
 In nine patients whose blood and marrow were studied simultaneously the results were concordant (two positive and seven negative).
 Twenty-three patients transplanted in chronic phase (CP) with unmanipulated donor marrow were studied.
 Blood cells from nine of these patients were studied 3 to 6 months post-BMT and six were PCR positive; three were negative on subsequent studies.
 Blood cells from 18 patients studied between 8 months and 8 years post-BMT were all PCR negative.
 Nine patients transplanted in CP with T-cell-depleted marrow cells were studied.
 Blood from five was positive 3 to 24 months post-BMT; blood from five was negative 3 to 6 years post-BMT.
 Four patients no longer in first CP were studied after BMT with unmanipulated donor marrow.
 Blood from all four was positive 5 to 19 months post-BMT.
 Based on the known clinical results of transplant in these three cohorts we conclude that PCR may be positive within 6 months of BMT in patients who can expect long-lasting remission, whereas PCR positivity later after BMT may indicate that the probability of cure is reduced.
 Thus, the technique may prove useful for early assessment of new transplant protocols that might inadvertently increase the risk of relapse.
",3
646,"The reliability of palpation in the assessment of tumours.
 There is now a joint UICC-AJC classification for cervical lymph nodes based mainly on the size of the nodes.
 There is a recognized error in palpation, not only for detecting the presence of tumour but also its size.
 This study used an animal tumour model system to compare the ability of 6 independent observers of varying experience to detect and stage superficially transplanted growths.
 A preclinical medical student was as good as a Consultant ENT Surgeon in predicting the presence of tumour but the ability to stage tumours accurately was related to experience.
 Whilst the most experienced observers accurately estimated the size of tumours less than 2 cm, they were less accurate for larger (greater than 2 cm) tumours which were constantly understaged.
 This phenomenon may have important clinical implications particularly related to current nodal staging criteria.
",3
647,"Epidemiology of primary osteogenic sarcoma in the San Francisco Bay Area of California.
 This epidemiologic study represents an analysis of all registered new cases of osteogenic sarcoma (OGS) during the 14-year period from January 1973 to December 1986 in five San Francisco Bay counties.
 Inclusion into the study was limited to patients who were diagnosed in the first three decades of life and who were residents within the Bay Area at the time of diagnosis.
 To determine epidemiologic characteristics of OGS, records on 96 patients from the Bay Area Resources for Cancer Control with histologically proven OGS were reviewed.
 The incidence of OGS was influenced by age, gender, and race, but none of the effects were statistically significant.
 A geographic variation in the incidence of OGS was discovered, although it was not statistically significant.
 The results are presented in support of a continued search for environmental variables that may someday reveal the etiologic factors of OGS.
",3
648,"Solitary fibromatosis of bone. A rare variant of congenital generalized fibromatosis.
 Congenital generalized fibromatosis is part of the spectrum of the fibromatoses of infancy and childhood.
 The lesions are usually multiple and fibrous in nature.
 They may appear in virtually every organ outside the central nervous system.
 Congenital generalized fibromatosis can be limited to the skeleton and rarely manifests itself as a solitary bone lesion.
 Solitary osseous lesions often behave differently than multiple osseous lesions.
 Solitary lesions often do not regress without treatment and can have a high incidence of recurrence with less than marginal excision.
 Multiple osseous lesions often regress without treatment.
",3
649,"Assessment of ""squamous cell carcinoma antigen"" (SCC) as a marker of epidermoid carcinoma of the anal canal.
 We measured squamous cell carcinoma antigen (SCC) in epidermoid carcinoma of the anal canal in 66 patients.
 Samples were taken at diagnosis, before treatment, and during follow-up; 353 samples were analyzed.
 The positive threshold was taken as 2 ng/ml.
 At diagnosis, the sensitivity of the marker was 44 percent and its specificity 92 percent.
 In our series, the pretherapeutic level of SCC does not correlate with T as in Papillons' Clinical Staging System, but it does correlate with nodal invasion (P less than 0.05).
 It is of no prognostic value at the time of diagnosis.
 During follow-up, at relapse the level of SCC is 20.3 +/- 43 ng/ml.
 This increase is significant (P less than 0.01): the sensitivity of the marker is 77 percent.
 In patients who have relapsed, development of the illness correlates with the level of SCC, which is of prognostic value (P less than 0.01).
 In conclusion, the level of SCC should be associated with the clinical follow-up of patients with epidermoid carcinoma of the anal canal.
",3
650,"Anti-tumor X anti-lymphocyte heteroconjugates augment colon tumor cell lysis in vitro and prevent tumor growth in vivo.
 Cross-linking an anti-tumor antibody, specific for tumor cell surface antigens, and an anti-lymphocyte antibody, specific for the T lymphocyte receptor complex (TCR/CD3), produces a heteroconjugate that can direct T cells to lyse tumor cells.
 We tested the ability of anti-tumor X anti-lymphocyte (CD3) heteroconjugates to redirect human peripheral blood lymphocytes (PBLs) to lyse human colon cancer cells in cytotoxicity assays and in a murine colon tumor model.
 We demonstrated in vitro, that cultured human PBLs alone produced low levels of tumor lysis, but PBLs treated with anti-tumor X anti-CD3 heteroconjugates produced significantly greater tumor cell lysis (P less than 0.0025).
 Similarly, nude mice injected with LS174T human colon cancer cells and treated with cultured human PBLs and anti-tumor X anti-CD3 heteroconjugates survived significantly longer than saline control mice (P less than 0.01), or mice treated with PBLs alone (P less than 0.01), or heteroconjugates alone (P less than 0.05).
 F(ab')2 heteroconjugates were equally as effective in prolonging animal survival, but irrelevant heteroconjugates and monoclonal anti-tumor antibodies showed no therapeutic benefit.
 Anti-tumor X anti-CD3 heteroconjugates may represent an effective approach to tumor-specific cellular immunotherapy.
",3
651,"Polyamine levels in healthy and tumor tissues of patients with colon adenocarcinoma.
 Tissue polyamine levels were determined in patients with colon adenocarcinoma to try to identify biochemical indicators able to characterize the growth and the metabolism of human solid tumors.
 Polyamine content was determined in the tumor and in the ""healthy"" mucosa sampled at different distances within the resection edges.
 For each patient the polyamine content in the tumor was compared with that in the mucosa.
 The results demonstrated that the spermidine concentration was higher in the tumor than in the healthy mucosa; the differences were statistically significant.
 However, spermine in the tumor increased to a lesser degree.
 No statistically significant differences were observed among these mucosae at different localizations, but the spermine concentration in the mucosa after the tumor showed values very close to those of the neoplasia.
",3
652,"Isolation and characterization of normal and neoplastic colonic epithelial cell populations.
 The aim of the present study was to characterize rat mucosal colonic cells harvested from the crypt continuum during differentiation and dimethylhydrazine-induced neoplasia.
 The collection of colonocytes was performed using a modified nonenzymatic isolation procedure based on Ca2+ chelation and gentle mechanical dissociation.
 Light and electron microscopy histomorphological examinations, [3H]thymidine incorporation studies, and activity gradients of alkaline phosphatase, thymidine kinase, and cytoskeleton-associated protein tyrosine kinase indicated that distinct cell populations were harvested from the various crypt regions in a temporal sequence mirroring their zonal and functional distribution in situ.
 After dimethylhydrazine administration, marked protein tyrosine kinase activity was noted in colonic cells harvested from upper crypt zones.
 The misplaced and sustained kinase activity preceded the actual polyp or tumor formation.
 This observation is consistent with the expansion of colonic proliferative compartments beyond allowable boundaries during the preneoplastic period.
 Companion studies in human colonic epithelial specimens corroborate the findings observed in normal and transformed murine colonocytes.
 It is believed that the characterization and manipulation of colonocytes using our in vitro model will provide important clues to the molecular events underlying the differentiation program and carcinogenic process in the colonic cell.
",3
653,"A human CD5+ B cell clone that secretes an idiotype-specific high affinity IgM monoclonal antibody.
 We previously demonstrated the occurrence of a naturally arisen human anti-idiotypic B cell clone, that we transformed with EBV (EBV383).
 We show evidence that EBV383 not only expresses the CD5 surface Ag, but also contains the 2.7-kb mRNA transcript encoding this protein.
 In addition, we show the presence of the 3.6-kb mRNA precursor.
 Most Ig produced by CD5+ B cells are polyreactive natural IgM antibodies encoded by unmutated copies of germline VH genes.
 However, in this study we present data demonstrating the monoreactive high affinity character of the anti-idiotypic antibody (mAb383) produced by EBV383.
 These data are in agreement with our previous observations, showing that the VH chain of mAb383 is encoded by an extensive somatically mutated VHV gene in a way that is consistent with an Ag-driven immune response.
 A possible role for this remarkable anti-idiotypic antibody in the maintenance of B cell memory is discussed.
",3
654,"MHC-restricted recognition of autologous melanoma by tumor-specific cytotoxic T cells. Evidence for restriction by a dominant HLA-A allele.
 Autologous melanoma-specific CTL recognize a common tumor-associated Ag (TAA) in the context of HLA class I antigens.
 We have demonstrated that HLA-A2 can be a restricting Ag and, in T cell lines homozygous for HLA-A2, that CTL can be generated by stimulation with HLA-A2 allogeneic melanomas.
 In the current study, we have investigated T cell lines from patients who are heterozygous at HLA-A region locus, to determine the relative importance of each A-region allele in this MHC-restricted recognition of tumor.
 We have shown that HLA-A1 can be a restricting Ag, and that allogeneic melanomas expressing HLA-A1 can substitute for the autologous tumor in the generation of HLA-A1-restricted CTL.
 However, when T cell lines express both HLA-A1 and HLA-A2, the HLA-A2 allele governed restriction of the melanoma TAA.
 Three autologous-stimulated HLA-A1, A2 CTL lines all demonstrated restriction by the HLA-A2 allele, when examined in cytotoxicity assays, cold-competition assays, and proliferation assays.
 There was no evidence of restriction by the second HLA-allele, HLA-A1.
 Although the autologous-stimulated CTL use a single A-region allele for tumor recognition, the autologous HLA-A1, A2 tumors are lysed by both HLA-A1-restricted and HLA-A2-restricted CTL.
 The dominance of restricting alleles was further demonstrated when HLA-matched allogeneic melanomas were used as the stimulating tumor to generate tumor-specific CTL.
 Stimulation of the heterozygous (HLA-A1, A2) lymphocytes with HLA-A2-matched allogeneic melanomas resulted in CTL specific for the autologous tumor, and restricted by the HLA-A2 Ag.
 However, stimulation with an HLA-A1-matched allogeneic melanoma failed to induce tumor-specific CTL restricted by the HLA-A1 Ag.
 The data suggest there is a dominance of HLA-A region Ag at the level of the T cell, such that only one is restricting in the recognition of the autologous melanoma.
 At the level of the tumor, however, the TAA is expressed in the context of both HLA-A region alleles.
 We can generate specific CTL from lymph node cells or PBL and HLA-A region matched allogeneic melanomas; however, because most patients are heterozygous at the HLA-A region locus, an understanding of the dominant restricting alleles must be obtained so that an appropriately matched allogeneic melanoma can be selected.
",3
655,"Cytotoxic T cell clones isolated from ovarian tumor-infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumor cells.
 CTL clones were developed from tumor infiltrating lymphocytes (TIL) from the ascites of a patient with ovarian carcinoma by coculture of TIL with autologous tumor cells and subsequent cloning in the presence of autologous tumor cells.
 These CTL clones expressed preferential cytolytic activity against autologous tumor cells but not against allogeneic ovarian tumor cells and the NK-sensitive cell line K562.
 The cytolytic activity of these CTL against autologous tumors was inhibited by anti-TCR (WT31 mAb), anti-HLA class I, and anti-CD3 mAb but not by the NK function antibody Leu 11b.
 Cloning of the autologous tumor cells in vitro revealed that the CTL clones of the ovarian TIL expressed differential abilities to lyse autologous tumor cell clones.
 The specificity analysis of these autologous tumor specific CTL suggested that they recognize several antigenic determinants present on the ovarian tumor cells.
 Our results indicate the presence of at least three antigenic epitopes on the tumor cells (designated OVA-1A, OVA-1B, and OVA-1C), one of which (OVA-1C) is unstable.
 These determinants are present either simultaneously or separately, and six types of ovarian clones can be distinguished on the basis of their expression.
 These results indicate that CTL of the TIL detect intratumor antigenic heterogeneity.
 The novel heterogeneity identified within the ovarian tumor cells in this report may be of significance for understanding cellular immunity in ovarian cancer and developing adoptive specific immunotherapeutic approaches in ovarian cancer.
",3
656,"Evidence for the functional binding in vivo of tumor rejection antigens to antigen-presenting cells in tumor-bearing hosts.
 Spleen cells of BALB/c mice bearing a syngeneic CSA1M fibrosarcoma were treated with anti-Thy-1.2 antibody plus C, yielding a T cell-depleted, APC-containing fraction.
 The APC-containing fraction was first tested for its capacity to present exogenous modified-self or another tumor (Meth A) Ag after in vitro pulsing.
 The results showed comparable Ag-presenting capacities to those obtained by APC-containing fraction from normal spleen cells, indicating that APC function is not affected in tumor-bearing mice.
 We next examined whether APC from CSA1M-bearing mice bind endogenously generated CSA1M tumor Ag onto its surfaces to stimulate tumor-specific T cells.
 Five rounds of inoculation of APC-containing fraction from CSA1M-bearing mice without further in vitro pulsing resulted in the induction of potent anti-CSA1M immune resistance.
 The involvement of anti-CSA1M T cells in the induction of anti-CSA1M immunity was excluded by the fact that the in vivo immunity was excluded by the fact that the in vivo immunity was delivered by Thy-1+ cell-depleted, but not by Thy-1+ cell-enriched fractions of spleen cells from CSA1M-bearing mice.
 Moreover, the failure of Sephadex G10-passed spleen cells to deliver anti-CSA1M resistance demonstrated the absolute requirement of APC for inducing the in vivo immunity.
 Finally, this in vivo resistance was found to be tumor specific, because APC fractions from CSA1M-bearing and Meth A-bearing BALB/c mice induced immune resistance selective against the corresponding tumor cell challenge.
 These results indicate that APC from tumor-bearing hosts can not only exert unaffected APC function against exogenous Ag, but also function to present tumor Ag generated endogenously in the tumor-bearing state and to produce tumor-specific immunity in vivo.
",3
657,"Multiple spinal epidural metastases; an unexpectedly frequent finding.
 In a prospective study, patients with known malignant disease who were suspected of having a spinal epidural metastasis, had myelography which was not confined to the clinically suspected site, but included at least the whole lumbar and thoracic spinal canal.
 Fifty four of the 106 myelograms revealed at least one epidural metastasis.
 Twelve of these 54 myelograms showed two separate lesions, and four myelograms showed three separate lesions.
 In all 16 cases with multiple lesions at least one of the lesions was asymptomatic at the time of the diagnosis.
 It is concluded that multiple spinal epidural metastases are of common occurrence and occur in about one third of the cases.
 This finding may have important clinical implications.
 Examination of the spinal canal for epidural metastases should not be confined to the clinically suspected site, but should include as extensive an area as possible of the spinal canal, whatever technique is to be used.
",3
658,"Gemistocytic astrocytomas: a reappraisal.
 Although gemistocytic astrocytomas are considered slow-growing astrocytomas, they often behave aggressively.
 To clarify the biological and clinical behavior of these rare tumors, the authors retrospectively identified 59 patients with gemistocytic astrocytoma whose tumors were diagnosed and treated between June, 1976, and July, 1989.
 Three patients who were lost to follow-up review were excluded, as were two whose original slides could not be obtained and three whose tumors were diagnosed at recurrence or at autopsy.
 The pathological material of the remaining 51 patients was reviewed using two sets of histological criteria.
 Thirteen patients (Group A) had ""pure"" gemistocytic astrocytoma, defined as a glial tumor with more than 60% gemistocytes/high-power field and a background of fibrillary astrocytes.
 Fifteen patients (Group B) had ""mixed"" gemistocytic astrocytoma, defined as a glial tumor with 20% to 60% gemistocytes/high-power field and a background of anaplastic astrocytes.
 Twenty-three tumors did not meet these criteria and were excluded from analysis.
 The median age of the patients was 48.5 years in Group A and 38.3 years in Group B (p less than 0.05).
 In both groups, the median Karnofsky Performance Scale score was greater than 90%.
 All patients underwent surgical procedures (four total and 19 partial resections, and five biopsies) and postoperative radiation therapy.
 The majority also had interstitial brachytherapy, chemotherapy, or both.
 Ten patients had one reoperation for tumor recurrence and one had two reoperations; other treatments for recurrence included brachytherapy, chemotherapy, and repeat irradiation.
 All four patients who originally underwent gross total resection are still alive; all five who had a biopsy have died.
 There was no significant difference in median survival times between groups: 136.5 weeks in Group A (range 10 to 310+ weeks) and 135.6 weeks in Group B (range 31 to 460+ weeks).
 Analysis of all 28 patients showed a better prognosis for patients less than 50 years of age (185 vs.
 36 weeks survival time; p less than 0.001), patients with preoperative symptoms lasting for more than 6 months (228.1 vs.
 110.2 weeks survival time; p less than 0.05), and patients with seizures as the first symptom (185.7 vs.
 80 weeks survival time; p less than 0.01).
 Survival time did not correlate with the presence of perivascular lymphocytic infiltration.
 The authors conclude that the presence of at least 20% gemistocytes in a glial neoplasm is a poor prognostic sign, irrespective of the pathological background.
 It is proposed that gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated accordingly.
",3
659,"Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma.
 Between 1975 and 1989, 108 children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor (MB/PNET) of the posterior fossa were treated at the authors' institution.
 The patients were managed uniformly, and treatment included aggressive surgical resections, postoperative staging evaluations for extent of disease, and craniospinal radiation therapy with a local boost.
 Beginning in 1983, children with MB/PNET were prospectively assigned to risk groups; those with ""standard-risk"" MB/PNET were treated with radiation therapy alone, while those in the ""poor-risk"" group received similar radiation therapy plus adjuvant chemotherapy with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), vincristine, and cisplatin.
 The 5-year actuarial disease-free survival rate for all patients treated between 1975 and 1982 was 68%, and 73% when patients who died within 2 weeks after operation were excluded.
 This survival rate was statistically better for patients treated after 1982 (82%) compared to those treated between 1975 and 1982 (49%) (p less than 0.004).
 There was no difference in disease-free survival rates over time for children with standard-risk factors; however, there was a significant difference in the 5-year survival rate for poor-risk patients treated prior to 1982 (35%) compared to those treated later (87%) (p less than 0.001).
 For the group as a whole, a younger age at diagnosis correlated with a poorer survival rate; however, this relationship between age and outcome was significant only for children treated before 1983 (p less than 0.001).
 These results demonstrated an encouraging survival rate for children with MB/PNET, especially those treated with aggressive surgical resection followed by both radiation therapy and chemotherapy.
 The results strongly suggest that chemotherapy has a role for some, and possibly all, children with MB/PNET.
",3
660,"Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas.
 Malignant gliomas have been difficult to treat with chemotherapy.
 The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum.
 To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers.
 Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure.
 In this Phase I-II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant.
 Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking.
 The polymer releases the therapeutic drug for approximately 3 weeks.
 Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels.
 There were no adverse reactions to the BCNU wafer treatment itself.
 The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group.
 The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation.
 The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery.
 Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer.
 Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy.
 Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started.
 The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.
",3
661,"Characterization of astrocytomas, meningiomas, and pituitary adenomas by phosphorus magnetic resonance spectroscopy.
 Phosphorus magnetic resonance (MR) spectroscopy allows noninvasive measurement of phosphate-containing compounds and pH within brain cells.
 The authors obtained localized phosphorus MR spectra from 10 normal brains, four low-grade astrocytomas, six glioblastomas, four meningiomas, and three pituitary adenomas and found differences in the spectra of each tumor type.
 Compared to normal brain, the spectra from low-grade astrocytomas showed a significant reduction of the phosphodiester (PDE) peak.
 Glioblastomas were characterized by a significant reduction of the PDE peak, elevation of the phosphomonoester (PME) peak, and a relatively alkaline intracellular pH.
 The spectra from meningiomas and pituitary adenomas were markedly different from the glial tumors.
 Meningiomas showed significant reductions in phosphocreatine, PDE, and inorganic phosphate, as well as a relatively alkaline pH.
 Pituitary adenomas resembled meningiomas, but had a much higher PME peak.
 Although the number of tumors studied was small, there appears to be a characteristic spectrum associated with these different tumor types.
 The present findings can be useful in the preoperative identification of these tumors and in furthering understanding of their growth and metabolism in vivo.
",3
662,"Hemangiopericytoma of the sciatic nerve. Case report.
 The authors report the case of a hemangiopericytoma arising in a sciatic nerve.
 It was found to be invasive within the epineurium but sparing surrounding tissues.
 Adequate resection required sacrifice of the nerve.
 Hemangiopericytomas can be added to the short list of mesodermal peripheral-nerve tumors.
",3
663,"Dose dependency of time of onset of radiation-induced growth hormone deficiency.
 Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease.
 All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment.
 Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years.
 Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses.
 The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose.
 We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis.
",3
664,"Deep femoral lymphadenectomy with preservation of the fascia lata. Preliminary report on 42 invasive vulvar carcinomas.
 Forty-two patients with primary invasive vulvar carcinoma were treated with radical vulvectomy and deep femoral lymphadenectomy with preservation of the fascia lata and cribriform fascia.
 The rationale for using this technique was based on anatomic knowledge of the topographic distribution of groin lymph nodes, which was confirmed by the study of 50 cadavers.
 The preliminary data show that the number of superficial and deep femoral lymph nodes removed from the 42 patients (mean number of nodes, 20; range, 8-32) was similar to the number reported in anatomy books.
 In addition, the five-year actuarial survival rate, 70%, was comparable to that in the literature.
 These preliminary results suggest that the surgical technique used in this study is as radical an oncologic procedure as Way's classic groin lymphadenectomy, which consists of removing the fascia lata and cribriform fascia.
",3
665,"Breast self-examination in relation to the occurrence of advanced breast cancer.
 Two hundred nine female enrollees of the Group Health Cooperative of Puget Sound who developed advanced-stage breast cancer during the period 1982-1988 were interviewed about their practice of breast self-examination (BSE), use of other breast cancer screening modalities, and medical and reproductive histories.
 Each subject's description of how she performed the examination was scored according to her mention of up to 10 recommended BSE techniques.
 A random sample of 433 women without advanced-stage breast cancer from the same population was interviewed for comparison.
 Relative to women not practicing BSE, the risk of advanced-stage breast cancer among BSE users was 1.15 (95% confidence interval, 0.73-1.81).
 Frequency of BSE did not differ between women with advanced-stage breast cancer and control subjects, whether in all subjects or in subgroups defined by age, use of mammography, or frequency of clinical breast examinations.
 While self-described proficiency in BSE was generally low in both case and control subjects, the small percentage of women reporting more thorough self-examinations, regardless of frequency, had about a 35% decrease in the occurrence of advanced-stage breast cancer compared to women who did not perform BSE.
 These results suggest that, while carefully performed BSE may avoid the development of some advanced-stage breast cancers, BSE as practiced by most Seattle-area women is of little or no benefit.
",3
666,"Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis.
 The nm23 gene was identified in murine melanoma cells, in which its expression is associated with the cells' metastatic potential.
 Expression of nm23 has been detected in human breast tumors by means of hybridization and immunocytochemistry.
 We measured nm23 mRNA in 71 patients with primary breast cancer and found variable levels of nm23 expression.
 The nm23 gene was expressed at higher levels in well-differentiated tumors (P less than .02).
 There was a significant inverse relationship between nm23 expression and nodal status (P less than .02).
 Expression of nm23 was positively associated with longer disease-free survival and overall survival, and the relationships were significant (P less than .002 and P less than .003, respectively).
 This study showed that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype.
",3
667,"Long-term follow-up of patients with recurrent malignant gliomas treated with adjuvant adoptive immunotherapy.
 Between August 1986 and October 1987, the Denver Brain Tumor Research Group conducted a clinical trial using autologous human recombinant interleukin-2 (rIL-2)-activated lymphocytes to treat 20 patients with recurrent high-grade gliomas.
 The trial involved surgical resection and/or decompression followed by intracavitary implantation of lymphokine-activated killer (LAK) cells and autologous stimulated lymphocytes (ASL) along with rIL-2 in a plasma clot.
 One month later, stimulated lymphocytes and rIL-2 were infused through a Rickham reservoir attached to a catheter directed into the tumor bed.
 The LAK cells were rIL-2-activated peripheral blood lymphocytes cultured for 4 days; the ASL were lectin- and rIL-2-activated peripheral blood lymphocytes cultured for 10 days.
 Of the 20 patients treated, 11 were evaluated as a group (mean age, 44 years, range, 15-61 years; mean Karnofsky rating, 69, range, 50-100; mean Decadron dose at entry, 14 mg/d, range, 0-32).
 The average number of lymphocytes implanted was 7.6 x 10(9) (range, 1.9-27.5 x 10(9], together with 1 to 4 x 10(6) U of rIL-2.
 To date, 10 of the 11 patients died, all from recurrent tumor growth.
 The median overall survival time was 63 weeks (range, 36-201; mean, 86).
 The median survival time after immunotherapy was 18 weeks (range, 11-151; mean, 39).
 No significant difference in survival after immunotherapy was found between those patients who had received previous chemotherapy and those who had not.
 The use of steroids or prior chemotherapy did not influence the in vitro generation of ASL or LAK cells.
",3
668,"Disposition of cerebral metastases from malignant melanoma: implications for radiosurgery 
 Radiosurgery is becoming more generally available and indications for its use continue to be defined.
 Cerebral metastases from malignant melanoma are often treated with whole-brain irradiation, but with limited benefit.
 Innovative treatments, such as radiosurgery, make possible the delivery of doses of radiation that are higher than usual.
 To determine how many patients might be candidates for radiosurgery, a retrospective analysis of computed tomographic brain scans performed on 41 patients with cerebral metastases from malignant melanoma was undertaken.
 One-third of these patients were found to have cerebral metastases amenable to a radiosurgical approach, as illustrated radiation dose-volume histograms.
 Patient and tumor characteristics suggest that this series is represent with cerebral metastases from malignant melanoma.
 The implications of radiosurgery for normal tissue radiation tolerance and its effects on melanoma are discussed.
",3
669,"Early diagnosis of breast cancer. Universal screening is essential.
 Breast cancer strikes 1 in 10 women in the United States.
 Early diagnosis of breast cancer improves chances of survival.
 With universal screening and expert evaluation of early clinical signs and symptoms of breast cancer, mortality rates can be reduced by 30% to 40%.
 Physicians can help achieve this goal by taking an active role in patient education and promoting the availability of affordable screening mammography.
",3
670,"Primary CT diagnosis of abdominal masses in a PACS environment 
 Whether the display medium--film versus cathode ray tube (CRT)--affects observer performance during interpretation of computed tomographic (CT) images is an important research issue in these times of implementation and growth of picture archiving and communications systems in radiology.
 The authors performed a multiobserver receiver operating characteristic (ROC) study to determine the performance of radiologists who read abdominal CT studies displayed on film, as well as on a high-resolution workstation (video monitor) that made use of three different display modes.
 A total of 166 examinations were evaluated by eight radiologists, who recorded their ordinal confidence ratings of the demonstration of presence or absence of abdominal masses.
 ROC analysis showed small differences in the confidence ratings assigned by individual readers for the detection and interpretation tasks.
 Results for the group as a whole showed no significant reduction or improvement in observer performance when ratings for any one of the workstation display modes were analyzed.
 The results of this study demonstrate that current CRT display technology is adequate for enabling the primary detection of abdominal masses with CT examinations.
",3
671,"Zollinger-Ellison syndrome: prospective assessment of abdominal US in the localization of gastrinomas.
 The ability of abdominal ultrasound (US) to help localize gastrinomas was prospectively studied in 79 patients with Zollinger-Ellison syndrome.
 The results were assessed by means of laparotomy, autopsy, or percutaneous liver biopsy.
 For hepatic gastrinoma, US had a sensitivity of 63% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 89%.
 US was slightly less sensitive for detecting gastrinoma in the liver than were computed tomography (CT) (66%) and selective angiography (78%).
 For detection of extrahepatic gastrinoma, US had a sensitivity of 30%, a specificity of 94%, a positive predictive value of 100%, and a negative predictive value of 25%.
 US enabled detection of tumor in eight cases not detected with CT and in four not detected with angiography.
 Specificity for extrahepatic gastrinoma was similar for all three modalities (89%-95%).
 CT and US were equally effective for the detection of extrahepatic gastrinoma, and angiography was significantly more effective than both US and CT (P less than .01).
 The authors conclude that US, although of low sensitivity, remains useful as the initial imaging modality in patients with Zollinger-Ellison syndrome.
",3
672,"Epithelial tumors of the ovary: CT findings and correlation with US.
 One hundred thirty patients with 170 epithelial ovarian tumors were prospectively studied with computed tomography (CT) before surgery.
 Ultrasound (US) was performed in 108 patients with 138 tumors.
 At pathologic examination, 78 tumors (46%) were benign, 14 (8%) borderline, and 78 (46%) malignant.
 CT results were compared with surgical and pathologic findings in all patients.
 CT enabled detection of 148 of 170 tumors (87%), and US enabled detection of 118 of 138 tumors (86%).
 Benign serous cystadenomas (n = 42) were correctly characterized with a sensitivity of 69% at CT and 70% at US.
 Benign mucinous cystadenomas (n = 21) were correctly characterized with a sensitivity of 62% at CT and 50% at US.
 Malignancy was suggested in nine of 14 patients (64%) with borderline tumors at CT and in five of 14 (36%) at US.
 The overall accuracy of characterization of benign versus malignant tumors (including borderline tumors) was 94% with CT and 80% with US.
 In the 108 patients studied with both CT and US, the sensitivity of CT was significantly superior to that of US (P less than .03), whereas there was no significant difference in specificity (P = .125).
",3
673,"Intraoperative I-125 seed implantation for extensive recurrent head and neck carcinomas.
 From 1978 to 1988, 41 patients with extensive recurrent carcinomas of the head and neck were treated with surgical resection plus intraoperative iodine-125 seed implantation.
 Surgery was performed to resect the tumors and to expose the tumor beds for implantation.
 I-125 seeds were implanted intraoperatively, with a spacing of 0.75-1 cm between adjacent seeds, either into the soft tissue in the tumor bed or onto small patches of gelatin sponges to cover the bone, nerve, or blood vessel involved with disease.
 Reconstructive flaps were used in 18 patients.
 The average I-125 dose delivered by the implanted seeds was 8,263 cGy.
 The determinate 5-year actuarial survival rate for the entire group was 40%.
 The 5-year local disease control rate was 44%.
 Major complications were transient wound infection (32%), flap necrosis (24%), fistula formation (10%), and carotid blowout (5%).
 These results indicate that surgical resection plus I-125 seed implantation provides a potentially curative treatment for patients with extensive recurrent head and neck carcinomas that would be considered traditionally unresectable and that would be treated only with palliative therapy.
",3
674,"The value of symptom directed evaluation in the surveillance for recurrence of carcinoma of the breast.
 Specific postoperative tests used to diagnose recurrent carcinoma of the breast were evaluated for their ability to have an impact on the over-all course of the disease.
 Sixty-four patients with recurrent or new contralateral primary disease were divided into two groups based on the method of diagnosis.
 Those patients with a new complaint at an interval between scheduled follow-up visits and who went on to have tests to document a recurrence were categorized as interval follow-up.
 Those who were seen at a prearranged regular follow-up period and received tests as recommended by the attending physician or surgeon and had a documented recurrence were classified as routine follow-up.
 Thirteen patients presented with new contralateral primary disease and 51 with metastatic disease (16, bone; 13, lung; 11, local; three, liver, and eight, multiple).
 The median time to discovery of recurrence from the primary treatment was 29 and 28 months for the interval and routine groups, respectively.
 Ninety per cent of the failures occurred by 53 months.
 The survival time after recurrence was significantly greater in those patients diagnosed routinely (p = 0.003).
 However, the over-all survival time (from primary therapy to death) was only significantly improved for the routine group when the contralateral new primary diseases were included (p = 0.009).
 The method of diagnosis of a contralateral primary carcinoma was physical examination and mammogram.
 Strong recommendations for follow-up testing can be limited to mammogram and physical examination.
",3
675,"Axillary lymphadenectomy for intraductal carcinoma of the breast.
 During a ten year period, 175 axillary lymph node dissections were done as part of the treatment for intraductal carcinoma of the breast; 98 patients were treated with modified radical mastectomy and 77 were treated by mammary preservation, consisting of excision of the lesion, axillary dissection and radiation therapy.
 One of 175 axillary node dissections yielded positive nodes.
 Axillary dissection for intraductal carcinoma of the breast is unlikely to yield involved nodes and is not indicated for use in most instances.
 It should be reserved for lesions demonstrating microinvasion.
",3
676,"Expression of beta 1 integrins in normal human keratinocytes.
 The majority of cell adhesive events to the extracellular matrix are mediated by cell surface receptors, beta 1 integrins.
 Keratinocytes express at least six different polypeptides of beta 1 integrin class, namely beta 1, alpha 2, alpha 3, alpha 5, and alpha 6 (alpha 6 is mainly associated with beta 4 polypeptide).
 These epithelial cells use alpha 2 beta 1 as a collagen receptor and alpha 3 beta 1 as a fibronectin receptor, while alpha 6 beta 4 is the major basement membrane receptor.
 Expression of alpha 5 beta 1 complex is low.
 Processing of beta 1 integrins is fast in keratinocytes; half-maximal maturation takes only 3 hours.
 In addition to their function in cell-matrix interactions, beta 1 integrins (alpha 2 beta 1 and alpha 3 beta 1) have also a role in maintaining keratinocyte cell-cell interactions.
 It is possible that resting basal keratinocytes use beta 1 integrins as cell-cell adhesion receptors, and during activation, like in wound healing, these receptors relocalize to mediate events involving cell-matrix interactions.
",3
677,"Using a state cancer registry to increase screening behaviors of sisters and daughters of breast cancer patients.
 The Pennsylvania Cancer Registry was used to contact breast cancer patients and, through them, their adult sisters and daughters.
 The sisters and daughters were counseled concerning their higher than average risks for breast cancer and their need for mammography and breast self-examination.
 Results showed a 9 percent increase in mammography and a 10 percent increase in breast self-examination rates for the counseled over control group.
 Costs were $49 per counseled sister or daughter indicating a need to increase cost effectiveness before implementation is practical.
",3
678,"Subscapular elastofibroma in a young pitcher. A case report.
 Subscapular elastofibromas and scapulothoracic bursitis can cause symptomatic masses in baseball pitchers.
 Both processes appear to represent reactive soft tissue responses to repetitive stress at the inferior border of the scapula.
 It is assumed that most masses in the subscapular area represent scapulothoracic bursitis rather than an elastofibroma.
 However, it is possible that some of the masses treated conservatively as scapulothoracic bursitis may be elastofibromas.
 A study is currently under way to evaluate the incidence of subscapular masses in college and professional pitchers in the United States.
 A follow-up report is anticipated when the study has been completed.
 The author requests information concerning any confirmed cases of elastofibroma in baseball pitchers.
",3
679,"The glucose transporter and blood-brain barrier of human brain tumors.
 The glucose transporter of the human brain has been localized to endothelial cells expressing the blood-brain barrier, but little is known regarding its mechanism of induction or whether its expression is exclusively linked with restricted vascular permeability.
 We investigated glucose transporter expression by vessels in human astrocytic tumors and pulmonary metastases to the brain using immunohistochemical techniques.
 Vessels in 9 of 10 low-grade astrocytomas and 8 of 10 anaplastic astrocytomas were positive for glucose transporter.
 Glioblastoma vessels were transporter-positive in only 2 of 10 specimens.
 Vessels in all three metastatic tumors were negative for the glucose transporter.
 The decrease in transporter expression observed in higher-grade tumors occurred independently of increases in vascular permeability.
 In low-grade astrocytomas and glioblastomas transporter expression and contrast enhancement were inversely related, but vessels in 6 of 9 anaplastic astrocytomas were transporter-positive despite contrast enhancement.
 These findings suggest that separate mechanisms induce the glucose transporter and the permeability restrictions of the human blood-brain barrier.
 They also have potential implications for the therapy and prognosis of astroglial neoplasms.
",3
680,"Effects of treatment on long-term survivors with malignant astrocytomas.
 We reviewed the records of 160 consecutive patients with glioblastoma and anaplastic astrocytoma to evaluate the long-term consequences of radiation therapy and chemotherapy.
 We defined long-term survivors as those patients with glioblastoma or anaplastic astrocytoma who lived at least 100% longer than median survival of historical controls, for example, 2 years for patients with glioblastoma and 4 years for patients with anaplastic astrocytoma.
 There were 9 (5.6%) long-term survivors.
 Three (30%) became demented and died without evidence of tumor recurrence.
 One, after survival of 10 years, died of tumor recurrence.
 Of the remaining survivors, 2 (22%) have significantly impaired short-term memory function and other neurological deficits such as gait apraxia.
 Three (30%) can function independently.
 It is likely but cannot be proved that it is radiotherapy and not chemotherapy that is the causal factor of this dismal therapeutic outcome.
 Our study suggests restraint in the use of radiotherapy for patients with brain tumors that have more favorable prognoses than glioblastomas and anaplastic astrocytomas, such as low-grade astrocytomas and oligodendrogliomas.
",3
681,"Chemotherapy for medulloblastoma/primitive neuroectodermal tumors of the posterior fossa.
 Chemotherapy has only marginal efficacy in adult malignant brain tumors.
 In contrast, drug therapy is considerably more effective in medulloblastoma/primitive neuroectodermal tumors (MB/PNET) of the posterior fossa, the most common childhood primary central nervous system tumor.
 At the time of disease recurrence, a variety of different single agents and drug combinations result in tumor shrinkage and increased survival.
 The addition of chemotherapy to standard radiotherapy improves the rate and length of disease-free survival for those children with MB/PNET who have the most extensive tumors at diagnosis.
 It remains to be determined which drug or drug combinations are the most effective in MB/PNET, and which patients are most likely to benefit from chemotherapy.
 Chemotherapy may be useful to reduce or, in selected cases, obviate the need for radiotherapy and reduce treatment-related sequelae.
",3
682,"Comparative in vitro activities of newer quinolones against Pseudomonas species and Xanthomonas maltophilia isolated from patients with cancer.
 The in vitro susceptibilities of three Pseudomonas species (Pseudomonas aeruginosa, Pseudomonas putida, and Pseudomonas fluorescens) and Xanthomonas maltophilia to quinolone antimicrobial agents were determined.
 Several newer agents, particularly PD117558, PD117596, PD127391, sparfloxacin (AT-4140), A-56620, and temafloxacin, were active against Pseudomonas species.
 X.
 maltophilia isolates were generally less susceptible than were Pseudomonas isolates but were inhibited by some of the newer quinolones.
",3
683,"Therapeutic outcome of patients suffering from malignant melanomas of the conjunctiva.
 Eighty-one cases of conjunctival melanoma treated between 1960 and 1988 were studied to determine factors that might affect outcome in patients with such lesions.
 The therapeutic procedures performed were local excision (16), local excision followed by brachytherapy with Sr-90/Y-90 (32), local excision followed by cryotherapy with liquid nitrogen (16), brachytherapy with Sr-90/Y-90 (12), local excision followed by external beam irradiation (3), and local excision followed by brachytherapy and cryotherapy (2).
 The median follow-up period was 5.5 years (longest 26, shortest 1 year).
 Sixty two patients (76.5%) showed a complete regression of the melanoma, 19 (23.5%) developed recurrences, and 15 (18.5%) died from metastases.
 The melanomas had developed with almost equal frequency from a pre-existing naevus (25.9%), from primary acquired melanosis (25.9%), and 'de novo' (30.9%).
 Small tumours had a higher chance of regressing (80.6%) than larger ones (68.6%).
 The cumulative survival rate was 76% after five years and 60% after 10 years from any causes of death and 87.6% after five years and 76.3% after 10 years from deaths caused by metastases.
 Most deaths from metastases occurred within 5 years.
 At 88.5%, the cumulative survival rate of patients with small tumours (less than one quadrant of the bulbar conjunctiva and less than 2 mm thickness) was significantly higher than that of patients with larger tumours (more than one quadrant of the bulbar conjunctiva and/or more than 2 mm thickness) with 65% after eight years.
 Local excision followed by beta ray irradiation (Sr-90/Y-90) or cryotherapy can be recommended as the treatment of choice.
 Nevertheless the behaviour of conjunctival melanomas remains unpredictable in individual cases.
",3
684,"Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody.
 An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated.
 This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells.
 We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab.
 As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used.
 When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr-labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab.
 Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity.
 CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab.
 However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets.
 These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.
",3
685,"Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody.
 Multiple myeloma is a disease in which conventional chemotherapy has only limited value, but which may be ideal for treatment with passive antibody against a suitable cell surface antigen on the neoplastic plasma cell.
 The CD38 antigen is known to be present on the majority of neoplastic plasma cells, and this was confirmed by detailed examination of bone marrow aspirates from three patients.
 Strong expression of CD38 was confined to cells which, by the criteria of light-scattering profiles and possession of cytoplasmic Ig, were plasma cells.
 The vast majority of neoplastic plasma cells appeared to be involved.
 Using a cell line as a model, it was found that the CD38 antigen acts as a target for a chimeric antibody prepared from the antibody OKT10.
 The chimeric antibody consists of the Fab portion of the mouse monoclonal antibody linked by a stable thioether bond to an Fc molecule derived from human IgG1, thereby forming mouse Fab-human Fc.
 In contrast to the parent antibody, the chimeric molecule mediates antibody-dependent cellular cytotoxicity (ADCC) very efficiently with human blood mononuclear effector cells, and is effective at low concentration.
 Also, even though the CD38 antigen is present on natural killer cells, there appears to be little deleterious action of the antibody on effector cell function.
 The antibody also failed to affect the growth of progenitor cells of the granulocyte/macrophage or erythroid lineages present in normal bone marrows, despite the suspicion that these cells express the antigen.
 Other advantages of the CD38 molecule are that it is not found in the serum of patients with myeloma, and it does not appear to modulate in vitro.
 Fourteen patients with florid myeloma and on various chemotherapeutic regimes had an undiminished capacity to mediate ADCC with the chimeric antibody, when compared with normal individuals.
 The maintenance of ADCC activity, coupled with the known suppression of the antibody response in these patients, augers well for treatment with chimeric antibody.
",3
686,"Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors.
 Juvenile chronic myelogenous leukemia (JCML) is a good model for the study of myeloproliferation because JCML hematopoietic progenitor cells grow in vitro at very low cell densities without the addition of exogenous stimulus.
 Previous studies have demonstrated that this proliferation is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF), and that removal of monocytes from the cell population before culture eliminates this ""spontaneous"" myeloproliferation, suggesting a paracrine role of monocyte stimulation.
 However, subsequent studies have shown that increased GM-CSF production from the JCML monocytes is not a consistent finding and therefore not a plausible sole mechanism.
 In examining hematopoietic growth factor dose-response curves, both JCML GM and erythroid nonadherent progenitor cell populations displayed a marked and selective hypersensitivity to GM-CSF.
 Responses to interleukin-3 and G-CSF were identical to control dose-response curves.
 This is the first demonstration of a myeloid leukemia in which hypersensitivity to a specific growth factor appears to be involved in the pathogenesis of the disease.
",3
687,"Expression of laminin and its receptor LBP-32 in human and rat hepatoma cells.
 Dramatic cellular changes that occur during hepatocarcinogenesis are associated with major alterations in extracellular matrix formation and in the relationships between cells and their microenvironment.
 We have studied the expression of laminin, the major noncollagenous glycoprotein of basement membrane, and the laminin receptor 32 kD laminin-binding protein in two rat (Faza 967 and HTC) and two human (HepG2 and HBGC2) hepatoma cell lines that express a variety of liver-specific functions.
 Laminin was found in the rough endoplasmic reticulum of these cells when the indirect immunoperoxidase method and electron microscopic examination were used.
 Radiolabeled laminin, immunoprecipitated from both media and cell extracts, was resolved by electrophoresis on sodium dodecyl sulfate gel in two major polypeptides that comigrated with the A and B subunits from Engelbreth-Holm-Swarm tumor laminin.
 Immunoblot analysis showed that the Mr = 400,000 polypeptide did not correspond to the A subunit of laminin.
 Northern blot analyses demonstrated large amounts of B1 and B2 mRNAs but no A chain mRNA.
 We conclude that the tumor cells produce the laminin B chains only.
 In contrast, normal adult hepatocytes from either man or rat lacked laminin mRNAs, whereas in 1-day primary culture, B chain mRNAs became detectable.
 The steady-state level of 32 kD laminin-binding protein mRNA was 10-fold and threefold higher in rat hepatoma cells than in freshly isolated and 1-day cultured normal rat hepatocytes, respectively.
 In human hepatocytes, the steady-state levels of 32 kD laminin-binding protein mRNAs varied depending on the donor and never reached the level of the human hepatoma cells.
",3
688,"Cyclosporine enhances the growth of carcinogen-induced enzyme-altered foci in rat liver.
 Cyclosporine, a powerful immunosuppressant, has been used successfully for organ transplantation.
 Its efficacy on liver transplants of patients with primary hepatic tumors remains controversial because of a high rate of recurrence of the original tumors in the transplanted livers.
 In this study, we experimentally tested whether cyclosporine exerts any effects on the growth of carcinogen-initiated liver cells using the short-term assays of rat liver carcinogenesis.
 Dietary cyclosporine, which maintained sufficient levels of blood cyclosporine and suppressed host immune functions, enhanced the development of the glutathione S-transferase, placental form-positive hepatocyte foci in the liver of male F-344 rats treated with a single weekly dose of diethylnitrosamine (75 mg/kg) for 3 wk.
 Dietary cyclosporine also accelerated the growth of preformed glutathione S-transferase, placental form-positive foci induced by a single dose of diethylnitrosamine (250 mg/kg) followed by the promoting regimen of a choline-deficient diet.
 It is possible that the enhancement of the size of hepatocyte foci by cyclosporine could be due to stimulation of growth or inhibition of regression.
 The mechanisms by which cyclosporine modifies the growth of preneoplastic lesions in the liver are not yet fully understood.
 Possible involvement of immunologically relevant cells in the liver, Kupffer cells and pit cells in the process is suggested.
",3
689,"Hepatitis B virus integration in hepatitis B virus-related hepatocellular carcinoma in childhood.
 In Taiwan, hepatocellular carcinoma is one of the major malignancies in children between 5 and 14 yr of age.
 We studied the status of hepatitis B virus DNA in the hepatocellular carcinoma and nontumorous liver tissues of eight children with positive serum HBsAg and maternal HBsAg.
 The hepatocellular carcinoma tissues from five of the eight children showed integration of hepatitis B virus DNA into host cellular DNA sequences.
 A pattern of single-site integration in four children and a multiple-site integration pattern in one child were demonstrated.
 In the remaining three children, hepatitis B virus DNA could not be demonstrated in the tumor tissues.
 Using subgenomic fragments of the hepatitis B virus genome as probes, we found that the X gene fragment and the surface antigen gene fragment were the most conserved sequences.
 The single-site integration of hepatitis B virus DNA in childhood hepatocellular carcinoma may have hit the critical region, resulting in insertional mutagenesis and early development of hepatocellular carcinoma.
 With a short incubation period and less exposure to environmental carcinogens during early life, childhood hepatocellular carcinoma may provide a good model to study the carcinogenic potential of hepatitis B virus.
",3
690,"Liposarcoma arising in the cheek: report of a case and review of the literature.
 The following points can be made about liposarcoma of the oral cavity: 1) it is rare and slow growing; 2) it is often mistaken for a benign lesion; 3) there is a direct correlation of microscopic appearance with biological behavior and prognosis; 4) treatment is primarily surgical, with radiation used for selected cases; and 5) the better-differentiated tumors seem to respond more favorably to radiation.
",3
691,"A cohort study of fat intake and risk of breast cancer.
 Between 1982 and 1987, 519 newly incident, histologically confirmed cases of breast cancer were identified in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study.
 These women had completed a dietary questionnaire before the occurrence of their breast cancer, and this has been used to estimate their intake of dietary fat and several other nutrients.
 There is evidence of a positive association between breast cancer and total fat intake, with a relative risk of 1.35 (95% confidence interval, 1.00-1.82) per 77 g per day, and some evidence of a dose-response relationship (P = .052).
",3
692,"A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer.
 Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis and tumor growth in the rodent colon.
 We assessed NSAID use in relation to risk of human large-bowel cancer in a hospital-based, case-control study of 1326 patients with colorectal cancer and 4891 control patients.
 For regular NSAID use that continued into the year before interview, the multivariate relative risk estimate was 0.5 (95% confidence interval, 0.4 to 0.8); the estimate decreased as the duration of use increased, but the trend was not statistically significant.
 Similar results were obtained whether cancer or non-cancer controls were used, and the inverse association was apparent for both colon cancer and rectal cancer in men and women and in subjects younger and older than 60 years.
 Regular NSAID use that had been discontinued at least 1 year previously and non-regular use were not associated with risk.
 Almost all regular NSAID use was of aspirin-containing drugs.
 The present data suggest that the sustained use of NSAIDs reduces the incidence of human large-bowel cancer.
",3
693,"Rising incidence of adenocarcinoma of the esophagus and gastric cardia 
 Analyses of cancer incidence data from nine areas of the United States revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia.
 The increases among men in this period ranged from 4% to 10% per year, and thus exceeded those of any other type of cancer.
 In contrast, there were relatively stable trends for squamous cell carcinoma of the esophagus and slight declines for adenocarcinoma of more distal portions of the stomach.
 Adenocarcinomas of the esophagus and gastric cardia disproportionately affected white men and rarely occurred among women.
 By the mid-1980s, among white men, adenocarcinomas accounted for about one third of all esophageal cancers, while cardia cancers accounted for about one half of all stomach cancers with specified subsites.
 The rising incidence rates and similar demographic patterns point to the need for investigation into the causes of these poorly understood cancers.
",3
694,"Influence of chromosomal integration on glucocorticoid-regulated transcription of growth-stimulating papillomavirus genes E6 and E7 in cervical carcinoma cells.
 In most cervical carcinoma cells the E6 and E7 genes of specific human papillomaviruses are transcribed from viral sequences integrated into host cell chromosomes.
 Glucocorticoids activate the promoter elements of various human papillomaviruses in transient-expression assays.
 We have analyzed the effect of dexamethasone on the transcription rate of human papillomavirus 18 E6 and E7 genes integrated at different chromosomal sites in four cervical cancer cell lines.
 Dexamethasone led to an increase in the transcription rate of the integrated E6-E7 sequences in C4-1 and C4-2 cells but led to a decrease in SW 756 cells and did not affect the transcription rate in HeLa cells.
 However, when the viral promoter elements derived from HeLa or SW 756 cells, in which dexamethasone does not activate transcription of the integrated E6-E7 sequences, were tested in transient-expression assays within the same cell lines, dexamethasone consistently activated the viral promoter.
 It thus appears that dominant regulatory mechanisms presumably depending on the chromosomal integration site are able to override the response of the viral promoter to steroid hormones.
 The growth rate of all dexamethasone-treated cell lines correlated consistently with the expression of the papillomavirus E6 and E7 genes, supporting their role in the maintenance of the proliferative phenotype of cervical carcinoma cells.
 Since human papillomaviruses are integrated into the host cell genome at variable, presumably randomly selected chromosomal loci, regulatory mechanisms that influence viral gene expression, and hence cell growth, may differ among cancers of independent clonal origin.
",3
695,"Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form.
 A cDNA clone for human catechol-O-methyltransferase (hCOMT; S-adenosyl-L-methionine:catechol O-methyltransferase; EC 2.1.1.6) was isolated from a human hepatoma cell line (Hep G2) cDNA library by hybridization screening with a porcine cDNA probe.
 The cDNA clone was sequenced and found to have an insert of 1226 nucleotides.
 The deduced primary structure of hCOMT is composed of 271 amino acid residues with the predicted molecular mass of 30 kDa.
 At its N terminus it has a hydrophobic segment of 21 amino acid residues that may be responsible for insertion of hCOMT into the endoplasmic reticulum membrane.
 The primary structure of hCOMT exhibits high homology to the porcine partial cDNA sequence (93%).
 The deduced amino acid sequence contains two tryptic peptide sequences (T-22, T-33) found in porcine liver catechol-O-methyltransferase (COMT).
 The coding region of hCOMT cDNA was placed under the control of the cytomegalovirus promoter to transfect human kidney 293 cells.
 The endogenous COMT activity, which was approximately 9.98 units per mg of protein in the untransfected cells, increased to 206 units per mg of protein upon transfection with a plasmid containing the COMT cDNA.
 The COMT activity of recombinant protein was inhibited competitively (IC50 = 700 nM) by the selective COMT inhibitor Ro 40-7592.
 An anti-COMT monoclonal antibody recognized, on immunoblots, a major polypeptide with apparent molecular mass of 29 kDa, in reasonable agreement with the predicted molecular mass.
 The recombinant hCOMT was shown by immunoblot analysis to be mainly associated with the membrane fraction.
 RNA blot analysis revealed one COMT mRNA transcript of 1.4 kilobases in Hep G2 poly(A)+ RNA.
",3
696,"Stimulation of cAMP and phosphomonoester production by melanotropin in melanoma cells: 31P NMR studies.
 A major part of the present understanding of the molecular basis of signal transduction has been gained from in vitro studies using classical biochemical methods.
 In this study, we used 31P NMR spectroscopy to investigate the response of live M2R mouse melanoma cells to stimulation by melanocyte-stimulating hormone (MSH; melanotropin).
 In the presence of 3-isobutyl-1-methylxanthine and a synergistic dose of forskolin (1.67 microM), MSH induced a transient (approximately 60-min) rise in the cellular concentration of 3',5'-cyclic adenosine monophosphate (cAMP), which coincided in time with an equivalent decrease (approximately 40%) in ATP.
 However, no detectable change in phosphocreatine concentration was observed.
 Concomitantly, MSH induced a striking and unexpected increase in the concentration of three phosphomonoester (PME) metabolites (approximately 2-fold increase in total PME signal area); one signal has been assigned to phosphoethanolamine.
 The levels of the PMEs remained high for 2-4 hr and declined slowly (approximately 10 hr) to basal level, following perfusion with fresh culture medium.
 The increase in PME was also observed after stimulation with MSH alone.
 In contrast, stimulation with a high dose of forskolin (50 microM) and isobutylmethylxanthine (0.2 mM), although effective in stimulating the production of cAMP, did not induce the PME response.
 Evaluation of the cells' energetics indicated that the enhanced production of phosphoethanolamine is probably not due to ethanolamine phosphorylation.
 Therefore, it is likely to result from hydrolysis of phosphatidylethanolamine by a specific phospholipase C.
 The response of the PMEs appears to be regulated by a cAMP-independent process, suggesting the existence of an alternative transduction pathway controlled by MSH.
",3
697,"Mononuclear phagocytes: a major population of effector cells responsible for rejection of allografted tumor cells in mice.
 To understand the in situ mechanism of immunological response of recipient animals to allografted tumor cells, the types of cells that infiltrated into the rejection site were examined.
 When Meth A cells (H-2d) were given i.p.
 to an allogeneic [C57BL/6 (H-2b)] strain of mouse, the tumor cells ceased to grow on the 6th day, accompanied by an i.p.
 infiltration of leukocytes.
 The tumor cells were totally eliminated from the peritoneal cavity around the 12th day.
 The highest cytotoxic activity against Meth A cells was obtained with the peritoneal exudate cells harvested on day 8.
 On this day, the exudate cells consisted of three populations when examined by flow cytometry, and each was isolated by sorting.
 Each of them appeared to be homogeneous, and they were morphologically identified as lymphocytes; granulocytes; and medium-sized, mononuclear, less-granular cells.
 The cytotoxic activity was confined exclusively to the last population.
 The effector cells (H-2b) were cytotoxic against not only Meth A cells (H-2d) but also concanavalin A-stimulated allogeneic spleen cells [C3H/He (H-2k), CBA/N (H-2k), A/J (H-2a), BALB/c (H-2d), and DBA/2 (H-2d) strains of mouse].
 The effector cells were totally inert against concanavalin A-activated syngeneic spleen cells [C57BL/6 (H-2b) and C57BL/10 (H-2b) strains of mouse].
 The effector cells were phenotypically (Thy-1.2- CD3- Lyt-1- Lyt-2- L3T4- immunoglobulin- asialo GM1-), morphologically, and functionally distinct from cytotoxic T cells, natural killer cells, and lymphokine-activated killer cells but were adherent mononuclear phagocytes.
",3
698,"Intracranial chordoma in a preadolescent. Case report.
 Chordomas are rare tumors derived from notochord remnants occurring primarily in the sacrum, clivus, and cervical regions.
 Exceptionally, these tumors occur in children, though usually in the sacrum.
 Eight cases of clivus chordoma have been described in preteenagers.
 In this report, a clival chordoma with unusual radiologic features is described in an 11-year-old boy.
 The literature regarding this entity is reviewed.
",3
699,"Immunochemical studies on the differential binding properties of two monoclonal antibodies reacting with Tn red cells.
 Two monoclonal antibodies (MoAbs), BRIC 66 (IgM) and BRIC 111 (IgG1), were produced by immunizing mice with ovarian cyst blood group A1 glycoprotein and Tn red cells (RBCs), respectively.
 Their specificities were determined by inhibitions using Tn sialoglycoproteins (SGPs), mucins (armadillo [ASG] and ovine [OSG] submaxillary glycoproteins), and monosaccharides.
 BRIC 66 agglutinated both Tn and group A RBCs and reacted immunohistochemically with both the vascular endothelium and tumor cells from a group A adenocarcinoma, BRIC 66 was inhibited by N-acetylgalactosamine (GalNAc), Tn SGPs, and mucins on both hemagglutination inhibition tests and radioimmunoassay.
 BRIC 111 agglutinated Tn RBCs only, and it specifically stained tumor cells from a group O patient's breast carcinoma and a group A patient's adenocarcinoma.
 In hemagglutination inhibition tests, BRIC 111 was readily inhibited by Tn SGPs, only partially inhibited by GalNAc, and not inhibited by mucins.
 In a sensitive radioimmunoassay, BRIC 111 was inhibitable by GalNAc.
 Tn SGP was 2000-fold more effective as an inhibitor than the mucins (ASG and desialized OSG), which contain a high content of terminal alpha-GalNAc-O-serine (threonine) residues.
 It is postulated that BRIC 66 is specific for terminal alpha-GalNAc units in carbohydrate chains.
 The exclusive reaction of BRIC 111 with Tn SGP indicates a combining site larger than GalNAc alpha-1, which probably includes amino acid residues in juxtaposition to GalNAc in Tn SGP.
 In view of its specific agglutination of Tn RBCs, BRIC 111 is a useful reagent for the examination of polyagglutinable RBCs.
",3
700,"Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens 
 The authors investigated the humoral and tissue expression of six antigens associated with medullary thyroid cancer (MTC): calcitonin (CT), calcitonin gene-related peptide (CGRP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), somatostatin (SRIF), and thyroglobulin (TG).
 The antigens were studied in the neoplastic C cells using immunohistochemistry with specific antisera and in the plasma using specific radioimmunoassay.
 Eighteen patients (8 male and 10 female patients, aged 12-72 years) were studied.
 Mean follow-up was 70.7 months (range, 2-179 months).
 Nine patients (50%) died of their disease after a mean follow-up of 47.2 months (range, 2-116 months).
 By immunostaining, primary tumors expressed CT and CEA in all cases and NSE was positive in 90%, CGRP in 66%, SRIF in 63%, and TG in 58%.
 Metastatic tissues were positive in all cases of CT staining, 92.8% of CEA, 71.4% of NSE, 73.3% of CGRP, 38.5% of SRIF, and only 13.3% of TG staining.
 In positive cases the percentage of positive cells and the degree of staining were variable among the different antigens.
 The expression of an antigen in the neoplastic cells was associated with the hypersecretion of the corresponding antigen in the circulation in the case of CT and CEA.
 The levels of these antigens were elevated in all patients with metastases and could accurately predict the appearance of new metastases or indicate the effective treatment of previous metastases by surgery.
 In the case of NSE, CGRP, and SRIF, few patients had increased plasma concentrations of the antigens and these usually occurred during very advanced phases of the disease.
 Detectable levels of serum TG were never observed.
 When the outcome of the disease was compared with the expression of CT, CEA, NSE, CGRP, and TG, no correlation could be found.
 On the contrary, SRIF expression in the primary tumor could differentiate two groups of patients with different survival rates.
 SRIF-positive patients had survival rates of 100% and 50% at five and seven years, respectively, whereas SRIF-negative patients had survival rates of 40% at five years and 25% at seven years.
",3
701,"Small cell carcinomas of the large intestine.
 The authors studied the clinical and pathologic features of 38 small cell carcinomas of the large intestine.
 Most were located in the right colon.
 Overlying adenomas were present in 45% and squamous differentiation in 21% of tumors.
 Endocrine differentiation was present in all tumors by at least one method; neuron-specific enolase, dense-core granules, and synaptophysin were present in most cases.
 Seventy-one percent of tumors metastasized to the liver; 64% of patients were dead at five months follow-up.
 Twenty-one poorly differentiated adenocarcinomas and undifferentiated carcinomas of the large intestine accessioned during the same period showed less endocrine (7 of 21) and squamous differentiation (1 of 15) and fewer liver metastases (4 of 15) than did small cell carcinomas.
 Among all 59 tumors studied, small cell histologic characteristics correlated better with liver involvement than did endocrine markers or other histologic features.
 Small cell carcinomas of the large intestine are aggressive tumors with a propensity for early liver involvement.
 Although there is a spectrum of squamous, endocrine, and glandular features in large bowel tumors of low degrees of differentiation, the identification of a small cell component appears to be most clinically relevant.
",3
702,"Automated immunohistochemical estrogen receptor in fixed embedded breast carcinomas.
 The authors immunohistochemically assessed the presence of estrogen receptor (ER) in formalin-fixed, paraffin-embedded tissue sections of 68 breast carcinomas by an automated method using Pronase (CalBiochem, La Jolla, CA) predigestion and alkaline phosphatase detection (Method 1).
 These results were compared with those obtained by an automated peroxidase-antiperoxidase method with DNAse pretreatment of fixed embedded sections (Method 2), with ER immunostain on frozen sections (Method 3), and with biochemical results (dextran-coated charcoal cytosolic [DCC] assay).
 Compared with the DCC assay, Methods 1, 2, and 3 gave sensitivities of 54%, 25%, and 89%, respectively.
 The sensitivity for Method 1 was increased to 74% in those cases with DCC results showing greater than 50 fmol/mg protein.
 These findings indicate that ER immunohistochemical studies on formalin-fixed paraffin-embedded tissues (as assayed by Method 1) provide useful clinical information when the results are positive.
 A negative result, especially if surrounding normal elements are not positive, may indicate no receptors, receptor levels less than 50 fmol/mg protein, or improper tissue preservation.
 In the absence of fresh tissue for ER assay by DCC assay or of frozen sections for immunostaining, and with an understanding of its limitations, this method may be useful.
",3
703,"Ovarian myxoma. A study of two cases with long-term follow-up.
 Two cases of the so-called ovarian myxoma are reported.
 One was from a 13-year-old girl who had a 31-year follow-up and no evidence of recurrence.
 The second case, from a 65-year-old woman, recurred intraperitoneally, 19 years after the surgery.
 Both tumors were myxoid, with round to stellate cells.
 Immunohistochemical, electron microscopic (EM), and DNA flow cytometric (FCM) studies were performed on formalin-fixed, paraffin-embedded tissue of the second patient on both the primary tumor and the recurrence.
 Tumor cells expressed vimentin and were focally positive for desmin and myoglobin.
 EM findings suggested a fibroblastic differentiation.
 An aneuploid cell population was present in the recurrent tumor by DNA-FCM studies.
 Only four other cases of so-called ovarian myxoma were reported to date, and the follow-up does not exceed 18 months.
 The authors conclude that the presence of aneuploidy and the late recurrence of one of their cases suggest that certain ovarian myxomas might behave like low-grade sarcomas.
 The histogenesis of this tumor remains unsettled, but similarities were found with myxomas in other locations.
",3
704,"Local reactions to radioiodine in the treatment of thyroid cancer.
 PURPOSE: To compare the rate of local complications resulting from radioiodine ablation of thyroid cancer in patients with a residual intact thyroid lobe to that in patients who had more extensive surgical treatment prior to radioiodine administration.
 PATIENTS AND METHODS: We retrospectively studied 59 patients who had received 131I between 1979 and 1989.
 The patients were divided into two groups, depending on the extent of their previous surgical thyroid excision.
 Group 1 comprised 10 patients with a lobectomy or hemithyroidectomy before the ablative radioiodine dose, and Group 2 comprised 49 patients with more extensive thyroid excision (near-total or subtotal thyroidectomy) before the radioiodine treatment.
 RESULTS: Sixty percent of the 10 patients in Group 1 experienced some degree of neck pain or tenderness following radioiodine ablation of their residual thyroid.
 In one case, the local reaction was very severe and accompanied by the development of transient hyperthyroidism.
 There was only a 6% local complication rate in the patients who had undergone more extensive thyroid excision before ablative therapy (p less than 0.001), and none had a severe reaction.
 CONCLUSIONS: Patients with only unilateral surgical excision before radioiodine therapy have a higher rate of local complications than do patients treated with more extensive surgery prior to radioiodine ablation.
 If radioiodine is to be employed in such patients, they should be informed of this possible complication.
 Since evidence supports a dose effect in the pathogenesis of the complications, we recommend using a dose of less than 30 mCi for the initial ablation in these patients even though it may be necessary to repeat this dose to complete thyroid ablation.
",3
705,"Suddenly symptomatic brain tumors at altitude.
 High-altitude cerebral edema can present with a wide variety of neurologic manifestations; these symptoms resolve with descent.
 The persistence of neurologic symptoms after descent suggests an intracranial lesion.
 Brain tumors suddenly becoming symptomatic at altitude have not been reported previously.
 We report three cases of previously unsuspected brain tumors that suddenly became symptomatic at high altitudes.
",3
706,"Surgical staging of cervical cancer.
 Noninvasive radiologic methods to detect paraaortic lymph node metastases are reliable when combined with FNA of enlarged lymph nodes.
 However, the sensitivity is low, and undetected microscopic metastases leads to treatment failure.
 These patients with paraaortic lymph node metastasis are not treated with extended-field radiation, and they all die within 3 years.
 The CT scanning is probably the best diagnostic method to evaluate cervical cancer, because it can assess the primary tumor, the urinary tract, gastrointestinal tract, liver parenchyma, and retroperitoneum.
 It also permits the guidance of FNA and the arrangement of radiation ports.
 Surgical staging provides the direct assessment of the peritoneal cavity and the retroperitoneal spaces.
 Metastatic tumor, including enlarged lymph nodes, can be resected, but this is of dubious benefit.
 The operative morbidity is acceptable, with fewer intestinal complications when the extraperitoneal approach is used, and long-term morbidity is minimal when appropriate paraaortic radiation doses are employed (less than 5,000 cGy).
 Surgical staging has provided data on the frequency of paraaortic lymph node metastasis by stage of cervical cancer, and thus, treatment strategies can be better developed.
 Extended-field radiation results in 5-year survival rates of 20-25% in patients with microscopic paraaortic lymph node metastasis, patients who would not survive without the treatment.
 However, surgical staging has produced only a modest boost in survival rates, because of the high rate of pelvic and systemic failure.
 When extended-field radiation is used prophylactically or in patients with probable lymph node metastasis seen on radiographic studies, survival rates are similar to patients irradiated after surgical staging finds paraaortic lymph node disease.
 As our ability to predict, and detect nonsurgically, positive paraaortic node disease improves, extended radiation (or other adjuvant therapy) could be used more frequently without operation in patients who are at high risk for metastatic disease.
 In a study by Haie et al, prophylactic paraaortic radiation was given to patients at high risk for paraaortic metastasis.
 In patients with a high probability of local disease control, paraaortic radiation significantly reduced the incidence of paraaortic and distant metastases.
 Patients with known paraaortic lymph node metastases frequently have occult systemic metastases.
 In these same patients, pelvic failure is also common.
 Thus, until effective systemic therapies emerge, a marked improvement in survival is unlikely in patients who have paraaortic lymph node metastasis.(ABSTRACT TRUNCATED AT 400 WORDS).
",3
707,"The management of malignant bone tumors in children and adolescents.
 A series of 205 pediatric patients affected by osteosarcoma, Ewing's sarcoma, fibrosarcoma, and malignant fibrous histiocytoma of bone were treated from 1978 to 1988.
 Ninety-eight percent of the patients received chemotherapy and 63% had a surgical resection.
 Sixty-five percent of all patients were alive at 30 months and were considered disease free.
 The functional results after surgery were evaluated according to the Musculoskeletal Tumor Society score.
 In all diaphyseal resections and resections of the upper extremity and pelvis, the results were excellent or good in 60% of the cases.
 In resections of the proximal femur, distal femur, or proximal tibia and reconstruction with nonexpansible prostheses, the results were excellent or good in 75%.
 On the other hand, when arthrodeses of the lower extremity were used, only 14% of cases had a good result.
 This correlates with the resulting lack of articulation and serious limb shortening seen with progression of skeletal growth.
",3
708,"Dexamethasone-nonsuppressible cortisol in two cases with aldosterone-producing adenoma.
 Forty-one patients with aldosterone-producing adenoma (APA) were subjected to a dexamethasone suppression test (DST) before surgery.
 Serum cortisol and urinary excretion of 17-hydroxycorticosteroids were suppressed by dexamethasone in 39 patients [DST(+)].
 In two patients (cases A and B), they were not suppressed [DST(-)].
 Clinical manifestations of the two DST(-) patients were similar to those of DST(+) patients.
 Hypertension, hypokalemia, high serum aldosterone levels, and suppressed PRA were found in all of the patients.
 The cut surfaces of the adenomas from all of the patients, including cases A and B, were golden yellow, which is typical of APA.
 However, atrophies of the adjacent normal tissues were evident exclusively in the two DST(-) patients.
 After removal of the affected adrenals, the serum cortisol level was suppressed by dexamethasone in one of the DST(-) patients (case B).
 These findings suggested autonomous cortisol production by APA.
 To evaluate whether cortisol could be produced from the adenoma tissue, the presence of several steroidogenic enzymes was studied by immunohistochemistry and mRNA analysis in the adenomas and the adjacent nonneoplastic adrenals from the 2 DST(-) and 5 DST(+) patients.
 Immunohistochemical analysis demonstrated that steroidogenic enzymes were expressed in APA tumor tissues from both DST(-) and DST(+) patients.
 In both groups, mRNAs coding steroidogenic enzymes were present not only in the nonneoplastic but also in the tumor tissues.
 Quantitative analysis of the mRNA levels revealed that in the adrenals from DST(+) patients, the mRNAs were more abundant in nonneoplastic tissue than in tumor tissue.
 However, in those from DST(-) cases, the mRNAs were much more abundant in the tumor tissues than in the nonneoplastic tissues.
 These results indicate that tumor cells of the two DST(-) patients autonomously synthesized not only aldosterone but also cortisol.
 The diameters of the tumors from the two DST(-) patients exceeded 3 cm, while those from other DST(+) patients were smaller.
 In patients with large APA, adrenal insufficiency should be anticipated upon removal of the tumor.
",3
709,"Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.
 A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver.
 QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does.
 Staining was uniformly strong and clear in all histological variants of these two tumours.
 QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver.
",3
710,"Generation of ""soft x-rays"" by using the free electron laser as a proposed means of diagnosing and treating breast cancer.
 The diagnosis and treatment of breast lesions may be markedly enhanced by the use of a unique new source of near-monochromatic x-rays.
 Concentric beams of near-monochromatic x-ray photons may be generated by collision of the free electron laser (FEL) electron beam with the optical beam in an interaction zone that delivers the x-rays to a shirtsleeve environment.
 The absence of Compton scatter and the photoelectric interaction within tissues improves conspicuity of lesions by two to six times.
 Increased attenuation of x-rays in malignant vs.
 normal tissues makes tumors more obvious.
 K-edge subtraction allows chemical analysis of tumors in vivo--all at radiation doses that are one-tenth to one-fiftieth that delivered by the lowest-dose mammographic x-ray technique available.
 This allows for an increased sensitivity and specificity and permits prediction of histology, negating necessity for biopsies.
 Selective bond-breaking at depth in tissues as well as x-ray-activated photodynamic therapy are also being explored.
",3
711,"Effective surgical adjuvant therapy for high-risk rectal carcinoma 
 BACKGROUND.
 Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival.
 In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy.
 We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone.
 METHODS.
 Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU).
 RESULTS.
 After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent).
 Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent).
 In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent).
 Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia.
 These effects were seldom severe.
 Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups.
 CONCLUSIONS.
 The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis, as compared with postoperative radiation alone.
",3
712,"Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia of childhood.
 BACKGROUND.
 Leukemic cells in 15 to 25 percent of patients with acute lymphoblastic leukemia (ALL) express myeloid antigens as well as lymphoid antigens (the latter reflecting B-cell or T-cell lineage).
 The relations of myeloid-antigen expression to other features of ALL and to prognosis have been controversial.
 METHODS.
 We analyzed clinical and laboratory features present at diagnosis in 236 consecutive cases of ALL in children.
 Immunophenotyping, including single- and dual-fluorescence analyses, was used to classify leukemic cells as B or T lymphoblasts and also to identify myeloid-antigen expression--the simultaneous expression of lymphoid-associated antigens and at least one of three myeloid-associated antigens (CD33, CD13, and CD14) on cells classified as L1 or L2 according to the French-American-British system.
 RESULTS.
 Forty-five of 185 patients with B-lineage ALL had myeloid-antigen expression, as did 8 of 41 patients with T-lineage ALL.
 In 10 patients, the lineage could not be determined.
 Myeloid-antigen expression was associated with L2 morphology (P less than 0.05), but it did not correlate with other prognostic features recognized previously.
 Multivariate analysis showed that myeloid-antigen expression was an important predictor of relapse in childhood ALL and the most significant prognostic factor statistically (P less than 0.0001).
 A white-cell count greater than or equal to 50 x 10(9) per liter at diagnosis was also an important and highly significant prognostic feature (P less than 0.001).
 After 40 months, the estimated disease-free survival for patients with ALL was 84 percent for those without myeloid-antigen expression and with a low white-cell count, 57 percent for those without myeloid-antigen expression and with a high white-cell count, 47 percent for those with myeloid-antigen expression and a low white-cell count, and 26 percent for those with myeloid-antigen expression and a high white-cell count (P less than 0.00001).
 CONCLUSIONS.
 Myeloid-antigen expression is an important independent predictor of a poor response to chemotherapy in childhood ALL.
",3
713,"Interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors.
 Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia.
 Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%.
 There were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3 adenocarcinomas.
 Catheters were implanted stereotactically after computed tomography-based preplanning.
 Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes.
 The goal was to heat as much of the tumor as possible to 42.5 degrees C for 30 minutes.
 Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy.
 Most patients had no sensation of heating.
 Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3.
 Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression.
 Ten patients underwent reoperation for persistent tumor and/or necrosis.
 Eleven of 28 patients are alive 40 to 97 weeks after treatment.
 Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus.
 The median survival was 55 weeks overall.
 Median survival has not yet been reached for the anaplastic astrocytoma subgroup.
 We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible.
 The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.
",3
714,"Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors.
 Ribonucleic acid was isolated from a wide spectrum of central nervous system tumors to examine the expression of platelet-derived growth factors (PDGF) A and B, tumor growth factors (TGF-beta) 1 and 2, and ros messenger ribonucleic acid.
 Eight glioblastoma cell lines were examined as well as cell cultures from 22 tumor explants.
 The explants included 6 glioblastomas, 4 anaplastic astrocytomas, 5 astrocytomas, 3 ependymal tumors, 2 meningiomas, 1 medulloblastoma.
 and 1 ganglioglioma.
 For comparison, 2 nontumor glial cell cultures were included.
 The PDGF B-chain was expressed in 5 of 8 glioblastoma cell lines, 2 of 6 glioblastomas, and in 3 of 4 anaplastic astrocytoma explants.
 There was no PDGF B expression in 4 astrocytomas, 3 ependymomas of varying malignancy, in the remainder of the tumors, or in the nontumor glial cells.
 The PDGF A-chain was expressed in all of the tumors, with the exception of the malignant ependymoma and in both nontumor glial cell cultures.
 TGF-beta 1 was expressed in all of the tumors and in nontumor glial cells.
 The expression of TGF-beta 2 was expressed in many of the benign and malignant tumors and also in both nontumor glial cell cultures.
 The ros messenger ribonucleic acid was expressed in 1 of 5 glioblastoma cell lines and in 2 of 6 glioblastoma cell explants, but in none of the other tumors or in the nontumor glial cells.
",3
715,"Spinal glioblastomas: report of seven cases and review of the literature.
 Intramedullary glioblastomas are uncommon tumors.
 They occur chiefly in the cervicothoracic segments, have a slight tendency to occur in the early decades of life, and have a short clinical history before diagnosis.
 We report seven cases and discuss the salient features of these tumors, particularly the pathological features and treatment, in light of the relevant literature.
",3
716,"Oral cancer: a survey of 566 cases from the University of Connecticut Oral Pathology Biopsy Service, 1975-1986.
 A survey of the University of Connecticut Oral Pathology Biopsy Service was undertaken to analyze cases of oral cancer accessioned during the 12-year period, 1975 through 1986 inclusive.
 Of 33,429 total specimens accessioned, there were 546 malignant oral neoplasms diagnosed and reported.
 Sixty-five (11.5%) originated from out of state.
 Invasive intraoral squamous cell carcinoma was the predominant tumor (69.7% of total), whereas lip cancer constituted only 2.8% of all malignancies.
 Minor salivary gland adenocarcinomas accounted for 11% of total malignancies whereas verrucous carcinoma, carcinoma in situ, and miscellaneous other forms of oral cancer accounted for the remainder (4.6%, 5.3%, and 6.6%, respectively).
 Cases of invasive squamous cell carcinoma were further analyzed by year, sex distribution, location subsite, age at diagnosis, and histologic grade.
 With the exception of histologic grading, we found that the characterization of cases of squamous cell carcinoma within the biopsy service tended to parallel results from a separate but related statewide analysis of both oral cancer and intraoral squamous cell carcinoma from Connecticut over a much longer time span.
 We concluded that the picture of oral cancer as characterized by cases within the University of Connecticut Oral Pathology Biopsy Service is generally reflective of the disease on a statewide level.
",3
717,"Ectatic blood vessels in port-wine stains lack innervation: possible role in pathogenesis.
 The innervation pattern of port-wine stains was investigated using indirect immunohistochemistry with antibodies to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), calcitonin gene-related peptide (CGRP), and neurofilament (NF).
 The pathologically dilated vessels in the middle and deep dermis were found to have defective innervation with only single or no nerve fibers in their vicinity, while other structures in the skin showed a normal density of fibers.
 NSE- and PGP-like immunoreactive (-LI) nerve fibers were observed innervating vessels with a normal morphology and other structures in the skin, such as sweat glands and hair follicles, as free nerve endings and in nerve bundles.
 The nerve bundles were often seen to pass the ectatic vessels without giving off any branches.
 CGRP-LI nerve fibers were detected running toward epidermis, whereas no fibers were found around the ectatic vessels.
 NF-LI fibers were seen innervating normal vessels in dermis, while in relation to the dilated vessels, no or only occasional fibers were observed.
 The lack of innervation may be of importance for the development of the disease as a result of decreased tonus of the vessels and/or a loss of neuronal trophic factors.
",3
718,"A community study of delay in presenting with signs of melanoma to medical practitioners.
 In the absence of more effective treatment for advanced tumors, early diagnosis and treatment of localized tumors is the most effective way of reducing the burden of illness associated with melanoma.
 This study examined the following factors: prevalence of signs of melanoma (a mole changing in size, shape, appearance, or color, itching or tingling, bleeding or weeping, becoming raised) in 1344 individuals in a randomly selected sample of 1075 households; the length of delay in seeking medical advice; the factors associated with either going to a medical practitioner or not going/delaying; and the actions of the medical practitioners when first presented with these signs.
 The results indicate that a large proportion of the sample (11.9%, n = 156) had observed signs of melanoma in the previous 12 months.
 Of the sample reporting signs that had first appeared in the previous 5 years, only 32% sought medical advice about the signs within the recommended period.
 Of the sample either not seeking advice at all or delaying, 49% reported that they thought the sign ""wasn't serious/would clear up."" Furthermore, 30% of the sample either did not known or underrated the importance of early detection and treatment of lesions.
 These results indicate that there is a deficit in the knowledge of the general public about the signs of melanoma, the severity of the disease, and the possible risks associated with delay.
",3
719,"The potential role of postoperative hepatic artery chemotherapy in patients with high-risk hepatomas.
 The relationship between operative findings of hepatoma and the postoperative prognosis was studied to clarify indications for adjuvant hepatic arterial chemotherapy after hepatectomy.
 The results of adjuvant hepatic arterial chemotherapy using 0.4 mg/kg of doxorubicin and 0.12 mg/kg of mitomycin C and infusion of 5-fluorouracil were reported.
 One hundred sixty patients who had undergone hepatectomy for hepatoma were studied.
 In the operative findings of hepatoma, with a surgical margin of less than 10 mm, intrahepatic metastasis, tumor embolus in the second or more proximal branch of the portal vein, or lack of capsule formation related to the prognosis were the risk factors for recurrence.
 In 132 patients with these risk factors the survival rate of 19 patients with adjuvant arterial chemotherapy was significantly higher than for the 113 patients without it.
 Adjuvant hepatic arterial chemotherapy thus may be an effective therapy and should be studied prospectively in patients undergoing hepatectomy for high-risk hepatoma.
",3
720,"Surgical management of 552 carcinomas of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded). Results of the French Surgical Association Survey.
 Five hundred fifty-two cases of primary carcinoma of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded) collected from 55 surgical centers were reviewed retrospectively.
 Three hundred seven patients (56%) had upper-third lesions (proximal carcinoma), whereas 71 (13%) and 101 (18%), respectively, had middle-third and lower-third bile duct carcinomas.
 The remaining patients had diffuse lesions.
 Resectability rates were 32% for upper-third localization compared to 47% and 51% for middle-third and lower-third localization, respectively.
 The operative mortality rate for proximal carcinomas was significantly lower with resection (16%) compared with palliative surgery (31%) (p less than 0.05).
 Overall 1-year survival (operative deaths excluded) was 68% after tumor resection compared to 31% after palliative surgery (p less than 0.001).
 Long-term results after surgical resection correlated with local and regional extension of the disease.
 The results of this study show that resection of extrahepatic bile duct carcinomas, particularly in an upper-third localization, often is associated with worthwhile long-term survival.
",3
721,"Bronchoalveolar carcinoma: factors affecting survival.
 One hundred thirty-four consecutive patients (65 men and 69 women) underwent pulmonary resection for bronchoalveolar carcinoma.
 Mean age was 65 years.
 Lobectomy was done in 100 patients, pneumonectomy in 10, segmentectomy in 5, and wedge excision in 19.
 Only 10 patients had lymph node metastases (7.5%).
 The neoplasm was solitary in 111 patients (82.8%); 97 were in stage I, 4 were in stage II, 9 were in stage IIIa, and 1 was in stage IIIb.
 There were two operative deaths (1.5%).
 Thirty-nine complications occurred in 31 patients.
 Median follow-up was 5.1 years.
 Recurrent bronchoalveolar carcinoma developed in 45 patients.
 Five- and 10-year survival for patients in stage I was 75.2% and 62.0%, respectively.
 Survival for patients with T1 N0 M0 neoplasms was identical to expected survival and was 90.5% at 5 years, as compared with 55.4% for patients with T2 N0 M0 disease, only 35.9% for patients with multiple bilateral disease, and 0.0% for patients with bilateral disease (p less than 0.0001).
 Other significant factors adversely affecting survival included the presence of signs and symptoms, diffuse malignant invasion, mucin-producing tumors, and the histological absence of scar.
 We conclude that bronchoalveolar carcinoma has a unique natural history that is more influenced by local neoplastic processes than by lymph node metastases.
 Early aggressive pulmonary resection is safe and offers the potential for cure.
 The presence of bilateral cancer, however, is ominous.
",3
722,"Primary cysts and tumors of the mediastinum.
 A retrospective analysis was performed on 230 patients with primary cysts and tumors of the mediastinum seen at our institution from January 1944 to April 1989.
 We divided these patients into two groups.
 Group 1 was seen before 1970 and group 2 was seen from January 1970 to April 1989.
 There was a significant increase in the prevalence of malignancy in group 2 (47.2% versus 17.1%; p less than 0.0001) due to an increase in the number of lymphomas (22.6% versus 3.5%; p less than 0.001) and malignant neurogenic tumors (6.8% versus 1.1%; p = 0.0528).
 There was a significant increase in the number of malignant tumors in the anterior (59.5% versus 30.9%; p = 0.0022) and paravertebral (28.5% versus 2.8%; p = 0.0027) compartments in group 2.
 More patients with these tumors were symptomatic in group 2 (63.6% versus 5%; p = 0.0422).
 There was an increase of ancillary diagnostic studies performed to evaluate these tumors (76.0% versus 34.5%; p = 0.0422).
 Logistic regression analysis identified date of presentation (p less than 0.005), symptoms (p less than 0.01), size (p less than 0.005), and the anterior mediastinal compartment (p less than 0.005) as preoperative predictors of malignancy.
 The surgical approach to these tumors included more median sternotomy (30.1% versus 10.7%; p = 0.0008), anterior mediastinotomy, and cervical mediastinoscopy in group 2 (1.1% versus 17.5%; p = 0.0002).
 Long-term results support surgical resection in benign lesions and an aggressive multimodality approach to malignant lesions.
",3
723,"Surgical management of carcinoid heart disease 
 Metastatic carcinoid tumor is often seen with flushing, diarrhea, and cardiac symptoms--the carcinoid syndrome.
 Cardiac failure is often associated with major morbidity and mortality in carcinoid disease.
 In this report, a case of successful cardiac valvar surgical intervention has resulted in prolonged alleviation of cardiac symptoms and survival.
",3
724,"Inflammatory breast cancer.
 Historically, the prognosis of inflammatory breast cancer has been poor.
 We conducted a retrospective review to evaluate the recent Memorial Sloan-Kettering Cancer Center experience, to evaluate the role of combination chemotherapy, and to compare the effect of surgery and radiation on local/regional failure.
 Fifty-six patients with local/regional inflammatory breast cancer diagnosed between 1975 and 1984 were identified.
 All were treated with combination chemotherapy.
 Overall 5-year survival was 45% with a 5-year disease-free survival rate of 37%.
 Twenty-one patients were treated with induction chemotherapy followed by mastectomy and adjuvant chemotherapy.
 Survival and disease-free survival rates were similar to those achieved in patients treated with mastectomy followed by chemotherapy.
 Residual cancer was found in all 21 patients treated with induction chemotherapy, with extensive disease present in 18, including six of seven complete responders.
 The local/regional failure rate was 34%.
",3
725,"Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence.
 The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months.
 The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage.
 In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival.
 Recurrent disease was found in 42% of patients, excluding patients with stage IV disease.
 The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences.
 Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease.
 The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence.
 Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment.
 The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease.
",3
726,"Prognostic factors in primary retroperitoneal soft-tissue sarcomas.
 We analyzed independent treatment variables (age, sex, signs and symptoms, site, size, histopathologic findings, grade, and clinical presentation) and treatment-dependent variables (resectability, type of operation, surgical margins, surgical boundaries, microscopic margins, adjuvant radiotherapy, and adjuvant chemotherapy) in 80 patients with primary retroperitoneal soft-tissue sarcomas admitted from 1982 through 1988.
 Both univariate and multivariate analysis of survival and disease-free survival were performed.
 The major factor in survival outcome was the ability to completely resect the lesion.
 When the 62 patients who underwent complete resection were examined, the only independent prognostic factor for both survival and disease-free survival was grade.
 We conclude that completeness of resection and grade of the lesion are primary determinants of survival.
 Once all tumor is macroscopically removed, no advantage could be demonstrated by more extensive surgical resection or current adjuvant therapy.
",3
727,"Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal cancer.
 Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand-held gamma detecting probe.
 We report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer.
 One hundred four patients with primary, suspected, or known recurrent colorectal cancer received an intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4 x 10 Bq of iodine 125.
 Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined.
 Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe.
 The overall sensitivity was 77% and a predictive value of a positive detection was 78%.
 A total of 30 occult sites in 26 patients were identified.
 In patients with recurrent cancer, the antibody study provided unique data that precluded resection in 10 patients, and in another eight patients it extended the potentially curative procedure.
",3
728,"Radical resection for carcinoma of the ampulla of Vater.
 One hundred four consecutive patients who underwent radical resection for ampullary cancer between 1965 and 1989 were retrospectively reviewed.
 Frequent clinical findings included jaundice (67%), significant (greater than 10%) weight loss (42%), and anemia (27%).
 Eighty-seven patients (84%) underwent a subtotal pancreatectomy, and 17 patients (16%) underwent a total pancreatectomy.
 The postoperative mortality was 5.7% (six patients), and reoperation for postoperative complications was required in six patients.
 The 5- and 10-year survival rates were 34% and 25%, respectively.
 Eight patients died of tumor recurrence more than 5 years after resection.
 Patient survival was significantly impaired by microscopic lymphatic invasion, regional nodal metastasis, tumor grade, and the epithelium of origin.
 In a multivariate analysis, only microscopic lymphatic invasion significantly reduced patient survival.
 Radical resection for ampullary cancer can be performed with a low morbidity and mortality and should remain the procedure of choice for ampullary carcinoma.
",3
729,"5-year results of cisplatin and fluorouracil infusion in head and neck cancer.
 As part of the developmental process for the Head and Neck Intergroup trial of adjuvant chemotherapy for advanced resectable head and neck carcinoma, in 1981 the Radiation Therapy Oncology Group, Philadelphia, Pa, conducted two nonrandomized pilot studies using chemotherapy consisting of three courses of cisplatin and fluorouracil infusion.
 Chemotherapy was administered prior to surgery in 42 patients (induction) and after surgery in an additional 29 patients (sequential).
 The populations were roughly comparable with respect to tumor site and stage.
 Twelve of the 42 patients in the induction group and seven of the 29 in the sequential group are alive and with no evidence of disease at the last reported follow-up.
 The median survival was 31 months in the sequential group vs 20 months in the induction group.
 Only two of the 26 patients with less than a complete clinical response following induction chemotherapy are still alive.
 Twenty-seven of the 42 patients who received induction chemotherapy did not undergo surgery as initially planned.
 Despite the lack of surgery, at 5 years the survival between the two groups was not significantly different (27% for the induction group vs 23% for the sequential group).
",3
730,"Effective destruction of cervical intraepithelial neoplasia (CIN) 3 at 100 degrees C using the Semm cold coagulator: 14 years experience 
 A total of 1628 women with CIN 3 treated with the Semm cold coagulator between 1975 and 1989 was followed primarily by cytology.
 The standard suitability criteria for ablation were adhered to except that patients were treated at their first visit when the colposcopist expected that the diagnosis would be no worse than CIN 3.
 Overall 97% of the women were treated at their first visit.
 In 30 women (2%) the histology was glandular or worse than expected, but 22 of these showed no persistent cervical disease subsequently.
 Follow-up was achieved for 87% at 10 years.
 In actuarial terms the primary success rate was 95% at 1 year and 92% at 5 years, it was similar for all age groups.
 Repeat cold-coagulation for persistent/recurrent CIN 3 was less successful and is not advised.
 The outcome for 226 pregnancies established after treatment is known.
 The rates for miscarriage, preterm or operative delivery were not increased.
 Cold-coagulation of CIN 3 at 100 degrees C as performed by us is as effective as any other treatment and calls into question the need for more expensive practices.
",3
731,"Vaginal epithelial abnormalities in patients with CIN: clinical and pathological features and management.
 Of 4147 women who had CIN treated by laser at the Regional Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, 103 (2.5%) had co-existing vaginal epithelial abnormalities.
 CIN 3 was the histological diagnosis most often associated with vaginal lesions.
 The upper vagina was almost always involved.
 In 67% the lesion in the cervix appeared to be confluent with that in the vagina.
 Even when the lesions were confluent, biopsies form the cervical and vaginal components did not always show the same grade of intraepithelial neoplasia and in some biopsies they showed different lesions.
 Laser treatment appears to be effective for the vaginal lesions and is therefore recommended although, in selected patients, careful follow up alone may suffice.
",3
732,"Carcinoma of the breast: measurement and the management of treatment. I. The value of the data.
 This is the first of a series of papers in which we shall explore some insights into the biological changes which accompany the treatment of human tumours which may be obtained through estimation of volume changes in relation to treatment.
 We have adopted a working hypothesis that regression slopes reflect the composition of individual tumours and, indirectly, their intrinsic growth rate rather than the effectiveness of treatment.
 The breast has proved to be a suitable site for measurement and our interpretation of the results has led to the development of a new style of management for carcinoma of the breast: measurement based sequential therapy (MBST).
 In this paper the method of measurement and detailed statistical evaluation of the quality of the data from 262 patients (263 tumours) is presented.
 Exponential regression lines have been fitted to describe volume changes in relation to treatment by radiation, chemotherapy and hormones.
 A simple classification of steepness of slopes is introduced.
",3
733,"Detection of colorectal liver metastases using intraoperative ultrasonography.
 Intraoperative ultrasonography of the liver has been carried out in 99 patients undergoing surgery for colorectal cancer.
 Palpation of the liver, preoperative abdominal ultrasonography and computed tomography scanning were also performed in all patients.
 Metastases were identified in 26 of the 99 patients (26 per cent).
 Intraoperative ultrasonography diagnosed more metastases than palpation, abdominal ultrasonography or CT scanning, identifying metastases in 24 of the 26 patients, including six patients in whom the metastases were not detected by any other technique.
 Identification and localization of impalpable liver metastases is therefore possible using intraoperative ultrasonography.
",3
734,"Primary papillary carcinoma of a thyroglossal duct cyst: report of a case and literature review.
 Thyroglossal duct cysts are the most common anomaly in thyroid development.
 They are twice as frequent as branchial cleft abnormalities and, in children, are second only to enlarged cervical lymph nodes as the cause of neck mass.
 Generally, duct cysts are benign, but 1 per cent of cases may be malignant.
 From the world literature, 114 cases of malignant thyroglossal cysts were available for review.
 With the addition of our own case, we discuss 115 instances of duct cysts.
 The different types of neoplasia described included thyroid papillary carcinoma in 81.7 per cent, mixed papillary-follicular carcinoma in 6.9 per cent, squamous cell carcinoma in 5.2 per cent, follicular and adenocarcinoma in 1.7 per cent each, and malignant struma, epidermoid carcinoma and anaplastic carcinoma in 0.9 per cent each.
 Of the 115 cases surveyed, 35 thyroid glands were examined microscopically; of these, four (11.4 per cent) contained malignant foci.
 Whether these are primary malignancies of the thyroglossal duct cysts or metastases is discussed.
",3
735,"The value of radioimmunoguided surgery in first and second look laparotomy for colorectal cancer.
 Radioimmunoguided surgery (RIGS) using an anti-CEA (A5B7) monoclonal antibody has been assessed in 52 patients (43 primary excisions and nine second look procedures) undergoing surgery for colorectal carcinoma.
 The antibody localized in 97.8 percent of primary tumours and in 88.8 percent of the principal tumor in second look procedures.
 Additional information concerning the extent of primary tumor was obtained in 11 of 43 patients (25.5 percent) undergoing excision of primary carcinoma and five of nine patients (55 percent) in the second look series.
 Incorrect information was obtained about the extent of the primary tumour in six patients (11.3 percent), whereas no incorrect information was obtained during second look procedures.
 RIGS correctly predicted the subsequent Dukes' staging in 77 percent of first look cases (sensitivity 65 percent, specificity 90 percent), although accurate identification of individual nodes was impossible.
 The technique influenced the surgical procedure performed in 2 of 43 cases (4.6 percent) in primary surgery and in three of nine patients undergoing second look laparotomy (33 percent).
 RIGS in primary colorectal carcinoma may provide additional information concerning extent of locally advanced tumors in particular and the principle that the subsequent surgery may be influenced has been established.
 The technique appears to have a greater role in second look procedures where it may help determine the extent of recurrent tumour.
 Larger follow-up series are required to define how the additional information provided by this technique may best be exploited.
",3
736,"Nuclear shape as a prognostic discriminant in colorectal carcinoma.
 In search for a more reliable prognostic discriminant, a retrospective analysis of 100 cases of colorectal carcinoma having undergone curative resection and followed for at least 5 years were assessed by nuclear morphometry.
 Each case was staged according to the Dukes' classification as well as graded histologically.
 For all patients in this series, the perimeter, area, and nuclear shape factor of 50 interphase nuclei were determined for each carcinoma.
 The information was obtained through the use of an image analysis system by tracing the nuclear profiles (magnification 1000x) as digitized on a video screen.
 The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0.
 A nuclear shape factor greater than 0.84 was associated with poor outcome.
 Multiple regression models showed that the single nuclear parameter of the shape factor was the most highly significant predictor of survival (P less than 0.0001).
 This variable remained highly significant even when corrected for sex, age, histologic grade, and Dukes' classification.
 These findings indicate that a nuclear shape factor greater than or equal to 0.84 as determined by nuclear morphometry is an independent morphometric nuclear variable of great importance in the prognosis of large bowel carcinoma.
",3
737,"Primary de novo adenocarcinoma of the colon measuring 8 mm in diameter with lymph node metastases. Report of a case.
 Colonic adenocarcinomas measuring less than 10 mm are rare.
 Herein, we report a carcinoma measuring 8 mm in diameter associated with subserosal extension through a ""locus minoris resistentiae"" and metastases to lymph nodes, an association not previously reported.
 No residual adenomatous tissue was found, suggesting a de novo carcinoma.
",3
738,"Development and characterization of a new, highly specific antibody to the human chorionic gonadotropin-beta fragment.
 In addition to high concentrations of hCG, pregnancy urine contains even higher concentrations of a fragment of the hCG beta-subunit.
 This biologically inactive material complicates immunological measurement of hCG, since it cross-reacts with many polyclonal and monoclonal antibodies to the hCG beta-subunit that are employed for assays of hCG in urine.
 Although we and others have developed antibodies to this fragment, specific measurement of the fragment in the presence of free hCG beta has remained difficult due to intrinsic cross-reactivity of these antibodies with the intact hCG beta.
 Rather than attempt to increase specificity by assay optimization, we developed a new, highly specific monoclonal antibody, designated B210, which cross-reacts less than 0.1% with the free hCG beta-subunit in both liquid and solid phase immunoassay formats.
 We have used this new monoclonal antibody in immunoradiometric assays to measure specifically the hCG beta fragment in urine throughout pregnancy as well as in the sera of two individuals with cancers producing the hCG beta-subunit.
 We discovered that the hCG beta fragment can bind three monoclonal antibodies simultaneously, indicating that although the epitope for antibody B210 is a new determinant exposed on the hCG beta fragment and not on intact hCG or on free hCG beta-subunit, the hCG beta fragment retains at least two other hCG beta-related epitopes intact, i.e.
 those that bind monoclonal antibodies B108 and B201.
",3
739,"Calcium transport by plasma membranes from a glucose-responsive rat insulinoma.
 Inside-out plasma membrane vesicles from a glucose-responsive rat insulinoma showed an ATP- and Mg2(+)-dependent uptake of Ca2+.
 The Km (concentration giving half-maximal activity) for Ca2+ was 60 nM.
 In the presence of 0.4 microM free Ca2+, the Km for ATP was 15 microM, and the Km for Mg2+ was 4 microM.
 Glucose (30 mM) decreased Ca2+ uptake by 50%, while other insulin secretagogues had no effect, except for glyceraldehyde, which stimulated Ca2+ uptake.
 Calmodulin increased the uptake of Ca2+, while trifluoperazine and vanadate inhibited the uptake.
 The Ca2(+)- and Mg2(+)-dependent ATPase from this tumor has a 10- to 20-fold higher requirement for Ca2+, which suggests that this enzyme is not responsible for Ca2+ transport, rather, Ca2+ transport activity represents only a small fraction of the total Ca2(+)-ATPase activity.
 The physiological importance of Ca2+ transport in insulin secretion is evident from the inhibition of Ca2+ uptake by glucose, which leads to a decrease in Ca2+ efflux from the cell.
 This inhibition would lead to an increase in intracellular free Ca2+ and insulin release.
",3
740,"Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells.
 Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation.
 In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation.
 Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs.
 An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA.
 The responses were dose-dependent and were maximal at 100 nM for both mRNAs.
 Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs.
 Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin.
 A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription.
 We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels.
 IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin.
 The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect.
 The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I.
",3
741,"Regulation of insulin, epidermal growth factor, and transforming growth factor-alpha levels by growth factor-degrading enzymes.
 The mechanisms by which growth factors are degraded and the role this process plays in the regulation of cell growth are not well understood.
 Insulin degradation is believed to be mediated by a specific metalloprotease, insulin-degrading enzyme (IDE).
 We have previously shown that IDE can also degrade transforming growth factor-alpha (TGF alpha), but not epidermal growth factor (EGF), in vitro.
 This selectivity was surprising, since TGF alpha and EGF are structurally similar and bind to the same receptor with comparable affinities.
 Using a spectrum of protease inhibitors, we have now analyzed the degradation of TGF alpha, EGF, and insulin by human hepatoma HepG2 cells.
 The results suggest that bacitracin-sensitive metalloproteases are involved in the degradation of TGF alpha and EGF as well as insulin, and that the degradation of TGF alpha, but not EGF, is mediated in part by IDE.
 Inhibiting the activity of these metalloproteases decreased growth factor depletion, suggesting that these enzymes play an important role in the control of extracellular growth factor levels.
 The existence of separate degradative pathways for EGF and TGF alpha may explain how the two factors exert differential effects in some systems, and degradation of TGF alpha by IDE would provide a possible mechanism for interaction between the insulin and TGF alpha/EGF signalling systems.
",3
742,"Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma.
 Independent and interactive effects related to the development of hepatocellular carcinoma were assessed using a community-based case-control study for hepatitis B virus, habitual alcohol drinking, cigarette smoking, peanut consumption and history of hepatocellular carcinoma among the immediate family.
 All 200 male newly diagnosed hepatocellular carcinoma patients were recruited consecutively through the period of study as the case group from two teaching medical centers in northern and southern Taiwan.
 Healthy community residents matched one-to-one with cases on age, sex, ethnic group and residential area were selected as the control group.
 The carrier status of HBsAg and HBeAg was determined by blind radioimmunoassays, and other risk factors were obtained through standardized interviews according to a structured questionnaire.
 Conditional logistic regression analysis showed a significant association between hepatocellular carcinoma and the carrier status of HBsAg and HBeAg with an odds ratio of 16.7 and 56.5, respectively, for carriers of HBsAg alone and for carriers of both HBsAg and HBeAg.
 There was a dose-response relationship between cigarette smoking and hepatocellular carcinoma with an odds ratio of 1.1, 1.5 and 2.6, respectively, for those who smoked 1 to 10, 11 to 20 and more than 20 cigarettes a day.
 A significant association with hepatocellular carcinoma was also observed for the habitual alcohol consumer with an odds ratio of 3.4.
 Those whose immediate family had a history of hepatocellular carcinoma were more likely to have the disease develop, with an odds ratio of 4.6.
 However, the frequency of peanut consumption was not significantly associated with hepatocellular carcinoma.
",3
743,"Usefulness of pulsed Doppler ultrasound in detection of angiographically evident recurrence of hepatocellular carcinoma after arterial embolization treatment.
 Because hepatocellular carcinoma treated by transcatheter arterial embolization often regains its size, routine follow-up is necessary.
 The usefulness of pulsed Doppler ultrasound for detection of this type of recurrence was compared with ultrasonography and computed tomography in 21 such hepatocellular carcinomas.
 Of 15 hepatocellular carcinomas diagnosed by angiography as showing recurrence, four were detected with ultrasonography and five were detected with computed tomography.
 Doppler signals were obtained in the peripheral portions corresponding to tumor vessels or stains on angiograms in 14 of these 15 hepatocellular carcinomas, but they were undetectable in six hepatocellular carcinomas with no recurrence.
 All signals disappeared after transcatheter arterial embolization.
 One false-negative hepatocellular carcinoma with pulsed Doppler ultrasound showed faint tumor stains on angiograms; these were also negative on ultrasonography and computed tomography.
 Pulsed Doppler ultrasound may be superior to ultrasonography and computed tomography as a routine procedure to detect the recurrence of hepatocellular carcinoma treated by transcatheter arterial embolization.
",3
744,"Acquired cisplatin resistance in human ovarian cancer cells is associated with enhanced repair of cisplatin-DNA lesions and reduced drug accumulation.
 Studies were undertaken to investigate acquired resistance to cisplatin in human ovarian cancer cells.
 The cell lines A2780 and A2780/CP70 were studied to assess their respective characteristics of drug accumulation and efflux, cytosolic inactivation of drug, and DNA repair.
 All experiments were performed using 1-h drug exposures.
 The A2780/CP70 cell line was 13-fold more resistant to cisplatin than A2780 cells.
 When studied at their respective IC50 doses, drug accumulation rates were similar for the two cell lines.
 However, the resistant cell line was twofold more efficient at effluxing drug, which was associated with reduced total drug accumulation for equivalent micromolar drug exposures.
 At equivalent levels of total cellular drug accumulation, the two cell lines formed the same levels of cisplatin-DNA damage, suggesting that cytosolic inactivation of drug does not contribute to the differential in resistance between these cell lines.
 Resistant cells were also twofold more efficient at repairing cisplatin-DNA lesions in cellular DNA and in transfected plasmid DNA.
 We conclude that in these paired cell lines, alterations in drug uptake/efflux and in DNA repair are the major contributing factors to acquired resistance to cisplatin.
",3
745,"Biology of basal cell carcinoma (Part I).
 Basal cell carcinoma is the most common malignancy in humans.
 Although rarely metastatic, it is capable of significant local destruction and disfigurement.
 This two-part article reviews the current understanding of basal cell carcinoma biology.
 Part I examines significant clinical, histologic, and ultrastructural features that relate to invasive potential.
 Genetic characteristics, including tumor growth rate, chromosomal abnormalities, and oncogene presence, are discussed, and expression of important cell and matrix proteins, including keratin, fibronectin, and HLA antigens, are reviewed.
 Further topics to be explored in Part II include host immunologic responses, theories of pathogenesis, and valuable second-line therapeutic regimens for treatment of multiple cancers.
",3
746,"Late metastases of cutaneous melanoma: case report and literature review.
 The development of delayed metastases, although rare, is well documented in patients with invasive cutaneous melanoma.
 Only 24 cases, including ours, are clearly documented in the literature.
 We describe a 56-year-old woman who had an acral lentiginous melanoma of the right hand (thickness 1.2 mm).
 Thirteen years after excision and postoperative irradiation, a subcutaneous metastasis developed in the right arm.
 One year later the patient died with disseminated bone metastases.
 This case, as with most of those with delayed metastases, has typical features: female sex; location at a site other than the back, arm, neck, or scalp; and primary tumor thickness between 1.2 and 2.5 mm.
",3
747,"Multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child.
 We describe an 11-year-old girl in whom multiple cutaneous granular cell tumors were associated with a giant speckled lentiginous nevus and an extensive nevus flammeus.
 An association between granular cell tumors and pigmented skin lesions has been reported twice previously and supports a neural origin for these tumors.
 An abnormality of neural crest development is proposed to explain the coexistence of three uncommon and unusually extensive cutaneous disorders in this patient.
 This case may represent a further variant of phakomatosis pigmentovascularis.
",3
748,"Abnormal epidermal changes after argon laser treatment.
 A 26-year-old woman with a congenital port-wine stain on the forehead was treated three times at 2-month intervals with an argon laser.
 Six months after the last treatment, moderate blanching and mild scaling confined to the treated area was observed.
 A biopsy specimen of the treated area revealed a significant decrease in ectatic vessels.
 However, epidermal changes similar to those of actinic keratosis with disorganized cell layers and marked cytologic abnormalities were seen.
 Analysis of peripheral blood lymphocytes for a defect in DNA repair was negative.
 Multiple, argon laser-induced photothermal effects may be responsible for the changes observed in our case and may lead to premalignant epidermal transformation.
",3
749,"Systematic computer-aided search of optimal staging system for colorectal cancer.
 Two hundred and ninety-eight patients with curatively resected colorectal cancer were classified into 12 categories according to the depth of tumour penetration (T1-T4), and lymph node status (N0-N2).
 Using a computer, these categories were grouped into 2-12 stages in every possible combination, so a total of 146,975 logical classifications were generated.
 The optimal model was selected for each group of classifications with equal stage number, thus giving the greatest prognostic information on 5-year survival according to the Akaike criterion.
 The results showed that (1) 13% of the total classifications, including 85% of the 3-stage classifications, were better than the Dukes system in predicting our patients' outcomes; (2) the T-level was a stage-determinant even more important than the N-level; and (3) major changes in prognosis occurred at more advanced stages than the classical ""turning points"".
 We conclude that in order to find an optimal staging of cancer, systematic computer-aided search through all the possible classifications is necessary, using the appropriate database.
",3
750,"Usefulness of epidurally evoked cortical potential monitoring during cervicomedullary glioma surgery.
 This report describes a patient with an intramedullary ependymoma at the region of the cervicomedullary junction in whom there was an abolition of somatosensory evoked potentials following median nerve stimulation.
 During intraoperative monitoring of cortical potentials elicited by epidural cervical cord stimulation, the tumor was removed.
 Posterior epidural stimulation appeared to depolarize more ascending fibers than did stimulation of a single peripheral nerve.
 We recommend that, in cases of operations in this vital area, epidurally evoked cortical potentials be monitored intraoperatively.
",3
751,"The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer 
 The importance of the interval between methotrexate (MTX) and fluorouracil (5-FU) was studied in 168 patients with previously untreated, measurable, advanced colorectal cancer.
 They were randomized to receive MTX 200 mg/m2, followed by 5-FU 600 mg/m2 either 24 hours (arm A) or 1 hour (arm B) after MTX.
 All patients received leucovorin (LV) 24 hours after MTX, 10 mg/m2 orally every 6 hours for six doses.
 The regimen was repeated every 2 weeks, with 5-FU escalation as tolerated.
 Arm A was significantly better than arm B with respect to overall response rate (29% v 14.5%, P = .026), time to progression (TTP; median, 9.9 months v 5.9 months, P = .009), and survival (median, 15.3 months v 11.4 months, P = .003).
 Significant differences between arms were not found in response rate, median TTP, or median survival for the subgroup of patients with rectal primaries who comprised 20% of the patients in each arm.
 Significant factors prognostic for survival were performance status and number of metastases, as well as treatment.
 Age did not influence survival.
 Toxicity was similar in both arms and was primarily gastrointestinal.
 More mucositis was seen in arm A.
 There were four toxic deaths secondary to neutropenia and infection (one from arm A and three from arm B) and three other deaths (two from arm A and one from arm B) that were possibly drug-related.
 The combination of MTX with LV rescue and 5-FU is an active regimen in advanced colorectal cancer; its efficacy is increased in colon, but not rectal cancer, when the interval between MTX and 5-FU is long (24 hours) rather than short (1 hour).
",3
752,"Clonogenic growth in vitro: an independent biologic prognostic factor in ovarian carcinoma 
 A retrospective analysis was performed to investigate the prognostic value of growth in a human tumor clonogenic assay system for 84 ovarian cancer patients.
 A significant difference in survival probability (determined by the method of Kaplan-Meier) was found by univariate analysis between patients with ovarian carcinoma whose tumors manifested clonogenic growth (defined as growth of greater than or equal to five colonies per plate) and patients whose tumors did not grow.
 Clonogenic growth in vitro was associated with worse prognosis (P = .007, log-rank test).
 A number of generally accepted prognostic factors, International Federation of Gynecology and Obstetrics (FIGO) stage (P = .003), residual tumor mass (P less than .001), and grade (P = .011), were also of prognostic importance in our patient population.
 Multivariate analysis, based on the Cox regression model, identified clonogenic growth as a significant independent prognostic parameter in ovarian carcinoma (P = .031), in addition to the conventional risk factors.
 Estimation of survival of individual patients was best accomplished by combining the factors of residual tumor mass (P less than .05), age (P less than .01), and clonogenic growth (P less than .05) (in sequence of decreasing potential of risk).
",3
753,"Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin.
 In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs.
 Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program.
 Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs).
 The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%).
 Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs.
 Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate.
 In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy.
",3
754,"Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation.
 Combination chemotherapy is capable of curing many patients with newly diagnosed intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of relapsed NHL remains problematic.
 Bone marrow transplantation (BMT) offers the best chance for disease-free survival, but interim chemotherapy is often necessary while awaiting BMT, especially for patients with bulky disease.
 We report here 39 patients (median age, 44 years) who failed primary therapy with doxorubicin-based regimens and subsequently were treated with one to six cycles of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100 mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x two doses on day 2 (DHAP) before the planned BMT.
 Histologies included 16 diffuse large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic, and eight other.
 Twenty-eight patients had stage IV disease, 13 had B symptoms, and 20 had an elevated lactate dehydrogenase (LDH).
 Patients had been treated with a median of three previous chemotherapy regimens.
 Sixty-one percent of patients had high tumor burdens according to the MD Anderson criteria.
 Objective responses to DHAP were seen in 26 patients (67%) including nine complete responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted a median of 7.5 months.
 Myelosuppression was the major toxicity, but there were no treatment-related deaths.
 To date, 17 patients have undergone subsequent BMT with a projected 3-year disease-free survival of 15%.
 We conclude that the DHAP regimen is effective short-term salvage therapy for relapsed NHL patients, but the long-term prognosis of multiply relapsed patients remains poor.
",3
755,"Second primary cancer following Hodgkin's disease: updated results of an Italian multicentric study.
 The risk of second primary cancer (SPC) was evaluated in 947 patients treated for Hodgkin's disease (HD) during the period January 1969 to December 1979.
 The median follow-up of this series was 10.5 years (range, 9 to 19).
 Treatment categories included radiotherapy (RT) alone (115 patients, 12%), chemotherapy (CHT) alone (161 patients, 17%), combined RT plus CHT (381 patients, 40%), and salvage treatment for resistant or relapsing HD (290 patients, 30.6%).
 Fifty-six SPCs were observed, occurring between 1 and 17 years from initial treatment.
 Among these, secondary acute nonlymphoid leukemia (s-ANLL) was the most frequent SPC (23 cases).
 Secondary non-Hodgkin's lymphoma (s-NHL) occurred in 5 patients, whereas a secondary solid tumor (s-ST) was observed in 28 patients.
 The calculated actuarial risk (+/- SE) of developing SPC was 5.0% (+/- 0.9%) and 23.1% (+/- 5.8%) at 10 and 19 years, respectively.
 Concerning treatment modalities and s-ANLL risk, no cases were observed in the radiotherapy group, whereas CHT plus RT and salvage groups showed the highest actuarial risk.
 This was, in fact, at 10 and 19 years, 3.1% (+/- 0.9%) and 8.1% (+/- 4.0%) in the former group, and 1.8% (+/- 1.0%) and 16% (+/- 9.0%) in the latter.
 A statistically significant difference was observed when the CHT plus RT group was compared with CHT and RT groups (P = .04).
 Concerning the relationships with chemotherapeutic regimens, 12 s-ANLL cases occurred in the mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus RT group, and only one case in the group receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus RT.
 A statistically significant difference of s-ANLL actuarial risk was found comparing patients receiving MOPP plus RT to all other treatment groups (P = .04).
 With respect to s-ST, the actuarial risk at 10 and 19 years was 2.0% (+/- 0.6%) and 13.0% (+/- 3.8%), respectively.
 No significant differences were found among groups treated with different modalities.
 These data were confirmed by a multivariate analysis, which indicated treatment modality and age as independent variables for s-ANLL and s-ST development, respectively.
 Based on the prolonged follow-up analysis, the actuarial SPC risk at 10 years hereby reported should reflect the real SPC incidence in our series.
",3
756,"The pattern of intrathoracic Hodgkin's disease assessed by computed tomography.
 Computed tomography (CT) was used to define the sites of intrathoracic abnormality in Hodgkin's disease, determine a pattern of progression of disease in the thorax, and establish the place of this pattern of spread in the differential diagnosis of thoracic abnormalities.
 One hundred eight patients with newly diagnosed Hodgkin's disease were studied by chest CT.
 Seventy-seven patients had intrathoracic abnormalities.
 The pattern seen was one of contiguous spread from the anterior mediastinal/paratracheal area to the other mediastinal lymph node groups (aortopulmonary, subcarinal, posterior mediastinal, and internal mammary), to the hila, and then into the lung by extension or as discrete nodules.
 Involvement of the pleura, pericardium, or chest wall occurred only after the anterior mediastinal/paratracheal mass had enlarged to greater than 30% of the thoracic diameter.
 The probability that this pattern of contiguous lymph node spread occurred by chance alone was very small.
 Hodgkin's disease spreads from the anterior mediastinal/paratracheal area in a contiguous manner.
 Exceptions are unusual enough that when they occur, diagnoses other than Hodgkin's disease are more likely.
",3
757,"Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients.
 The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM).
 Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989.
 The treatment groups did not show significant differences with respect to major prognostic factors.
 Median overall survival was 33.8 months.
 In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P less than .068) of the patients achieved an M component reduction greater than 50%.
 No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P less than .66) and survival (31.6 v 37.0 months, P less than .28).
 Patients younger than 65 years did not show any advantage from the alternating polychemotherapy.
 At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (beta 2-m) were evaluated in 173 and 183 patients, respectively.
 A significantly reduced survival was observed for patients with LI greater than or equal to 2% (16.4 months) or beta 2-m greater than or equal to 6 mg/L (20.4 months).
 Even in these poor-risk subgroups, VMCP/VBAP was not superior to MP.
",3
758,"A phase I clinical, plasma, and cellular pharmacology study of gemcitabine.
 A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial.
 Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks.
 The maximum-tolerated dose (MTD) was 790 mg/m2.
 The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia.
 Nonhematologic toxicity was minimal.
 Two responses in patients with adenocarcinomas of the colon and lung were documented.
 The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered.
 Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent.
 The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine.
 The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2.
 No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation.
 The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk.
",3
759,"Interleukin-2: prospects for lymphocyte-mediated destruction of pediatric malignancies.
 Immunologic therapy of cancer was speculated on at the turn of the century.
 In animals, in vitro, and most recently in patients, irrefutable evidence has been obtained that lymphocyte responses can have a reproducible and beneficial antitumor effect.
 These results indicate that ""biologic response modification"" may truly become a fourth modality for cancer treatment, to be integrated into the standard approaches of radiation, chemotherapy, and surgery.
 To what extent these immune approaches may enable eradication of microscopic amounts of residual diseases in children who would otherwise have a recurrence of their malignancies remains the critical issue for testing over the next decade.
 Enthusiasm regarding this approach is abundant, but critical evaluation of all clinical trials is essential to best focus these mechanisms into effective therapy.
",3
760,"Alternating hepatic intra-arterial floxuridine and fluorouracil: a less toxic regimen for treatment of liver metastases from colorectal cancer.
 Hepatic intra-arterial (HIA) infusion of floxuridine (FUDR) via an implanted pump has shown promise in the treatment of colorectal cancer metastasized to the liver.
 However, the potential benefit of this therapy may be offset by the high incidence of treatment-limiting biliary toxicity.
 Although weekly HIA bolus of fluorouracil (5-FU) is effective against metastatic colorectal cancer to the liver with no biliary toxicity, it is limited by systemic side effects.
 In December 1986, we began a phase II trial of alternating HIA FUDR and 5-FU via the implanted pump in an attempt to extend the duration of treatment by obviating the limiting biliary (FUDR) and systemic (5-FU) drug toxic effects.
 Patients received continuous HIA FUDR at 0.1 mg/kg of body weight per day on days 1 through 8 followed by an HIA bolus of 5-FU at 15 mg/kg given via the pump sideport on days 15, 22, and 29, with the cycle repeated every 35 days.
 Sixty-eight patients were enrolled in this trial, and 64 were fully evaluable.
 Of the 64 patients, 30 (47%) previously had received chemotherapy.
 Major response (complete response plus partial response) was observed in 32 (50%) of 64 patients, and the median survival from pump implantation in all patients was 22.4 months.
 In contrast to the experience with the single-agent HIA FUDR regimen, no patient had treatment terminated because of drug toxicity.
 Alternating HIA FUDR and 5-FU has efficacy similar to that of HIA FUDR given alone, but when closely monitored and adjusted appropriately, is not associated with toxic effects requiring treatment termination.
",3
761,"Preferential localization of human adherent lymphokine-activated killer cells in tumor microcirculation.
 The efficacy of adoptive immunotherapy for solid tumors with lymphokine-activated effector cells presumably depends on the ability of these cells to localize adequately in tumor tissues.
 We present here the first quantitative study of the in vivo movement of fluorescently labeled adherent lymphokine-activated killer (A-LAK) cells.
 These cells were injected intra-arterially along with low-dose interleukin-2 into normal (mature granulation) tissue and an implant of VX2 carcinoma grown in the rabbit ear chamber.
 A small proportion of A-LAK cells accumulated preferentially in the tumor microcirculation in vivo because of an increased frequency of long-term adhesive interactions with the tumor vasculature.
 Stasis of blood flow in the tumor vasculature was observed 1 to 2 days after injection.
 Subsequent necrosis of the tumors was observed, along with diffuse infiltrates of lymphocytes, monocytes, and granulocytes in the interstitial space within the tumor.
 Development of necrosis despite low ratios of effector cells to target cells suggests that in addition to direct cytotoxicity, the response to adoptive immunotherapy is mediated via the tumor vasculature.
 This novel mechanism for adoptive immunotherapy must be taken into account in the development of improved strategies for cancer treatment.
",3
762,"Cancer in populations living near nuclear facilities. A survey of mortality nationwide and incidence in two states.
 Reports from the United Kingdom have described increases in leukemia and lymphoma among young persons living near certain nuclear installations.
 Because of concerns raised by these reports, a mortality survey was conducted in populations living near nuclear facilities in the United States.
 All facilities began service before 1982.
 Over 900,000 cancer deaths occurred from 1950 through 1984 in 107 counties with or near nuclear installations.
 Each study county was matched for comparison to three ""control counties"" in the same region.
 There were 1.8 million cancer deaths in the 292 control counties during the 35 years studied.
 Deaths due to leukemia or other cancers were not more frequent in the study counties than in the control counties.
 For childhood leukemia mortality, the relative risk comparing the study counties with their controls before plant start-up was 1.08, while after start-up it was 1.03.
 For leukemia mortality at all ages, the relative risks were 1.02 before start-up and 0.98 after.
 For counties in two states, cancer incidence data were also available.
 For one facility, the standardized registration ratio for childhood leukemia was increased significantly after start-up.
 However, the increase also antedated the operation of this facility.
 The study is limited by the correlational approach and the large size of the geographic areas (counties) used.
 It does not prove the absence of any effect.
 If, however, any excess cancer risk was present in US counties with nuclear facilities, it was too small to be detected with the methods employed.
",3
763,"Esophageal ultrasound and the preoperative staging of carcinoma of the esophagus.
 Esophageal ultrasound allows the esophageal wall to be viewed as five discrete layers.
 Lymph nodes are easily identified, and their size, shape, margin, and internal structure can be assessed.
 This provides an alternative method of preoperative (clinical) evaluation of the primary tumor [T] and the regional lymph nodes [N] of patients with carcinoma of the esophagus.
 Esophageal ultrasound was attempted in the clinical staging of 28 patients with carcinoma of the esophagus.
 Six patients (21%) were not assessed because of the inability to pass the esophageal ultrasound probe through the malignant stricture.
 The staging system for carcinoma of the esophagus developed by the International Union Against Cancer and the American Joint Committee on Cancer was used.
 Twenty-two patients had the true T determined by pathologic review of the resected esophagus.
 Esophageal ultrasound correctly identified T in 13 patients (59% accuracy).
 In four patients (18%) the disease was overstaged by esophageal ultrasound; all these patients had early T1 tumors confined to the submucosa.
 In five patients (23%) the disease was understaged by esophageal ultrasound; all of these patients had advanced tumors (four T3 and one T4) that invaded beyond the esophageal wall.
 Seven of the nine incorrect esophageal ultrasound determinations were called T2 (three T1, three T3, one T4), which suggests that the borders of the muscularis propria require careful attention when evaluated by esophageal ultrasound.
 Twenty patients had the true N determined by pathologic review of the resected specimen.
 Esophageal ultrasound correctly identified N in 14 patients (70% accuracy).
 Three patients were falsely identified as having N1 disease and three were falsely identified as having N0 disease.
 The sensitivity, specificity, positive predictive value, and negative predictive value for N assessment by esophageal ultrasound were 70%.
 Esophageal ultrasound provides an alternative method of visualization of the esophageal wall and regional lymph nodes.
 Our early experience shows promise for esophageal ultrasound in the clinical staging of carcinoma of the esophagus.
",3
764,"Lack of effect of pregnancy on outcome of melanoma. For The World Health Organisation Melanoma Programme 
 To determine the effect of pregnancy on prognosis in melanoma we investigated 388 women treated for stage 1 primary cutaneous disease during their childbearing years.
 85 women had been treated before any pregnancy, 92 during pregnancy, 143 after they had completed all pregnancies, and 68 between pregnancies.
 Women who had received treatment while pregnant had primary tumours of significantly greater thickness than did those in the other three groups (p = 0.002).
 Other possible confounding factors (site, age, parity) did not differ between the groups.
 Once tumour thickness was controlled for, survival rate of women in whom melanoma was diagnosed and treated while they were pregnant did not differ from that in the other three groups.
 Cox regression analysis showed no differences between the three groups of women who were not pregnant at diagnosis.
 Women with melanoma should be advised about pregnancy on the basis of thickness and site of tumour and evidence of vascular spread, and not hormonal status.
",3
765,"Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis.
 Epstein-Barr virus (EBV), a human herpesvirus, establishes a persistent asymptomatic infection of the circulating B-lymphocyte pool.
 The mechanism of virus persistence is not understood but, given the limited lifespan of most B cells in vivo, it seems most likely that EBV-infected cells must gain access to the long-lived memory B-cell pool.
 Here we show in an in vitro system that EBV, through expression of the full set of eight virus-coded 'latent' proteins, can protect human B cells from programmed cell death (apoptosis), the deletion mechanism which normally restricts entry into memory.
 We have found that EBV-positive Burkitt's lymphoma (BL) cell clones retaining the original tumour cell phenotype and expressing only one of the virus latent proteins, the nuclear antigen EBNA 1, are extremely sensitive to apoptosis; in this respect they resemble the tumour's normal cell of origin found in the germinal centres of lymphoid tissue.
 By contrast, isogenic BL cell clones which have activated expression of all eight EBV latent proteins are resistant to the induction of apoptosis.
 The EBV latent proteins should therefore be seen not just as activators of B-cell proliferation but, perhaps more importantly, as mediators of enhanced B-cell survival.
",3
766,"The nursing role in limb salvage surgery.
 Limb salvage surgery has proven itself as a valuable option for sarcoma patients.
 The reconstruction options are vast and include metallic implants, allografts, and a combination of both.
 The nursing implications for these patients are unlimited.
 The patient needs to be educated and assessed closely for complications such as infections, nonunion of the allograft, and limited mobility.
 Although the nursing care is more complicated, the rewards with working with these patients are great.
",3
767,"Why patients delay seeking care for cancer symptoms. What you can do about it.
 Patient delay in seeking care for cancer symptoms is common and well documented by research studies.
 Fear and denial, lack of information about cancer, and financial considerations all contribute to this delay.
 Patient education may be an important factor in decreasing the length of delay and thereby improving treatment outcome.
 By making good use of opportunities for patient education, primary care physicians may positively influence the prognosis of several types of cancer, particularly breast cancer and malignant melanoma of the skin.
",3
768,"Characteristics of erythroleukemia cells selected for vincristine resistance that have accelerated inducer-mediated differentiation.
 The induction of murine erythroleukemia cells (MELC; DS19/Sc9) to terminal differentiation by hexamethylenebisacetamide (HMBA) is characterized by a latent period of 10-12 hr before onset of commitment to terminal-cell division and increased transcription of globin genes.
 MELC variants, derived from this parental cell line, selected for resistance to vincristine (VC), can be induced to differentiate with little or no latent period.
 This study shows that accelerated HMBA-induced commitment is characteristic of MELC with a low level (2- to 5-fold) of VC resistance in four independently derived cell lines.
 Both resistance to VC and accelerated differentiation are stable phenotypes for at least 50 passages (approximately 5 months) in the absence of VC.
 Low-level VC-resistant MELC do not display increased levels of P-glycoprotein or mdr1, mdr2, and mdr3 mRNAs, nor do they exhibit cross-resistance to colchicine or doxorubicin.
 These cells do show (i) increased level of protein kinase C activity, (ii) reduced accumulation of [3H]VC, and (iii) restoration of VC sensitivity in the presence of verapamil.
 MELC selected for higher levels of VC resistance (approximately 500-fold) do express high levels of P-glycoprotein and the mdr3 gene.
 During HMBA-induced differentiation, DS19/Sc9 decrease [3H]VC accumulation, but P-glycoprotein content does not change.
 A VC-transport-associated protein, also critical for the process of induced differentiation, may be constitutively present in VC-resistant MELC, accounting for their enhanced sensitivity to inducer.
 This protein accumulates by exposure of VC-sensitive cells to HMBA, contributing to their differentiation and decreased level of VC accumulation.
",3
769,"Effects of site-directed mutagenesis at residues cysteine-31 and cysteine-184 on lecithin-cholesterol acyltransferase activity.
 Native lecithin-cholesterol acyltransferase (LCAT; phosphatidylcholine-sterol acyltransferase; phosphatidylcholine:sterol O-acyltransferase, EC 2.3.1.43) protein, and LCAT in which either or both of the enzyme free cysteines had been replaced with glycine residues by site-directed mutagenesis, has been expressed in cultured Chinese hamster ovary cells stably transfected with the human LCAT gene.
 The mass of LCAT secreted, determined by immunoassay, did not differ in the native and mutant species.
 LCAT specific activity was also unchanged in the mutant species.
 In particular, the cysteine-free double mutant, in which Cys-31 and Cys-184 had both been replaced, was fully active in the synthesis of cholesteryl esters.
 This result is not consistent with a catalytic role for LCAT free cysteine residues.
 The classical inhibitor of LCAT activity, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), which strongly (89%) inhibited the native enzyme, had partial (45%) inhibitory activity with mutant enzyme species containing a single -SH residue, while the double mutant was not significantly inhibited by DTNB.
 These data are interpreted to suggest that Cys-31 and Cys-184 are vicinal both to each other and to the ""interfacial binding site"" at residues 177-182, and that DTNB exerts its effect by steric inhibition.
",3
770,"Transfection of C6 glioma cells with connexin 43 cDNA: analysis of expression, intercellular coupling, and cell proliferation.
 C6 glioma cells express low levels of the gap junction protein connexin 43 and its mRNA and display very weak dye coupling.
 When implanted into the rat cerebrum, these cells quickly give rise to a large glioma.
 To investigate the role of gap junctions in the tumor characteristics of these cells, we have used Lipofectin-mediated transfection to introduce a full-length cDNA encoding connexin 43.
 Several transfected clones were obtained that exhibited various amounts of connexin 43 mRNA transcribed from the inserted cDNA.
 Immunocytochemical analysis revealed an increase in the amount of connexin 43 immunoreactivity in the transfected cells, being localized at areas of intercellular contact as well as in the cytoplasm.
 The level of dye coupling was also assessed and found to correlate with the amount of connexin 43 mRNA.
 When cell proliferation was followed over several days, cells expressing the transfected cDNA grew more slowly than non-transfected cells.
 These transfected cells will be useful in examining the role of gap junctions in tumorigenesis.
",3
771,"Differentiation of HL-60 leukemia by type I regulatory subunit antisense oligodeoxynucleotide of cAMP-dependent protein kinase.
 A marked decrease in the type I cAMP-dependent protein kinase regulatory subunit (RI alpha) and an increase in the type II protein kinase regulatory subunit (RII beta) correlate with growth inhibition and differentiation induced in a variety of types of human cancer cells, in vitro and in vivo, by site-selective cAMP analogs.
 To directly determine whether RI alpha is a growth-inducing protein essential for neoplastic cell growth, human HL-60 promyelocytic leukemia cells were exposed to 21-mer RI alpha antisense oligodeoxynucleotide, and the effects on cell replication and differentiation were examined.
 The RI alpha antisense oligomer brought about growth inhibition and monocytic differentiation, bypassing the effects of an exogenous cAMP analog.
 These effects of RI alpha antisense oligodeoxynucleotide correlated with a decrease in RI alpha receptor and an increase in RII beta receptor level.
 The growth inhibition and differentiation were abolished, however, when these cells were exposed simultaneously to both RI alpha and RII beta antisense oligodeoxynucleotides.
 The RII beta antisense oligodeoxynucleotide alone has been previously shown to specifically block the differentiation inducible by cAMP analogs.
 These results provide direct evidence that RI alpha cAMP receptor plays a critical role in neoplastic cell growth and that cAMP receptor isoforms display specific roles in cAMP regulation of cell growth and differentiation.
",3
772,"Titrated intravenous barbiturates in the control of symptoms in patients with terminal cancer.
 Patients with terminal cancer may have a series of severe and dehumanizing physical and psychologic symptoms.
 To improve symptom control in the final days and hours of life, we administer intravenous barbiturates continuously to provide heavy sedation or continuous somnolence.
 Titrated dosage is then reduced to a minimum, after a desired steady-state has been achieved.
 Improved symptom control is provided, and the patient's dignity is maintained until death.
",3
773,"Management of soft tissue sarcomas of the extremities.
 The management of soft tissue sarcomas has undergone and continues to undergo important changes.
 The purpose of this report is to review the presentation, diagnosis, and natural history of soft tissue sarcomas.
 In so doing, the importance of a careful and rigorous method of evaluation will be emphasized.
 Furthermore, the results of multidisciplinary treatment, with a goal towards limb salvage, will be reviewed.
 With appropriate and timely intervention, selected patients with pulmonary metastases may still experience long-term survival.
 Throughout this review, the importance of early and continuing multidisciplinary treatment and evaluation will be emphasized.
",3
774,"Giant cell tumor of bone.
 Giant cell tumor is the second most common benign tumor of bone.
 Plain radiographs may demonstrate distinctive features but can also be misleading.
 The diagnosis may be aided by the use of other imaging modalities, such as bone scan, computed tomography and angiography.
 The recurrence rate is high, but some of the newer treatments seem to be associated with better outcomes.
",3
775,"Lack of effect of chronic administration of oral beta-carotene on serum cholesterol and triglyceride concentrations.
 Previous studies suggest that chronic oral administration of retinol and other retinoids causes elevation of plasma triglyceride concentrations.
 The effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations have not been well studied; therefore, we studied 61 subjects over 12 mo while they were enrolled in a skin-cancer-prevention study in which patients were randomly assigned to receive either placebo (n = 30) or 50 mg beta-carotene/d orally (n = 31).
 At study entry and 1 y later, fasting blood samples were obtained for measurement of triglycerides, total cholesterol, HDL cholesterol, retinol, and beta-carotene.
 Retinol concentrations changed minimally in both groups; beta-carotene concentration increased an average of 12.1 +/- 47 nmol/L in the placebo group and 4279 +/- 657 nmol/L in the active-treatment group.
 Both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in HDL cholesterol.
 Daily oral administration of 50 mg beta-carotene/d did not affect plasma lipid concentrations.
",3
776,"Beta-carotene's effects on serum lipoproteins and immunologic indices in humans.
 Doses of beta-carotene for cancer-prevention trials have been chosen based on epidemiologic data.
 Mechanisms of the putative antineoplastic effects by beta-carotene are unknown but may involve modulation of the immune system.
 We measured plasma carotenoid concentrations and selected immunologic indices at baseline and at 2 and 4 wk in 50 healthy humans (5 groups of 10 each) ingesting 0, 15, 45, 180, or 300 mg beta-carotene/d for 1 mo in this randomized placebo-controlled, open-label, parallel study.
 Plasma beta-carotene concentrations were markedly increased by 2 wk and were correlated with dose.
 Beta-carotene concentrations plateaued between 2 and 4 wk except for the 300-mg group.
 Thus, we developed a dose-concentration curve to optimize beta-carotene-dose selection to achieve target plasma concentrations.
 We were unable to identify any effects of beta-carotene ingestion on the immunologic indices studied, but modest increases in high-density-lipoprotein cholesterol were observed in all beta-carotene-treated groups.
",3
777,"Development of intrapancreatic transplantable model of pancreatic duct adenocarcinoma in Syrian golden hamsters.
 Intrapancreatic and subcutaneous (SC) inoculation of cultured pancreatic cancer cells, derived from an induced primary pancreatic cancer in a Syrian hamster, resulted in tumor take in all recipient hamsters.
 The intrapancreatic allografts grew rapidly, were invasive, and metastasized into the lymph nodes and liver in 2 of 9 cases.
 In comparison, SC tumors grew relatively slower and formed a large encapsulated mass without invasion and metastases.
 Histologically, tumors of both sites showed fairly well-differentiated adenocarcinomas of ductal/ductular type resembling the induced primary cancer.
 Similar to the primary induced pancreatic cancers, tumor cells of both allografts expressed blood-group-related antigens, including A, B, H, Le(b), Le(y), Le(x), and tumor-associated antigen TAG-72.
 The tumor cells did not express Le(a), CA 19-9, 17-1A, or DU-PAN-2.
 The expression of these antigens was retained in the metastases and presented the same patterns of reactivity as the allografts.
 Thus intrapancreatic transplantation provides a rapid model for production of pancreatic cancer with morphologic similarities to human pancreatic cancer.
",3
778,"Epithelial cells immortalized by human papillomaviruses have premalignant characteristics in organotypic culture.
 Three HPV-16--and four HPV-18--immortalized human foreskin keratinocyte cell lines were analyzed on organotypic epidermal raft cultures at various passage levels.
 This culture system allowed normal cultured keratinocytes to stratify and differentiate in a manner similar to normal epidermis.
 All seven HPV-immortalized cell lines displayed epidermal morphologies on organotypic cultures, which were clearly abnormal and resembled premalignant lesions in vivo.
 Features of premalignant lesions that were shared by all of the HPV-immortalized cell lines included disorganized tissue architecture, mitotic cells present throughout the living layers of the epidermal sheet, abnormal mitoses, enlarged nuclei, and variable cell size and shape.
 Most HPV-immortalized cell lines were stable in terms of epidermal morphology with long-term passage in culture.
 Two of the HPV-18--immortalized cell lines, however, lost all morphologically apparent terminal squamous differentiation potential after long-term passage in monolayer culture.
 These results strongly support the idea that immortalization of squamous epithelial cells in culture by HPV-transforming genes generates a morphologically premalignant cell.
",3
779,"Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases.
 'Very late antigen' (VLA) proteins are members of the integrin superfamily with cell-surface receptor function and are involved in the cell-cell matrix interaction.
 They are heterodimers with a common beta 1 chain and different alpha chains counted through VLA-1 to VLA-6.
 The VLA-2 complex (alpha 2/beta 1) was found to act as collagen receptor on platelets and the VLA-6 complex (alpha 6/beta 1) as laminin receptor.
 Using monoclonal antibodies and an indirect immunoperoxidase method, we investigated the expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in 20 normal colonic mucosa samples, in 20 colonic adenomas, and in 96 carcinomas together with 10 accompanying liver metastases.
 All three proteins were expressed throughout the colonic epithelium, except for VLA-alpha 2, which was present in the cryptic gland but was absent on the mucosal surface in some cases.
 In general, adenomas were strongly positive for the VLA proteins but 3 of 20 cases showed focal VLA-alpha 2-negative areas.
 The carcinomas revealed considerable heterogeneity of VLA-alpha 2 expression; ie, 59 tumors were completely positive, 35 tumors revealed a focal loss of antigen, and 2 cases were negative.
 This reduced antigen expression was statistically associated with Dukes' stage C/D (P = 0.003).
 VLA-alpha 6 was expressed throughout in all tumors.
 VLA-beta 1 was found extensively expressed in 77 carcinomas, partially expressed in 17 carcinomas, and was absent in 2 carcinomas.
 As compared to their primary tumors, liver metastases showed roughly corresponding patterns of antigen expression.
 The down regulation/loss of VLA proteins in a subset of epithelial colon tumors might cause a disturbed cell-cell/cell-matrix interaction that might augment the invasive property of their cells.
",3
780,"Basal cell-specific and hyperproliferation-related keratins in human breast cancer.
 In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained.
 A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas.
 Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used.
 One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas.
 However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected.
 A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67.
 This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating.
",3
781,"Musculoskeletal infection, microbial adhesion, and antibiotic resistance.
 Osteomyelitis and intra-articular infection are septic diseases that present pathogenic features characteristic of molecular mechanisms involving adhesion to substrata.
 In this review, mechanisms of microbial adhesion to bone and cartilage as substrata are presented and related to host tissue response and to antibiotic treatment.
",4
782,"Diagnostic imaging of osteomyelitis.
 There are many imaging procedures for diagnosing osteomyelitis, each with unique strengths and weaknesses.
 Plain radiographs are inexpensive and can be very accurate but may provide a delayed diagnosis.
 Computed tomography and magnetic resonance imaging are both excellent at differentiating soft tissue infection from osteomyelitis.
 Computed tomography, magnetic resonance imaging, and bone scans are accurate diagnostic tools for use when the bone has not be violated by surgery, trauma, or other structural alterations.
 When such changes are present, an Indium-111 leukocyte or Indium-111 polyclonal antibody study may be necessary for accurate diagnosis.
",4
783,"Antibiotic therapy for osteomyelitis.
 Antibiotic therapy for osteomyelitis has dramatically changed within the past twenty years.
 The diagnostic criteria for osteomyelitis remain confusing to practicing physicians.
 Bone biopsy culture is now the standard for determining specific antimicrobial therapy.
 Many of the newest and most potent antimicrobials are now used to treat the increasingly broad bacterial spectrum of etiologies of osteomyelitis.
 There are tremendous economic incentives for outpatient and/or oral therapy.
 The third-generation cephalosporins and the new fluoroquinolones have replaced older, more toxic regimens, especially those containing aminoglycoside used to treat gram-negative osteomyelitis due to susceptible organisms.
",4
784,"Surgical approaches in osteomyelitis. Use of laser Doppler flowmetry to determine nonviable bone.
 The surgical management of osteomyelitis includes radical debridement on nonviable bone.
 Laser Doppler flowmetry is a method for directly assessing the functional microcirculation in bone.
 The early results of the use of this technique as a surgical adjunct in the management of osteomyelitis are promising.
",4
785,"Infectious arthritis.
 Any patient who presents with an acute monarticular arthritis, especially a new asymmetric effusion with underlying joint disease, should be suspected of having a bacterial process.
 Because synovial fluid findings (leukocyte counts and glucose) may not be predictive of infection, bacteriologic analysis by smear and culture is necessary in the evaluation of any new synovial effusion.
 A chronic monarticular process is highly likely to be infectious also, but mycobacterial or fungal etiologies frequently require appropriate culture of synovial tissue in addition to processing fluid.
 Acute polyarticular syndromes are seen as manifestations of disseminated gonococcal infections (DGI) and certain viral infections in adults.
 Diagnostic clues include historic and physical findings (exposure history and type of rash).
 The major pathogen in adults remains Staphylococcus aureus, so initial therapy is directed at this organism unless urinary tract infection is present also.
 Proper recommended therapy for DGI is ceftriaxone because penicillin-resistant strains are present in many urban centers.
 Early recognition and treatment of bacterial arthritis may prevent poor outcome, particularly in elderly patients or those with underlying joint diseases.
 For chronic mycobacterial or fungal infections, surgery may need to be combined with medical management.
",4
786,"Vertebral osteomyelitis.
 Vertebral osteomyelitis can be caused by a variety of microorganisms.
 The hematogenous pyogenic form is characteristically a disease of people over age 50, predominantly in the male population, and most frequently caused by S.
 aureus.
 In IVDAs, however, younger patients and a heavier predominance of males are seen, and P.
 aeruginosa is one of the most commonly seen pathogens.
 The disease is generally monomicrobial, unless it is secondary to a contiguous process such as a pressure sore, in which polymicrobial infection with participation of anaerobes is the general rule.
 Lumbar, greater than thoracic, greater than cervical involvement is the rule in the general population, but cervical spine involvement is frequently seen more often than thoracic involvement in IVDAs.
 Diabetic patients are over-represented among patients with vertebral osteomyelitis, and they also have a tendency for higher morbidity and mortality.
 Simultaneous involvement of adjacent vertebral end plates and the intervening disk is the general rule.
 The vertebrae are generally involved, and the posterior elements of the spine are involved infrequently.
 Posterior element involvement is seen more commonly in actinomycosis, coccidioidomycosis, and neoplasms.
 Newer diagnostic modalities, such as CT, MRI, and radionuclide scans, may detect the disease earlier than conventional radiographs.
 Immunobilization by bed rest and appropriate antimicrobial therapy are generally sufficient in the therapy of pyogenic, as well as tuberculous, vertebral osteomyelitis.
 In selected circumstances, such as in the presence of marked instability of the spine, the presence of new neurologic deficits, or with progression of previous neurologic deficits, surgical intervention may be necessary.
 With prompt diagnosis and proper management, the prognosis should generally be good.
",4
787,"Zygomatic approach to skull-base lesions.
 A modification of the preauricular skull-base approach is described.
 After sectioning and downward displacement of the zygomatic arch, the coronoid process of the mandible is dissected and sectioned at its base.
 The temporal muscle, with its coronoid insertion, is then retracted upward.
 This approach provides direct and unobstructed access to the temporal and infratemporal fossae.
 Adequate vascularity of the temporal muscle is maintained.
 The exposure encompasses the internal carotid artery in the neck for vascular control.
 Extensive reconstruction is eliminated.
 The described technique was used in seven patients with lesions of the skull base.
 There was no operative mortality, and morbidity consisted of temporary restriction of mandibular opening in two patients.
",4
788,"A simple technique of posterior wiring in traumatic instability of the mid to lower cervical spine. Technical note.
 Wiring without bone fusion in the treatment of traumatic cervical instability is an uncommon procedure.
 The authors describe a semirigid wiring technique for stabilizing the acute injured movement segment in the mid and lower cervical spine.
 Results are briefly discussed.
",4
789,"Management of delayed union and nonunion of maxillary osteotomies.
 Delayed union and nonunion of maxillary osteotomies are unusual, but have been seen with a variety of surgical moves.
 Management of these problems can be divided into early and late therapy.
 Four cases are presented illustrating some of these methods of treatment.
",4
790,"Composite temporalis pedicle flap as an interpositional graft in temporomandibular joint arthroplasty: a preliminary report.
 Fifteen temporomandibular joint patients were evaluated preoperatively and postoperatively to evaluate the effectiveness of a composite (fascia, muscle and periosteum) temporalis pedicle flap as an interpositional disc replacement.
 A modified Craniomandibular Index (CMI) and Symptom Severity Index (SSI) were used to assess clinical and subjective symptoms.
 Eighteen months postoperatively there was a significant reduction in the CM and SS indices (P less than .001), with significant clinical improvement of the mandibular range of motion (P less than .05).
 However, a significant reduction of translation (P less than .01) was evident indicating that the increased mandibular opening was owing to a compensatory rotational movement.
 This study indicates that the composite temporalis pedicle flap is a good autogenous tissue for the reconstruction of the temporomandibular joint.
",4
791,"Tissue response to composite ceramic hydroxyapatite/demineralized bone implants.
 This study evaluated the tissue reactions to two materials: ceramic hydroxyapatite (CHA), and a composite material of demineralized bone powder (DBP) and CHA (ratio of 4:1) in a collagen vehicle.
 The materials were tested in a subcutaneous pocket, a mandibular onlay, and in a calvarial onlay model.
 Specimens were evaluated histologically at 7, 10, 14, and 21 days postimplantation.
 Ceramic hydroxyapatite, implanted subcutaneously, elicited a fibrous response with minimal inflammation, but did not induce bone formation.
 In specimens of subcutaneously implanted composite material, induced bone was evident in association with the DBP.
 In CHA onlay specimens, there was a small amount of reactive bone extending from the host bone into the implant.
 In composite onlays, bone filled the entire body of the implant.
 The results of this study indicate that CHA particles were not osteoinductive in heterotopic sites and that osteoconductive ingrowth was minimal in onlays.
 Bone was induced by DBP even when mixed with CHA particles and implanted in subcutaneous and intraosseous sites.
 It was concluded that composite implants may provide a means of combining the osteoinductive properties of DBP with the bulk and structural support of osteoconductive CHA particles.
",4
792,"Bone response to hydroxyapatite particles of different shapes in rabbit tibia.
 Four holes drilled in rabbit tibia were filled with different commercial hydroxyapatite products.
 All particles caused a mild inflammatory reaction, which disappeared in 2 months.
 The line between the new and original bone was visible even after 6 months.
 No differences in healing pattern were discovered for the various products.
 When bone cavities are filled with hydroxyapatite particles, the shape of the particles does not seem to affect the healing process.
",4
793,"A protocol for management of temporomandibular joint ankylosis.
 A management protocol for temporomandibular joint (TMJ) ankylosis consisting of 1) aggressive resection, 2) ipsilateral coronoidectomy, 3) contralateral coronoidectomy when necessary, 4) lining of the TMJ with temporalis fascia or cartilage, 5) reconstruction of the ramus with a costochondral graft, 6) rigid fixation, and 7) early mobilization and aggressive physiotherapy is presented.
 The protocol was retrospectively evaluated in the first 14 patients (18 involved TMJs) treated and followed postoperatively for at least 1 year.
 The facial asymmetries present in all unilateral cases remained corrected.
 The mean maximum postoperative interincisal opening at 1 year was 37.5 mm (292.36% mean increase), lateral excursions were present in 16 of 18 joints (vs 0 of 18 joints preoperatively), and pain was present in 2 of 18 joints (vs 13 of 18 preoperatively).
 The results of this study indicate that this protocol is effective for treatment of TMJ ankylosis.
",4
794,"Magnetic resonance imaging appearance of the muscles in childhood dermatomyositis.
 Documentation of muscle involvement in a child thought to have dermatomyositis may require the performance of invasive procedures such as electromyography and/or muscle biopsy.
 We describe four patients with dermatomyositis in whom magnetic resonance imaging (MRI) demonstrated the muscle involvement.
 The involved muscles had increased signal intensity on the T2-weighted images (SE 2500/80) and normal appearance on the T1-weighted images (SE 600/20).
 The involvement of the muscles was not uniform.
 There was good correlation between the distribution of muscle involvement by MRI and functional testing.
 Follow-up MRI scans in patients with favorable outcome demonstrated that the affected muscles had returned to normal signal intensity.
 Although the MRI findings are not specific, in the proper clinical context they may be helpful in establishing the diagnosis of dermatomyositis.
 MRI may also be used in establishing an appropriate muscle biopsy site.
 In addition, MRI may be used for monitoring the progress of the disease.
",4
795,"A modification of the Health Assessment Questionnaire for the spondyloarthropathies [published erratum appears in J Rheumatol 1991 Feb;18(2):305]
 A functional status measure was developed by adding 5 items to the Health Assessment Questionnaire (HAQ-S), and compared to anthropometric measures of spinal mobility.
 Forty-four patients with spondylitis were evaluated by the HAQ-S and measures of spine flexibility (finger-to-floor, Smythe test, neck rotation, and chest expansion).
 Modification of the HAQ raised the mean difficulty score by 29% from 0.38 (SD = 0.49) to 0.49 (SD = 0.51), indicating increased ability to capture functional limitations.
 Neck rotation correlated most strongly with the HAQ-S score (r = -0.57), which suggests an important role for this measure in clinical management and followup of spondylitis.
",4
796,"Vitamin D and bone.
 Recent studies of the effects of vitamin D on bone include characterization of the receptors for 1,25-(OH)2D3 in bone and bone derived cells.
 The receptors show similar affinities in the different tissues.
 The receptor concentration is affected by the stage of the cell cycle.
 Glucocorticoid treatment affects the number of receptor sites.
 The most extensively studied effects of 1,25-(OH)2D3 on macromolecular synthesis in bone have been on collagen, where both anabolic and antianabolic effects are found.
 Differences in the response may reflect the state of differentiation of the cells.
 Significant effects are seen on osteocalcin synthesis, although the role of this protein in vitamin D action on bone is still unclear.
 1,25-(OH)2D3 influences the activity of alkaline phosphatase and 25-OH-D3 24-hydroxylase in bone.
 Receptors for growth factors, and production of cytokines may be influenced by 1,25-(OH)2D3 treatment.
 Although some of these findings would be consistent with direct anabolic effects of vitamin D or its metabolites on bone, such a process has yet to be integrated into the complete picture of vitamin D action at physiological and pharmacological levels in vivo.
 Recent studies are consistent with earlier results that indicate that hypercalcemic effects of 1,25-(OH)2D3 are mediated by a direct effect on bone.
 Studies with analogs of 1,25-(OH)2D3 suggest that the stimulation of bone resorption can be dissociated from effects on differentiation of cells of the monocyte lineage.
",4
797,"Spinal bone loss and ovulatory disturbances 
 BACKGROUND.
 Osteoporosis develops in women with estrogen deficiency and amenorrhea who lose bone at an accelerated rate.
 It is not known to what extent bone loss differs between ovulatory women with regular menstrual cycles who are training intensely and those who are sedentary.
 METHODS.
 We measured the density of cancellous spinal bone from the 12th thoracic vertebra to the 3rd lumbar vertebra by quantitative computed tomography on two occasions one year apart in 66 premenopausal women 21 to 42 years of age.
 All the women had two consecutive ovulatory cycles immediately before entering the study.
 Twenty-one women were training for a marathon, 22 ran regularly but less intensively, and 23 had normal levels of activity.
 The lengths of the women's menstrual cycles and luteal phases, diet, exercise levels, and hormonal levels were also determined.
 We defined ovulatory disturbances as anovulatory cycles and cycles with short luteal phases.
 RESULTS.
 The mean (+/- SD) spinal bone density in the 66 women decreased 3.0 +/- 4.8 mg per cubic centimeter per year (2.0 percent per year) (P less than 0.001).
 Amenorrhea did not develop in any woman during the year of observation (only 2.7 percent of the cycles were greater than 36 days long).
 Ovulatory disturbances occurred in 29 percent of all cycles, however.
 Bone loss was strongly associated with these disturbances (r = 0.54, 24 percent of the variance).
 The 13 women who had anovulatory cycles lost bone mineral at a rate of 6.4 +/- 3.8 mg per cubic centimeter per year (4.2 percent per year).
 The women training for a marathon had menstrual cycles similar to those of the women in the other two groups.
 CONCLUSION.
 Decreases in spinal bone density among women with differing exercise habits correlated with asymptomatic disturbances of ovulation (without amenorrhea) and not with physical activity.
",4
798,"Effect of estrone sulfate on postmenopausal bone loss.
 Estrogen replacement therapy confers many beneficial effects to postmenopausal women, such as slowing the rate of bone loss and decreasing the risk of coronary artery disease.
 This multicenter, placebo-controlled study evaluated the lowest effective daily dose of estrone sulfate (0.3, 0.625, or 1.25 mg) combined with 1000 mg elemental calcium supplementation for preventing bone loss in the immediate supplementation for preventing bone loss in the immediate postmenopausal period.
 Spinal bone mineral density was measured using quantitative computed tomography.
 Compared with baseline, bone mineral density increased significantly (P less than .05) after 12 months of 0.625 mg daily (+ 1.9%) or 1.25 mg daily (+ 2.5%).
 The difference between the 0.625-mg and 1.25-mg doses was not statistically significant.
 Estrone sulfate administration (0.625 and 1.25 mg) produced significant changes in various lipid measurements at both the 6- and 12-month observation points.
 The prevalence rates for adverse events were comparable among the estrone sulfate groups and the placebo group.
 Estrone sulfate 0.625 mg daily, combined with 1000 mg elemental calcium supplementation, was the minimum effective dosage to prevent loss of spinal bone mineral density in postmenopausal women over a 12-month period.
",4
799,"Bone trabecular pattern analysis in Down syndrome with the use of computed panoramic radiography. Part II: Visual pattern analysis with the frequency and gradational enhancement.
 Visual pattern analysis of mandibular bone trabeculation of 51 patients with Down syndrome and 78 normal persons was performed by using rotational panoramic radiography with a laser scan system.
 The findings for patients with Down syndrome were consistent with geromorphism, one of the somatic characteristics of Down syndrome.
",4
800,"Silicone rubber fossa implant removal via partial arthrotomy followed by arthroscopic examination of the internal surface of the fibrous capsule.
 Thirteen temporomandibular joints were examined arthroscopically for evaluation for fibrous encapsulation of silicone elastomer disk replacement implants.
 Partial arthrotomies were performed with removal of silicone rubber implants, followed by arthroscopic examination of the internal surfaces of the fibrous capsule as a pseudodisk and to verify the continuity of the fibrous barrier between the condyle and the fossa.
",4
801,"Triple bone labeling of canine mandibles.
 Fluorescence microscopy was used for evaluation of new bone formation in 16 canine mandibles augmented with hydroxylapatite (HA) granules.
 Three fluorochromes were injected at different time intervals during therapeutic radiation treatment.
 Oxytetracycline, DCAF, and alizarin-complexone were given intravenously to mark the bone level at these times, respectively.
 Oxytetracycline, which defined the baseline of bone at implantation of HA, was detectable in 42% of animals that were irradiated and in no animal of the nonirradiated control group.
 The marker DCAF, designating levels of bone at the start of radiation, was demonstrated in 92% of irradiated animals, and in 75% of animals in the control group.
 The uptake of alizarin-complexone determined the level of bone found at the end of irradiation.
 This marker was demonstrated in 50% of the dogs irradiated and in 75% of the control dogs.
 Bony trabeculae were found between and at the surface of the HA granules.
 New generation of bone directly on the HA granule and in the surrounding haversian systems as part of normal bone turnover was demonstrated to take place more than 5 months after implantation of HA.
",4
802,"Peripheral giant cell granuloma: evidence for osteoclastic differentiation.
 Nine cases of peripheral giant cell granuloma of the oral cavity have been immunohistochemically analyzed to assess the nature of the giant cells.
 Giant cells were unreactive when tested with antibodies recognizing myelomonocytic and macrophage markers (lysozyme, MAC 387, HAM 56) but showed strong immunoreactivity with MB1, an antibody reactive with osteoclasts.
 It is concluded that giant cells characterizing giant cell granuloma exhibit a phenotype distinct from other giant cells found in sites of chronic inflammation and may be true osteoclasts.
",4
803,"The Le Fort III advancement osteotomy in the child under 7 years of age.
 This is a longitudinal study of 12 patients with craniofacial synostosis syndromes (Crouzon's, Apert's, Pfeiffer's) who underwent Le Fort III advancement under the age of 7 years (average age 5.1 years, range 4.0 to 6.7 years).
 The average follow-up was 5.0 years and included clinical, dental, and cephalometric examinations according to a prescribed protocol.
 The study demonstrated that the procedure could be safely performed in the younger child with an acceptable level of morbidity.
 There was a remarkable degree of postoperative stability of the maxillary segment.
 However, although vertical (inferior) growth or movement of the midfacial segment was demonstrated, there was minimal, if any, anterior or horizontal growth.
 Any occlusal disharmony developing during the period of follow-up could be attributed to anticipated mandibular development and could be corrected by orthognathic surgery.
 The roles of surgical overcorrection and anterior-pull headgear therapy after release of intermaxillary fixation are also discussed.
 The Le Fort III osteotomy is justifiably indicated during early childhood for psychological and physiologic reasons.
",4
804,"Polyurethane foam-covered implants and capsular contracture: a laboratory investigation.
 Experiments were conducted in rabbits comparing polyurethane foam-covered implants with otherwise identical smooth silicone gel implants.
 Using five objective methods of measurement of capsular contracture, no significant difference could be identified.
 The foam-covered implants consistently developed capsular contracture, although in most cases this was of mild degree and would not have been clinically significant.
 In the two foam-covered implants with hard contractures, there was no evidence of hematoma or separation of the foam.
",4
805,"A new dynamic lumbrical simulating splint for claw hand deformity.
 The claw hand deformity, resulting from low ulnar or combined low ulnar and median nerve palsy, is an incapacitating situation.
 The splint described herein reverses the clawing by substituting for the lumbricals and interossei.
 If started early, it not only prevents the permanent stiffness of fingers in the claw position, but also effectively restores function without hampering day to day work because it is a surface splint.
",4
806,"Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production.
 Inhibitory factors towards IL-1 have been identified in the urine and in the supernatants of human monocyte cultures and have been shown to act as receptor antagonists.
 We have investigated whether a natural inhibitor purified from human urine (uIL-1ra) and a recombinant molecule expressed using the gene for an IL-1 antagonist isolated from monocytes (rIL-1ra) can alter responses to human rIL-1 alpha in organ cultures of fetal rat long bones and neonatal mouse calvariae.
 The two preparations probably contained similar or identical molecules, because an antibody to rIL-1ra reacted with uIL-1ra by Western blot analysis.
 uIL-1ra and rIL-1ra specifically blocked stimulation of bone resorption by rIL-1 in both culture systems, as well as the increase in PGE2 production in cultured calvariae.
 Resorptive effects of parathyroid hormone and TNF-alpha were not blocked.
 The uIL-1ra preparation had some intrinsic resorbing activity, but on gel chromatography this appeared in fractions that eluted earlier than uIL-1ra.
 Concentration ratios of rIL-1ra to rIL-1 as low as 10 could block the resorptive response of fetal rat long bones, whereas concentration ratios of 100 to 1000 were required to block IL-1 action on neonatal mouse calvariae.
 The inhibitory effects appeared to be competitive, because increasing concentrations of IL-1 overcame the block of bone resorption in both systems and the inhibition of PGE2 production in calvariae.
",4
807,"The operative management of basilar impression in osteogenesis imperfecta.
 Four patients with osteogenesis imperfecta and neurologically significant basilar impression have been treated over the past 8 years.
 The experience has resulted in changes in our therapeutic strategy for this particularly difficult problem.
 These cases are discussed with respect to the disease process, neurological involvement, radiological findings, and modes of surgical therapy.
 The errors in management as well as the success resulting from our learning experience are described.
 Currently, we recommend the extensive removal of the anterior bony compression by a transoral approach.
 This should be followed by a posterior rigid fixation that transfers the weight of the head to the thoracic spine, in an effort to prevent further basilar invagination.
",4
808,"Microcomputer reconstruction for analysis of spinal deformity and lung volume in hypokyphotic scoliosis.
 Current techniques for imaging chest deformity are limited to two-dimensional representations, and clinical testing for lung volume measurements are based on pulmonary function studies that are effort-dependent.
 The authors evaluated spine deformity and lung volume by using a new three-dimensional microcomputer imaging technique.
 Results from preoperative and postoperative chest computed tomograms underwent boundary detection by expert human observers.
 Data were then processed by polygon surface tiling to create three-dimensional color images of the spine and lungs for display.
 This computer technique allowed: 1) visualization of the anatomic relationships from any angle, 2) assessment of spinal deformity in relation to lung volume, and 3) measurement of individual lung volumes.
 Three-dimensional microcomputer imaging is a useful technique in objectively measuring lung volume and assessing postoperative changes.
",4
809,"Cobb angle versus spinous process angle in adolescent idiopathic scoliosis. The relationship of the anterior and posterior deformities.
 The standard clinical measurement for adolescent idiopathic scoliosis is the Cobb angle, measured from the end-plates of the end vertebral bodies in a standing radiograph.
 This measurement of anterior column structures describes the anterior spinal deformity.
 The posterior spinal deformity can be described by the ""spinous process angle,"" measured from a curve joining the tips of the spinous processes.
 A computer model, and a radiographic study of Cobb angle, spinous process angle and vertebral rotation show that adolescent idiopathic scoliosis results in larger angulations of the anterior elements than posterior elements.
 This helps to explain some of the inherent limitations of posterior instrumentation, including Cotrel-Dubousset instrumentation, and of noninvasive posterior surface measurement systems.
",4
810,"Digital radiography can reduce scoliosis x-ray exposure.
 Digital radiology is a new computerized system of acquiring x-rays in a digital (electronic) format.
 It possesses a greatly expanded dose response curve that allows a very broad range of x-ray dose to produce a diagnostic image.
 Potential advantages include significantly reduced radiation exposure without loss of image quality, acquisition of images of constant density irrespective of under or over exposure, and reduced repeat rates for unsatisfactory films.
 The authors prospectively studied 30 adolescents with scoliosis who had both conventional (full dose) and digital (full, one-half, or one-third dose) x-rays.
 They found digital made AP and lateral image with all anatomic areas clearly depicted at full and one-half dose.
 Digital laterals were better at full dose and equal to conventional at one-half dose.
 Cobb angles were easily measured on all one-third dose AP and on 8 of 10 one-third dose digital laterals.
 Digital clearly depicted the Risser sign at one-half and one-third dose and the repeat rate was nil in this study, indicating digital compensates well for exposure errors.
 The study indicates that digital does allow radiation dose to be reduced by at least one-half in scoliosis patients and that it does have improved image quality with good contrast over a wide range of x-ray exposure.
",4
811,"Results of treatment of idiopathic scoliosis with the Charleston bending orthosis.
 The authors present a preliminary retrospective review of the treatment of 32 patients with idiopathic scoliosis with the Charleston bending thoracolumbosacral orthosis (TLSO), a new, low-profile spinal orthosis.
 At the onset of treatment, the patients' mean age was 12.5 years and the mean Risser stage was 0.4.
 Females achieved menarche at an mean of 1.8 months after starting orthotic treatment.
 Single structural curves were treated in all patients.
 At this time, 2 patients have failed treatment, their curves progressing 12 degrees and 8 degrees, respectively.
 An additional 11 patients have successfully completed treatment, having reached skeletal maturity with no more than 5 degrees of curve progression.
 Their mean curve change was a 2.2 degrees decrease.
 The other 19 patients remain under treatment.
 The Charleston bending TLSO is worn only during nighttime sleeping hours.
 It is well tolerated, with excellent patient compliance and low psychological stress, and it may be as successful at curve control as other orthoses.
 Experience with more patients and longer follow-up is needed.
",4
812,"Surface electrical stimulation versus brace in treatment of idiopathic scoliosis.
 Surface electrical stimulation using the ScoliTron device was applied to 40 adolescent patients for treatment of idiopathic scoliosis.
 Adequate follow-up was available for 30 of these patients.
 The overall failure rate was 15 of 30 or 50%.
 Due to curve progression while using the ScoliTron, these patients either went on to a fusion (9 of 15) or were changed to a brace (6 of 15).
 The remaining 15 patients were considered successes with no curve progression (10 of 30 or 33%) or successful/failures with slight curve progression not requiring a change in treatment (5 of 30 or 17%).
 None of the various parameters analyzed were found to be useful indicators of successful treatment using the ScoliTron device.
 Electrical stimulation was found to be ineffective in preventing curve progression for idiopathic scoliosis.
",4
813,"Fusion levels and hook patterns in thoracic scoliosis with Cotrel-Dubousset instrumentation.
 This study reports the results of treatment of adolescents with King Types 2, 3, and 4 idiopathic curves using Cotrel-Dubousset instrumentation.
 Imbalance was seen in Types 2 and 4 curves when distraction direction hook patterns crossing the thoracolumbar junction were employed.
 Imbalance was not seen when a modified hook pattern employing compressing forces across the thoracolumbar junction was employed.
 No imbalance was observed in Type 3 curves using the basic right thoracic curve hook pattern.
 In Type 4 curves, a second modified hook pattern is required to obtain improved correction and balance.
 The mechanism of production of imbalance is explained by a three dimensional analysis of the deformity and of the forces generated by the Cotrel-Dubousset system.
",4
814,"Sagittal plane analysis in idiopathic scoliosis patients treated with Cotrel-Dubousset instrumentation.
 One hundred sixty patients with idiopathic scoliosis underwent preoperative and postoperative sagittal plane analysis of the thoracic spine, thoracolumbar junction, and lumbar spine.
 The data suggest that mild to moderate improvements in thoracic hypokyphosis are possible.
 When crossing the thoracolumbar junction, reversal of rod bend and reversal of hooks on the derotation rod appears to provide the most physiologic sagittal contour.
 Cotrel-Dubousset instrumentation to the mid and distal lumbar spine can preserve and, at times, enhance lumbar lordosis.
",4
815,"Immediate complications of Cotrel-Dubousset instrumentation to the sacro-pelvis. A clinical and biomechanical study.
 The authors reviewed the early complications in all patients fused to the sacro-pelvis using Cotrel-Dubousset instrumentation at the Texas Scottish Rite Hospital.
 Sixteen patients were studied with an average follow-up of 13 months.
 Three methods of sacro-pelvis fixation were evaluated: iliosacral screws, sacral screws, and a technique whereby the caudle ends of the Cotrel-Dubousset rods were fashioned and inserted into the posterior iliac crest using the Galveston technique.
 Seven of the 16 sets of sacral screws (44%) failed during and after surgery.
 Two of the 7 sets of iliosacral screws failed postoperatively (28%).
 No failures occurred in the 8 sets of Cotrel-Dubousset rods placed with the Galveston technique.
 Seven of the nine medical complications observed (77%) occurred in the sacral screw group.
 Using calf spines, a biomechanical evaluation of each system was undertaken to determine strength of fixation.
 Each system was failed in flexion 3 times.
 The sacral screws were the weakest, pulling directly out of the sacrum at 40 N-M.
 Cotrel-Dubousset rods inserted with the Galveston technique were the strongest, experiencing rod deformities before flexion failure at 70 N-M.
 Iliosacral screws were of intermediate strength failing by rotation on the axis of the screws or pulling directly out of the ilium at 55 N-M.
 The authors conclude that using Cotrel-Dubousset rods inserted with the Galveston techniques was the strongest and safest method of sacro-pelvis fixation of the three tested.
",4
816,"Surgical treatment of scoliosis in a spinal muscular atrophy population.
 Seventy-eight patients were diagnosed with spinal muscular atrophy between 1969 and 1988.
 Scoliosis developed in 34 of these patients, an incidence of 60%.
 Thirty-one patients could be retrospectively reviewed by chart review or interview.
 The average follow-up was 11.5 years.
 Onset of scoliosis averaged 8.8 years.
 Twenty-two patients were treated nonsurgically and nine surgically.
 Patients had improved sitting balance and endurance after surgery.
 Complications of surgery included loss of correction in one patient, one pseudarthrosis, and one patient who required prolonged ventilatory support.
 The prolonged survival of patients with spinal muscular atrophy justifies aggressive orthopaedic management of scoliosis to prevent progression of deformity and improve sitting comfort.
",4
817,"Factors affecting fusion rate in adult spondylolisthesis.
 The authors examined factors affecting fusion rate in the surgical treatment of 89 consecutive adult patients with spondylolisthesis.
 Two factors significantly improved fusion rate: combined anterior and posterior fusion and rigid postoperative immobilization in the cast.
 In 65 patients with isthmic spondylolisthesis, the fusion rate was raised from 70% when posterior fusion alone was used to 88% when combined anterior and posterior fusion was used.
 In 20 patients with degenerative spondylolisthesis, frequent use of combined anterior and posterior fusion contributed to a high overall fusion rate of 95%.
 Among patients with isthmic spondylolisthesis, postoperative cast immobilization resulted in a higher fusion rate of 90% compared with a fusion rate of 63% obtained after brace immobilization.
",4
818,"Normal dystrophin in McLeod myopathy.
 Dystrophin and its gene were studied in a patient with McLeod syndrome.
 This X-linked recessive myopathy has been localized to Xp21, as has the Duchenne muscular dystrophy gene locus, which codes for dystrophin.
 Histopathological study of the patient's muscle showed mild subclinical myopathy.
 Immunological studies of dystrophin in two separate biopsy specimens and analysis of dystrophin gene DNA from a blood sample did not detect an abnormality.
 This suggests that the Duchenne muscular dystrophy gene, albeit close to the McLeod locus, is not involved in McLeod myopathy.
",4
819,"Magnetic resonance imaging of sacroiliac joint inflammation.
 A consecutive series of 27 patients with symptoms compatible with sacroiliitis underwent magnetic resonance imaging (MRI) of the sacroiliac joints.
 The diagnostic sensitivity of MRI was similar to that of computed tomography or conventional radiography.
 However, MRI seems to have the potential of providing unique information about the disease process in sacroiliitis by demonstrating abnormalities in subchondral bone and periarticular bone marrow.
 The results of this study suggest that early inflammatory changes in sacroiliitis occur in the subchondral structures of the sacroiliac joints.
",4
820,"Chondrons from articular cartilage. III. Morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage.
 Chondrons were isolated from human and canine osteoarthritic cartilage using low-speed homogenization techniques.
 Changes in chondron morphology were evaluated using differential interference-contrast microscopy, phase-contrast microscopy, and histochemical and ultrastructural methods.
 Chondrocyte viability was assessed using fluorescein diacetate staining, and chondron metabolism was investigated using autoradiography.
 The results suggest that initial changes in the collagen and proteoglycan distribution within the chondron are followed by chondrocyte proliferation to form clusters.
 These techniques offer the potential to study cell matrix interactions in degenerative osteoarthritis.
",4
821,"Progression of osteoarthritis of the hand and metacarpal bone loss. A twenty-year followup of incident cases.
 We examined the prospective relationship between metacarpal bone mass and osteoarthritis (OA) of the hand, using incidence data from the historical cohort in the Tecumseh Community Health Study (Tecumseh, MI).
 Women were examined for radiographic evidence of OA and for bone mass twice, 20-23 years apart (1962-1965 and 1985; 683 subjects with an age range of 55-74 in 1985).
 Two measures of OA were evaluated: the highest score assigned to any of the 32 wrist/hand joints, and the sum of scores for all wrist/hand joints.
 After adjustment for age, women who were classified as having OA (by either measure of OA) in 1985 were more likely to have more cortical area at baseline, which indicates greater bone mass.
 Women who developed OA in the 23-year period were more likely to experience a significantly greater widening of the medullary cavity over time, an indicator of increased bone resorption.
 Women with increasing levels of OA involvement also had an increased likelihood of greater cortical area loss.
 We conclude that women who later developed OA were more likely to have higher baseline bone mass than women who did not develop OA, but these women also had a greater likelihood of bone loss over time.
",4
822,"Suppression of type II collagen-induced arthritis by monoclonal antibodies.
 Some mouse monoclonal antibodies raised against chicken type II collagen suppressed or delayed the onset of chicken type II collagen-induced arthritis in DBA/1 mice.
 This was correlated with the suppression of anti-mouse type II collagen antibody responses following immunization with chicken type II collagen.
 The epitopes recognized by the suppressive antibodies were found to be present on cyanogen bromide (CB)-digested collagen peptides CB-11 and CB-12.
 This was also confirmed by the finding that administration of the CB-11 or CB-12 peptide suppressed the induction of arthritis.
",4
823,"Osteolytic monostotic Paget's disease of the fifth lumbar vertebra. A case report.
 Osteolytic monostotic Paget's disease or osteitis deformans of the fifth lumbar vertebra occurred in a 55-year-old woman.
 An isolated lytic process involving the entire vertebral body and posterior elements and an open biopsy showed extensive remodeling with cement lines, myelofibrosis, and osteoclastic resorption typical of Paget's disease.
",4
824,"Scapular allografts. A report of two cases.
 Some malignant tumors of the scapula can be adequately treated by limb-sparing, partial, or total scapulectomy.
 However, resection of the glenoid portion of the scapula and total scapulectomy result in an unsightly shoulder.
 In an attempt to minimize the functional impairment and restore stability and cosmesis, scapular glenoid allografts offer a reasonably good biologic replacement.
 This report describes the cases of a 45-year-old woman and a 32-year-old man in whom massive osteoarticular allografts were used.
 In one patient, good stability, cosmesis, and function were restored after resection of the glenoid portion.
 In the other patient, shoulder stability, cosmesis, and limited function were restored after total scapulectomy.
 No reports of scapular allografts seem to have been previously published in the literature.
",4
825,"Bilateral femoral retroversion associated with acetabular dysplasia. A case report.
 Retroversion of the proximal femur is associated with a number of acquired conditions but is unusual in a congenital form.
 It is even more unusual to be associated with acetabular dysplasia.
 A 38-year-old woman with bilateral hip pain had roentgenographic evidence of acetabular dysplasia with valgus neck-shaft angles.
 Physical findings were consistent with femoral retroversion, and computed tomography demonstrated 28 degrees of retroversion on both sides.
 Symptomatic relief was obtained with bilateral varus internal rotation osteotomies of the proximal femur.
 To date, a case of retroverted femora associated with acetabular dysplasia seems not to have been reported in the literature.
",4
826,"Simple bone cysts. The effects of methylprednisolone on synovial cells in culture.
 Ten years ago, a protocol using Depo-Medrol injections was developed for the treatment of unicameral bone cysts.
 This concept, designed by tumor surgeons and based on theory, has been cautiously approached.
 However, reproducible results have gradually increased clinical acceptance.
 Understanding the healing process has been restricted because of the lack of an experimental model.
 In an attempt to elucidate this mechanism of healing, a cell culture model was used to investigate the effects of methylprednisolone on synovial cells.
 Initially, three doses of the drug were tested and maximal changes were noted with the concentration of 40 mg/ml.
 Changes were then quantified by morphology, DNA assay, cell protein analysis, and electron microscopy.
 Results suggest that methylprednisolone may have a direct effect on the cellular component of unicameral bone cysts.
",4
827,"Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to stimulate neutrophils. Characterization of intraarticular apo E and demonstration of apo E binding to urate crystals in vivo.
 Factors that modulate the ability of monosodium urate crystals to stimulate leukocytes could regulate gouty inflammation.
 Lipoproteins that bear apo B-100 and apo E bind to urate crystals and suppress crystal-neutrophil interaction.
 In this study, we observed that urate crystals, coated with apo E of monocyte origin, had a diminished ability to stimulate neutrophils.
 Apo E was also detected on the surface of urate crystals recovered from gout patients.
 Thus, we analyzed apo E in noninflammatory synovial fluid, and found it to be associated with particles of heterogeneous size and of predominantly alpha and pre-beta electrophoretic mobility.
 Local articular synthesis of at least a portion of synovial fluid apo E was suggested because (a) the synovial fluid/plasma concentration ratio of apo E was significantly higher than that for both apo B and apo A-I, which are not widely synthesized by extrahepatic tissues, (b) cultured rheumatoid synovial cells in first passage secreted apo E, (c) a portion of synovial fluid apo E was heavily sialylated.
 We conclude that synovial fluids contain apo E that appears partly of local origin.
 Apo E binds to urate crystals and could modulate gouty inflammation.
",4
828,"Cartilage expression of a type II collagen mutation in an inherited form of osteoarthritis associated with a mild chondrodysplasia.
 In a family who expressed severe dominantly inherited osteoarthritis, the underlying mutation was traced by genomic sequencing to a single base change which predicts an amino acid substitution of cysteine for arginine at residue 519 of the triple-helical domain of the type II collagen molecule (Ala-Kokko, L., C.
 T.
 Baldwin, R.
 W.
 Moskowitz, and D.
 J.
 Prockop.
 1990.
 Proc.
 Natl.
 Acad.
 Sci.
 USA.
 87:6565-6568).
 In the present study we examined whether this predicted protein phenotype was evident in articular cartilage obtained from an affected family member who underwent hip surgery.
 The cartilage collagen was solubilized by CNBr digestion.
 Cysteine residues were labeled by reduction and alkylation with 14C-iodoacetate.
 Collagen CNBr-peptides were fractionated by ion exchange and reverse phase column chromatography.
 One peptide from the alpha 1(II) chain, alpha 1(II) CB8, was found to be radiolabeled.
 Tryptic peptides were prepared from it and identified by microsequence analysis.
 The results show that approximately one-quarter of the alpha 1(II) chains present in the polymeric extracellular collagen of the patient's cartilage contained the Arg519-to-Cys substitution.
 The protein exhibited other abnormal properties including disulfide-bonded alpha 1(II)-dimers and signs of posttranslational overmodification.
 The premature cartilage failure and osteoarthritis are presumably a result of the abnormal type II collagen being expressed in the cartilage matrix.
",4
829,"A report of fluorosis in the United States secondary to drinking well water.
 A 54-year-old female resident of Wellston, Okla, was found to have osteosclerosis on a routine chest roentgenogram.
 Subsequent investigation disclosed the cause of her osteosclerosis to be fluorosis secondary to the ingestion of well water containing 429 mumol/L of fluoride (recommended levels, 11 to 58 mumol/L).
 Water samples were also obtained from the 12 wells on properties adjacent to the index case.
 In three other wells, all at similar depths as the well of the index case, the fluoride concentration of the water was greater than 212 mumol/L.
 Urine samples from members of the four households who obtain their drinking water from these wells contained elevated urinary fluoride levels.
 Thus, fluorosis may develop in certain areas of the United States as a result of the natural occurrence of fluoride in the groundwater.
 Consequently, in known endemic areas, it would appear reasonable to measure the fluoride concentration of the well water at the time of drilling.
",4
830,"In vivo muscle magnetic resonance spectroscopy in the clinical investigation of mitochondrial disease.
 We have investigated the sensitivity and specificity of a rapid phosphorus magnetic resonance spectroscopy (MRS) protocol for detecting metabolic abnormalities in vivo in skeletal muscle of patients with mitochondrial disease.
 We examined 17 patients with mitochondrial myopathies.
 Sixteen had only mild or minimal myopathic signs and symptoms.
 Phosphorus magnetic resonance spectra from the resting gastrocnemius muscles showed an abnormal intracellular energy state (marked by an increased intracellular inorganic phosphate concentration) in 14/17.
 In 3/17, this was associated with a decreased phosphocreatine concentration.
 We also studied 20 patients with other diseases of muscle (inflammatory myopathies, metabolic myopathies, muscular dystrophies, and myasthenia gravis) that can present with similar clinical features.
 Spectra showed increased intracellular inorganic phosphate concentrations in 6/20.
 All of these muscle diseases were associated with evidence of muscle fiber necrosis.
 Abnormalities in the muscle energy state in these cases may be due to secondary mitochondrial dysfunction.
 Except for cases of polymyositis and dermatomyositis, these 6 other myopathies could be readily distinguished from the mitochondrial myopathies on the basis of the clinical examination and blood tests.
 We conclude that phosphorus MRS of resting muscle is practical in a clinical setting and has a useful sensitivity and specificity for mitochondrial myopathies when used in conjunction with standard noninvasive tests.
",4
831,"Centronuclear myopathy heterogeneity: distinction of clinical types by myosin isoform patterns.
 We studied muscles from 3 patients with centronuclear myopathy (CNM) by immunocytochemistry using myosin heavy chain (MHC)-specific monoclonal antibodies to determine whether subtypes of CNM express prenatal MHC and to assess if there is an arrest in development of these muscles.
 Muscle from a woman with childhood-onset CNM did not express prenatal MHC, yet this prenatal MHC was strongly expressed in the muscle fibers of 2 brothers with X-linked CNM.
 This finding represents the 1st immunocytochemical evidence of the expression of a prenatal myosin isoform in nonregenerating postnatal human muscle and suggests that the X-linked form of CNM differs from the other types because of a true arrest in maturation of the muscle.
",4
832,"Clinical evaluation of the ITI (F-type) hollow cylinder implant.
 In 1976 the hollow cylinder implant was introduced.
 A number of articles have been published about the ITI implant system.
 In this article, short-term results of 102 ITI F-type implants in 40 patients are reported.
 The results showed this one-stage implant to be at least comparable to other well-known implant systems.
",4
833,"Massive osteolysis of the maxillofacial bones. Report of two cases.
 Two cases of massive osteolysis were encountered, one affecting the mandible and the other the maxilla and mandible.
 Only 13 cases have been reported so far in the existing literature for massive osteolysis of the mandible.
 It is indeed a rare disease.
 Our two cases were surgically treated and were clinically and histopathologically assessed.
",4
834,"African Burkitt's lymphoma: case report and light and electron microscopic findings.
 An African Burkitt's lymphoma occurred in a 9-year-old American boy who had jaw tumors, proptosis, and abdominal masses.
 Histologically, the tumor consisted of a monotonous overgrowth of undifferentiated lymphocytes with a ""starry sky"" appearance.
 The differential diagnosis of African versus American form and Burkitt's lymphoma versus non-Burkitt's lymphoma is discussed.
",4
835,"Inherited diseases of bone density in children.
 In this article the radiographic manifestations of various genetic diseases predominately affecting bone mineralization are considered.
 Osteogenesis imperfecta and other diseases of diffuse osteopenia, hereditary rickets and rachiticlike conditions, and osteopetrosis and other diseases of increased bone density are emphasized.
 Recognition of the radiographic manifestations allows accurate diagnosis, therapeutic intervention when possible, and determination of recurrence risk for genetic counseling.
",4
836,"Metabolic bone disease. Morphometry.
 The history of the development of radiologic morphometric techniques is traced, emphasizing their pathophysiologic background and relevance to possible therapies.
 The techniques are described and longitudinal and comparative studies assessed.
 Technical limitations of the various methods are presented.
",4
837,"The pathology of metabolic bone disease.
 The skeletal manifestations of the diverse group of metabolic bone diseases are mediated through the altered function of osteoblasts and osteoclasts and abnormal rates of mineralization.
 Appropriate understanding of their pathologic conditions requires familiarity with the normal anatomy and physiology of the skeleton.
 The accurate identification of metabolic bone disease frequently demands histologic confirmation and sophisticated analysis of undecalcified bone specimens labeled with tetracycline by histomorphometric techniques.
 These procedures allow the assessment of many morphologic features that characterize specific disease states.
 The most common types of metabolic bone diseases are acquired disorders; nonetheless, rare forms frequently are genetically based and cause intrinsic alterations in the bone-cell populations.
",4
838,"Radiographic appearance of osteopenia.
 The radiographic appearance of bone is the result of two physiologic processes: the resorption of bone and the remodeling of bone in response to the stresses applied to it.
 The relative rates of these two processes will determine the structural and, therefore, the radiographic appearance of the affected bone.
",4
839,"Osteoporosis. Current techniques and recent developments in quantitative bone densitometry.
 Knowledge about the proper use and interpretation of bone densitometry studies and an understanding of appropriate medical interventions are not universal among physicians, nor are instrumentation and technical performance of bone density studies of uniformly high quality.
 Indeed, this deficiency of medical and technical expertise is the principal deterrent to widespread implementation of our recommended clinical applications at this time.
 Nonetheless, given the current impetus to disseminate information about osteoporosis, to make newer instrumentation more readily available, and to limit the cost of these techniques, we anticipate that our recommendations may soon become standard medical practice.
",4
840,"Osteoporosis.
 Osteoporosis, a condition of decreased bone tissue that increases the likelihood of fracture, places a significant burden on our society in terms of health cost and morbidity.
 The most common type of osteoporosis is involutional, and two subtypes are recognized: type 1 and type 2.
 Type 1, or postmenopausal, osteoporosis is most commonly seen in perimenopausal and postmenopausal women from ages 51 to 75.
 Estrogen deficiency is the most dominant factor in the pathogenesis of this disorder.
 Type 2, or aging related, osteoporosis is seen in elderly women and men aged 70 or more.
 Bone loss in this group is related to aging, estrogen deficiency, negative calcium balance, and a variety of environmental and genetic factors.
 The best approach to the management of osteoporosis is to develop a lifelong strategy that maximizes peak bone mass and minimizes aging-related and postmenopausal bone loss.
 Estrogen is the only medication approved for the prevention of bone loss that is in general use.
 Other strategies to prevent bone loss (and maximize peak bone mass) include adequate calcium intake, adequate exercise, and avoidance of excess alcohol, tobacco, and caffeine use.
",4
841,"Functional stability of the canine cervical spine after injury. A three-month in vivo study.
 Although clinical instability is an in vivo problem, most spinal instability criteria are either subjective or are based on in vitro experiments.
 The authors performed an in vivo experiment using a canine model to study the natural history of spinal instability as a function of healing time up to 12 weeks.
 Three injuries were produced surgically: sham; laminectomy at C4; and bilateral facetectomy at C4-C5.
 Three 1.5-mm steel balls were implanted into C3 to C6 vertebrae at the time of surgery.
 Standardized functional flexion-extension stereoradiographs of the cervical spine were obtained before injury, immediately after injury and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7.5, 9, and 12 weeks postinjury and immediately after killing the animals.
 In general, the authors found decreased ranges of motion (ROM) at the C4-C5 level, compared with the pre-injury values, for all injuries, but most significantly for the facetectomy.
 The maximum decrease occurred between 0 and 0.5 weeks postinjury.
 Between 2 and 12 weeks, there was recovery in the ROM, especially for the two less severe injuries.
 The changes in the ROM at each spinal level were explained by simultaneous presence of a destabilizing factor, caused by the three different injuries with the sham as the least and the facetectomy as the most destabilizing injury, and a stabilizing mechanism of muscle spasm in the beginning and of healing and other adaptive responses in the late phase after injury.
 Because of the significant differences between the canine model and the human cervical spine, the present findings should be extrapolated to the human situation with caution.
",4
842,"Analysis of the chondroitin sulfate proteoglycan core protein (CSPGCP) gene in achondroplasia and pseudoachondroplasia.
 Achondroplasia and pseudoachondroplasia are autosomal dominant skeletal dysplasias resulting in short-limbed dwarfism.
 Histologic and ultrastructural studies of the cartilage in pseudoachondroplasia and in homozygous achondroplasia have suggested a structural abnormality in chondroitin sulfate proteoglycan (CSPG), a major structural protein in the extra-cellular matrix.
 The gene encoding CSPG core protein (CSPGCP) is thus a logical ""candidate gene"" for analysis in these conditions.
 cDNA probes encoding CSPGCP were used to identify restriction fragment length polymorphisms (RFLPs) in DNA from a panel of control individuals.
 No gross alterations at the CSPGCP locus were noted in DNA from 37 individuals with achondroplasia and 5 individuals with pseudoachondroplasia.
 In addition, allelic frequencies of the RFLPs were not significantly different among controls and patients with either condition.
 In one three-generation family with achondroplasia, close linkage of the CSPGCP locus and the skeletal dysplasia was excluded using a Bgl II polymorphism.
 Similarly, in a three-generation family with pseudoachondroplasia, the CSPGCP gene was not tightly linked to the disease phenotype.
 These results indicate that mutations at the chondroitin sulfate proteoglycan core protein locus do not cause achondroplasia or pseudoachondroplasia in these families.
",4
843,"Muscle conditioning in late poliomyelitis.
 To study the adaptability of postpolio muscles, 12 subjects (mean age 54 years) participated in a high-intensity resistance exercise program.
 Seventy-five percent met the criteria for postpolio syndrome.
 Isometric and isokinetic strength and muscle endurance were measured.
 Polio-affected muscles were identified in muscle biopsies.
 The biopsies were also used for measurements of enzymatic activities and for histochemical and histopathologic analyses.
 Pretraining strength values were less than half those of healthy controls, mean fiber areas were twice those of healthy controls, and oxidative enzyme activity was low.
 After training, a significant increase in isometric (mean 29%) and isokinetic (mean 24%) strength was observed and maintained for some time.
 This demonstrates remaining adaptability in muscles already compensated from long-standing polio.
",4
844,"Corticosteroid injections in adhesive capsulitis: investigation of their value and site.
 Forty-eight patients with frozen shoulder for less than six months were assigned at random to receive three shoulder injections into the subacromial bursa or glenohumeral joint at weekly intervals.
 The treatment groups were (1) intra-articular methylprednisolone and lidocaine, (2) intrabursal methylprednisolone and lidocaine, (3) intra-articular lidocaine, (4) intrabursal lidocaine.
 The same physical therapy program was carried out for all patients.
 Assessments of pain and range of motion were performed by a physical therapist who was uninformed about the nature of the injection therapy.
 There was no significant difference in outcome between intrabursal injection and intra-articular injection.
 Injection of steroid with lidocaine had no advantage over lidocaine alone in restoring shoulder motion, but partial, transient pain relief occurred in two thirds of the steroid-treated patients.
",4
845,"Bracing for patellar instability.
 Knee pain secondary to problems with patellar tracking is common.
 The initial treatment for these problems is conservative.
 Patellar orthotics have been used extensively to treat a variety of extensor mechanism problems.
 Millions of health care dollars are spent annually on the use of these braces.
 There are many different patellar orthotics on the market today.
 The use and design of most of these devices are unclear and often lack a solid biomechanical foundation.
 The practical mechanical function of these braces is to reduce the lateral displacement of abnormal patellofemoral tracking.
 Orthotics that are designed and tested using practical biomechanical principles for applying a medially directed force to the patella seem to have a role in treating patients with knee pain secondary to patellar malalignment and instability.
 Well-defined and controlled clinical studies of the use of patellar braces are lacking.
",4
846,"Magnetic resonance imaging of the shoulder. Sensitivity, specificity, and predictive value.
 The sensitivity, specificity, and predictive value of magnetic resonance imaging in the diagnosis of lesions of the rotator cuff, glenohumeral capsule, and glenoid labrum were evaluated in ninety-one patients and fifteen asymptomatic volunteers.
 Magnetic resonance imaging demonstrated 100 per cent sensitivity and 95 per cent specificity in the diagnosis of complete tears, and it consistently predicted the size of the tear of the rotator cuff.
 There was a definite correlation between atrophy of the supraspinatus muscle and the size of a complete, chronic tear of the rotator cuff.
 The sensitivity and specificity of magnetic resonance imaging in the differentiation of tendinitis from degeneration of the cuff were 82 and 85 per cent, and in the differentiation of a normal tendon from one affected by tendinitis with signs of impingement the sensitivity and specificity were 93 and 87 per cent.
 The formation of spurs around the acromion and acromiocalvicular joint correlated highly with increased age of the patient and with chronic disease of the rotator cuff.
 The sensitivity and specificity of magnetic resonance imaging in the diagnosis of labral tears associated with glenohumeral instability were 88 and 93 per cent.
 The study showed that high-resolution magnetic-resonance imaging is an excellent non-invasive tool in the diagnosis of lesions of the rotator cuff and glenohumeral instability.
",4
847,"Tests for posterolateral instability of the knee in normal subjects. Results of examination under anesthesia.
 An apparently normal knee was examined in each of 100 subjects while they were under general or epidural anesthesia for an unrelated operation.
 The Lachman, anterior drawer, posterior drawer, and pivot-shift tests were negative in all knees.
 All knees were stable to varus and valgus stress at both 0 and 30 degrees of flexion.
 The external-rotation recurvatum test also was negative in all knees.
 A positive reversed pivot-shift sign was present in 35 per cent of the knees, suggesting that it may not signify abnormality, at least not without a negative test on the contralateral knee.
 The results of the posterolateral drawer test were variable, difficult to quantify, and did not always have a firm end-point.
 The amount of maximum external rotation of the tibia, measured from the reference line of the medial border of the foot, was extremely variable at both 30 and 90 degrees of flexion of the knee.
 External rotation, as determined by this reference, was slightly greater (averaging 9 degrees) at 90 than at 30 degrees of flexion.
 The normal range of maximum external rotation of the foot was 10 to 45 degrees at 30 degrees of flexion of the knee and 15 to 70 degrees at 90 degrees of flexion.
 The presence of a large angle of external rotation and a positive reversed pivot-shift sign correlated strongly with increased ligamentous laxity and mild varus alignment of the knee.
",4
848,"Effect of a single infusion of aminohydroxypropylidene on calcium and bone metabolism in healthy volunteers monitored during 2 months.
 Recently, bisphosphonates have been used to prevent postmenopausal bone loss.
 As the effects of bisphosphonates on normal bone metabolism are unknown, 3-amino-1-hydroxypropylidene-1,1-diphosphonate (APD) was studied in healthy subjects.
 The effects of a single 20-mg APD infusion on biochemical parameters of calcium and bone metabolism were investigated during 2 months in 10 healthy male volunteers.
 This single moderate dose of APD reduced biochemical parameters of bone resorption during the time of follow-up.
 After 2 months, urinary hydroxyproline excretion was still below the basal level.
 The decreased serum calcium levels did not return to basal values.
 Biochemical parameters of bone formation, serum alkaline phosphatase and osteocalcin, showed a slight increase during the first month after stimulation of the parathyroids and a corresponding increase in serum 1,25-dihydroxyvitamin D.
 These formation parameters decreased thereafter, probably representing coupling between bone resorption and bone formation.
",4
849,"Estrogen and progestin therapy to prevent osteoporosis: attitudes and practices of general internists and gynecologists.
 STUDY OBJECTIVE: To assess combined hormone therapy (CHT) prescribing patterns, possible impediments to CHT prescribing, and use of endometrial biopsy to monitor therapy.
 DESIGN: Mailed questionnaire survey.
 SUBJECTS: Gynecologists and general internists at two Boston teaching hospitals.
 MEASUREMENTS AND MAIN RESULTS: Based on a 71% response rate, 72% of internists and 100% of gynecologists reported ever having prescribed CHT.
 Almost 60% of internists, compared with 8% of gynecologists, reported that over half of their female patients were older than 50 years of age.
 By logistic regression analysis of the internists' data, female gender of physician (odds ratio 11.0), belief that CHT decreases myocardial infarction risk (odds ratio 3.4), and knowledge of CHT's benefits and risks (odds ratio 2.8) were associated with prescribing.
 Endometrial biopsy was performed by a majority of physicians only when unexpected vaginal bleeding occurred and in cases of unclear menopausal transition.
 Physicians who were concerned about litigation were seven times more likely to perform baseline endometrial biopsy.
 CONCLUSIONS: In the authors' sample, as well as nationally, internists are more likely to provide care for menopausal women.
 Among internists, gender and knowledge are strongly associated with CHT prescribing.
 These findings have important educational implications if internists are to routinely provide information and counseling to women about osteoporosis and CHT.
",4
850,"Schwartz-Jampel syndrome with dominant inheritance.
 The Schwartz-Jampel syndrome (SJS) is a rare congenital multisystem disorder of unknown pathogenesis which is characterized by distinct faces, skeletal deformities, joint contractures, short stature, muscle hypertrophy, clinical myotonia, and continuous muscle fiber activity.
 The inheritance pattern of SJS has been assumed to be autosomal recessive.
 We report the occurrence of the classic SJS syndrome in both a father and son in a non-consanguineous family, suggesting that SJS has the potential for a dominant pattern of inheritance.
",4
851,"Identification of alpha-motor nerve fiber potentials in lumbar epidural space and its clinical significance.
 The alpha-efferent component of spinal root potentials (SRPs) was recorded in the lumbar epidural space stimulating the tibial and peroneal nerves for clinical diagnosis and clinical treatment.
 Five normal volunteers and 15 clinical cases with lumbar disc herniation (LDH) were examined.
 The SRP by the tibial nerve stimulation in the normal control group consisted of two kinds of potentials with different latency.
 Simultaneous electromyogram (EMG) recording from the stimulated muscles indicated that the shortest latency potential (first potential) was the ascending volley, including orthodromic afferent and antidromic alpha-efferent volleys; and that the long latency potential (second potential) was the descending volley of reflexively evoked alpha-efferents by the Group Ia afferents.
 The component of alpha-efferent fiber potential was recorded in the following two methods by changing the intensity of stimulation: 1) identifying alpha-efferent components in the first potential and 2) recording the second potential.
 Conduction blockage of spinal roots in 15 clinical cases was demonstrated as abnormal positivity and prolonged duration of the potentials.
 New methods were introduced to estimate two parameters quantitatively.
 The present study showed either of these signs in all patients tested.
 The examination was helpful to determine the level(s) of lumbar motor radiculopathies, and the extent of pathologic neuropathy.
",4
852,"Magnetic resonance imaging of lumbar disc herniation. Comparison with myelography.
 Fifty-three patients with surgically confirmed lumbar disc herniation at 55 levels were studied retrospectively to compare the diagnostic accuracy of high-field strength surface coil magnetic resonance imaging (MRI) with that of myelography.
 Disc herniation was classified into three groups according to MRI findings, namely, unilateral single-disc herniation, central single-disc herniation, and multilevel disc herniation.
 Magnetic resonance imaging diagnosis of unilateral single-disc herniation was extremely reliable, so myelography was considered to be unnecessary.
 Conversely, MRI findings of central single-disc herniation and multilevel disc herniation were less definite, in that myelography was necessary in locating the disc causing symptoms.
",4
853,"Ultrasonic level diagnosis of lumbar disc herniation.
 Although the use of diagnostic ultrasound to measure the spinal canal has been proposed, the value of ultrasound for lumbar disc herniation has not been yet fully assessed.
 The purpose of this investigation was to evaluate the effectiveness of ultrasound in the level diagnosis of herniated nucleus pulposus.
 Prospective ultrasound examinations were performed on 80 consecutive patients with clinically suspected lumbar disc herniation.
 In 41 discs of those 40 patients with surgically confirmed lumbar disc herniation, there were 32 discs (78%) with true-positive ultrasound diagnoses, 37 discs (90%) with true-positive myelographic diagnoses, and 20 patients (50%) with true-positive neurologic diagnoses.
 Conversely, ultrasound diagnoses showed positive echogram in 24 (60%) of 40 nonoperative patients.
 These results suggest that ultrasound is of value as an aid for diagnosing the level of lumbar disc herniation.
",4
854,"The system and procedures of percutaneous intradiscal laser nucleotomy.
 Since 1986, percutaneous intradiscal laser nucleotomy (PILN) has been studied in the authors' laser laboratory.
 The purpose of this report is to develop PILN as an alternative to chemonucleolysis and percutaneous discectomy, which are currently applied, and to establish a safe, easy, accurate and short-time therapy method for lumbar disc herniation.
 After laser irradiation, intradiscal pressures (IDP) decreased and the nucleus pulposus was gradually replaced with cartilaginous fibrous tissue.
 The evaluation of heat distribution with thermocouples and thermography was done to determine safe optimum irradiating conditions and to develop a new double-lumen needle and a bare quartz fiber.
 Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser devices have been improved for easy and safe use, and a new tip type pressure transducer has been made for improved therapeutic results using this new method.
",4
855,"Unstable lumbar spine without hypermobility in postlaminectomy cases. Mechanism of symptoms and effect of spinal fusion with and without spinal instrumentation.
 The morbid conditions of unstable lumbar spine that are not associated with hypermobility in postlaminectomy cases were studied.
 The dura and the nerve roots with adhesion could be affected by minimal movement of the spine, which seemed to be the mechanism of symptoms of instability without hypermobility.
 The effects of spinal instrumentation on this particular instability were studied.
 The spinal instrumentation provides instantaneous rigid fixation, and maintains it until fusion is obtained, which might prevent adhesion, new bone formation, and re-stenosis.
 Spinal instrumentation seemed to be the effective treatment for this particular instability.
",4
856,"Lumbar trapezoid plate for lumbar spondylolisthesis. A clinical study on preoperative and postoperative instability.
 The authors studied the effects of a ""lumbar trapezoid plate"" (spinal plate and pedicle screwing), performed for lumbar spondylolisthesis, observing the effect on the remaining adjacent discs with regard to preoperative and postoperative instability.
 The authors examined changes in preoperative and postoperative lumbar ROM (range of motion), displacement of motor unit levels, and occurrence of instability in the remaining discs, such as horizontal and rotational displacement, in 26 patients who were followed up for a mean of 29 postoperative months; 13 patients had spondylolytic spondylolisthesis and 13 patients degenerative spondylolisthesis.
 The authors studied the effects of the fused vertebral angle and reduction of spondylolisthesis on the remaining upper and lower adjacent discs and the preoperative and postoperative fused disc heights.
 Intervertebral fusion must affect the remaining adjacent discs, but compensatory function of the remaining motor unit level was more influenced by the fused intervertebral angle than by repositioning of the spondylolisthesis.
 Fusion at a physiologically lordotic position is quite necessary.
 For this purpose, it is considered important to prevent grafted bones of the posterior lumbar interbody fusion (PLIF) from collapse and to maintain the achieved alignment of the lumbar spine.
",4
857,"Natural history of degenerative spondylolisthesis. Pathogenesis and natural course of the slippage.
 To clarify the natural course of degenerative spondylolisthesis, the mechanism and progression of disk slippage were studied clinically and radiographically in 40 patients.
 Progressive slippage was observed in 12 patients (30%).
 No progression of slippage was noted in patients who showed narrowing of the intervertebral disk, spur formation, subcartilaginous sclerosis, or ossification of ligaments.
 These suggest that the mechanisms of spinal restabilization prevent progression of the disease.
 General joint laxity was observed in many patients (65%), and this was believed to be involved in the pathogenic mechanism of this disease.
 There was no correlation between the clinical symptoms and progression of slippage.
 These findings suggest that careful consideration of the natural mechanisms of spinal restabilization as well as the natural course of the disease is important.
",4
858,"Long-term results of anterior interbody fusion for treatment of degenerative spondylolisthesis.
 Thirty-nine patients, 34 women and five men, underwent anterior decompression and interbody fusion for degenerative spondylolisthesis between February 1958 and August 1988.
 Their average age at surgery was 51 years (range, 34-74 years), and their average follow-up period was 12 years 7 months (range, 6 months to 30 years).
 Clinical evaluation was done by the score rating system of the Japanese Orthopaedic Association (JOA Score).
 Patients with JOA scores of 25 points or more were rated as ""satisfactory."" Survivorship was analyzed by the method of Kaplan and Meier to determine the cumulative percentage of patients with satisfactory results.
 The following results were obtained: Seventy-six percent of the patients had satisfactory results for 10 years after the anterior interbody fusion, 60% for 20 years, and 52% for 30 years.
 Irrespective of their age at surgery, the patients generally maintained satisfactory results up to 65 years of age.
",4
859,"Clinical study on stability of combined distraction and compression rod instrumentation with posterolateral fusion for unstable degenerative spondylolisthesis.
 The authors examined the stability of combined distraction and compression rod instrumentation with posterolateral fusion in 40 consecutive patients with unstable degenerative spondylolisthesis.
 All operations were performed by floating fusion of L3-4 or L4-5 after decompression procedures.
 Mobility at the fused level was checked every 4 weeks after operation by the disc space angle on the functional radiographic films without brace.
 The average period of postoperative follow-up was 26 months.
 In 30 patients, no mobility was found at any time.
 In six patients, any mobility disappeared within 24 weeks, and in three patients, within 1 year.
 Pseudoarthrosis was found in one patient.
 The solid fusion rate was 97.5%.
 The values of percent slippage and slip angle were slightly improved.
 Lumbar lordosis was in the normal range at follow-up.
",4
860,"The relationship of complement-mediated microvasculopathy to the histologic features and clinical duration of disease in dermatomyositis 
 Accumulating evidence indicates that a complement-mediated microvasculopathy may play a pathogenic role in dermatomyositis.
 In a previous study, we demonstrated neoantigens of the C5b-9 complement membrane attack complex in the muscle microvasculature of childhood and adult cases of dermatomyositis.
 To further characterize the relationship between the vascular complement deposits and histologic changes, quantitative histopathologic analyses were performed on 39 dermatomyositis biopsy specimens (26 adult, 13 children).
 There was a significant correlation between the percentage of fascicles with fibers having focal myofibrillar loss, a change seen early in the evolution of ischemic muscle fiber damage, and the percentage of fascicles having capillary deposits of membrane attack complex.
 Conversely, in biopsy specimens with a higher percentage of fascicles with perifascicular atrophy, membrane attack complex deposits were significantly less common.
 A fascicle-by-fascicle analysis supported these observations.
 Patients whose biopsy specimens were negative for microvascular membrane attack complex had clinical weakness for a significantly longer time than those patients with vascular complement deposits.
 These data support the hypothesis that the complement-mediated vasculopathy is a primary immunopathogenic event in the evolution of muscle lesions in dermatomyositis.
",4
861,"Magnetic resonance imaging of primary skeletal muscle diseases: patterns of distribution and severity of involvement.
 Magnetic resonance imaging of the lower extremities was performed with a low field system in 51 patients representing three different categories of biopsy-proven primary skeletal muscle disease; muscular dystrophies, congenital myopathies and polymyositis.
 The intermuscular distribution of abnormal signal intensity and the grade of involvement of individual muscles were assessed.
 Large differences in the degree of pathological signal intensity between individual muscles were found in all categories.
 In the muscular dystrophy and polymyositis patients, the overall involvement was significantly more severe than in patients with congenital myopathy.
 Definite patterns of selective involvement were seen.
 Statistical evidence of selective muscle sparing was found; the gracilis muscle was significantly less affected than the other muscles in all three disease groups.
 Other muscles with significant sparing include the rectus femoris and sartorius muscles of the thigh and the tibialis posterior muscle of the leg.
 Common anatomical and functional characteristics of muscles may be related to the distribution of muscular disease.
",4
862,"Identification of osteoclast precursors in multilineage hemopoietic colonies.
 The osteoclast is known to be derived from the hemopoietic stem cell, but its lineage and the mechanisms by which its differentiation is regulated are largely unknown.
 There is evidence that osteoclastic differentiation is induced through a contact-dependent interaction between bone marrow stromal cells and hemopoietic precursors.
 To analyze osteoclastic lineage, colonies were generated in semi-solid medium from mouse spleen cells in the presence of erythropoietin with either Wehi 3B-conditioned medium or interleukin 3 (IL3).
 After 7 days, individual colonies were picked.
 Half of each colony was phenotyped by the morphology of cells in cytospin preparations; the second half of each was incubated for 7 days with a bone marrow-derived cell line (ts8) that induces osteoclastic differentiation from hemopoietic cells, on bone slices in the presence of 1,25-dihydroxyvitamin D3.
 After incubation, bone resorption was assessed by scanning electron microscopy.
 No resorption was induced in cells derived from single-lineage colonies, but resorptive cells differentiated in 17% of granulocyte-macrophage (GM) colonies and 38% of multilineage colonies.
 Since only a minority of GM colonies contained osteoclastic precursors, this suggests that the GM colonies that contained osteoclasts were not typical GM colonies but may have been a form of multilineage colony analagous to other multilineage colonies that contain granulocytes, macrophages, and a third cell type.
 No resorptive cells were formed when IL3-derived colonies were incubated on bone slices without ts8 cells.
 The results suggest that osteoclasts are derived from a multilineage precursor, upon which IL3 acts to generate cells capable of osteoclastic differentiation, which form resorptive cells upon incubation with bone marrow stromal cells in the presence of 1,25-dihydroxyvitamin D3.
",4
863,"High concentrations of 17 beta-estradiol stimulate trabecular bone formation in adult female rats.
 Although the effects of low concentrations of 17 beta-estradiol (E2) on bone formation and resorption are well described, little is known of the effects of E2 on bone at concentrations that circulate during pregnancy.
 We, therefore, investigated the effects of administration of high dose E2 to 3-month-old female Wistar rats on biochemical and histomorphometric indices of bone formation and resorption.
 Animals receiving exogenous E2 (4 mg/kg.day for 17 days; n = 9) showed a mean serum E2 concentration of 17.5 +/- 2.9 nM, compared with 0.6 +/- 0.2 nM in those receiving vehicle alone (n = 10).
 The bone formation rate, measured at the proximal tibial metaphysis after the administration of double fluorochrome labels, was greatly increased in the E2 group (13.6 +/- 2.0 x 10(-2) microns3/microns2.day) compared to controls (3.9 +/- 0.9), as was serum alkaline phosphatase (E2, 133.6 +/- 10.1 IU; controls, 87.5 +/- 5.5).
 This increase in the rate of bone formation was associated with a significant increase in trabecular bone volume.
 E2 treatment did not affect urinary hydroxyproline excretion or histomorphometric indices of bone resorption.
 These findings suggest that high concentrations of E2 strongly stimulate the formation of trabecular bone.
 This may represent an important mechanism by which calcium stores are accumulated during pregnancy in rats, in anticipation of the mineral requirements of lactation.
",4
864,"Differential diagnosis between osteitis condensans ilii and sacroiliitis [published erratum appears in J Rheumatol 1991 May;18(5):790]
 Sacroiliitis of seronegative spondyloarthropathy may sometimes show on pelvis plain films findings indistinguishable from those of osteitis condensans ilii.
 Computed tomography (CT) can differentiate earlier than plain radiography between the 2 conditions; furthermore, it should also be possible to make this differentiation clinically.
 The aim of our study was to verify whether the criteria recently proposed by the European Spondylarthropathy Study Group (EESG) for the classification of spondyloarthropathy are useful.
 CT scans through the synovial part of the sacroiliac joints of 7 consecutive patients meeting the ESSG criteria and showing typical findings of osteitis condensans ilii on plain films were mixed with those of 15 consecutive patients with osteitis condensans ilii not meeting the ESSG criteria.
 Scans were examined for joint space and surface abnormalities blindly and independently by 2 observers.
 Six patients in the spondyloarthropathy group and one in the osteiitis condensans ilii group showed clear erosions and/or joint space narrowing of less than 2 mm in at least one joint.
 The difference was statistically significant (p less than 0.001).
 Our results suggest that by using criteria valid for the whole group of seronegative spondyloarthropathies, it is possible to differentiate clinically between seronegative spondyloarthropathies with sacroiliitis mimicking osteitis condensans ilii and ""true"" osteitis condensans ilii.
",4
865,"Trigger finger secondary to anomalous lumbrical insertion: a case report and review of the literature.
 Trigger finger is a relatively common clinical entity, most frequently caused by stenosing tenosynovitis.
 Several other conditions not related to tenosynovitis also have been described as a cause of triggering, and these have been reviewed.
 We present a rare anomaly of the fourth lumbrical muscle insertion as a cause of triggering of the right little finger.
 This was completely relieved following excision of the anomalous muscle.
 This rare anatomic variant should be added to the list of potential causes of trigger finger.
",4
866,"Internal derangement of the temporomandibular joint: a histochemical study.
 The purpose of this study was to correlate histologic findings in temporomandibular joint (TMJ) condyles and discs with their macroscopic appearance at surgery.
 The 24 patients with internal derangement of the joint included 20 women and 4 men (mean age, 37 years; range, 18 to 61 years).
 The tissue lesions varied in degree from mild soft-tissue fraying and bone remodeling to extensive resorption and new cartilage and bone formation with high phosphatase enzyme activities, and even to loss of articular soft tissue and breakdown of cortical bone.
 Reactions may arise in the hard tissues before they occur in the articular surface layers.
",4
867,"Drugs to lower uric acid levels. How to avoid misuse in gouty arthritis.
 Several points regarding the use of drugs to lower uric acid levels deserve emphasis.
 First, these agents are not useful in the management of acute gout.
 Second, all forms of the drugs should be initiated at low dose with gradual increments to achieve a serum uric acid level between 5 and 6 mg/dL.
 There are no data to support the widely presumed notion that dropping the uric acid level to a very low range (1 to 3 mg/dL) hastens resorption of tophi or improves joint function.
 Third, the uricosuric agents probenecid (Benemid) and sulfinpyrazone (Anturane) interact with a number of drugs, and both the patient and physician should be aware of this.
 Finally, and most important, careful and frequent monitoring is needed during the first several months of therapy with these drugs.
",4
868,"Chronic fatigue syndrome: is it real?
 Epstein-Barr virus is no longer considered an important cause of chronic fatigue syndrome.
 Instead, the disease is probably related to an underlying psychiatric disorder, subtle immunologic dysfunction, or an interaction between these two factors.
 A carefully taken history, physical examination, and simple laboratory testing are usually sufficient to establish the diagnosis.
 Therapy with antidepressants or nonsteroidal anti-inflammatory drugs may be effective in selected patients.
 Thorough follow-up conducted with empathy and optimism is important in all cases.
",4
869,"Laboratory tests for rheumatic diseases.
 A carefully taken history and thorough physical examination remain the most crucial aspects of diagnosing rheumatic disorders.
 Non-rheumatologic conditions also need to be kept in mind.
 Laboratory tests should be looked on as mostly supportive or confirmatory, because many of the tests are relatively nonspecific and may lack sensitivity.
 If their limitations are recognized, however, the tests can be invaluable tools when the clinician confronts the task of differentiating an array of rheumatologic disorders.
",4
870,"Histopathology of metastatic temporal bone tumors.
 Temporal bone metastasis is now being reported with increasing frequency.
 To understand the process of temporal bone metastasis, complete histologic evaluation of the temporal bones is essential.
 In this study, 60 temporal bones from 33 patients were evaluated.
 Different patterns of temporal bone involvement were noted depending on the mode of spread to the temporal bone.
 Involvement of the temporal bone usually occurs late in the disease process and is often asymptomatic.
",4
871,"Familial chondrocalcinosis due to calcium pyrophosphate dihydrate crystal deposition in English families.
 Familial predisposition to chondrocalcinosis (CC) due to calcium pyrophosphate dihydrate (CPPD) crystal deposition is described in five English kindreds.
 Two families were characterized by premature-onset polyarticular CC with little associated structural arthropathy.
 In one of these families, recurrent childhood fits were strongly associated with subsequent development of CC.
 Affected members of the other three families resembled sporadic disease in showing predominantly late-onset, oligoarticular CC with mild arthritis and destructive change in only one case.
 Knee synovial fluid levels of inorganic pyrophosphate (PPi) and nucleoside triphosphate pyrophosphate (NTPP) did not differ from those of 59 sporadic cases of CC due to CPPD, although PPi and NTPP levels in both groups were higher than in normal knee synovial fluid (P less than 0.0001).
 Urinary PPi levels were not different from normal controls.
 Screening for other metabolic abnormality was negative in all cases.
 This is the first report of familial CC in the UK, and the first to associate this condition with childhood fits.
 Absence of overt primary abnormality of PPi metabolism suggests that other factors relating to crystal nucleation/growth may be more relevant to predisposition in these cases.
",4
872,"Treatment of Freiberg's disease. A new operative technique.
 A method of treating Freiberg's disease of the metatarsal head by shortening the metatarsal bone is described.
 This operation has been performed in 15 patients (16 feet).
 Excellent relief of pain was obtained, although most patients had persistent stiffness of the metatarsophalangeal joint.
",4
873,"Correction of coxa vara in childhood. The use of Pauwels' Y-shaped osteotomy.
 The long-term results following the correction of coxa vara by Pauwels' Y-shaped intertrochanteric osteotomy have been evaluated in 14 children.
 Ten of the children had unilateral hip disease and were otherwise normal while four had bilateral hip disease due to generalised skeletal dysplasias.
 In each case, the growth plate was vertical, the femoral head was displaced inferiorly and there were abnormalities in the metaphysis of the femoral neck.
 The results indicate that this osteotomy provides lasting correction of the deformity, regardless of the cause, as long as the inclination of the growth plate is corrected to 40 degrees or less and adequate support is provided for the metaphyseal defect and the displaced femoral head.
",4
874,"Joint proprioception in normal, osteoarthritic and replaced knees.
 We measured joint position sense in the knee by a new method which tests the proprioceptive contribution of the joint capsule and ligaments.
 The leg was supported on a splint, and held in several positions of flexion.
 The subjects' perception of the position was recorded on a visual analogue model and compared with the actual angle of flexion.
 Eighty-one normal and 45 osteoarthritic knees were examined, as were 10 knees with semi-constrained and 11 with hinged joint replacements.
 All were assessed with and without an elastic bandage around the knee.
 There was a steady decline in joint position sense with age in subjects with normal knees.
 Those with osteoarthritic knees had impaired joint position sense at all ages (p less than 0.001).
 Knee replacement improved the joint position sense slightly (p less than 0.02); semi-constrained replacement had a greater effect than hinged replacement.
 The effect of an elastic bandage in subjects with poor position sense was dramatic, improving accuracy by 40% (p less than 0.001).
 It is proposed that reduced proprioception in elderly and osteoarthritic subjects may be responsible for initiation or advancement of degeneration of the knee.
",4
875,"Natural history of nontraumatic avascular necrosis of the femoral head.
 We studied the natural history of nontraumatic avascular necrosis of the femoral head (ANFH) in 115 hips in 87 patients, 69 steroid-induced, 21 related to misuse of alcohol and 25 idiopathic.
 The average length of follow-up was over five years.
 Collapse occurred most often when the focus of bone necrosis occupied the weight-bearing surface of the femoral head.
 Flatness of the head due to subchondral fracture was an early manifestation of collapse.
 Classification into six types based upon the radiographic findings provided an accurate prognosis for individual cases of ANFH which is useful in planning treatment and in assessing its outcome.
",4
876,"Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links.
 Pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) are two cross-links of collagen molecules that are present in the extracellular matrix and released during its degradation.
 In contrast to the wide distribution of collagen, Pyr is present in bone and cartilage, but not in significant amounts in other connective tissues, and D-Pyr appears to be specific for bone tissue.
 Therefore, the urinary excretion of Pyr and D-Pyr might be a sensitive marker of bone matrix degradation.
 Using a specific high pressure liquid chromatography assay we have measured Pyr and D-Pyr cross-links in a 24-h and a fasting urine sample in 60 early postmenopausal women and 19 premenopausal women matched for age.
 Menopause induced a 62% increase in Fu Pyr (49.8 +/- 18.7 vs.
 30.8 +/- 8.0 pmol/mumol creatinine; P less than 0.001) and an 82% increase in Fu D-Pyr (8.2 +/- 3.4 vs.
 4.5 +/- 1.4 pmol/mumol creatinine; P less than 0.001).
 In 20 postmenopausal women on hormone replacement therapy, urinary Pyr and D-Pyr returned to premenopausal levels within 6 months, contrasting with unchanged levels during placebo treatment.
 The 24-h excretion of Pyr and D-Pyr was significantly lower than the fasting excretion, but was similarly decreased after hormone replacement therapy.
 Pyr and D-Pyr excretion measured in the same urinary sample were highly correlated (r = 0.85 for fasting and 0.83 for 24-h sampling), but correlations between fasting and 24-h values were weak (D-Pyr, r = 0.30; Pyr, r = 0.29; P less than 0.05 for both).
 Correlations between urinary cross-links and other markers of bone turnover (Fu hydroxyproline/creatinine and plasma osteocalcin) were significant but low (Pyr vs.
 osteocalcin, r = 0.29, P less than 0.05; Pyr vs.
 hydroxyproline, r = 0/.34; P less than 0.01; D-Pyr vs.
 osteocalcin, r = 0.39; P less than 0.01), except for D-Pyr vs.
 hydroxyproline (r = 0.24; P = 0.07), suggesting that these markers reflect different events of bone metabolism.
 Finally, a single measurement of the fasting excretion, but not of the 24-h excretion, of cross-links was significantly correlated (Pyr, r = 0.34; P less than 0.05; D-Pyr, r = -0.46; P less than 0.01), with the subsequent spontaneous rate of bone loss assessed by repeated measurements of the radial bone mineral content in 37 postmenopausal women.(ABSTRACT TRUNCATED AT 400 WORDS).
",4
877,"Correlation between serum osteocalcin and 24,25-dihydroxyvitamin D levels in Paget's disease of bone.
 We have studied the possible correlation between serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] and osteocalcin levels (sBGP) in Paget's disease of bone.
 We measured serum calcium, phosphate, PTH, 25-hydroxyvitamin D, 1,25-(OH)2D, 24,25-(OH)2D, alkaline phosphatase (sAP), and the urinary hydroxyproline/creatinine ratio (UOH prol/creat) in 19 patients with Paget's disease of bone and 16 age- and sex-matched controls.
 As expected, sAP, UOH prol/creat, and sBGP levels were significantly elevated, and there was a tendency to a decrease in serum levels of 24,25-(OH)2D in Pagetic patients with respect to the control group.
 There was no significant difference between patients and controls in serum calcium, phosphate, PTH, 25-hydroxyvitamin D, and 1,25-(OH)2D.
 The Pagetic patients were subdivided into two subgroups; subgroup A had normal sBGP levels (less than 5 ng/mL), and subgroup B had increased sBGP levels (greater than 5 ng/mL).
 Serum 24,25-(OH)2D levels in subgroup B were significantly lower than those in controls, while subgroup A showed levels similar to those in the control group.
 We also found a positive linear correlation between sAP and sBGP and between sAP and UOH prol/creat as well as a negative linear correlation between sBGP and 24,25-(OH)2D and between 24,25-(OH)2D and UOH prol/creat in Pagetic patients.
 These results point to a possible role of 24,25-(OH)2D in disease activity.
",4
878,"Hyposomatomedinemia in men with post-poliomyelitis syndrome.
 The age of onset of the post-poliomyelitis syndrome (PPS) coincides with the tendency for declining activity of the growth hormone/somatomedin C (GH/SmC) axis.
 The normal plasma SmC range in men before the age of 40 is 0.50 to 1.50 units/mL.
 After age 40 about 30% of men have a plasma SmC level below 0.35 units/mL, signifying no detectable spontaneous GH secretory pulses.
 Because the GH/SmC axis stimulates DNA, RNA, and protein synthesis in muscle cells and increases their size and number, a deficiency of the GH/SmC axis could theoretically contribute as a secondary factor to the occurrence or severity of the PPS.
 Accordingly, the authors measured the plasma SmC level in 10 men with PPS, ages 35 to 63, and in 94 healthy men of similar age.
 In the PPS men, 100% of the values were less than or equal to 0.40 units/mL, and 90% were less than or equal to 0.35 units/mL.
 The corresponding proportions in the healthy men were 40% and 27%.
 Analysis of variance including age as a factor showed SmC to be significantly lower in the PPS men than in the healthy men.
 In an additional comparison, totally immobile nursing home men did not have lowered SmC values.
 In fact their SmC values were slightly higher than those of healthy men of similar age.
 The data revealed a new biochemical feature of PPS, hyposomatomedinemia, which might play a contributory role in the pathogenesis of the syndrome.
",4
879,"Stimulation of dorsal root ganglia and degradation of rabbit annulus fibrosus.
 The authors sought to determine whether narrowing of the intervertebral neural foramen, by itself and in association with vibration, would stimulate the mechanosensitive dorsal root ganglia and result in degradation of proteoglycan and collagen of the annulus fibrosus, as proposed in their working model of dorsal root ganglia-neuropeptide-mediated degeneration of the spinal motion segment.
 Degradation of proteoglycan and collagen of rabbit annulus was observed when there was narrowing of the neural foremen and the degradation process was accelerated by vibration.
 Vibration alone, in the absence of structural abnormalities of the spinal motion segment, did not induce matrix degradation probably because of a less pronounced stimulation of the dorsal root ganglia.
 Biological events similar to those postulated here, fomented by a combination of structural abnormalities and environmental factors, could be involved in human disc degeneration.
",4
880,"Coexistence of cervical and lumbar disc disease.
 A retrospective analysis of 200 patients requiring cervical disc surgery was performed to determine the frequency of coexistent lumbar disc or spine abnormalities.
 The duration of follow-up ranged from 5 to 25 years, averaging 14 years.
 Sixty percent were women and 40% were men, their ages ranging from 25-73 years.
 Antecedent motor vehicle injury had occurred in 49 cases and work injury to the spine in 23.
 Sixty-four percent had no history of prior back injury.
 It was found that over 31% had undergone lumbar disc surgery, and a high number of patients demonstrated abnormal lumbar radiographs or myelograms, including 78 with bulging discs, 100 with major root defects, 78 with minor root defects, 8 with spinal stenosis, and 7 with spondylolisthesis.
 Myelograms were normal in 22 cases.
 The sites of lumbar abnormalities included L4-5 (110), L5-S1 (90), and multilevel (8).
 There was a higher incidence of lumbar disc abnormalities associated with multilevel cervical spondylosis.
 There also was a relationship between residual symptoms and myelographic abnormalities.
 Two studies in the authors' institution suggest an autoimmune basis for the frequent coexistence of cervical and lumbar disc disease, namely the demonstration of antigenic properties in the nucleus pulposus and high serum immunoglobulins.
",4
881,"Nighttime bracing for adolescent idiopathic scoliosis with the Charleston bending brace. Preliminary report.
 The authors report their preliminary experience with the Charleston bending brace for the treatment of adolescent idiopathic scoliosis.
 This brace holds the patient in the position of maximum side bend correction and is worn only at night.
 Patients in this prospective multicentered study met all the following criteria: skeletal immaturity (Risser 0, 1+, or 2+), curvature greater than 25 degrees before bracing, no prior treatment, and greater than 1-year follow-up since initiation of treatment.
 There were 191 structural curves in the 139 patients.
 One hundred fifteen patients (83%) showed improvement or less than 5 degree change in curvature.
 Twenty-four patients (17%) demonstrated an increase in curvature greater than 5 degrees.
 Based on these preliminary results, continued use of bending brace treatment at nighttime only is justified for adolescent idiopathic scoliosis.
 Patients with double curves should be observed closely for increase in compensatory curves.
",4
882,"Analysis of sagittal plane instability of the lumbar spine in vivo.
 Segmental instability secondary to degenerative disc disease may result in chronic low-back pain.
 In the sagittal plane, segmental instability can be characterized during lumbar motion from full extension to full flexion.
 The authors studied this movement using a translational method for the kinematic analysis, implementing a new concept known as the instability factor.
 Both translational and angular components of motion are evaluated.
 By computing the incremental motion parameters at different stages of spinal bending, the total amount of translation and angulation is obtained and combined in a ratio termed the instability factor.
 This factor increases with linear instability and decreases with rotational instability.
 The authors reviewed 12 control subjects and 36 patients with chronic low-back pain.
 The diagnoses of patients were categorized into three groups: idiopathic low-back pain, lumbar disc prolapse, and degenerative disc disease.
 Lateral radiographs of each subject's spine at the L4-5 level were obtained using low dose radiography and were performed serially as the subjects moved from full extension to full flexion.
 It was found that the group of patients with degenerative disc disease had an average age-corrected instability factor of 37.3 (mm/radian), which was significantly larger than that of normal subjects 25.5 (mm/radian), (P = 0.0065).
 No significant difference was seen in the instability factor of patients with idiopathic low-back pain or lumbar disc prolapse.
",4
883,"Lumbar isthmic spondylolisthesis in children and adolescents. Radiologic evaluation and results of operative treatment.
 A clinical and radiologic follow-up study of a group of 75 children and adolescents, comprised of both boys and girls, who underwent spondylodesis for spondylolisthesis between the years 1979 and 1984 is reported.
 Sagittal rotation, lumbosacral joint angle, lumbar lordosis, wedging of olisthetic vertebrae, and the rounding of the upper sacrum showed considerable statistical correlation to the amount of slipping and accordingly should be noted when estimating the risk of progression of the spondylolisthesis.
 When the spondylolisthesis was accompanied by scoliosis, it was noted that seriousness of the former was closely correlated to that of the latter.
 Most patients profited by the operation, and solid fusion was achieved in almost all cases.
 The posterolateral spondylolysis performed using graft from the iliac crest, the interbody fusion technique, or their combination turned out to be the most reliable surgical methods.
 The combined technique was especially required in cases with a high degree of slipping.
",4
884,"Knodt rod distraction instrumentation in lumbosacral arthrodesis.
 Review of 40 patients undergoing lumbosacral fusions over a 4-year period was done to determine the value, efficiency, and safety of Knodt rod distraction instrumentation.
 The age range was 30-80 years.
 Mean age was 51 years.
 Follow-up was 1-4 years.
 Twenty patients underwent decompression and fusion for spinal stenosis, nine underwent spinal arthrodesis for instability, six underwent the same for spondylolisthesis, and five underwent fusions for other diagnoses.
 A posterior midline approach was used.
 Laminal hook sites were prepared, and care was taken to prevent dural compression or tenting.
 Balanced distraction was done to restore soft tissue tension and stability.
 No attempt was made to reduce deformity.
 A posterior and lateral mass fusion augmented with allograft bone was performed on all but three patients, in whom autogenous bone was used.
 The majority of patients were placed in a custom-molded lumbosacral orthosis for 3-6 months after operation.
 There were no neurologic complications, dural tears, or pseudomeningoceles.
 The first sacral laminas were instrumented in 22 patients.
 Nine of the 40 patients underwent rod removal.
 Reasons for removal were pain due to loosening in five patients and failure of fusion in two.
 On rod removal in two patients, no abnormality was found.
 Insertion within the sacral laminas did not lead to neurologic complications.
 The major problem appeared to be loosening, which necessitated rod removal in 12% of the patients.
 Knodt rod distraction instrumentation is a safe and effective method of internal fixation for lumbosacral fusions.
",4
885,"Microscopically assisted posterior lumbar interbody fusion.
 Microscopically assisted posterior lumbar interbody fusion was performed on 27 patients who had either spondylolisthesis or chronic lower back pain after previous lower back surgery.
 Overall improved satisfactory results occurred in 22 of 27 patients.
 Roentgenographic, stable, interbody fusion occurred in 22 of 27 patients.
 The poorest results and highest rate of pseudarthrosis occurred in patients with double-level fusions.
 Pseudarthrosis occurred in four of six patients with double-level fusions and unsatisfactory clinical results occurred in five of six patients with double-level fusions.
 Advantages of the microscopic technique are better examination of the surgical site, less blood loss, and less surgical dissection than other surgical salvage techniques.
 This procedure should be reserved for single-level pathology in the lumbosacral spine.
",4
886,"The role of the supraspinatus and infraspinatus muscles in glenohumeral kinematics of anterior should instability.
 To investigate a socket mechanism responsible for controlling the kinematics in the statically positioned glenohumeral joint, a suprascapular nerve block was performed in 13 selected patients, with recurrent anterior instability and defects of the labrum.
 Kinematics were then documented by roentgenograms in four positions within the horizontal motion plane.
 Combined paralysis of the supraspinatus and infraspinatus muscles resulted in abnormal anterior translation in only two of 47 roentgenograms.
 Normal ball-and-socket kinematics were retained in the remaining 45 roentgenograms.
 The consistent arthroscopic findings were an undamaged glenoid articular surface with a detached or absent labrum.
 The injury to the labrum reduced the depth of the socket by one-half.
 The other one-half of the socket provided by the contour of the glenoid remained intact.
 A balanced muscle envelope was not required to maintain normal kinematics in selected, actively positioned, unstable shoulders.
 The retained glenoid depth was sufficient to produce the observed ball-and-socket kinematics.
 Further in vivo study of shoulder kinematics will be needed to clarify the interactive roles of the socket and muscle envelope in maintaining glenohumeral stability during the more demanding stresses during active shoulder motion.
",4
887,"A histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease.
 The articular cartilage, synovial membrane, and meniscus from ten patients who had calcium pyrophosphate dihydrate (CPPD) crystal deposition disease showed strong immunoreactivity for dermatan sulfate proteoglycan, Type I collagen, and S-100 protein in hypertrophic chondrocytes around the crystals, their pericellular matrix, and deposits of the crystals.
 Electron microscopy revealed that small crystals were formed around the hypertrophic chondrocytes, especially in the degenerated matrix containing electron-dense granular materials and cellular debris.
 Chondrocytes of this kind were never observed in the articular tissue from ten patients who had osteoarthrosis.
 These hypertrophic chondrocytes with several unique immunohistochemical characteristics may initiate the formation of CPPD crystals.
",4
888,"Familial cervical dysplasia.
 Nine of twelve family members from three generations were affected by an inherited form of cervical vertebral dysplasia.
 All of the affected people had an abnormality of the first cervical vertebra.
 Some also had defects of the axis and caudad to it.
 The mode of transmission of the disorder is autosomal dominant, with apparently complete penetrance and variable expressivity.
 Two patients had symptoms.
 One had a passively correctable tilt of the head, with an associated audible clunk and hypoplasia of the left superior facet of the second cervical vertebra.
 This patient had no local symptoms, neurological involvement, or muscle spasm.
 In the other patient, suboccipital pain developed.
 Radiographs revealed an anterior atlanto-occipital dislocation.
 The symptoms resolved after reduction and arthrodesis.
 Because of the apparently complete penetrance of this disorder, physicians caring for patients who have this type of congenital malformation of the cervical spine should consider examination of closely related members of the family.
 Clinical findings such as tilting of the head, torticollis, or limitation of cervical motion suggest that additional evaluation should be done.
 The examination should include lateral radiographs of the cervical spine in flexion and extension.
 Three-dimensional computed-tomography reformatting was helpful in demonstrating the complex cervical anatomy in our patients.
 Patients who have recognized abnormalities should be followed and should be re-examined whenever local or neurological symptoms develop.
 A magnetic resonance image of the spine in flexion and extension was valuable for identification of the potentially disastrous situation of impending damage to the cord in patients who had instability and evolving symptoms.
",4
889,"Tibial collateral ligament bursa: MR imaging.
 The bursa of the tibial collateral ligament (TCL) may be visualized at magnetic resonance (MR) imaging when it becomes distended with fluid.
 In the authors' experience, this finding signifies a pathologic condition either in the medial capsuloligamentous complex or in the bursa itself.
 Such a finding may indicate TCL bursitis.
 TCL bursitis can be suspected in the setting of isolated pain in the medial joint line in the absence of mechanical symptoms.
 Prolonged relief of symptoms after injection of steroid into the bursa is supportive of the diagnosis.
 Seven cases are presented in which a fluid-filled TCL bursa was identified at MR imaging.
 In five cases, TCL bursitis was suspected.
 The differential diagnosis for the MR findings is discussed.
",4
890,"Deposition of calcium pyrophosphate dihydrate crystals in the ligamentum flavum: evaluation with MR imaging and CT.
 Four patients had spinal canal stenosis associated with deposition of calcium pyrophosphate dihydrate within the ligamentum flavum.
 Radiologic evaluation was performed with magnetic resonance imaging or computed tomography, and surgery was performed on all four patients.
 Pathologic examination of the surgical specimens demonstrated deposits of calcium pyrophosphate crystals within the ligamentum flavum.
 Focal enlargement of the ligamentum flavum was present in the cervical spine (n = 1), while a more diffuse, bilateral enlargement was identified in the lumbar spine (n = 3).
 Enlargement of the ligament either caused or was a component of spinal stenosis that caused neurologic signs or symptoms.
 Three of the patients had evidence of calcium pyrophosphate deposition elsewhere.
 Deposition of calcium pyrophosphate dihydrate within the ligamentum flavum causing either focal or diffuse enlargement can be associated with significant spinal stenosis.
",4
891,"Anterior tibial translation during a maximum quadriceps contraction: is it clinically significant?
 Quadriceps exercises are used sparingly in the early rehabilitation of ACL reconstructions because of concern about prematurely stretching the ACL graft.
 The aim of this study was to determine if a maximum isometric quadriceps contraction significantly translates the tibia anteriorly at 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 75 degrees of flexion.
 Secondly, the role of the ACL in knee stability was analyzed by comparing the amount of tibial translation in normal, ACL deficient, and reconstructed knees.
 Thirdly, the location in the motion arc where a quadriceps contraction produces anterior tibial translation was determined.
 Anterior tibial translation was measured using an arthrometer (KT-1000) during an 89 N and manual maximum translation applied to the knee at rest.
 The manual maximum translation test determines the magnitude of anterior tibial translation produced by a high anterior force applied directly to the proximal calf.
 These translations were compared to the tibial translation intrinsically induced by a quadriceps contraction.
 Testing was performed in normal (N = 22), ACL deficient (N = 10), and reconstructed (N = 10) knees.
 Anterior tibial translation produced by a maximum quadriceps contraction was measured at 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 75 degrees of flexion.
 The extension exercise resulted in less anterior tibial displacement than an 89 N drawer and half the translation produced by a manual maximum translation (P less than 0.001).
 Instrumented laxity testing produced greater anterior translation of the tibia than a maximum isometric quadriceps contraction.
 Anterior tibial translation was the same during maximum isometric knee extension in all tested knees.
",4
892,"The contribution of the glenohumeral ligaments to anterior stability of the shoulder joint.
 The purpose of this study was to investigate the ligamentous stabilizing mechanisms preventing anterior instability in the glenohumeral joint.
 Six freshly thawed, unembalmed cadaveric shoulders were dissected, preserving the joint capsule and glenohumeral ligaments, the coracohumeral ligament, and the subscapularis tendon.
 Hall-effect strain transducers were placed on the superior, middle, and inferior glenohumeral ligaments.
 The humerus and scapula were fixed in a specifically designed mounting apparatus that allowed the glenohumeral joint to be placed in 0 degree, 45 degrees, or 90 degrees of abduction.
 The mounting apparatus was placed in a model TTC Instron Universal Testing Instrument, which applied an external rotation torque to the humerus.
 Strain produced in the three glenohumeral ligaments was recorded on a three-channel X-Y chart recorder.
 At 0 degree of abduction, the superior and middle glenohumeral ligaments developed the most strain.
 At 45 degrees of abduction, the inferior and middle glenohumeral ligaments developed the most strain, with considerable strain also being developed in the superior glenohumeral ligament.
 At 90 degrees of abduction, the inferior glenohumeral ligament developed the most strain, with strain also seen in the middle glenohumeral ligament.
",4
893,"Mineral balance in infantile cortical hyperostosis: effects of corticosteroids.
 The effects on mineral metabolism of therapeutic doses of corticosteroids were investigated in infantile cortical hyperostosis; in four untreated cases the calcium, phosphorus, and magnesium balances were strongly positive.
 In one severe case, treatment with prednisolone was associated with an alteration to negative calcium and magnesium balance, and faecal losses of calcium were particularly high.
 This effect persisted for at least three months after the steroids had been discontinued, and during this period there was pronounced retardation of linear growth.
 Six months after the treatment had been stopped mineral balance was again positive and there was rapid 'catch up' in growth.
 In infancy, the negative effect of corticosteroids on calcium, phosphorus, and magnesium metabolism may contribute to inhibition of bone growth and steroid stunting.
",4
894,"Bone resorption, stability, and soft-tissue changes following large chin advancements.
 Large advancement genioplasties were performed in 10 patients (mean advancement, 11.7 mm) by horizontal osteotomy of the inferior border of the mandible, with preservation of a musculoperiosteal pedicle to the advanced genial segment.
 Preoperative, immediate postoperative, and long-term follow-up lateral cephalometric radiographs were retrospectively analyzed to evaluate the osseous and soft-tissue changes of the chin.
 After a mean follow-up period of 15 months, 76% of the initial advancement was preserved, representing 24% osseous resorption.
 The enveloping soft tissues of the chin followed the bony movement in a ratio of 1:0.88.
 Horizontal osteotomy of the inferior border of the mandible was a relatively stable procedure when used for large chin advancements.
 The broadcast possible musculoperiosteal pedicle should remain attached to the advanced genial segment to minimize osseous resorption and to achieve more predictable soft-tissue changes.
",4
895,"Application technique of Cotrel-Dubousset instrumentation for scoliosis deformities.
 Used in over 600 cases, the posterior Cotrel-Dubousset spinal instrumentation device has become the device of choice.
 This technique allows the most effective correction for all kinds of spinal deformities.
 It requires lengthy preoperative planning and is a technically demanding surgical procedure; however, because of its versatility it can be adapted to most spinal deformities.
 The Cotrel- Dubousset technique is a rigid system of immobilization, and, because it does not require any postoperative immobilization, patients are able to resume their normal lives and activities very quickly.
",4
896,"Minor anatomic abnormalities of the hip joint persisting from childhood and their possible relationship to idiopathic osteoarthrosis.
 A retrospective review was made of roentgenograms from 30 patients with idiopathic osteoarthrosis of the hip.
 The roentgenograms were taken before the onset or very early in the course of the disease.
 Nine measurements were made on the anteroposterior and cross-table lateral roentgenograms.
 These were compared to 54 hips from normal patients.
 Twenty-nine of 30 patients had abnormal measurements, with as many as seven in a single individual, when compared to normal patients.
 There were no abnormalities in the control group.
 The availability of lateral views allowed an additional dimension to be added to previous studies in the literature.
 This study lends further support to the biomechanical theory of the etiology of idiopathic osteoarthrosis of the hip.
",4
897,"Radiocolloids in the management of hemophilic arthropathy in children and adolescents.
 Radiocolloids have been used in the treatment of hemophilic arthropathy.
 Fifty-eight joints of 35 patients were injected with 2-5 mCi of yttrium-90 silicate under local anesthesia.
 A preinjection arthrogram was performed to ensure correct placement of the needle.
 Plaster of paris cast immobilization of the joint was used for three days.
 After a mean follow-up period of seven years (range, two to 12 years), 47 joints were pain free, and 13 joints had not experienced another hemorrhagic episode.
 The mean hemorrhagic frequency had decreased from four per month to two per year.
 The radiation risk was far outweighed by the benefits of the procedure.
 Forty-seven of the 58 joints were rated as improved by the patients.
 The roentgenographic appearance of the joints had changed little.
 Only five complications occurred: three needle-track necroses because of extravasation of the radiocolloid, two severely painful joints immediately after injection, and one massive hemorrhagic episode.
 This form of treatment is suggested for hemophiliacs who have failed to respond to intensive physical and hematologic therapy, and for those patients who have inhibitors.
",4
898,"Congenital anomalies of the cervical spine.
 Congenital anomalies of the cervical spine are uncommon.
 The majority of afflicted individuals are asymptomatic or have only mild restriction of neck motion.
 If symptoms develop, they are usually due to cervical instability or degenerative osteoarthrosis.
 Recent information indicates that patients with upper cervical anomalies such as atlantooccipital fusion, anomalies of the odontoid, or the transverse atlantal ligament have a great propensity to develop early instability and neurologic problems secondary to minor traumatic events.
 If symptoms occurs in the lower cervical spine, it is usually in adult life and due to degenerative arthritis in the hypermobile articulations adjacent to the area of synostosis.
 The relatively good prognosis of cervical lesions is overshadowed by the ""hidden"" or unrecognized associated anomalies.
 There is a high incidence of significant scoliosis, Sprengel's deformity, renal anomalies, deafness, and neurologic malformations.
 Early recognition and treatment of these problems may be of substantial benefit, sparing the patient further deformity or serious illness.
",4
899,"Osteoarthrosis retards the development of osteoporosis. Observation of the coexistence of osteoarthrosis and osteoporosis.
 The clinical, roentgenographic, and biochemical features of the dorsal and lumbar spine were reviewed in 72 postmenopausal women.
 Nineteen women had both osteoporosis (vertebral collapse) and osteoarthrosis.
 These patients were compared with 26 patients who had only osteoarthrosis of the spine and 27 who had only vertebral collapse.
 The patients who had both spinal osteoporosis and osteoarthrosis were older, more advanced in menopause, and physically smaller in stature and body weight than the other groups.
 They also had higher serum parathyroid hormone level, used nonthiazide diuretics more frequently, and had more nulliparity than the other two groups.
 These patients had osteoarthrosis of the hip to a lesser degree than patients affected by osteoarthrosis alone, and they had fewer fractures of the forearm and other sites than patients with osteoporosis alone.
 The incidence of femoral neck fractures in both groups, however, was comparable.
 These results suggest that osteoarthrosis or a related factor might have a protective effect on the progression of osteoporosis.
 These results confirm earlier observations that postmenopausal osteoporosis and osteoarthrosis are two distinct diseases and not the result of normal aging.
",4
900,"Analysis of 61 cases of vertebral osteomyelitis.
 Sixty-one cases of bacterial vertebral osteomyelitis from July 1969 to July 1979 were analyzed.
 The ages of the 49 men and 12 women ranged from 21 to 66 years.
 The portal of entry was hematogenous in 58 cases, gunshot wounds in two cases, and and adjacent retroperitoneal abscess in one case.
 Biopsy was performed in 60 patients.
 There were 15 complications related to the disease.
 Gram-negative rods were the predominant bacteria isolated.
 Blood culture was positive in 13 of the 26 (50%) patients tested.
 Eleven of the 13 (85%) organisms isolated from the blood cultures correlated with organisms recovered from biopsy specimens.
 Eleven of the patients had more than one disk level involved.
 Of the 61 patients, 29 went on to spontaneous fusion, 17 were lost to follow-up study, 11 failed to fuse, three had surgical fusion, and one patient died.
 Recommendations for diagnosis included the collection of blood cultures and radionuclide bone scans.
 Management recommendations included systemic antibiotics for at least three weeks and immobilization with either bed rest or spinal orthoses.
 Surgery was indicated if an abscess was present, neurologic complications occurred, instability became a factor, or the medical treatment failed.
",4
901,"Fractional lengthening of the flexor tendons in clubfoot surgery.
 Massive scarring of the Z-lengthened flexor digitorum and flexor hallucis longus is a constant finding in clubfoot surgery.
 A method of fractional lengthening of the tendons is described.
 This method has been proven effective in preventing this complication.
",4
902,"Histochemical localization of calcium with potassium pyroantimonate in the articular tissues in calcium pyrophosphate dihydrate crystal deposition disease.
 The ultrastructural localization of calcium in the articular cartilage, meniscus, and synovium of patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease was examined by using potassium pyroantimonate.
 Focal areas with deposition of CPPD crystals in each tissue showed electron-dense precipitates of the antimony-calcium complex: (1) in the cytoplasm of hypertrophic chondrocytes around CPPD crystals, especially on the margins of intracellular lipid droplets or within electron-dense amorphous material or both; and (2) on the margins of lipid droplets and within electron-dense amorphous material in the degenerated matrix surrounding the hypertrophic chondrocytes.
 The slender rodlike structures consisting of electron-dense precipitates of the antimony-calcium complex, suggestive of the precursor to rodlike CPPD crystals, were also observed in the degenerated matrix.
 These findings suggest that the hypertrophic chondrocytes may contribute to the formation of CPPD crystals by intracellular accumulation of calcium and subsequent release of high concentration of calcium into their surrounding matrix.
",4
903,"A method of assessment of the clubfoot deformity.
 The literature on clubfeet is inadequate because a common method language for assessing the deformity is lacking.
 Different severities of clubfoot deformity will give different results for a standard procedure: a less severe deformity can be corrected by limited releases, whereas a severe deformity requires radical procedures.
 This paper presents a language of assessment that has been used for a number of years.
 The importance of developing a language of assessment to be able to identify the various types of clubfoot deformity is important if the treatment of this condition is to develop within the field of pediatric orthopedics.
",4
904,"A perspective on recent trends for scoliosis correction.
 The basic principles for scoliosis surgery learned during the Harrington era are still valid today.
 Experience has confirmed the need for careful selection of the vertebrae to be instrumented, the value of anterior release for rigid curves in imparting convertibility of the deformity, and the importance of careful fusion techniques.
 During the last decade, further development has occurred because of an increased knowledge of the biomechanical needs for the internally instrumented spine and a three-dimensional appreciation of the scoliotic curve.
 Biomechanical advances have centered on an understanding of the load-sharing properties afforded by the multiple spinal purchase sites (segmental spinal instrumentation) and the value of two-rod systems linked by couplers.
 These advances have provided an increased stiffness of the instrumental spine, a reduction in correction loss, improved fatigue properties of the implant, and fewer pseudarthroses.
 The most important advance of the last decade is an improved awareness of the three-dimensional approach to the scoliotic deformity with the need to preserve or improve sagittal contours.
 In particular, the importance of the loss of normal thoracic kyphosis or lumbar lordosis has been emphasized.
 These conceptual gains have led to the development of many new instrument systems to correct deformity.
 Each is associated with advantages, problems, and risks that must be understood to make intelligent choices for treatment.
",4
905,"Recovery from osteopenia in adolescent girls with anorexia nervosa.
 Osteopenia is a frequent complication of anorexia nervosa (AN).
 To determine whether the deficit in bone mineral changes during the course of this illness, we studied 15 adolescent patients prospectively for 12-16 months using dual photon absorptiometry of the spine and whole body.
 At follow-up, mean weight, height, and body mass index (BMI) had increased significantly, although 6 girls had further weight loss or minimal gain (less than 1.2 kg).
 Spontaneous menses occurred in 2 girls, and 3 others were given estrogen replacement.
 Bone mineral density of the lumbar spine did not change significantly (mean +/- SD, 0.836 +/- 0.137 vs.
 0.855 +/- 0.096 g/cm2), while whole body bone mineral density increased (0.710 +/- 0.118 vs.
 0.773 +/- 0.105; P less than 0.05).
 Despite gains in bone mineral, 8 patients had osteopenia of the spine and/or whole body.
 Changes in weight, height, and BMI were significant predictors of change in bone mineral density.
 Increased bone mass occurred with weight gain before return of menses; conversely, weight loss was associated with further decreases in bone density.
 In 1 patient who failed to gain weight, estrogen therapy resulted in increased spinal, but not whole body, bone mineral.
 We also studied a second group of 9 women who had recovered from AN during adolescence.
 All 9 had normal whole body bone mineral for age, but 3 had osteopenia of the lumbar spine.
 We conclude that osteopenia in adolescents with AN reflects bone loss, perhaps combined with decreased bone accretion.
 Weight rehabilitation results in increased bone mineral before the return of menses.
 Estrogen may have an independent effect on bone mass.
 The persistence of osteopenia after recovery indicates that deficits in bone mineral acquired during adolescence may not be completely reversible.
",4
906,"A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
 A prospective double blind placebo controlled study was carried out to compare the effects of subacromial injection of triamcinolone and oral diclofenac in patients with rotator cuff tendinitis over a 4-week period.
 Both forms of treatment were superior to placebo in reducing pain, improving active abduction and reducing functional limitation.
 Triamcinolone showed the greatest effect in these respects, and was significantly superior to diclofenac when patients showing improvements in all 3 variables together (responders) were considered.
",4
907,"Growth promoting peptides in osteoarthritis: insulin, insulin-like growth factor-1, growth hormone.
 Alterations of cartilage and bone, as seen radiographically, are fundamental features of osteoarthritis (OA).
 Endogenous compounds that regulate bone and cartilage metabolism were quantified by radioimmunoassay in patients with OA and in suitable normotensive controls matched for age, sex, race, height, and weight.
 Levels of 3 growth promoting compounds were abnormal in OA as demonstrated by low levels of insulin-like growth factor-1 (IGF-1) and elevated levels of insulin and growth hormone (GH) compared to controls.
 Our findings support a role for these peptides in the pathophysiology of OA.
",4
908,"Asymptomatic versus symptomatic herniated thoracic discs: their frequency and characteristics as detected by computed tomography after myelography.
 We retrospectively reviewed the myelograms of 433 patients and identified those who had no symptoms or signs referable to the thoracic cord, roots, or nerves.
 By post-myelography computed tomographic scan criteria, our frequency of asymptomatic thoracic herniated discs (ATHDs) was calculated.
 Post-myelography computed tomographic scans of 68 ATHDs were analyzed.
 Their imaging characteristics were compared with our own series of 5 symptomatic thoracic herniated discs and symptomatic thoracic herniated discs in the literature.
 We were unable to identify any imaging features that could reliably classify a disc as an ATHD or a symptomatic thoracic herniated disc.
 Our results call into question the propriety of prophylactic surgery for ATHDs, even when the lesions are radiographically impressive.
",4
909,"Spinal Charcot arthropathy.
 Charcot joints of the spine are well-documented clinical entities most commonly associated with tabes dorsalis.
 Spinal neuropathic joints, however, may be produced by other disease processes including syringomyelia.
 In this review, the authors discuss the cause and treatment of spinal Charcot arthropathy with emphasis on surgical therapy and results.
",4
910,"Radiographic manifestations of congenital anomalies of the skull.
 Congenital anomalies of the pediatric skull are caused by a diverse group of disorders.
 For the purposes of this discussion, these entities can be classified according to the radiographic appearance of the skull, which may be similar in a variety of different diseases.
 Enlarged parietal foramina, sinus pericranii, aplasia cutis congenita, anterior fontanelle dermoid, cephaloceles, and craniolacunia are all examples of loceles, and craniolacunia are all examples of calvarial defects.
 Although there are numerous causes for wormian bones (Table 1), OI, cleidocranial dysplasia, congenital hypothyroidism, and hypophosphatasia are disorders that are commonly associated with defective ossification and the appearance of wormian bones.
 Osteopetrosis is an important example of rare bony dysplasias that cause sclerosis and hyperostosis of the skull.
 A partial list of other disorders causing similar radiographic findings is found in Table 2.
 Craniosynostosis results in an abnormality of skull shape.
 The suture(s) involved may be predicted by the deformed calvarial configuration.
 Knowledge of the growth and development of the skull and an understanding of the varied causes of congenital skull anomalies can enable the radiologist to provide the diagnosis or an informed differential diagnosis when confronted with a specific radiographic finding.
",4
911,"Mild spondyloepiphyseal dysplasia (Namaqualand type): genetic linkage to the type II collagen gene COL2A1.
 Namaqualand spondyloepiphyseal dysplasia (NSED) is a mild autosomal dominant form of spondyloepiphyseal dysplasia in which changes are maximal in the femoral capital epiphyses and the vertebral bodies.
 The condition is present in a large multigeneration South African family, and it is clinically important by virtue of severe progressive degenerative osteoarthropathy of the hip joint, which frequently necessitates prosthetic joint replacement in adulthood.
 Linkage studies using molecular markers have shown that the loci for the NSED and type II collagen genes are linked (LOD score 7.98 at a recombination fraction of .00).
",4
912,"Quantitative gait analysis in unilateral and bilateral total hip replacements.
 By qualitative and quantitative analysis of gait we evaluated the outcomes in 41 patients after total hip arthroplasty for degenerative arthritis.
 Patients with unilateral and bilateral degenerative hip disease were evaluated in an effort to characterize preoperative and postoperative gait characteristics.
 Patients were evaluated using a subjective hip-rating scale and a gait-evaluation mat.
 Data were compared with those obtained from a control group of 91 patients.
 All patients showed a marked improvement in both subjective ratings and measured quantitative gait parameters.
 Patients with unilateral hip disease improved to a greater extent than those with bilateral disease after arthroplasty.
 We have concluded that total hip arthroplasty can greatly improve the gait characteristics of patients with degenerative arthritis, and that this improvement can be quantified, documented, and followed by using a system of gait evaluation.
",4
913,"Indomethacin inhibition of middle ear bone resorption.
 Localized osteoclastic bone resorption is responsible for the pathological changes within the middle and inner ear, which result in hearing loss and vertigo in chronic otitis media and otosclerosis.
 The local control of osteoclastic bone resorption is incompletely understood.
 Various small, locally active molecules, cytokines, have been shown to affect resorptive processes.
 Additionally, prostaglandins and their inhibitors have been shown to modulate the resorptive process in a number of in vitro studies.
 In this study, indomethacin, a cyclooxygenase inhibitor, was tested in a model of localized bone resorption, the pressurized gerbil bulla.
 After the experimental period, indomethacin was found to inhibit the number of osteoclasts and the resorptive area on the inner surface of the bulla.
 Therefore, it is likely that endogenous cyclooxygenase metabolites are intermediates in the sequence of cellular events, which results in localized bone resorption as in some systemic models.
",4
914,"Muscle performance, voluntary activation, twitch properties and perceived effort in normal subjects and patients with the chronic fatigue syndrome.
 The decrease in maximal force-generating capacity, the degree of central activation of the muscle, and the subjective perception of effort were measured during prolonged submaximal isometric exercise in 12 male patients suffering from the 'chronic fatigue syndrome' and 13 naive, healthy male subjects.
 Maximal voluntary isometric torque generated by the elbow flexors was measured before, and at 5 min intervals during an endurance sequence of 45 min of repetitive isometric contractions (6 s duration, 4 s rest interval) producing 30% of the initial maximal voluntary torque.
 Electrical stimuli were also delivered to the elbow flexors to measure the contractile force in the intervals between voluntary contractions.
 The degree of central motor activation during maximal voluntary contractions was assessed using a sensitive method of twitch interpolation.
 In addition, the perceived effort required to achieve the target submaximal contractions was recorded using a standardized self-report scale.
 A high degree of central activation was achieved in maximal contractions during the endurance sequence both in the patients (mean of maximal force 93.6%; SD 7.8%), and in the control subjects (mean 90.9%; SD 9.5%).
 The relative torque produced by either voluntary or electrically stimulated contractions was not significantly different between patients and control subjects throughout the test.
 There was no significant difference in the perceived exertion between the patients and control subjects.
 These findings support the concept that neither poor motivation, nor muscle contractile failure is important in the pathogenesis of 'fatigue' in patients with the chronic fatigue syndrome.
",4
915,"Differential regulation of insulin-like growth factor-I (IGF-I) and IGF-II release from cultured neonatal mouse calvaria by parathyroid hormone, transforming growth factor-beta, and 1,25-dihydroxyvitamin D3.
 In a previous study we found that PTH stimulated bone resorption and release of insulin-like growth factor-I (IGF-I) and IGF-II from cultured neonatal mouse calvaria.
 Since IGF-I and IGF-II stimulate osteoblast proliferation and collagen synthesis, these results suggested that increased release of IGFs during resorption could mediate in part coupling of bone formation to bone resorption.
 In the present study two other osteolytic agents, transforming growth factor-beta (TGF beta) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3 were examined for effects on IGF release from neonatal mouse calvaria.
 Like PTH, TGF beta stimulated resorption and increased release of IGF-I and IGF-II.
 1,25-(OH)2D3, however, stimulated resorption and IGF-II release comparable to PTH, but inhibited release of IGF-I.
 1,25-(OH)2D3 (0.1-100 nM) inhibited basal release of IGF-I, and 10 nM 1,25-(OH)2D3 inhibited release of IGF-I induced by PTH or TGF beta.
 The effects of 1,25-(OH)2D3 were specific to this vitamin D metabolite and did not occur with 25-hydroxyvitamin D3 or 24,25-(OH)2D3 at the same concentration.
 Calcitonin (50 mU/ml) decreased 1,25-(OH)2D3 stimulation of resorption, but did not affect 1,25-(OH)2D3 stimulation of IGF-II release and inhibition of IGF-I release.
 This evidence that effects of 1,25-(OH)2D3 on release of the IGFs were independent of bone resorption supports the conclusion that 1,25-(OH)2D3 modulated the production and secretion of IGF-I and IGF-II in calvarial cells.
 The results of this and the previous study suggest that PTH, TGF beta, and 1,25-(OH)2D3 differentially regulate mouse calvarial cell IGF-I and IGF-II production.
",4
916,"Cyclosporin-A in vitro decreases bone resorption, osteoclast formation, and the fusion of cells of the monocyte-macrophage lineage.
 We studied the in vitro effect of cyclosporin-A (CyA) on bone resorption using a fetal rat long bone-resorbing assay.
 CyA inhibited both PTH-stimulated and unstimulated bone resorption.
 The inhibitory effect of CyA on basal resorption was dose dependent, and it was more pronounced during the second period (less than or equal to 0.1 microgram/ml) of culture (days 5-7) than during the first period (days 2-4).
 A cytotoxic effect was ruled out by the absence of decrease in [3H]thymidine incorporation into bones up to a concentration of 5 micrograms/ml CyA.
 Histomorphometry performed after 4 and 7 days of culture showed that CyA (1 microgram/ml) decreased the number of osteoclasts per bone section after 7 days of culture (23.5 +/- 4.0 vs.
 41.7 +/- 2.9 osteoclasts/bone section; P less than 0.05), but not after 4 days (25.6 +/- 3.3 vs.
 23.0 +/- 2.5).
 These data suggested an effect of CyA on osteoclastic differentiation rather than on the function of mature osteoclasts.
 We further assessed the mechanisms of the inhibitory effect of CyA on osteoclastic differentiation in order to determine 1) the level of this action (proliferation and/or fusion of osteoclast precursors), and 2) if this action is direct or indirect.
 Autoradiographic studies were performed on bone sections after incubation of bones with [3H]thymidine for the last 48 h of culture.
 CyA decreased slightly but significantly the percentage of labeled nuclei per osteoclast and the number of osteoclasts containing at least one labeled nucleus (20.2 +/- 0.7 vs.
 33.2 +/- 3.5; P less than 0.02).
 Moreover the number of nuclei per osteoclast was decreased after 7 days in CyA-treated bones (2.4 +/- 0.05 vs.
 3.0 +/- 0.1; P less than 0.02).
 Taken together these results demonstrate that CyA slightly decreased the proliferation of osteoclast precursors, but markedly decreased their fusion.
 Similar effects were observed in cultures of rat marrow macrophages.
 CyA (1 microgram/ml) inhibited the fusion of macrophages into multinucleated cells elicited by 1 nM 1,25-dihydroxyvitamin D3, but had only a slight effect on the proliferation of these cells, as assessed by autoradiography.
 CyA also inhibited the formation of multinucleated cells and the fusion index in long term cultures of human cord blood monocytes, a cellular model for osteoclastic differentiation.
 By contrast, CyA had no effect on the formation of myotubes by fusion of cultured mononucleated rat myoblasts.(ABSTRACT TRUNCATED AT 400 WORDS).
",4
917,"Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism.
 In addition to its classical effects on growth, growth hormone (GH) has been shown to have a number of other actions, all of which are initiated by an interaction with specific high affinity receptors present in a variety of tissues.
 Purification of a rabbit liver protein via its ability to bind GH has allowed the isolation of a cDNA encoding a putative human growth hormone receptor that belongs to a new class of transmembrane receptors.
 We have previously shown that this putative growth hormone receptor gene is genetically linked to Laron dwarfism, a rare autosomal recessive syndrome caused by target resistance to GH.
 Nevertheless, the inability to express the corresponding full-length coding sequence and the lack of a test for growth-promoting function have hampered a direct confirmation of its role in growth.
 We have now identified three nonsense mutations within this growth hormone receptor gene, lying at positions corresponding to the amino terminal extremity and causing a truncation of the molecule, thereby deleting a large portion of both the GH binding domain and the full transmembrane and intracellular domains.
 Three independent patients with Laron dwarfism born of consanguineous parents were homozygous for these defects.
 Two defects were identical and consisted of a CG to TG transition.
 Not only do these results confirm the growth-promoting activity of this receptor but they also suggest that CpG doublets may represent hot spots for mutations in the growth hormone receptor gene that are responsible for hereditary dwarfism.
",4
918,"Characteristics of respondents and nonrespondents in a prospective study of osteoporosis.
 During 1981-1982, a cohort of elderly Japanese Americans living in Hawaii was recruited for an epidemiologic study of osteoporosis.
 The male subjects were simultaneously being examined for an epidemiologic study of heart disease.
 Baseline data collected from both the men and women at a previous heart disease examination were used to compare responders vs nonresponders.
 The target population for the osteoporosis study consisted of 1685 men and 1594 women.
 Of these, 1379 men (81.8%) and 1105 women (72.0%) participated in the initial osteoporosis examination.
 For each sex, nonrespondents were older and had higher systolic blood pressure levels than did the respondents.
 Male nonresponders had a higher stroke prevalence and more frequent recent use of vasodilator medicine.
 Female nonresponders had a less frequent history of having ever taken female hormones than did the responders.
 The responders and nonresponders were reasonably similar in other respects, as indicated by the comparison of more than 40 other variables.
 This suggests that nonresponse bias is probably not a major influence in exposure-disease associations in this osteoporosis cohort.
 We believe this is the first published report dealing with nonresponse characteristics in a cohort study of osteoporosis.
",4
919,"Nursing management of the adolescent with idiopathic scoliosis.
 Management of the adolescent idiopathic scoliosis patient has many intricate considerations.
 Whether the patient is braced or surgery is recommended, there is a lot of teaching, assessing, and compassion when dealing with adolescents whose biggest concern is being like their peers.
 It is important to allow as much independence in decision making as possible, whether it be about bracing or surgical intervention, as long as they clearly understand the consequences.
 Newer, better surgical instruments, anesthesia, nursing care, and postoperative mobility all have changed the management of the operative scoliosis patient significantly.
 Nursing assessment of neurologic, respiratory, function, emotional, and developmental needs of the adolescent patient, however, have not changed.
 If we, as nurses, understand the rationale for assessments, treatments, and restrictions, we can teach our patients and their families.
",4
920,"Spinal stenosis. When arthritis is more than arthritis!
 Spinal stenosis is the result of disc degeneration and narrowing accompanied by facet joint changes culminating in nerve root entrapment.
 Symptoms of back and leg pain appear gradually usually over a period of years and slowly worsen.
 Patients are usually in their 50s or older.
 Most patients are treated initially with nonoperative measures concentrating on pain relief and maintenance of activity.
 If the symptoms worsen, surgical intervention to relieve pain by decompressing the affected nerve roots is appropriate.
 Some patients with instability require a fusion.
 Most patients are satisfied with the results of surgery in relieving preoperative leg pain.
 Pain relief is often dramatic, allowing most patients to return to normal activity.
 Elderly patients tolerate this procedure surprisingly well.
 Old age alone should not be a contra-indication for this surgery.
 Therefore, the elderly should not be denied the benefits of surgical decompression.
 Nursing interventions can help these patients learn about spinal stenosis and assist them in pursuing appropriate treatment resulting in improved quality of living.
",4
921,"Rectal examination in general practice 
 OBJECTIVE--To investigate factors influencing a general practitioner's decision to do a rectal examination in patients with anorectal or urinary symptoms.
 DESIGN--Postal questionnaire survey.
 SETTING--General practices in inner London and Devon.
 SUBJECTS--859 General practitioners, 609 (71%) of whom returned the questionnaire.
 MAIN OUTCOME MEASURES--Number of rectal examinations done each month; the indication score, derived from answers to a question asking whether the respondent would do a rectal examination for various symptoms; and the confidence score, which indicated the respondent's confidence in the diagnosis made on rectal examination.
 RESULTS--279 General practitioners did five or fewer rectal examinations each month and 96 did more than 10 each month.
 Factors significantly associated with doing fewer rectal examinations were a small partnership and being a female general practitioner, and the expectation that the examination would be repeated.
 Lack of time in the surgery, and a waiting time of less than two weeks for an urgent outpatient appointment were also important.
 General practitioners were deterred from doing rectal examinations by reluctance of the patient (278), the expectation that the examination would be repeated (141), and lack of time (123) or a chaperone (39).
 Confidence in diagnosis was significantly associated with doing more rectal examinations, the perception of having been well taught to do a rectal examination at medical school, and being a male general practitioner.
 CONCLUSIONS--Factors other than clinical judgment influence the frequency of rectal examination in general practice.
 Rectal examination may become commoner with the trend towards larger group practices and if diagnostic confidence is increased and greater emphasis put on rectal examination in undergraduate and postgraduate teaching.
",5
922,"Gracilis muscle transposition for faecal incontinence.
 Transposition of the gracilis muscle for faecal incontinence was performed in 13 patients.
 Six gained satisfactory continence, four were improved, two did not benefit from the operation and one patient died from intercurrent disease before closure of a pre-existing colostomy.
 Anal manometry compared with a control group showed no alteration in resting and pressure at a median of 35 mmHg (range 5-63 mmHg), whereas maximum squeeze pressure increased from a median of 38 mmHg (range 5-79 mmHg) to 59 mmHg (range 10-143 mmHg) (P = 0.041) which was, however, significantly lower than 130 mmHg (range 81-236 mmHg) in the control group.
 All patients who benefited from the operation had an increase in maximum squeeze pressure.
 The ability to retain a viscous fluid in the rectum was measured in seven patients, four of whom had gained satisfactory continence and three of whom had improved continence.
 They were able to retain a median volume of 200 ml (range 50-225 ml) without leakage compared with 325 ml (range 250-400 ml) in the control group.
 These patients could retain the maximum amount of viscous fluid for 5-8 min, whereas all control subjects could do so for more than 15 min.
 It is concluded that, although gracilis transposition never results in normal continence, acceptable continence may be achieved in selected patients provided careful attention is paid to the technical details of the procedure and provided that systematic postoperative exercises are performed.
",5
923,"Anatomy of anal sphincters and related structures in continent women studied with magnetic resonance imaging.
 Five anally continent nulliparas of reproductive age were studied with magnetic resonance imaging.
 The internal and external anal sphincters could be easily delineated, as could the intervening longitudinal musculature, puborectalis muscle, anococcygeal raphe, anorectal lumen, vagina, uterus, bladder, urethra, coccyx, and pubis.
 The shape of the sphincters was nearly cylindrical, with an anterior component averaging 18.3 mm thick and 28.0 mm long.
 Fifty-four percent of this anterior thickness was attributable to the internal sphincter.
 The anorectal angle varied considerably, with a mean of 86.8 +/- 19.1 degrees (range 60-112).
 The angle between the portion of the rectal lumen supported by the anococcygeal raphe, or levator plate, and the plane of the puborectalis muscle was consistent at 149.0 +/- 6.3 degrees (138-154).
 The finding of anterior anal sphincters with substantial thickness and length contrasts markedly with a view often pictured in the literature of a female anal sphincter that narrows anteriorly to half its posterior length and forms a small bundle of muscle rather than a broad band.
 Knowledge of these relationships is important in primary repair of obstetric sphincter lacerations as well as in surgical correction of anal incontinence.
",5
924,"Final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones.
 One hundred and twenty-six patients with radiolucent gallstones in 'functioning' gallbladders were treated with 8-10 mg ursodeoxycholic acid (UDCA) kg/day and followed to a treatment conclusion.
 Complete or partial gallstone dissolution was achieved in 74 (59 per cent).
 However, only 22 achieved complete gallstone dissolution, as judged by two normal oral cholecystograms; ultrasonograms were performed in 16 of these patients, and all were normal.
 UDCA was stopped in 76 patients: because of cystic duct obstruction (n = 12), severe biliary pain (n = 13), non-response (n = 25) or partial stone dissolution with arrested progress (n = 26).
 Life-table analysis showed that complete gallstone dissolution rates at four years were 25-30 per cent (two normal oral cholecystograms) and 17-19 per cent (two normal oral cholecystograms plus one ultrasonogram).
 All patients with complete gallstone dissolution had shown partial stone dissolution at 6-12 months; of those with partial stone dissolution at six months, only 25 per cent went on to complete gallstone dissolution, and then always within two years.
 Efficacy correlated inversely with stone size but not with age, sex, obesity or on-treatment saturation indices.
 Acquired surface gallstone calcification developed in 13 patients (life-table analysis 22 +/- 7 per cent at four years); none of these patients achieved complete gallstone dissolution and only five achieved partial stone dissolution.
 Thus, despite relatively high partial gallstone dissolution rates, the ultimate efficacy of UDCA in achieving complete gallstone dissolution is low.
",5
925,"Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study.
 One hundred Chinese patients who received induction cytotoxic therapy for malignant lymphoma were prospectively studied to determine the incidence, morbidity, mortality, and predisposing factors for reactivation of hepatitis B virus replication during cytotoxic therapy.
 In 18 (67%) hepatitis B surface antigen-positive and 10 (14%) hepatitis B surface antigen-negative patients, hepatitis developed during cytotoxic therapy (P less than 0.0001).
 Hepatitis could be attributed to exacerbation or reactivation of chronic hepatitis B in 13 (72%) hepatitis B surface antigen-positive patients but in only 2 (20%) hepatitis B surface antigen-negative patients (P less than 0.0001).
 Sudden increase or reactivation of hepatitis B virus replication gave rise to icteric hepatitis, nonfatal hepatic failure, and death in 22.3%, 3.7%, and 3.7% of patients who were positive for hepatitis B surface antigen; in 2%, 2%, and 0% of those positive for hepatitis B antibodies; and in none of those who were seronegative.
 Among the hepatitis B surface antigen-positive patients, male sex was the only factor that was associated with an increased risk of reactivation of hepatitis B virus replication.
 We recommend that hepatitis B surface antigen-positive patients with malignancies receiving cytotoxic therapy be closely monitored.
",5
926,"Safety of same-day sequential extracorporeal shock wave lithotripsy and dissolution of gallstones by methyl tert-butyl ether in dogs.
 Passage of stone fragments after extracorporeal shock wave lithotripsy (ESWL) of gallstones has resulted in biliary colic, duct obstruction, and pancreatitis in some patients.
 Rapid dissolution of these fragments with methyl tert-butyl ether (MTBE) may prevent such side effects and achieve complete clearance of gallstones within hours rather than several months to a year or longer.
 This study examines the safety of same-day ESWL fragmentation and MTBE dissolution of surgically implanted human gallstones in 15 dogs.
 The animals were randomly assigned to one of four treatment groups to assess MTBE absorption from the gallbladder and to observe hematology and chemistry profiles after 0, 400, and 1,200 shock waves from a lithotriptor followed by MTBE dissolution therapy.
 They were sacrificed either immediately after treatment (12 dogs) or 2 weeks later (3 dogs).
 The results demonstrated that although ESWL causes moderate trauma to the gallbladder, this did not result in increased MTBE absorption or histologic evidence of mucosal disruption.
 Blood profiles demonstrated an increase in only the level of aspartate aminotransferase.
 The three dogs that were sacrificed 2 weeks after the combined treatment had no residual evidence of gallbladder injury or remaining stone material.
 In all animals, severe injury occurred where shock waves passed through lung or air-filled colon.
 This study suggests that same-day sequential fragmentation of gallstones by ESWL followed by dissolution of stone fragments with use of MTBE may be associated with only mild to moderate and reversible gallbladder trauma and can rapidly achieve clearance of gallstones.
",5
927,"Familial occurrence of inflammatory bowel disease.
 BACKGROUND AND METHODS.
 We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders.
 In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, asking whether their first- and second-degree relatives had this disorder.
 Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohn's disease) provided adequate information.
 RESULTS.
 As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohn's disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex.
 The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohn's disease was not significant in the relatives of patients with ulcerative colitis.
 The risk of ulcerative colitis in first-degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first-degree relative belonged and of the sex of the patient and the relative.
 The risk of ulcerative colitis in first-degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50, but the risk seemed to be independent of the current age of the relatives.
 The prevalence of the same disease as that of the patient (either ulcerative colitis or Crohn's disease) among second-degree relatives was increased; the prevalence of the other disease was not increased.
 CONCLUSIONS.
 The 10-fold increase in the familial risk of ulcerative colitis and Crohn's disease strongly suggests that these disorders have a genetic cause.
",5
928,"Retained intrahepatic stones: treatment with piezoelectric lithotripsy combined with stone extraction.
 Extracorporeal shock wave lithotripsy (ESWL) was performed in 11 patients with oriental cholangiohepatitis and intrahepatic stones associated with segmented strictures of intrahepatic ducts.
 All patients had previously undergone biliary surgery and basket extraction via a T-tube tract at the time of lithotripsy.
 The indication for ESWL was failure of, or anticipated difficulty with, basket extraction of the stones via a T-tube tract.
 A piezoelectric lithotriptor was used in all procedures.
 The average total number of shock waves administered was 29,756 (range, 10,000-61,395).
 The average number of treatment sessions was 3.1 (range, 1-6); the number of shock waves used in a single session ranged from 10,000 to 15,000 with a frequency of five shots per second and 30%-50% power.
 In six patients, the stones were successfully fragmented and completely removed; in three of the others of the stones were fragmented and removed.
 The overall success rate, including complete (54%) and incomplete (27%) success, was 82%.
 Difficulty in targeting stones, and severe strictures and deformities of intrahepatic ducts, were the factors responsible for failure.
 No significant complications were observed.
",5
929,"Oral cholecystography in contemporary gallstone imaging: a review.
 The introduction of nonoperative alternatives to elective cholecystectomy in the management of gallstones has resurrected use of oral cholecystography (OCG).
 This article reviews basic principles involved in the proper performance of OCG and interpretation of the resulting images.
 The role of OCG in the current management of gallstones is discussed.
",5
930,"Resting and total energy expenditure in patients with inflammatory bowel disease.
 Patients with inflammatory bowel disease often present with weight loss.
 Among possible causes, an elevated energy expenditure has frequently been suggested but is the least documented.
 In this study resting metabolic rate (RMR) and total daily energy expenditure (TDEE) were measured in 15 outpatients with inflammatory bowel diseases and in eight healthy control subjects.
 Measured RMR as a percentage of that predicted from fat-free mass was not significantly different for control subjects (102 +/- 9.8%, mean +/- SD) and patients (100 +/- 13.3%).
 TDEE, expressed as a multiple of RMR, was 1.70 +/- 0.31 for control subjects and 1.78 +/- 0.24 for patients.
 When patients were subgrouped as greater than or equal to 90% or less than 90% desirable body weight, a mean increase over RMR predicted from fat-free mass was seen in the underweight patients (106 +/- 9.3%) but not in normal-weight patients (99.0 +/- 15.6%).
 Mean TDEE/RMR values for the patient subgroups were 1.70 +/- 0.30 and 1.88 +/- 0.08, respectively.
 We conclude that stable outpatients with inflammatory bowel disease have only a minimal increase in energy needs.
",5
931,"Factors affecting the enterohepatic circulation of oral contraceptive steroids.
 Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver.
 Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing.
 The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed.
 Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation.
 Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol.
",5
932,"Efficacy of octreotide acetate in treatment of severe postgastrectomy dumping syndrome.
 The present study evaluates the acute and chronic use of a long-acting somatostatin analog, octreotide acetate, in the treatment of patients with severe postgastrectomy dumping syndrome.
 In the acute phase, 10 patients with severe dumping were studied over 2 consecutive days before and for 3 hours after the ingestion of a 'dumping breakfast' in a randomized double-blind fashion.
 On one day octreotide (100 micrograms) was given subcutaneously 30 minutes before the test meal and on the other day an equal volume of vehicle was injected.
 An additional group of six postgastrectomy patients without dumping were studied in a similar fashion and these acted as controls.
 During placebo treatment the test meal resulted in an immediate increase (p less than 0.01) in the pulse rate and in plasma levels of glucose, glucagon, pancreatic polypeptide, neurotensin, and insulin.
 Similar changes were seen in the control group with respect to placebo; however glucagon and neurotensin (p less than 0.05) did not show the same magnitude of increase as seen with placebo.
 Treatment with octreotide acetate prevented the development of both vasomotor and gastrointestinal symptoms and completely ablated all of the above responses in plasma peptides.
 These changes were associated with complete ablation of diarrhea (p less than 0.001).
 Pretreatment with octreotide acetate completely suppressed the rise in plasma insulin response to the meal and this ablated the late hypoglycemia of dumping.
 Treatment with octreotide acetate resulted in delayed gastric emptying and transit time (578 +/- 244 minutes) versus 76 +/- 23 minutes with placebo and 125 +/- 36 minutes in controls (p less than 0.05).
 Chronic daily treatment with octreotide acetate resulted in minimal side effects.
 These patients demonstrated a stable fasting plasma glucose, normal liver function tests, and an average weight gain of 11% during a 12-month period.
 In addition most patients were able to resume employment.
 The long-acting somatostatin analog, octreotide acetate, is highly effective in preventing the development of symptoms of severe dumping syndrome, both vasomotor and gastrointestinal.
",5
933,"Autologous implant of peritoneal mesothelium in rabbits and man.
 With the purpose of studying peritoneal physiology, original biopsy methods were devised and human and rabbit peritoneal mesothelial cells cultured and characterized.
 It was then decided to verify whether these cells could be implanted autologously during peritoneal dialysis in cases of acute loss of mesothelial surface.
 Staphylococcal peritonitis was induced in 12 rabbits and after 4 days of antibiotics, 6 of them were autoimplanted with cultured mesothelial cells, previously marked in 3 cases with thymidine (H3TdR).
 Implanted rabbits sacrificed after 3 and 6 days showed taking of the new mesothelial cells both by direct morphological observation and by autoradiography.
 Four uremic CAPD patients recovering from severe peritonitis were implanted with 300 million of their own peritoneal mesothelial cells, previously cultured and frozen.
 Morphological signs of taking were evident by laparoscopy and from peritoneal biopsies performed 3 and 6 days after implant.
 The fact that such implants are possible may have interesting applications in medicine and surgery.
",5
934,"Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin.
 Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes.
 To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate.
 They were compared with another group of 18 baboons fed an equivalent amount of the same diet (with or without ethanol), but devoid of lecithin.
 In the two groups, comparable increases in lipids developed in the ethanol-fed animals, but striking differences in the degree of fibrosis were seen.
 Whereas at least septal fibrosis (with cirrhosis in two) and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol, septal fibrosis did not develop in any animals fed lecithin (p less than 0.005).
 They did not progress beyond the stage of perivenular fibrosis (sometimes associated with pericellular and perisinusoidal fibrosis) and had a significantly lesser activation of lipocytes to transitional cells.
 Furthermore, when three of these animals were taken off lecithin, but continued on the same amount of the ethanol-containing diet, they rapidly (within 18 to 21 mo) progressed to cirrhosis, accompanied by an increased transformation of their lipocytes to transitional cells.
 These results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol.
 Because we had previously found that choline, in amounts present in lecithin, has no comparable action, the polyunsaturated phospholipids themselves might be responsible for the protective effect.
",5
935,"Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination.
 Hybrid HBV nucleocapsid-pre-S(2) fusion proteins were stably expressed in several aromatic-dependent attenuated Salmonella typhimurium and Salmonella dublin strains.
 When these live recombinant bacteria were administered i.p.
 to BALB/c mice they induced high titer anti-hepatitis B virus core Ag (HBc) and detectable anti-pre-S2 serum antibodies.
 Upon oral feeding of the recombinant salmonellae to mice, the rate of seroconversion to anti-HBc was dependent on the salmonella strain used.
 With the best carrier strain high titer anti-HBc antibodies and lower titer anti-pre-S2 serum IgG antibodies were observed two weeks after a single oral immunization.
 The Ig class and IgG subclass distribution of anti-HBc antibodies after i.p.
 and oral immunization is consistent with the induction of functional T cell help.
",5
936,"Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis.
 Autoantibodies to a novel nuclear Ag, Sp100, have recently been described that recognize a nuclear protein with an apparent molecular mass of 95 to 100 kDa and a dot-like distribution within cell nuclei.
 By immunoscreening of a lambda gt11 cDNA expression library derived from HeLa cells with an anti-Sp100 autoimmune serum a 0.7-kb cDNA (Sp26) coding for a fragment of Sp100 was isolated.
 Expression of this cDNA and use of the recombinant protein in ELISA revealed that the fragment carries major Sp100 autoepitopes and that anti-Sp100 autoantibodies predominantly occur in patients suffering from primary biliary cirrhosis (50/184).
 The Sp26 cDNA was used as hybridization probe for isolation of longer cDNA from human liver- and placenta-derived lambda gt10 cDNA libraries.
 Overlapping fragments were assembled to generate a full length cDNA coding for a protein with a molecular mass of 53 kDa and an isoelectric point of 4.7.
 The Sp100 autoantigen expressed in vitro from this cDNA and authenticated by a capture immunoblot assay, comigrated in SDS-PAGE with the authentic HeLa autoantigen of 95 to 100 kDa and thus showed an aberrant electrophoretic mobility.
 Computer based protein sequence analysis of the Sp100 autoantigen revealed regions of striking sequence similarities to the alpha 1 and alpha 2 domains of various human and non-human MHC class I Ag and to several transacting transcriptional regulatory proteins.
",5
937,"Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis.
 Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts, high titer autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction.
 The mechanism by which the autoimmune response is induced, the specificity of damage to the biliary epithelium, and the role of T cells in PBC are still unknown.
 To address these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with PBC, progressive sclerosing cholangitis, and chronic active hepatitis (CAH).
 C355.1, much like human autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro.
 In addition, we have also attempted to develop cloned T cell lines that react with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared with CAH.
 Although monoclonal C355.1 produced typical mitochondrial fluorescence on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it produced a distinct and intense reactivity when used to stain the bile ducts of patients with PBC.
 Nine of 13 PBC liver biopsies studied herein contained bile ducts on light microscopy, all of which reacted intensely at a 1:100 culture supernatant dilution of monoclonal C355.1.
 In contrast, although bile ducts of liver specimens from normals, CAH, and progressive sclerosing cholangitis also reacted with C355.1, such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1:2.
 More importantly, we generated CD4+, CD8-, alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH, that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.
",5
938,"The pharmacist as a health consultant--ten years later.
 Pharmacists remain a readily accessible and trusted source of information about health.
 In order to assess the quality of counseling on health matters and the progress of the profession in this activity over the last decade, a study similar to one reported in 1978 was conducted.
 We visited 46 community pharmacies and requested advice from the pharmacists concerning the proper treatment of an infant with diarrhea.
 Interviewers volunteered no additional information, but questions asked by the pharmacist were answered according to a predetermined hypothetical case involving an 18-month-old infant with diarrhea and vomiting.
 Findings include the following: approximately one-third of the pharmacists recommended a product without caution and less than 20 percent inquired about fever, nausea, vomiting, diet, or the infant's condition.
 We believe pharmacists should approach health counseling with an increased awareness of the harmful potential in providing inappropriate medical information.
",5
939,"Warner-Lambert/Parke-Davis Award lecture. Pathobiology of the intestinal epithelial barrier.
 The major route of passive permeation across intestinal epithelia is paracellular.
 The intercellular tight junction lies in and serves as the rate-limiting barrier in this paracellular pathway.
 Once viewed as static, it is now clear that the structure and permeability of the tight junction is highly dynamic.
 Not only may inflammatory events (cytokines, neutrophil transmigration) reversibly effect the tight junction but this key barrier also is regulated by physiologic events such as activation of absorptive cell Na(+)-nutrient cotransporters.
 Such physiologic regulation of the junction is of major importance to the absorption of nutrients via parcellular solvent drag.
",5
940,"Clinical features of misdiagnosed appendicitis in children.
 STUDY OBJECTIVE: To compare clinical features of children with misdiagnosed appendicitis with those of children with appendicitis initially diagnosed correctly.
 DESIGN: Retrospective review of hospital, emergency department, and clinic records.
 SETTING: University medical center with annual ED census of 40,000 patients.
 PARTICIPANTS: Children less than 13 years old admitted between May 1, 1979, and April 30, 1989, with a discharge diagnosis of appendicitis.
 MEASUREMENTS: Records were reviewed for historical, physical examination, laboratory, and pathologic features for all patients on their initial presentation to a physician and on final presentation during which the correct diagnosis was made.
 Using chi 2 analysis and Student's test, clinical features of misdiagnosed patients and patients diagnosed correctly were compared.
 RESULTS: One hundred eighty-one cases were identified with 50 initially misdiagnosed.
 On initial presentation, misdiagnosed patients were younger and more likely to have vomiting before pain onset, constipation, diarrhea, dysuria, and signs and symptoms of upper respiratory infections.
 Misdiagnosed cases were less likely to have right lower quadrant tenderness and documentation of bowel sounds, peritoneal signs, and rectal examinations.
 On final presentation, misdiagnosed patients were more likely to have pain duration of more than two days, temperature of more than 38.3 C, and to appear lethargic and irritable (P less than .05 for all measurements).
 CONCLUSION: Clinical features of children with misdiagnosed appendicitis differ from those of children with appendicitis initially diagnosed correctly.
",5
941,"Effect of tetrahydroaminoacridine on cognition, function and behaviour in Alzheimer's disease.
 OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer's disease.
 DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration.
 SETTING: Referral-based geriatric practice in a community hospital.
 PATIENTS: Thirty-four patients with moderate to severe Alzheimer's disease.
 Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin.
 INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo.
 RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose.
 For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour.
 The results for individual patients showed no subgroup of THA-responsive patients.
 CONCLUSION: THA has no clinically important benefits in Alzheimer's disease and is associated with appreciable toxic effects.
",5
942,"Primary cytomegalovirus infection and gastric ulcers in normal host.
 A 42-year-old woman presented with epigastric pain and vomiting.
 Upper gastrointestinal endoscopy revealed three gastric ulcers.
 Histologic examination of biopsies from the ulcers showed cytomegalovirus inclusion bodies.
 The appearance of IgM antibodies to cytomegalovirus indicated a recent and primary infection.
 Stored serum from her last pregnancy 17 months previously contained no cytomegalovirus antibodies.
 A thorough evaluation of her immune system revealed no abnormality.
 We are aware of only two other cases where seroconversion was documented in normal hosts.
 Cytomegalovirus infections in the gastrointestinal tract of normal hosts are very unusual but a common cause of morbidity in immunocompromised hosts.
 We believe that cytomegalovirus may have a role in the pathogenesis of gastrointestinal lesions in nonimmunocompromised patients.
",5
943,"Noninvasive measurement of portal venous blood flow in patients with cirrhosis: effects of physiological and pharmacological stimuli.
 The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man.
 This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension.
 Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo.
 In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied.
 In group 1, food intake caused a significant increase of portal blood flow (from 1038 +/- 539 to 1572 +/- 759 ml/min, P less than 0.02); this effect was due to a significant rise in mean blood velocity (from 18.5 +/- 3.7 to 23.9 +/- 3.9 cm/sec, P less than 0.02).
 In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985 +/- 491 to 625 +/- 355 ml/min, P less than 0.05); a significant decline of mean blood velocity (from 18.8 +/- 4.5 to 14.5 +/- 2.5 cm/sec, P less than 0.02) was observed.
 Placebo administration had no significant hemodynamic effects in either group.
 Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension.
",5
944,"Ulcerative proctitis in central Sweden 1965-1983. A population-based epidemiological study.
 Ulcerative proctitis has by tradition been regarded as a subgroup of ulcerative colitis.
 Population-based epidemiological studies of ulcerative proctitis are, however, virtually nonexistent.
 In an epidemiological study of inflammatory bowel disease in the Uppsala Health Care Region, 1065 cases of ulcerative proctitis were diagnosed from 1965 through 1983.
 Males predominated, with the male to female ratio 1.4:1.
 Annual incidence rates were higher in urban than in rural areas.
 The annual incidence rates increased threefold from 2.8 per 10(5) to 6.6 per 10(5) during the period, affecting all age groups over 14 years of age, in both urban and rural areas and in both sexes.
 Differences in temporal trends and certain other epidemiological characteristics between ulcerative proctitis and extensive ulcerative colitis suggest that ulcerative proctitis is a specific disease whose etiology differs from that of extensive ulcerative colitis.
",5
945,"The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden.
 Previous population-based incidence studies of inflammatory bowel disease are limited by small numbers, short duration, or inadequate case-finding.
 To address these problems, we identified all persons with confirmed ulcerative colitis (n = 2509) or Crohn's disease (n = 1469) in the Uppsala Health Care Region from 1965 to 1983.
 Age-specific incidence rates by sex were slightly greater for males with ulcerative colitis and females with Crohn's disease.
 Incidence rates for ulcerative colitis and Crohn's disease were higher in urban than rural areas.
 The annual incidence rate of ulcerative colitis increased from less than 7 per 100,000 to more than 12 per 100,000 during the study period, while the rate for Crohn's disease remained between 5 and 7 per 100,000.
 The increase in the incidence of ulcerative colitis was the result of a marked increase in the number of patients with ulcerative proctitis.
 Analyses by 5-year birth cohorts suggest that those born from 1945 through 1954 were at higher risk for ulcerative colitis and Crohn's disease, and that this effect was accounted for by those born in the first half of the year.
 The seasonality in the cohort effect, combined with the urban preponderance of disease, suggests that environmental causes may be involved in ulcerative colitis and Crohn's disease.
",5
946,"Induction of pS2 and hSP genes as markers of mucosal ulceration of the digestive tract.
 The recently discovered pS2 protein is expressed under estrogen control in a subset of estrogen receptor-positive breast cancers and in an estrogen-independent manner in normal stomach mucosa.
 The pS2 gene belongs to a family of genes encoding peptides that contain a conserved 5-cysteine domain, the P domains.
 Although the function of the pS2 protein is unknown, it has been suggested that it may have cell growth stimulatory activity.
 We report here that expression of the pS2 gene in the digestive tract, which is normally restricted to the stomach, is strongly induced by mucosal ulcerations elsewhere in the tract, most notably in Crohn's disease.
 pS2 gene expression is restricted to the mucosal layers adjacent to the ulcerations, in a region where a novel epidermal growth factor-secreting cell lineage was shown to be induced by mucosal ulceration.
 The human hSP gene, which contains a tandem duplication of the pS2 gene P domain and is coexpressed with the pS2 gene in normal stomach mucosa but not in breast cancers, is also expressed in Crohn's disease.
 We suggest that pS2 gene expression may provide a useful marker for mucosal ulcerations of the digestive tract.
",5
947,"Diarrhea in ciguatera fish poisoning: preliminary evaluation of pathophysiological mechanisms.
 Ciguatera fish poisoning is a clinical syndrome consisting of a combination of gastrointestinal and neurological symptoms occurring after eating toxin-containing tropical reef fish; it is a major cause of morbidity in Hawaii, the South Pacific, Australia, and the Caribbean.
 In an effort to define pathophysiological mechanisms responsible for the diarrheal component of the illness, we examined the effect of crude and fractionated toxin preparations on isolated rabbit ileal tissue in a Ussing chamber model.
 Both the crude toxin preparation (prepared from toxic Ctenochaetus strigosus) and 10% and 50% methanol-chloroform toxin fraction (prepared from a pool of toxic fish samples) gave a striking increase in transepithelial electrical potential difference and short-circuit current.
 Enterotoxic activity seemed to be mediated by calcium.
 When examined by light microscopy, the intestinal mucosa was not damaged by the toxin preparations used.
 Our data demonstrate that toxins involved in ciguatera fish poisoning directly stimulate intestinal fluid secretion without accompanying tissue damage and suggest that calcium is the ""second messenger"" mediating the process.
",5
948,"Localization of calcitonin gene-related peptide in human esophageal Langerhans cells.
 Previously undescribed calcitonin gene-related peptide-immunoreactive intraepithelial cells were seen in specimens of esophageal mucosa obtained by biopsy or surgical resection from 14 individuals.
 These calcitonin gene-related peptide-immunoreactive cells were sparsely seen in normal mucosa but increased markedly in esophagitis.
 They were inaccessible to routine histological stains, but osmication showed them as dendritic forms resembling Langerhans cells of the skin.
 Their cytological identity was determined with immunocytochemical tests for human antigenic markers such as Ia, HLA-DR, and OKT6 for Langerhans cells, Leu-M5 and Leu-M3 for intraepithelial macrophages, CD3 and TCR-1 for T-lymphocytes, Leu-14 for B-lymphocytes, S-100 for Merkel cells, and chromogranin for amine precursor uptake and decarboxylation cells.
 Double localization showed that calcitonin gene-related peptide immunoreactivity colocalized with Ia, HLA-DR, and OKT6 but not with the other markers.
 These studies show that intraepithelial Langerhans cells in the esophageal mucosa contain calcitonin gene-related peptide, which may serve as an immunomodulator.
",5
949,"Cirrhosis and portal hypertension in a patient with adult Niemann-Pick disease.
 A woman with known Niemann-Pick disease, type B, presented at age 33 with upper gastrointestinal bleeding, ascites, and peripheral edema.
 Evaluation showed massive hepatosplenomegaly, infiltration of the liver with Niemann-Pick cells, cirrhosis, and evidence of portal hypertension.
 Chronic gastrointestinal bleeding, thrombocyctopenia, and platelet dysfunction were treated successfully by splenectomy.
 Cirrhosis and portal hypertension have not been reported previously in adult Niemann-Pick disease in the absence of some other cause.
",5
950,"Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism.
 Our aim was to define mechanisms whereby conjugated estrogens (Premarin, exogenous estrogen; Ayerst Laboratories, New York) increase the risk of developing cholesterol gallstones and to determine the role, if any, of dietary cholesterol.
 We studied gallbladder motor function, biliary lipid composition and secretion, cholesterol absorption, cholesterol synthesis and esterification by peripheral blood mononuclear cells, the clearance of chylomicron remnants, and bile acid kinetics in 29 anovulatory women.
 13 were studied on both a low (443 +/- 119 mumol/d) and high (2,021 +/- 262 mumol/d) cholesterol diet.
 Premarin increased the lithogenic index of bile (P less than 0.05), increased biliary cholesterol secretion (P less than 0.005), lowered chenodeoxycholate (CDCA) pool (P less than 0.001) and synthesis (P less than 0.05), altered biliary bile acid composition [( CA + DCA]/CDCA increases, P less than 0.005), stimulated cholesterol esterification (P less than 0.03), and enhanced the clearance of chylomicron remnants (P = 0.07).
 Increases in dietary cholesterol stimulated the biliary secretion of cholesterol (P = 0.07), bile acid (P less than 0.05), phospholipid (P = 0.07), and as a result, did not alter lithogenic index.
 The reduction in CDCA pool and synthesis by Premarin was reversed by increasing dietary cholesterol.
 Off Premarin, only 24% of the increase in cholesterol entering the body in the diet was recovered as biliary cholesterol or newly synthesized bile acid.
 On Premarin, 68% of this increase in cholesterol was recovered as these biliary lipids.
 We conclude that Premarin increases biliary cholesterol by enhancing hepatic lipoprotein uptake and inhibiting bile acid synthesis.
 These actions of Premarin divert dietary cholesterol into bile.
",5
951,"Non-specific reactions in enzyme linked immunosorbent assays for serum antibody to entamoeba histolytica and Giardia lamblia in non-endemic areas.
 Serum samples from 20 Indian children with diarrhoea were compared with those from 20 children resident in the United Kingdom who had been diagnosed as having ulcerative colitis, or Crohn's disease, or indeterminate colitis using enzyme linked immunosorbent assays specific for Entamoeba histolytica and Giardia lamblia.
 More than 50% of the United Kingdom patients had high IgG responses in ELISAs for E histolytica and G lamblia.
 A confirmatory ELISA showed that the British sera reacted specifically to bovine serum proteins rather than to protozoal antigens.
 Prior incubation of sera with 5% bovine serum prohibited this reaction.
 Bovine serum is an integral part of the crude soluble antigen used in most ELISAs for E histolytica and G lamblia and needs to be replaced with purified antigen preparations.
 The British sera also reacted to other commonly used blocking agents such as bovine serum albumin, casein, and normal sheep serum.
 These reactions were attributed to uptake of dietary antigens or an enhanced immunological response to these antigens in patients with inflammatory bowel disease.
",5
952,"Biphasic modulation of acetaminophen bioactivation and hepatotoxicity by pretreatment with the interferon inducer polyinosinic-polycytidylic acid.
 Interferons and interferon induction can inhibit cytochromes P-450 and reduce the bioactivation and hepatotoxicity of acetaminophen.
 However, since P-450 inhibition often is followed by P-450 induction, which would enhance acetaminophen hepatotoxicity, the possibility of a biphasic modulation of acetaminophen hepatotoxicity by interferons was investigated.
 Outbred male CD-1 mice of various ages, and young inbred male C57BL/6 mice were given the interferon inducer, polyinosinic-polycytidylic acid (Poly I-C), 10 mg/kg intraperitoneally, followed 1 to 48 days later by a single dose of acetaminophen, 300 to 450 mg/kg intraperitoneally.
 Hepatotoxicity was assessed by the peak plasma concentration of alanine aminotransferase (ALT) occurring between 0 and 48 hr after acetaminophen treatment.
 Poly I-C inhibited the hepatotoxicity of acetaminophen given within 8 days, with maximal inhibition between 1 and 4 days.
 Conversely, a maximal 7-fold enhancement of ALT concentration was observed in CD-1 mice when 300 mg/kg of acetaminophen was given 32 days after Poly I-C (P less than 0.05).
 In the C57BL/6 strain, Poly I-C inhibited the hepatotoxicity of acetaminophen when given within 16 days, whereas a maximal 20-fold enhancement of ALT concentration was observed when 300 mg/kg of acetaminophen was given 24 days after Poly I-C (P less than 0.05).
 The mechanism of toxicologic enhancement was examined in male C57BL/6 mice using the same treatment regimen.
 Biochemical assessment of hepatotoxicity was confirmed by detailed histologic evaluation.
 Plasma concentrations of acetaminophen and metabolites were determined by high-performance liquid chromatography.
 Acetaminophen bioactivation was quantified by production of the glutathione-derived cysteine and mercapturic acid conjugates of acetaminophen.
 Poly I-C pretreatment produced a 5-fold increase in acetaminophen-induced ALT release (P less than 0.05), which correlated with histologic evidence of centrilobular necrosis.
 Poly I-C pretreatment produced respective 3-fold and 1.3-fold increases in the production of cysteine and mercapturic acid conjugates (P less than 0.05), which correlated with peak ALT concentrations (cysteine, r = 0.92, P less than 0.001; mercapturic acid, r = 0.75, P = 0.006).
 Thus, the hepatotoxicity of acetaminophen can be inhibited when given within days after interferon induction, and conversely enhanced when given after several weeks.
 The toxicologic enhancement appears to be due to increased P-450-catalyzed bioactivation of acetaminophen.
",5
953,"Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol.
 Acetaminophen (500 mg/kg i.p.) induced hepatotoxicity in fasted ICR mice in vivo.
 Acetaminophen also caused a long-lasting 50% reduction of the hepatic ATP content, an irreversible loss of hepatic xanthine dehydrogenase activity and a transient increase of the xanthine oxidase activity.
 All effects occurred before parenchymal cell damage, i.e., the release of cellular enzymes.
 The hepatic content of GSH and GSSG was initially depleted by acetaminophen without affecting the GSSG:GSH ratio (1:200), however, during the recovery phase of the hepatic GSH levels the GSSG content increased faster than GSH, resulting in a GSSG:GSH ratio of 1:18 24 h after acetaminophen administration.
 The mitochondrial GSSG content increased from 2% in controls to greater than 20% in acetaminophen-treated mice.
 The extremely elevated tissue GSSG levels were accompanied by a 4-fold increase of the plasma GSSG concentrations but not by an enhanced biliary efflux, although hepatic GSSG formation and biliary excretion were not affected by acetaminophen.
 Allopurinol protected dose-dependently against acetaminophen-induced cell injury, the loss of ATP and the increase of the GSSG content in the total liver and in the mitochondrial compartment without inhibiting reactive metabolite formation.
 High, protective as well as low, nonprotective doses of allopurinol almost completely inhibited hepatic xanthine oxidase and dehydrogenase activity, but only high doses prevented the increase of the mitochondrial GSSG content.
 The data indicate a long-lasting, primarily intracellular oxidant stress during the progression phase of acetaminophen-induced cell necrosis.
 The protective effect of allopurinol is unlikely to involve the inhibition of reactive oxygen formation by xanthine oxidase but could be the result of its antioxidant property.
",5
954,"Experimental reduction of portal hypertension by mechanical increase of liver portal flow 
 Studies on the isolated perfused rat liver demonstrated that an increase in portal pressure is associated with an increase in the portal blood flow in normal and in cirrhotic livers.
 In two pigs with portal hypertension mesenteric portal pressure was lowered by mechanically increasing the liver portal blood flow by means of a balloon pump around the portal vein.
",5
955,"Cholecystokinin enhanced hepatobiliary scanning with ejection fraction calculation as an indicator of disease of the gallbladder.
 Chronic acalculous cholecystitis represents 5 to 20 per cent of electively treated diseases of the gallbladder.
 A 70 per cent success rate in relieving these patients of chronic pain was reported when surgical treatment was recommended based on symptoms alone.
 The cholecystokinin ejection fraction, which is a quantitative measure of emptying of the gallbladder, was 95 per cent accurate in predicting which patients would be relieved of symptoms by surgical treatment.
 In this study, we report our consecutive experience during a 20 month period with 83 patients.
",5
956,"Computerized identification of pathologic duodenogastric reflux using 24-hour gastric pH monitoring.
 Duodenogastric reflux is a naturally occurring sporadic event, the incidence, occurrence, and detrimental effects of which have been difficult to assess.
 The reliability of 24-hour gastric pH monitoring to detect duodenogastric reflux was studied.
 Central to the use of pH monitoring for this purpose is confidence in its ability to measure and display pH data in a way that reflects changes in the gastric pH environment with sufficient sensitivity.
 To test this the gastric pH of 10 dogs was measured in the fasting state, after feeding, and after pentagastrin stimulation.
 The antrum was more alkaline in the fasting state (p less than 0.01) and the display of data by frequency distribution graph was sensitive enough to reflect induced pH changes.
 To test the consistency of gastric pH at a given position, simultaneous 24-hour gastric monitoring was performed in 12 normal subjects with two probes placed at either 5 or 10 cm below the lower esophageal sphincter.
 Only at the 5-cm position did the two probes read within 1 pH unit of each other more than 90% of the time.
 Based on these principles, gastric pH monitoring was performed 5 cm below the lower esophageal sphincter in 30 normal subjects and 11 patients, fulfilling Ritchie's clinical criteria for pathologic duodenogastric reflux.
 The data obtained was arranged into 71 variables and subjected to discriminant analysis.
 Sixteen variables were identified, each with a corresponding coefficient to be used as a multiplier to derive a score.
 A score of more than +2.2 indicated a high probability of pathologic duodenogastric reflux.
 The test was applied to a validation population consisting of 10 additional normal subjects and 10 patients meeting Ritchie's criteria.
 All normal subjects had a normal score and all but one (90%) of the patients had an abnormal score.
 When compared to O-diisopropyl iminodiacetic acid (DISIDA) scintigraphy in another group of 22 normal subjects and 60 patients, 24-hour gastric pH monitoring was superior in the detection of pathologic duodenogastric reflux.
 The study shows how the application of computer technology can be used to diagnose pathologic duodenogastric reflux in patients with complex foregut complaints.
",5
957,"A tongue force measurement system for the assessment of oral-phase swallowing disorders.
 A computer-aided measuring system using a highly sensitive beam transducer has been developed to provide a quantitative, reliable measure of tongue strength.
 This tool has application in both the diagnosis and treatment of dysphagic patients with oral-stage dysfunction.
 The device is customized to comfortably adapt to each individual.
 Audiovisual feedback is used to enhance subject interest and motivation.
 The device has proven reliable in measurements of upward and side tongue thrust in six able-bodied subjects measured during five separate sessions.
 It has also been used with two dysphagic patients.
",5
958,"Intussusception and the diagnostic value of testing stool for occult blood.
 A retrospective review was performed to determine the diagnostic value of testing for occult blood in stool of children suspect for intussusception.
 Ninety-six children had barium enema studies for suspected intussusception.
 Of the 57 children who had barium enema confirmed intussusception, 29 did not have history or physical findings of gross blood per rectum.
 Stool was tested for occult blood in 16 of these 29 patients, and 12 (75%) were positive.
 In comparison, three (20%) of the children who did not have intussusception had stool positive for occult blood.
 Stool with occult blood was significantly associated with intussusception (P less than .002).
 The only other clinical factor significantly associated with intussusception was abdominal mass (P less than .02).
 Vomiting, episodic irritability, poor feeding, abdominal pain and lethargy were not significantly different in the two groups.
 In conclusion, the authors suggest stool testing for occult blood when evaluating children who present with nonspecific signs and symptoms supportive of intussusception.
",5
959,"Plasma thrombin-antithrombin III complexes in the diagnosis of primary hepatocellular carcinoma complicating liver cirrhosis.
 Detection of hypercoagulable state might be helpful in the diagnosis of primary hepatocellular carcinoma (HCC) complicating liver cirrhosis (LC).
 Plasma levels of thrombin-antithrombin III complex (TAT) were determined in 50 patients of LC with or without HCC.
 The levels were above 2 ng/ml in 80% of 25 HCC patients, but only in 12% of 25 non-HCC patients (P less than 0.01).
 The levels over 2 ng/ml occurred even in five of six HCC patients whose serum alpha-fetoprotein levels were below 20 ng/ml as well as in two of three patients with HCC less than 2 cm in diameter.
 Those levels in HCC patients were significantly decreased within 8 days after treatment with transcatheter arterial embolization or infusion of antitumor agents, without affecting plasma antithrombin III levels.
 These results suggest that plasma TAT levels may be useful in the diagnosis of HCC complicating LC.
",5
960,"Appraisal of gut lavage in the study of intestinal humoral immunity.
 Direct investigation of intestinal humoral immunity requires collection of intestinal secretions or mucosal biopsy specimens, or both.
 A non-invasive technique of gut lavage, with a polyethyleneglycol electrolyte lavage solution as a means of collecting intestinal secretions for immunoglobulin and antibody studies, was evaluated.
 Fifty patients were studied--25 immunologically normal patients or volunteers, 15 patients with untreated coeliac disease, and 10 patients with active Crohn's disease.
 Protease inhibitors were added promptly to samples to prevent proteolysis of immunoglobulin content.
 Treated lavage samples were assayed by enzyme linked immunosorbent assay for immunoglobulin and antibody content.
 Studies of serial lavage specimens showed that early, faecally contaminated specimens contained negligible quantities of immunoglobulin, but once the specimens became clear a steady state was reached, with little variation in immunoglobulin content between serial specimens and with a uniform dilution (around 20%) of the ingested polyethyleneglycol.
 Gut lavage fluid IgA was predominantly secretory, comprising 92%, 81.6%, and 76.7% respectively of the total IgA gut lavage fluid content in the control, coeliac, and Crohn's groups.
 High values of total IgM and IgA and IgM antigliadin antibodies were detected in the coeliac group, and high values of IgG in the Crohn's disease group.
 This method of gut lavage is not only an effective bowel cleanser, but also a noninvasive means of obtaining intestinal secretions for the study of humoral immunity in gastrointestinal disease.
",5
961,"Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease.
 We compared the local intestinal immunoglobulin (Ig) secretion in six adult patients with coeliac disease and nine control subjects by perfusion of a small bowel segment under an occluding balloon and analysis of the perfusion fluid for the content of Ig and secretory component.
 The results were compared to the number of Ig-containing plasma cells in the test segment.
 There was, respectively, a two-fold and a fivefold increase in jejunal secretion rates of IgA (both monomeric and polymeric) and IgM in patients with coeliac disease compared with control subjects.
 The high IgA and IgM secretion rates parallel the increase of Ig-containing plasma cells in the lamina propria.
 In contrast, the IgG plasma cell density increase was barely significant in patients with coeliac disease and did not result in a high IgG secretion rate.
 The jejunal secretion rate of secretory component was significantly increased in patients with coeliac disease and no free dimeric IgA was present in the jejunal fluid.
 Antigliadin-IgA was detected in the serum and jejunal fluid of the six patients with coeliac disease.
 Antigliadin-IgA, however, was almost entirely polymeric IgA linked to secretory component in jejunal fluid, whereas 61% was dimeric IgA not linked to secretory component in serum.
 This result, combined with a raised secretory component secretion rate with no evidence of secretory component saturation, suggests that serum and intestinal antigliadin IgA might be of different origins in coeliac disease.
",5
962,"Inflammatory bowel disease and tobacco smoke--a case-control study.
 A case-control study was carried out in Stockholm, Sweden between 1984 and 1987 to evaluate the association of cigarette smoking and exposure to environmental tobacco smoke during childhood and the subsequent development of inflammatory bowel disease.
 Information on smoking was obtained by a postal questionnaire.
 The relative risk of Crohn's disease in current smokers compared with those who had never smoked was 1.33 (95% confidence limits 0.7; 2.6) in men and 4.99 (2.7; 9.2) in women; the corresponding results for ulcerative colitis were 0.96 (0.5; 1.8) and 0.72 (0.4; 1.4).
 The relative risk of ulcerative colitis in recent exsmokers compared with those who had never smoked was 2.18 (0.9; 5.0).
 Furthermore, an increase in the risk of Crohn's disease was found in those who were exposed to environmental tobacco smoke during childhood, the relative risk being 1.50 (1.0; 2.3).
 The corresponding relative risk of ulcerative colitis was 0.98 (0.6; 1.5).
",5
963,"Mortality and causes of death in Crohn's disease. Review of 50 years' experience in Leiden University Hospital.
 Six hundred and seventy one patients (52.5% women) with Crohn's disease seen at Leiden University Hospital between 1934 and 1984 were identified.
 Follow up was 98.2% complete.
 Sixty four (9.7%) of the 659 patients died.
 The cause of death was related to Crohn's disease in 34 patients, probably related to the disease in four, and unrelated, from incidental causes, in 25.
 The cause of death could not be identified in one patient.
 There was a significant decrease of deaths related to the disease after 1973.
 Causes of death such as amyloidosis and malnutrition have disappeared and postoperative deaths have decreased.
 The standardised mortality ratio showed an excess mortality of 2.23 for all patients.
 It was higher for women (3.30) than for men (1.76).
 A comparison of two recent 10 year periods showed a significant decrease in standardised mortality ratio in men but not in women.
 Patients whose disease started before the age of 20 years had an excess mortality compared with older patients.
 This study supports the view that the prognosis of Crohn's disease has improved in general but high quality medical and surgical management is important particularly for younger patients.
",5
964,"Efficacy of biofeedback training in improving faecal incontinence and anorectal physiologic function.
 The efficacy of biofeedback treatment on faecal incontinence and anorectal function was evaluated in eight patients with faecal incontinence treated with biofeedback training and medical therapy.
 Outcome and anorectal function were compared with nine faecal incontinent patients who received medical therapy alone.
 Three month follow up showed that 50% of patients in the biofeedback plus conventional treatment group and 56% of those treated conventionally only had improved.
 One year follow up showed that 13% in the biofeedback group were free of soiling and an additional 25% had improved.
 The results were similar in the conventionally treated group--11% were free of soiling and an additional 44% improved.
 Anal pressures at rest and squeeze, the rectal distension volume that induced sustained inhibition of both the external and internal anal sphincter, and continence to rectally infused saline were significantly reduced in both groups of patients compared with controls (p less than 0.05).
 Biofeedback treatment had no effect on these abnormal anorectal functions in either patients who improved or those who did not.
 The improvement in faecal incontinence was probably due to medical intervention or regression of symptoms with time, or both, and not the result of biofeedback training.
",5
965,"Comparison of gall bladder bile and endoscopically obtained duodenal bile.
 In 10 patients with gall stone disease (eight women, two men; mean (SD) age 47.4 (13) years), bile was obtained by endoscopic aspiration after stimulation of the gall bladder with ceruletid and also by fine needle puncture of the gall bladder under local anaesthetic.
 The total lipid concentration of the puncture bile samples was mean (SD) 11.9 (4.7) g/dl, significantly higher than the endoscopic bile samples (3.9 (3.3) g/dl, p less than 0.001).
 Total bile acids, phospholipids, and biliary cholesterol (expressed in mol%) and cholesterol saturation index showed no significant differences between the two types of samples.
 The glycocholic acid concentration in the endoscopically obtained bile (27.7 (6.6) mol% v 23.3 (5.4) mol%; p less than 0.01) was significantly higher than the puncture bile samples.
 Puncture bile exhibited a significantly shorter nucleation time (3.5 (3.3) days v 19.6 (11.9) days; p less than 0.001).
 For determination of the nucleation time, endoscopic bile aspiration after gall bladder stimulation with ceruletid led to adequately concentrated samples in 50% of the study subjects.
 Cholesterol monohydrate crystal formation in native bile was observed in six samples of puncture bile and in three samples of the endoscopically obtained bile.
 The presence of cholesterol crystals and the determination of nucleation time in the puncture bile were the best discriminants between cholesterol and pigment gall stones and correlated well with computed tomogram analysis.
",5
966,"Isolated lipase and colipase deficiency in two brothers.
 Two brothers of Arab origin, aged 15 and 10 years, with isolated congenital lipase and colipase deficiency are described.
 Both were normally developed with a history of passing greasy stools since early infancy.
 Both have remarkable steatorrhoea and low serum carotene and vitamin E concentrations.
 After exocrine pancreatic stimulation, lipase and colipase activities in the duodenal fluid were almost completely absent, while amylase trypsin, bile salt, and pH values were normal.
 No other aetiology for exocrine pancreatic insufficiency was found.
 This is the first report of congenital combined lipase and colipase deficiency in two brothers.
",5
967,"Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia.
 Porcine gastric inhibitory polypeptide (GIP) was infused iv (120 micrograms in 60 min) in seven patients with biopsy-proven hepatic cirrhosis who had surgical porta-caval anastomoses and hyperglucagonemia in the postabsorptive state.
 The infusions resulted in elevation of blood levels of immunoreactive GIP into the upper range of those observed after ingestion of large mixed meals.
 This was accompanied by significant increments in immunoreactive glucagon (IRG) in the plasma.
 Similar infusions in two cirrhotic patients with surgical porta-caval anastomoses who had normal plasma IRG levels in the postabsorptive state had no effect on the plasma IRG level.
 Ingestion of triglyceride (60 g) in hyperglucagonemic cirrhotic patients with porta-caval anastomoses also resulted in elevation of plasma immunoreactive GIP, and this was again associated with significant elevation of the plasma IRG level.
 Chromatography studies showed that the increments in plasma IRG after the administration of GIP or triglyceride were largely accounted for by increases in pancreatic-type glucagon.
 There were no significant effects of administration of GIP or triglyceride on the blood levels of glucose or immunoreactive insulin.
 It is concluded that porcine GIP is glucagonotropic in patients with cirrhosis of the liver who show elevated levels of IRG in the plasma in the postabsorptive state.
 This effect is not due to diversion of portal blood to the systemic circulation and may be attributable to hypersensitivity of the alpha-cells to stimulation by GIP.
",5
968,"Treatment of duodenitis with cimetidine: a clinical, endoscopic, and histologic study.
 We studied the effectiveness of cimetidine in the treatment of endoscopically diagnosed duodenitis.
 Sixty-nine patients with the solitary endoscopic finding of duodenitis (6% of 1,200 patients who underwent fiberoptic endoscopy of the upper gastrointestinal tract in our unit over 3 years) were studied retrospectively: a good clinical response was apparent in 45 of 69 patients treated with cimetidine (65%), and a fair response in another four (6%).
 In a controlled, randomized prospective study, we evaluated the effectiveness of cimetidine in duodenitis.
 Statistically significant improvement for the clinical and endoscopic scores was found in 10 patients treated with cimetidine (p less than 0.01).
 Improvement in the histologic score did not reach statistical significance.
 No such improvement was demonstrated in seven placebo-treated patients.
 We believe that duodenitis is a ""peptic syndrome,"" has a good response to cimetidine treatment, and behaves much like duodenal ulcer disease.
",5
969,"Colonic volvulus as a complication of celiac sprue.
 Colonic volvulus has been a rarely reported complication of celiac sprue.
 We describe two patients with long-standing celiac sprue, one in whom a recurrent sigmoid volvulus developed, and in the other, a cecal volvulus.
 Following surgery, both are now asymptomatic on a gluten-free diet.
 The association between celiac sprue and colonic volvulus was first reported in 1953.
 There have been only a few isolated cases documented, surprisingly so because the two major predisposing conditions for colonic volvulus are often seen in patients with celiac sprue.
 Colonic bacterial fermentation of malabsorbed carbohydrate (in celiac sprue) leads to excess gas production.
 Flaccid bowel loops with sigmoid redundancy, a long mesentery, or cecal hypermobility are not uncommon.
 A motility disorder in celiac sprue has also been proposed.
 Thus these factors together would suggest that the likelihood of development of colonic volvulus in celiac sprue would be relatively great.
 The possibility of underlying celiac sprue should be considered in patients with colonic volvulus who have a background history of recurrent abdominal distention or malabsorptive symptoms.
",5
970,"Six physicians with inflammatory bowel disease.
 This essay tells the stories of six physicians with inflammatory bowel disease (IBD) to emphasize how important denial and control become when a physician is a patient.
 Guilt at the supposed psychosomatic ""origin"" of IBD suggests that we as physicians should never blame our patients for getting sick.
",5
971,"Erythrocyte sedimentation as a measure of Crohn's disease activity: opposite trends in ileitis versus colitis.
 To test our hypothesis that the erythrocytic sedimentation rate (ESR) correlates well with clinical activity in inflammatory disease of the colon, but not of the small bowel, we stratified 49 Crohn's disease patients according to their anatomic involvement and then measured the correlations between ESR and clinical activity within each of these anatomical subgroups.
 For 18 patients with Crohn's disease involving primarily the colon, there was a trend toward a direct correlation between clinical score and ESR (p = 0.15).
 In the 14 patients with Crohn's disease limited to the colon, this direct correlation was even more pronounced and statistically significant (p less than 0.02).
 By contrast, an opposite trend was observed for patients with small bowel disease.
 For the 26 patients with disease involving predominantly the small bowel, as well as for the 22 with disease limited to small bowel, there were statistically significant inverse correlations between clinical score and ESR (p less than 0.04).
 This difference between the directions of the correlations for Crohn's colitis versus ileitis was statistically significant (p less than 0.05).
 This study provides further evidence for the importance of analyzing putative indications of disease activity separately for each of the protean forms in which Crohn's disease occurs.
",5
972,"Biliary sludge: a critical update.
 Biliary sludge has been for many years a poorly defined entity, usually with low amplitude, nonshadowing echoes within the most dependent part of the gallbladder, which shift under the influence of postural changes.
 From a sonographic point of view, the detection of sludge implies the coexistence of small-sized, solid components and of a gel-like embedding material.
 The chemical nature of biliary sludge has recently been recognized to be predominantly composed of a coaggregate of cholesterol monohydrate crystals and liquid crystalline droplets, and in some cases, such as obstructive jaundice or symptomatic liver diseases, by bilirubin granules, all embedded in a gel matrix of mucous glycoproteins.
 From a pathogenic point of view, biliary sludge is often associated with biliary stasis, or with conditions characterized by impaired gallbladder contraction, such as prolonged total parenteral nutrition, fasting, and pregnancy.
 Other causes include mucus hypersecretion, which may favor cholesterol nucleation and crystal growth, and bile infection.
 Sludge may be an intermediate step in the formation of different types of stones.
 From an epidemiological point of view, sludge is quite rare in the asymptomatic, free-living population, but may be common in selected series of symptomatic patients.
 From a clinical point of view, sludge often has a fluctuating course, including frequent disappearances and reappearances, suggesting that the early stages of gallstone formation are reversible.
",5
973,"Thoracic succussion splash: a new symptom and sign of achalasia.
 A patient with a ""thoracic succussion splash"" due to achalasia is described.
 She noted a splashing or sloshing sensation in her chest related to jogging and bending.
 On examination a splashing sound could be heard over the mid sternum and the posterior chest when the patient was rocked vigorously back and forth.
",5
974,"Gallbladder perforation: correlation of cholescintigraphic and sonographic findings with the Niemeier classification.
 We retrospectively analyzed the cholescintigrams and sonograms of 36 consecutive patients with gallbladder perforation to (a) determine the sensitivity of each for the preoperative detection of gallbladder perforation and (b) correlate the findings with the modified Niemeier classification.
 Cholescintigraphic criteria of perforation (free spill, pericholecystic hepatic activity, and scintigraphic gallstone ileus sign) were detected in 14 of 28 (50%) cases, while sonographic criteria of perforation (pericholecystic fluid or pneumobilia with gallstones) were present in 18% (4 of 22) of patients (p less than 0.05).
 Cholescintigraphic patterns of perforation associated with the Niemeier classification were: Type I (acute free perforation), 3 of 7 scans demonstrated free spill; Type II (subacute pericholecystic abscess), 9 of 19 scans showed pericholecystic activity; and Type III (chronic cholecystoenteric fistula), 1 of 3 scans showed a scintigraphic gallstone ileus.
 Thus, although cholescintigraphy appears superior to sonography, both modalities are relatively insensitive for the detection of gallbladder perforation.
",5
975,"Supportive evidence for the validity of the epidemiologic necropsy for gallstones 
 OBJECTIVE: The epidemiologic necropsy measures the occurrence of unsuspected disease through the examination of necropsy records of patients who died for other reasons.
 The estimates of unsuspected disease derived from the epidemiologic necropsy should approximate what actually occurs in the living population.
 DESIGN/SETTING: To test this hypothesis, all necropsy records of adult patients at the University of Kansas Medical Center from 1950 to 1984 were examined for the presence of gallstones.
 Patients with previous cholecystectomy or whose gallstones were diagnosed during life were excluded.
 The data were stratified by age and race and compared with those of a screening survey from Canada, a surgical series from New York, two screening surveys from Italy, and one from Denmark.
 The crude necropsy detection rates and the rates from the screening surveys were standardized to the 1970 federal census for Kansas City.
 RESULTS/CONCLUSIONS: The standardized occurrence rates were similar and suggest that the epidemiologic necropsy accurately assesses the occurrence of asymptomatic gallstones in the living population, thus strengthening its validity as a research tool.
",5
976,"Congenital hepatic fibrosis in autosomal-dominant polycystic kidney disease.
 Congenital hepatic fibrosis was found in four families with autosomal-dominant polycystic kidney disease.
 Congenital hepatic fibrosis is commonly though to be characteristic for autosomal-recessive polycystic kidney disease, but the reported families, show that it can also complicate autosomal-dominant polycystic kidney disease.
 In three families close linkage between the mutation causing the disease and DNA markers on chromosome 16 was demonstrated.
 The clinical course of the congenital hepatic fibrosis differed considerably; in one family the children with congenital hepatic fibrosis died soon after birth, in the three other families an approximately 20 years follow-up showed no detectable progression of the liver disease.
",5
977,"Sequential esophageal motility studies after endoscopic injection sclerotherapy: a prospective investigation.
 To assess prospectively the effects of endoscopic intravariceal sclerosis (EIS) on esophageal function, we performed esophageal manometry on 13 cirrhotic patients before EIS, 24 h after the second session and 4 wk after the fourth session.
 EIS had no impact on lower esophageal sphincter pressure.
 However, a significant decrease in the amplitude of peristaltic waves was observed immediately post-EIS in the lower two-thirds of the esophagus.
 There was no modification of duration or velocity of progression of peristaltic waves.
 A four-fold increase in simultaneous contractions was observed early after EIS.
 These changes were reversible, as assessed by late esophageal testing after EIS.
 No correlations were demonstrated between esophageal motor parameters and doses of sclerosant.
 We conclude that sclerosant injection into the esophageal wall acutely impairs esophageal motility, but motor function is partially restored 4 wk after completion of EIS, suggesting that dysmotility is reversible.
",5
978,"Reduction in hepatic venous pressure gradient as a consequence of volume contraction due to chronic administration of spironolactone in patients with cirrhosis and no ascites.
 The effect of plasma volume contraction induced by a 4-wk administration of spironolactone or furosemide on the hepatic venous pressure gradient was evaluated in consecutively allocated patients with cirrhosis and no ascites.
 In the spironolactone group (n = 15), the hepatic venous pressure gradient decreased significantly (p less than 0.005), by 21.8%, with a significant contraction of circulating plasma volume (p less than 0.01).
 Although there were no statistically significant correlations between the change in hepatic venous pressure gradient and changes in circulating plasma volume or in simultaneously determined systemic hemodynamics, a significant negative correlation (r = -0.74, p less than 0.01, n = 12) between the hepatic venous pressure gradient change and the post-treatment plasma aldosterone levels was found.
 However, in the furosemide group (n = 10), the hepatic venous pressure gradient and circulating plasma volume did not significantly decrease.
 Our data demonstrated a significant reduction in the hepatic venous pressure gradient on a chronic administration of spironolactone, which may have been due to volume contractions in patients with cirrhosis and no ascites.
",5
979,"The combination of prednisone and colchicine in patients with primary sclerosing cholangitis.
 Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary tract.
 The cause of the disease is unknown, and no effective medical treatment exists.
 In this study, 12 patients received a combination of low-dose prednisone (10 mg/day) and colchicine (0.6 mg bid).
 Their course was compared with that of a group of concurrent historical controls.
 At 6 and 12 months, there was significantly more improvement in liver test results over baseline values in patients receiving prednisone and colchicine than in the untreated controls.
 At 24 months, however, no significant differences in biochemical tests were appreciated between treated and untreated patients.
 Analysis of serial liver biopsies showed no differences in histologic change in the two groups.
 During the 2 yr of follow-up, there were two deaths in the control group but none in the treated group.
 Four untreated patients developed ascites; gastrointestinal bleeding developed in three untreated patients, one of whom developed ascites.
 In contrast, in the treated group, ascites and bleeding developed in only one patient.
 We conclude that the combination of colchicine and prednisone does not retard histologic progression or progression of standard liver tests after 2 yr of therapy.
 There is a trend toward less clinical deterioration and improved survival after 2 yr of treatment.
 On the basis of these findings, we would not advocate empiric use of these drugs for patients with primary sclerosing cholangitis, but suggest that, if they are to be used at all in PSC, they be evaluated in a controlled clinical trial as treatment for this as yet incurable disease.
",5
980,"Modified Kraske approach for disease of the mid-rectum.
 A modification of Dr.
 Paul Kraske's approach for removal of mid-rectal lesions has been used in 11 patients from 1977 to 1988 by the senior authors.
 Patients ranged in age from 56 to 89 yr, with an average of 67 yr.
 There were seven male and four female patients.
 Indications for surgery were as follows: villous adenoma (seven), carcinoid (one), recurrent dysplasia in a previous endoscopic polypectomy site (one), positive distal margin for neoplasm following low anterior sigmoid resection (one), and adenocarcinoma in one elderly poor-risk patient.
 All lesions were in the middle rectum (7-11 cm from the anal verge, average 9 cm).
 The postoperative stay ranged from 6 to 12 days with a mean of 8 days.
 The average follow-up for the 11 patients is 3 1/2 yr (1 month to 7 yr), with only one patient having a local recurrent lesion.
 There was no morbidity or mortality.
 We conclude that this modification of the Kraske approach offers a good alternative for excision of mid-rectal lesions in terms of technical ease, efficacy, safety, and patient tolerance.
 The modified Kraske approach is indicated in certain situations and should be a part of the surgeon's armamentarium.
",5
981,"Chemical peritonitis secondary to intraperitoneal vancomycin.
 Although previously reported in the literature, the existence of chemical peritonitis due to vancomycin in patients on peritoneal dialysis remains controversial.
 We report four similar episodes of sterile peritonitis in three patients receiving intraperitoneal (IP) vancomycin.
 The prior report implicated a change in the brand of vancomycin preparation, from Vancocin to Vancoled, as a contributing factor.
 We noted the occurrence of such episodes following a switch from Vancocin to a generic preparation from Abbott Laboratories.
 High-performance liquid chromatographic (HPLC) profiles of the three preparations show Vancocin to have a lower level of impurities than the other two; the presence of certain contaminants in the other brands may be contributing to the clinical difference observed.
 We conclude that chemical peritonitis due to IP vancomycin administration does occur, and that increased awareness of this entity could allow other cases to be identified.
",5
982,"Transmission of Rift Valley fever virus by adult mosquitoes after ingestion of virus as larvae [published erratum appears in Am J Trop Med Hyg 1991 Jun;44(6):580]
 We studied the ability of Culex pipiens, Aedes circumluteolus, and Ae.
 mcintoshi, exposed as larvae to liver tissue from a Rift Valley fever (RVF) virus-infected hamster, to become infected and transstadially transmit virus to the adult and for the adults to transmit virus by bite to hamsters.
 After exposure as larvae, 9% (5/54) of adult Cx.
 pipiens and 8% (38/505) of the adult Ae.
 (Neomelaniconion) species were infected.
 All of the infected Cx.
 pipiens and about half of the infected Ae.
 circumluteolus and Ae.
 mcintoshi tested transmitted RVF virus by bite to hamsters.
 Transmission rates for mosquitoes orally infected as larvae were higher than those for mosquitoes orally infected as adults.
 Animals infected with RVF virus may abort or die in the vicinity of mosquito larvae breeding habitats and infected tissue from these animals may contaminate the water.
",5
983,"The importance of intraoperative cholangiography during laparoscopic cholecystectomy.
 Laparoscopic cholecystectomy (LC) using electrocoagulation was successfully performed in 56 out of 58 selected patients.
 Cholangiography was performed in 53 patients.
 Six patients had common duct stones; five were unsuspected preoperatively.
 After the gallbladder was removed, three patients underwent open common duct exploration.
 In another five cases, anatomical anomalies were discovered.
 Cholangiography performed via the cystic duct before any structures are divided can prevent the most serious complication--common duct injury.
 Cholangiography should be attempted on all patients undergoing LC.
",5
984,"Inguinal hernia complicating flexible sigmoidoscopy.
 Flexible sigmoidoscopy has become part of routine preoperative workup for patients over the age of fifty who present with an inguinal hernia.
 A recent experience with two patients with a left inguinal hernia allowing sigmoid colon to herniate into the scrotum bring awareness of the possibility for an increased risk of perforation of the sigmoid colon during flexible sigmoidoscopy, or possible iatrogenic incarceration of the hernia.
 These cases are presented so this clinical entity can be recognized and the complications prevented.
",5
985,"Plasma glucagon concentration in cirrhosis is related to liver function but not to portal-systemic shunting, systemic vascular resistance, or urinary sodium excretion.
 We tested the hypothesis that increased plasma glucagon concentration resulting from portal-systemic shunting or liver dysfunction causes arterial vasodilation and thereby stimulates sodium retention in cirrhosis.
 Twenty-seven studies were performed in patients with alcoholic liver disease, 11 of whom had ascites.
 Liver function was quantitated as the elimination rate of antipyrine, caffeine, and stable isotopes of cholic acid administered both orally (2,2,4,4-2H) and intravenously (24-13C).
 Portal-systemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid.
 Cardiac output was measured by using Doppler echocardiography.
 Plasma glucagon concentration was increased in patients with ascites when compared with that in patients without ascites (474 +/- 180 pg/ml vs 245 +/- 120 pg/ml, p = 0.0007) but was unrelated to urinary sodium excretion, heart rate, mean arterial pressure, cardiac output, and systemic vascular resistance (r = -0.48, 0.35, -0.13, 0.18, and 0.22, respectively).
 Plasma glucagon concentration correlated with the half-lives of all model compounds (r = 0.58, p = 0.002; r = 0.62, p = 0.0008; r = 0.62, p = 0.001; and r = 0.64, p = 0.0005; for caffeine, antipyrine, oral and intravenous cholic acid, respectively) but not with shunt fraction (r = 0.14).
 Increased plasma glucagon concentration in cirrhosis is probably a result of diminished hepatic clearance.
 However, increased plasma concentration of glucagon does not appear to cause a hyperdynamic circulatory state or sodium retention.
",5
986,"Elevated plasma aluminum levels in normal infants receiving antacids containing aluminum.
 Aluminum toxicity is a documented cause of encephalopathy, anemia, and osteomalacia.
 Excretion is primarily renal; therefore, patients with renal insufficiency are at risk for aluminum accumulation and toxicity.
 This has been demonstrated in uremic children treated with aluminum-containing antacids.
 The purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum-containing antacid use.
 Ten study infants (mean age = 5.8 months), who had been receiving antacids for at least 1 week, were compared with 16 control infants (mean age = 9.8 months) not receiving antacids.
 The study patients consumed 123 +/- 16 mg/kg per day (mean +/- SEM) of elemental aluminum for an average of 4.7 weeks.
 Their plasma aluminum level (37.2 +/- 7.13 micrograms/L) was significantly greater than that of the control group (4.13 +/- 0.66 micrograms/L) (P less than .005).
 It is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum-containing antacids.
 The safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants, with careful monitoring of the aluminum dose and plasma level.
",5
987,"Gastric emptying in infants and children: limited utility of 1-hour measurement.
 Gastric emptying measurements were performed in infants and children at 1 and 2 hours after a liquid feeding.
 The 1-hour measurements were predictive of only 58% of the variability in the 2-hour measurements, indicating that the 1-hour measurement was not a good predictor of the 2-hour measurement.
 Gastric emptying measurements in children should be continued until 2 hours after feeding unless rapid emptying is observed during the 1st hour of the study.
",5
988,"Gallstone lithotripsy: relevant physical principles and technical issues.
 A basic understanding of shock wave generation is essential for the radiologist who performs gallstone lithotripsy.
 Shock waves differ from ordinary acoustic waves in that they have a rapid rise time, a positive pressure component that gives rise to compressive forces approaching 1,000 atm, and a low-amplitude sustained negative pressure (rarefactive) component.
 Shock waves are created by means of three different types of shock wave generators: spark-gap, electromagnetic, and piezoelectric.
 The authors describe and compare these three types of shock wave generators with regard to equipment selection.
 Regardless of how shock waves are generated, they share common interactions with tissue.
 These interactions are reviewed along with the proposed mechanisms of stone fragmentation.
",5
989,"Air in the fissure for the ligamentum teres: new sign of intraperitoneal air on plain radiographs.
 In each of four patients in whom an acute spontaneous pneumoperitoneum developed, a vertically directed area of hyperlucency in the right upper quadrant was seen on radiographs of the abdomen obtained with the patient supine.
 This finding, which appeared in the absence of other characteristic signs of free air on plain radiographs and which, to the authors' knowledge, has not been previously recognized, represented intraperitoneal gas confined to the fissure for the ligamentum teres (FLT).
 The location of the hyperlucent area was confirmed with computed tomography or laparotomy in each patient.
 The distinctive configuration of air in the FLT is a subtle but reliable indicator of pneumoperitoneum.
",5
990,"Liver cirrhosis: changes of Doppler waveform of hepatic veins [published erratum appears in Radiology 1991 Aug;100(2):586]
 The authors compared the Doppler ultrasonographic pattern of hepatic veins (HVs) in a group of 60 patients affected by liver cirrhosis and in 65 healthy subjects comparable for sex and age to (a) detect possible differences in HV waveform in the two groups and (b) investigate the relationship of these differences with the severity of the disease (according to Child-Pugh classification) and the modifications of systemic hemodynamics.
 The waveform of HVs was arbitrarily classified into three patterns: HV0, a normal waveform; HV1, lower oscillations without the reversed phase; and HV2, completely flat waveform.
 The resistivity index of the superior mesenteric artery, reflecting the peripheral splanchnic impedance and the hyperdynamic circulation, was also measured in a subgroup of 45 cirrhotic patients.
 The waveform of HVs in all healthy subjects corresponded to the HV0 pattern.
 Among cirrhotic patients, HV0 was found in 30 (50%), HV1 in 19 (31.7%), and HV2 in 11 (81.3%).
 The severity of functional impairment was greatest in the HV2 group and least in the HV0 group.
 This was significantly correlated with the decrease of the resistivity index in the superior mesenteric artery in the subgroup of 45 patients.
 Changes in the normal HV waveform could be considered a useful adjunctive tool for the noninvasive evaluation of liver disease.
 The pathophysiology of these changes in HV blood flow is still unclear.
 The significant correlation with the severity of the disease and with the decrease of splanchnic resistances indicates that these changes in the HV waveform occur in the presence of marked rearrangements of liver tissue and of hyperdynamic systemic circulation.
",5
991,"Sclerotherapy for esophageal varices.
 Endoscopic injection sclerotherapy (EIS) frequently is used for patients with esophageal varices, both for controlling acute hemorrhage and for prophylaxis.
 An old technique, interest in EIS increased when other methods did not improve patient outcomes.
 Clinical trials of EIS for acute hemorrhage demonstrated efficacy and improved outcome, although some researchers disagree with these findings.
 Recent data on prophylaxis with EIS fail to support the value of EIS for this indication.
 Ethanolamine oleate compares favorably with other sclerosing agents, and is the only one currently approved for EIS.
 The intravariceal method is used more frequently than the paravariceal method because it has better efficacy and can be performed more rapidly.
 The percentage of patients developing significant complications from EIS may be as high as 15 percent; common complications include retrosternal pain, pyrexia, and sepsis.
 EIS is currently an important clinical tool in the management of esophageal varices.
",5
992,"Glucose intolerance and hyperinsulinemia of cirrhosis are not results of spontaneous or surgical portosystemic shunting.
 To assess if spontaneous portosystemic shunting from collaterals contributes to the hyperinsulinemia of cirrhosis, 12 patients with alcoholic cirrhosis underwent a 5-hour oral glucose tolerance test 1 day before and 10 days after an elective side-to-side portacaval shunt.
 The glucose, insulin, and C peptide responses to oral glucose post-shunt were exaggerated but comparable to preoperative values.
 Compared with preoperative values, the fasting molar ratio of C peptide to insulin postoperatively had increased 40% (6.0 +/- 1.2 versus 8.4 +/- 0.7), indicating improved hepatic function.
 These results suggest that extrahepatic portosystemic shunting secondary to spontaneous splanchnic collaterals plays little or no role in the hyperinsulinemia of cirrhosis.
 It appears that decreased hepatic degradation of insulin in these patients is secondary to hepatocellular dysfunction rather than a result of shunting of portal blood around the liver.
",5
993,"Why does somatostatin cause gallstones?
 Long-term administration of the somatostatin analogue, octreotide, is complicated by gallstone formation.
 Somatostatin is known to inhibit hepatic bile secretion and gallbladder emptying.
 However, the effect of octreotide on gallbladder bile composition remains unknown.
 Therefore, we tested the hypothesis that octretide would alter hepatic bile composition and cause gallbladder stasis, thereby increasing gallbladder bile solute concentrations.
 Fourteen control prairie dogs received daily saline injections, whereas 10 animals received 1 micrograms of octreotide subcutaneously three times per day for 5 days.
 Cholecystectomy and common bile duct cannulation were then performed.
 Octreotide increased hepatic bile concentrations of bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.05), and total protein (p less than 0.01).
 Rsa, an index of gallbladder stasis, was decreased (p less than 0.01) in the octreotide group.
 Gallbladder bile total calcium (p less than 0.05), bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.01), total protein (p less than 0.05), and total lipids (p less than 0.05) were increased in the octreotide group.
 Animals receiving octreotide also had decreased hepatic (p less than 0.05) and gallbladder (p less than 0.001) bile pH.
 No differences in cholesterol saturation index were observed.
 These data suggest that in the prairie dog, octreotide (1) alters hepatic bile composition, (2) causes gallbladder stasis, and (3) increases gallbladder bile calcium, bilirubin, protein, lipid, and hydrogen ion concentrations.
 We conclude that octreotide causes alterations in gallbladder bile composition that increase the likelihood of cholesterol and calcium bilirubinate precipitation.
",5
994,"The Munich Gallbladder Lithotripsy Study. Results of the first 5 years with 711 patients.
 OBJECTIVE: To evaluate the long-term results of three types of shock wave treatment in patients with radiolucent gallbladder stones.
 DESIGN: Cohort study.
 SETTING: Single-center trial.
 PATIENTS: Of 5824 patients with gallstones, 19% were eligible; 711 patients were treated.
 INTERVENTIONS: Patients received extracorporeal shock wave lithotripsy as well as adjuvant therapy with bile acids.
 RESULTS: Lithotripsy was done in three ways, using a water-tank lithotriptor (group A), a water-cushion lithotriptor at low energy levels (group B), and a water-cushion lithotriptor at high energy levels (group C).
 The rate of complete fragment clearance 9 to 12 months after lithotripsy was done differed significantly among the three groups: Among patients with single stones of 20 mm or less in diameter, the rate of fragment clearance for group A was 76%; for group B, it was 60%; and for group C, it was 83% (P = 0.03).
 Among patients with single stones of 21 to 30 mm, the rate of fragment clearance for group A was 63%; for group B, it was 32%; and for group C, it was 58% (P less than 0.005).
 Among patients with two or three stones, the rate of fragment clearance for group A was 38%; for group B, it was 16%; and for group C, it was 46% (P = 0.01).
 Patients with fragments of 3 mm or less 24 hours after lithotripsy was done showed a higher probability of fragment disappearance than did those with larger fragments (P less than 0.001).
 The clearance rate was higher in patients who were compliant than in those who were noncompliant with bile acid therapy (P less than 0.001).
 Adverse effects included liver hematoma in 1 patients, biliary pain attacks in 253 patients (36%), mild biliary pancreatitis in 13 patients (2%), and cholestasis in 7 patients (1%).
 Elective cholecystectomy was done in 16 patients (2%), and endoscopic sphincterotomy was done in 4 patients (1%).
 CONCLUSIONS: The rate of complete disappearance of stones after shock wave therapy depends on the size and the number of the initial stones, the diameter of the largest fragment, and the mode of shock wave treatment.
 Adjuvant therapy with bile acids appears to be important for complete fragment clearance.
",5
995,"Nonsteroidal anti-inflammatory drugs and peptic ulcer disease.
 Evidence has accumulated that nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically important gastroduodenal ulcers.
 The pathogenesis, which involves the impairment of mucosal resistance to injury in an acid-peptic environment, is multifactorial and controversial.
 Ulcers caused by NSAIDs can occur either in mucosa inflamed because of infection with Helicobacter pylori or in histologically normal mucosa.
 The use of these drugs has been linked to an unexpectedly high incidence of ulcer complications, and a history of peptic ulcer disease is common in such cases.
 Nonsteroidal anti-inflammatory drugs thus appear both to exacerbate an underlying peptic diathesis and to cause de novo ulcers.
 The association between the use of these drugs and ulcer complications is supported by ulcer prevalence data from cross-sectional studies, and by data from case-controlled and cohort studies, and from randomized, experimental trials.
 Drug-induced gastric ulcers have been prevented by misoprostol, but not by H2 blocker therapy.
 Several therapies have been reported to promote ulcer healing despite continued use of NSAIDs, but adequate controlled trials have not been done.
 Small gastric and duodenal ulcers readily heal, whereas larger gastric ulcers require vigorous and prolonged therapy.
 The relative efficacies of various therapies in preventing ulcers, healing ulcers, or preventing complications remain to be established.
",5
996,"Stationary vs. mapping manometry in evaluating dysphagia.
 Two methods are used to assess esophageal motility.
 The mapping technique uses catheter withdrawal at 1 cm steps until the entire esophagus is evaluated.
 A simpler method is commonly used that involves keeping the catheter stationary for the entire evaluation.
 We compared these 2 techniques in 30 patients referred for the evaluation of dysphagia.
 Emphasis was placed on the distal 10 cm of the esophagus because this is the primary location of esophageal motility disorders.
 There was excellent correlation between techniques for mean distal amplitude (r = 0.945), mean distal duration (r = 0.942), and percentage of non-peristaltic contractions (r = 0.967).
 The overall manometry diagnosis was similar by both methods in 27 (90%) patients.
 Three patients had different manometry diagnoses resulting from use of the two techniques.
 However, the change in diagnosis was only clinically important in one patient in whom the mapping technique identified a segmental motility disorder that had been missed by the stationary technique.
 Stationary manometry had a 94% sensitivity and 93% specificity rate for identifying motility disorders compared to mapping manometry.
 We conclude that stationary manometry is a simple and accurate method for evaluating esophageal pressures and distal disorders.
 Only those patients with normal results of stationary studies may benefit by further mapping to identify rare segmental motility disorders.
",5
997,"Radiographic techniques and efficacy in evaluating esophageal dysphagia.
 The radiographic examination of the esophagus to determine structural and/or functional causes of dysphagia is best performed with multiple techniques.
 These include full-column studies to produce distended films with or without the use of a solid bolus, mucosal relief films to identify mucosal defects such as esophagitis or the presence of varices, double-contrast films, and motion recording (fluoroscopy).
 The efficacy of each technique depends on the quality of the study and the specific disorder to be detected.
 Esophageal lesions producing dysphagia are classified into extrinsic structural lesions, intrinsic structural lesions, and esophageal motility disorders.
 Radiographic studies are the preferred screening techniques for patients with dysphagia.
 Although not as sensitive for the evaluation of mucosal lesions, radiographic studies are superior to endoscopy for the detection of abnormal motility, esophageal rings, and strictures.
",5
998,"Symptoms of achalasia in young women mistaken as indicating primary anorexia nervosa.
 The case of a young women with dysphagia, regurgitation, and weight loss, who was diagnosed as having anorexia nervosa but in whom reevaluation showed that achalasia was causing the symptoms, is presented together with related observations.
 Misinterpretation of esophageal symptoms may occur not only as a consequence of inadequate history taking and of being biased by a patient's emaciation, age, and gender, which leads to view certain aspects of the patient's history and behavior as suggesting a pathologic attitude towards eating and body weight, but also as a consequence of a misinterpretation of the symptoms as indicative of an eating disorder by the patients themselves.
 In some cases a disordered attitude toward eating and body weight may develop together or coexist with achalasia.
 The clinical evaluation of patients with symptoms suggestive of anorexia nervosa but also of bulimia nervosa should include the taking of a thorough history regarding swallowing and vomiting in order to recognize a possible esophageal motor disorder.
",5
999,"Modulation of mediator release from human intestinal mast cells by sulfasalazine and 5-aminosalicylic acid.
 Intestinal mast cells are thought to contribute to the mucosal inflammation in ulcerative colitis and Crohn's disease through release of inflammatory mediators.
 Since sulfasalazine and its metabolite 5-aminosalicylic acid are effective therapeutic agents in inflammatory bowel disease and have been shown to inhibit generation of inflammatory products in other cells, we examined the effect of these agents in vitro on human intestinal mast cell mediator release.
 Sulfasalazine (5 x 10(-4)-10(-3) M) was found to significantly enhance goat anti-human IgE-induced histamine release from intestinal mast cells, which is the same response as seen in human blood basophils, whereas its metabolite 5-aminosalicylic acid was an effective inhibitor of stimulated histamine release in both mast cells and basophils.
 5-Aminosalicylic acid also inhibited production of prostaglandin D2 by the stimulated intestinal mast cells.
 Sulfasalazine alone, without immunologic stimulation, did not induce histamine release from mast cells or basophils, but the enhancement of ongoing mast cell activation by sulfasalazine may explain some cases of adverse reactions to the drug.
 The inhibition of mast cell histamine release and prostaglandin generation by 5-aminosalicylic acid demonstrates a potential therapeutic modality of this agent.
",5
1000,"Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report.
 Colon cells from patients with ulcerative colitis utilize short-chain fatty acids inefficiently and may be exposed to decreased concentrations of these compounds.
 To test whether irrigation of the inflamed mucosa with short-chain fatty acids is useful, we conducted a six-week preliminary trial in 12 patients with distal colitis.
 Each patient used twice daily rectal irrigations with 100 ml of a solution containing acetate (80 mM), propionate (30 mM), and butyrate (40 mM).
 Two patients stopped at three weeks, one because of no improvement and the other because of complete resolution of symptoms.
 Of the 10 who completed the trial, nine were judged to be at least much improved and showed a change in a mean disease activity index score from 7.9 +/- 0.3 (SE) to 1.8 +/- 0.6 (SE) (P less than or equal to 0.002) and in a mucosal histology score from 7.7 +/- 0.7 (SE) to 2.6 +/- 0.7 (SE) (P less than or equal to 0.002).
 Thus, ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates.
",5
1001,"Gallstone dissolution with methyl tert-butyl ether in 120 patients--efficacy and safety.
 Of 612 patients with cholesterol gallbladder stones, 120 were eligible for percutaneous transhepatic litholysis with methyl tert-butyl ether (MTBE).
 Puncture of the gallbladder was successful in 117/120 (97.5%).
 In 113/117 (96.6%) the stones dissolved.
 With solitary stones, treatment lasted for an average of 4 hr, with multiple stones 10 hr.
 Mean hospitalization was 3.6 days.
 In 3/117 (2.6%) patients a bile leakage developed; 33% reported mild complaints.
 After the end of treatment 34% had some residue in the gallbladder; two of these patients developed recurrent stones.
 MTBE is exhaled, is distributed in fatty tissue, and is excreted renally together with its metabolite tert-butanol.
 Methanol was found only in traces.
 Gallbladder histology of six patients showed chronic cholecystitis.
 Since these findings were independent of treatment time and the interval between treatment end and operation, they are most consistent with stone-related changes rather than caused by MTBE.
",5
1002,"Medical dissolution of gallstones. Clinical experience of d-limonene as a simple, safe, and effective solvent.
 Retained gallstones in the bile ducts account for 60-70% of all the cases of postcholecystectomy syndromes.
 A solvent d-limonene preparation was injected directly to the biliary system of 200 patients to dissolve or disintegrate the retained gallstones.
 The outcomes were: retained stones completely disappeared in 96 cases (48%); partial dissolution in 29 (14.5%); chelating agent was also used with partial dissolution in 16 (8%); ineffective in 59 (24.5%).
 To make this method more effective, several guidelines should be observed including an in vitro trial dissolution test.
 Cautious observation for possible side effects and frequent hepatic and pancreatic function tests during the treatment with this preparation also should be performed.
",5
1003,"Evaluation of portal-systemic shunting in rats from mesenteric and splenic beds.
 In rats with partial portal vein ligation, 95 +/- 0.9% of the splenic blood flow is shunted from the portal to the systemic circulation when an intrasplenic injection of microspheres is used to determine the degree of shunting.
 Despite this magnitude of portal-systemic shunting, several biochemical and endocrine consequences of portal-systemic shunting occur at levels below what is expected for the degree of shunting found.
 In an effort to resolve these discordant findings, shunting from both the splenic and the mesenteric bed was studied in anesthetized portal hypertensive rats with various degrees and/or duration of portal vein stenosis.
 The shunting from the mesenteric bed averaged 66.7 +/- 29.9% (range 5.1-99.1%) and was influenced both by the degree and duration of portal vein stenosis.
 In contrast, shunting from the splenic bed averaged 97.3 +/- 4.0% (range 79-99.9%) and demonstrated no variation between groups determined by the degree of portal vein stenosis.
 The shunting from the splenic bed was consistently greater than that found from the mesenteric bed.
 Mesenteric but not splenic shunting correlated with serum bile acid levels.
 Mesenteric shunting was related inversely to the weight-adjusted liver mass and to serum testosterone levels.
 Based upon these data obtained in portal hypertensive rats, it is concluded that splenic injections of microspheres overestimate portal-systemic shunting.
 In contrast, mesenteric injections of microspheres yield values for shunting that correlate well with independently determined biochemical and endocrine consequences of shunting.
 These observations support the validity of the mesenteric shunting measurements obtained.
",5
1004,"Distribution of cholesterol between vesicles and micelles in human gallbladder bile: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid.
 The present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients (n = 23) and gallstone-free subjects (n = 7).
 Nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy.
 The vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation, and a clear separation between the two phases was obtained.
 The vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 A.
 The proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group (40% +/- 4%) compared with the gallstone-free (28% +/- 3%), ursodeoxycholic acid (28% +/- 3%) and chenodeoxycholic acid (18% +/- 4%) groups.
 Despite a low cholesterol saturation of bile in the latter three groups (88% +/- 12%, 51% +/- 9% and 65% +/- 5%, respectively), a considerable part of the biliary cholesterol was carried in the vesicular fraction.
 The cholesterol/phospholipid ratio in the vesicular fraction averaged between 0.49 and 0.58 in the gallstone, gallstone-free and chenodeoxycholic acid groups, whereas the ursodeoxycholic acid group had a significantly lower ratio of 0.24.
 The nucleation time of bile from the gallstone group was short (2 +/- 1 days) compared with the gallstone-free, chenodeoxycholic acid and ursodeoxycholic acid groups (23 +/- 3, 24 +/- 6 and 14 +/- 3 days, respectively.
",5
1005,"Prophylactic sclerotherapy for esophageal varices: long-term results of a single-center trial.
 Survival after prophylactic sclerotherapy was assessed in a single-center study involving 99 cirrhotic (41 alcoholic) patients enrolled over 8-yr.
 The wedged hepatic vein pressure gradient was measured; those with pressure greater than or equal to 12 mm Hg were randomized to receive sclerotherapy or no treatment.
 The rest were not randomized.
 Patients in all three groups who bled were treated with emergency endoscopy and sclerotherapy.
 Stratification according to presence of ascites was also undertaken.
 Median follow-up was 61 mo (range = 14 to 107 mo).
 Survival among unrandomized patients was significantly longer than among randomized patients (p less than 0.006), but there was no significant difference between those treated by sclerotherapy and the controls (p = 0.27).
 Alcoholic cirrhotic patients undergoing sclerotherapy had better 2-yr survival than did the controls (80% vs.
 43%; p = 0.09), but this benefit was not sustained at 5 yr.
 Survival in the nonalcoholic patient groups was identical.
 Only 10 of 50 deaths were caused by variceal bleeding.
 Forty-eight percent of patients with large varices bled, compared with 20% of patients with small varices.
 Wedged hepatic vein pressure less than 12 mm Hg accurately identified alcoholic patients at low risk of variceal bleeding but not nonalcoholic patients.
 Only four episodes of variceal bleeding were attributable to elective sclerotherapy.
 We conclude that in our population, prophylactic sclerotherapy alone does not improve survival.
 The discrepancy in survival between alcoholic and nonalcoholic cirrhotic patients suggests that factors other than variceal hemorrhage may be responsible for the difference.
",5
1006,"Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis.
 Human leukocyte antigen typing was performed in 81 patients with primary sclerosing cholangitis to investigate reported associations between human leukocyte antigen type and this disease.
 The results showed a significant increase in the frequency of the antigens B8 and DR3 compared with controls (53% vs.
 23%, p less than 0.0005, and 56% vs.
 21%, p less than 0.0005).
 This was caused by a significant rise in the frequency of the human leukocyte antigen A1 B8 DR3 haplotype (32 of 81 patients, 40% vs.
 12 of 100 patients, 12%, p less than 0.0005).
 By contrast, a significant reduction was seen in the frequency of the antigens B44 and DR4 (12% vs.
 31%, p less than 0.005, and 12% vs.
 34%, p less than 0.001, pc less than 0.011) because of the complete absence of the B44 DR4 haplotype in the patient group (p = 0.027, Fisher's exact test).
 When all the DR3-positive individuals (including the DR2/DR3 heterozygotes) were eliminated, a significant secondary association with DR2 was noted, 25 (69%) of 36 remaining patients being DR2-positive compared with 27 (34%) of 79 DR3 negative controls (p less than 0.0005, pc less than 0.006).
 Only 9% of the patients were DR2-positive and DR3-positive.
 Kaplan-Meier analysis demonstrated that survival was not influenced by the presence of either haplotype nor by the individual antigens.
 Patients who were DR3-positive were first seen at a significantly younger age than those who were DR2-positive (mean ages = 33 yr and 44 yr, respectively, p less than 0.002, Student's t test).
",5
1007,"Significance of natural polymerized albumin and its receptor in hepatitis B infection of hepatocytes.
 Lack of information regarding the presence of native albumin polymer in serum and its structural similarity to the one produced by glutaraldehyde treatment casts doubt on the postulate that hepatitis B virus attachment to hepatocytes is mediated through polymerized albumin.
 We used a sandwich enzyme-linked immunosorbent assay with murine monoclonal antibodies raised against glutaraldehyde-polymerized albumin to detect native albumin polymer in human serum and its cross-reactivity with other albumin polymers.
 Presence of polymerized albumin receptor on the HepG2 cell was studied by radioreceptor assay.
 Purified hepatitis B virus and synthetic peptide analogous to part of pre-S2 sequence (120-145) were used to study polymerized albumin-dependent attachment of the virus to HepG2 cells.
 Antibodies raised against pre-S2 peptide were used to inhibit the pre-S2 and hepatitis B virus attachment to HepG2 cells.
 Glutaraldehyde-treated polymerized albumin was found to be immunologically cross-reactive with native albumin polymer.
 Its levels were found to be significantly raised in sera of patients with liver diseases.
 Polymerized albumin has specific saturable receptor on HepG2 cells with two classes of binding sites of different equilibrium dissociation constant (Kd1 = (16 +/- 9.6)pmol/L and Kd2 = (1,019 +/- 172)pmol/L.
 Albumin monomer was unable to compete for the polymerized albumin receptor sites on HepG2 cells.
 Anti-pre-S2 antibodies inhibit hepatitis B virus and pre-S2 binding to hepatocyte by 40% and 70%, respectively.
 Added extraneous polymerized albumin and the antibody against it did not interfere with virus attachment to HepG2 cells.
",5
1008,"Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship to pre-S- and S-encoded viral surface antigens.
 The polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic hepatitis B virus carriers.
 Hepatitis B virus DNA was detectable in the serum of HBsAg-positive virus carriers using aliquots as small as 100 al.
 The detection limit for cloned hepatitis B virus DNA was 100 ag.
 Primer pairs for different regions of the HBV genome resulted in different sensitivity.
 Detection of the amplified hepatitis B virus DNA by Southern blotting and subsequent scintillation counting or densitometry allowed a semiquantitative assay.
 Using several primer pairs in parallel for optimal detection, all HBeAg-positive HBsAg carriers, 80% of HBe antibody-positive symptomatic HBsAg carriers and 57% of asymptomatic HBe antibody-positive HBsAg carriers were found to have hepatitis B virus DNA in the serum.
 During antiviral therapy hepatitis B virus DNA disappeared by the polymerase chain reaction assay in patients who became HBeAg negative, but polymerase chain reaction detected a relapse earlier than did the conventional dot blot.
 Pre-S antigens were assayed in serum and liver samples from most chronic carriers by enzyme-linked immunosorbent assay and/or immunoblot.
 Although most viremic carriers were strongly positive for pre-S1 and pre-S2 antigens, some hepatitis B virus DNA-positive HBsAg carriers did not have detectable pre-S antigens, and vice versa.
 Our data show that assay of hepatitis B virus DNA in the serum by polymerase chain reaction is by far more proficient than by dot blot and that it cannot be replaced by serological assays of HBeAg or pre-S antigen.
",5
1009,"Detection of hepatitis B virus DNA by polymerase chain reaction in plasma of volunteer blood donors negative for hepatitis B surface antigen.
 Plasma samples from 206 volunteer blood donors were tested for hepatitis B virus (HBV) DNA by dot blot hybridization and polymerase chain reaction (PCR).
 All donors were negative for hepatitis B surface antigen (HBsAg) and had normal serum alanine aminotransferase levels.
 None of the 206 plasma samples was positive for HBV DNA by dot blot hybridization assay.
 However, nine samples were positive for HBV DNA by PCR using two primer pairs specific for surface and core regions.
 Nine persons received the HBV-DNA-positive plasma, and one developed posttransfusion non-A, non-B hepatitis; the others remained well 6 months later.
 Therefore, approximately 4% of blood donors in Taiwan have low titers of HBV DNA, and a more sensitive method to screen donors may be needed in the future, although the current serologic test remains the most practical at present.
",5
1010,"Comparison of shunt fraction estimation using transcolonic iodine-123-iodoamphetamine and technetium-99m-pertechnetate in a group of dogs with experimentally-induced chronic biliary cirrhosis.
 Portosystemic shunt fraction estimation using transcolonic iodine-123-iodoamphetamine (IMP) has been previously validated relative to portal vein macroaggregated albumin injections using an experimental model of cirrhosis.
 Transcolonic technetium-99m-pertechnetate (TcO4-) has been proposed as an alternative tracer to IMP to study portal circulation in cirrhotic patients.
 We compared shunt fraction estimates from paired transcolonic IMP and TcO4- studies performed on a group of dogs before and after common bile duct ligation surgery.
 Pertechnetate over-estimated shunt fraction in 6/7 postoperative studies relative to IMP.
 A good correlation between the two methods was demonstrated, however, the slope of the regression line was substantially less than 1.0 with TcO4- values reaching 100% at IMP shunt values of approximately 60%.
 This apparent inability to accurately assess high shunt flows may limit the quantitative aspects of TcO4- studies on patients with severe portosystemic shunting.
",5
1011,"Quantification of hepatobiliary function as an integral part of imaging with technetium-99m-mebrofenin in health and disease.
 A study was undertaken to check the feasibility of measuring the hepatic extraction fraction (HEF) and excretion T-1/2 values as an integral part of hepatobiliary imaging with technetium-99m-mebrofenin in health and disease.
 In 18 controls subjects, the HEF was 100% and the T-1/2 excretion mean +/- s.e.
 value was 15.23 +/- 1.4 min.
 The mean appearance times of the common bile duct (CBD), gallbladder (GB), and small intestine were 15.8 +/- 1.52, 20.2 +/- 2.7, and 23.8 +/- 3.08 min, respectively.
 Rising serum bilirubin in patients decreased HEF and increased T-1/2 excretion value resulting in delayed appearance of CBD, GB, and small intestine.
 In control subjects and patients with bilirubin less than 5 mg%, T-1/2 excretion values at 30, 40, and 50 min were similar to those values calculated using the entire 60 min of data, suggesting that the hepatic phase study time could be reduced to 30-40 min and still use the normal reference values established for 60 min.
 In patients with bilirubin greater than 5 mg%, the data collection duration should be continued for 60 min.
",5
1012,"Intestinal obstruction by distension of a Foley jejunostomy catheter.
 Jejunostomies can be effective in permitting postoperative nutritional support, particularly in the patient with complicated gastrointestinal disease.
 In the case presented, however, distension of the Foley balloon catheter, used as the jejunostomy tube, led to intestinal obstruction which was not initially detected.
 Following radiographic identification of the problem, removal of the air from the Foley balloon allowed the patient to complete his convalescence from surgery.
 The possibility of obstruction from the Foley jejunostomy catheter should be recognized as a potential problem in the postoperative period.
",5
1013,"Norwalk virus genome cloning and characterization.
 Major epidemic outbreaks of acute gastroenteritis result from infections with Norwalk or Norwalk-like viruses.
 Virus purified from stool specimens of volunteers experimentally infected with Norwalk virus was used to construct recombinant complementary DNA (cDNA) and derive clones representing most of the viral genome.
 The specificity of the clones was shown by their hybridization with post- (but not pre-) infection stool samples from volunteers infected with Norwalk virus and with purified Norwalk virus.
 A correlation was observed between the appearance of hybridization signals in stool samples and clinical symptoms of acute gastroenteritis in volunteers.
 Hybridization assays between overlapping clones, restriction enzyme analyses, and partial nucleotide sequence information of the clones indicated that Norwalk virus contains a single-stranded RNA genome of positive sense, with a polyadenylated tail at the 3' end and a size of at least 7.5 kilobases.
 A consensus amino acid sequence motif typical of viral RNA-dependent RNA polymerases was identified in one of the Norwalk virus clones.
 The availability of Norwalk-specific cDNA and the new sequence information of the viral genome should permit the development of sensitive diagnostic assays and studies of the molecular biology of the virus.
",5
1014,"Surgical options in postgastrectomy syndromes.
 The various operations performed for the treatment of peptic ulcer disease can lead to a variety of iatrogenic disorders collectively referred to as the ""postgastrectomy syndromes."" Although the etiology of most of these disorders remains unclear, loss of vagal innervation and bypass, ablation, or destruction of the pylorus clearly are involved in the pathogenesis of most, if not all, of these disorders.
 Unfortunately, there often is also a poorly understood psychological element involved in the pathogenesis.
 Of all ulcer operations, proximal gastric vagotomy results in the fewest physiologic abnormalities and the mildest postoperative symptoms.
 The continued popularity of this operation should effect a marked reduction in the incidence of disabling postgastrectomy syndromes.
 Fortunately, symptoms severe enough to necessitate remedial operation are uncommon, and conservative medical management is always indicated and usually suffices.
 When disabling symptoms are refractory, a thorough evaluation of the patient and an accurate classification of the syndrome are essential to guarantee a satisfactory result from surgical intervention.
 Although numerous surgical procedures have been developed to deal with the different syndromes, with varied results, the Roux-en-Y procedure has emerged as the operation of choice for most, if not all, postgastrectomy syndromes.
 However, the Roux-en-Y procedure has not been universally successful, and this operation can itself lead to the recently recognized postgastrectomy state of Roux-en-Y stasis syndrome.
 Prevention therefore remains the best form of therapy, and remedial operation should not be undertaken until adequate time has elapsed since the original operation and all forms of conservative treatment have failed.
",5
1015,"Reoperation versus alternatives in retained biliary calculi.
 Retained common bile duct stones can be treated by operation, dissolution, extraction, fragmentation, papillotomy, and reoperation.
 Each approach requires some expertise, and the likelihood of success of most depends on the composition and size of the stones.
 Good results often can be obtained nonoperatively, especially with a multidisciplinary team.
 Reoperation is rarely necessary.
",5
1016,"Mechanical sutures in perforation of the thoracic esophagus as a safe procedure in patients seen late.
 Between 1976 and 1988, we treated 13 perforations of the thoracic esophagus, excluding ruptured carcinoma and intraoperative wounds, by mechanical sutures without exclusion.
 The delay between perforation and treatment ranged from eight to 168 hours, more than 24 hours in 11.
 The length of perforation was 0.5 to 15.0 centimeters.
 Suture was covered with a flap in ten instances; an antireflux procedure was associated with five instances.
 No digestive ostomies were performed.
 There was one death; a patient who was comatose upon arrival.
 The results of this small series suggest that myotomy exposing the mucosa and a flap are two essential elements of the technique; perforations of less than 6 centimeters, even when seen late, may be treated by primary surgical closure.
",5
1017,"Stercoral perforation of the colon.
 Stercoral perforation of the colon is rare.
 The 64 reported cases are reviewed to define the syndrome of stercoral perforation, and to facilitate accurate diagnosis and treatment.
 Features of localized or generalized peritonitis were universal; however, only 11 per cent were correctly diagnosed before operation.
 Recognition that the disease involves a segment of colon rather than only the focal point of perforation is essential to adequate surgical treatment.
 It is postulated that this is the reason for the higher postoperative mortality following closure of the perforation and proximal colostomy (57 per cent) or exteriorization alone (43 per cent), compared with resection of the diseased segment and exteriorization (32 per cent).
 Resection and exteriorization is therefore the treatment of choice is most situations.
",5
1018,"Adrenergic control of the internal anal sphincter is abnormal in patients with idiopathic faecal incontinence.
 There is histological and functional evidence that the internal anal sphincter is abnormal in patients with idiopathic faecal incontinence.
 The in vitro responsiveness of the internal anal sphincter to noradrenaline (an important sympathetic neurotransmitter) and electrical field stimulation (known to stimulate the intrinsic innervation) has been studied.
 Muscle strips from eight patients with incontinence undergoing postanal repair and five controls undergoing resection for low rectal carcinoma were studied.
 The contraction-response curves for noradrenaline were significantly different, and the EC50, the concentration required to produce 50 per cent of maximum contraction, was higher in incontinent patients (P less than 0.001).
 Electrical field stimulation produced initial contractions in four of the control group which were blocked by phentolamine.
 This contraction was not present in the incontinent patients (P less than 0.01).
 These results indicate an abnormality in the adrenergic innervation of the internal anal sphincter in patients with idiopathic faecal incontinence.
",5
1019,"Achalasia of the cardia: long-term results of oesophagomyotomy and posterior partial fundoplication.
 Forty-eight patients with achalasia of the cardia were treated by Heller's myotomy with a posterior fundoplication of approximately 270 degrees, suturing the gastric fundus to the edges of the myotomy.
 The mean(s.d.) postoperative follow-up period was 5.4(2.8) years.
 The clinical results were good to excellent in 44 cases (92 per cent) and fair in four cases (8 per cent) (two with residual dysphagia and two with gastrooesophageal reflux).
 Barium studies showed a decrease in oesophageal diameter and disappearance of distal narrowing but normal oesophageal emptying did not occur.
 Postoperative manometric studies (29 patients) revealed a significant decrease in lower oesophageal sphincter pressure and a significant increase in the length of the infradiaphragmatic segment.
 In the oesophageal body a recovery of peristaltic waves in the proximal third was seen in ten of the patients (34 per cent).
 Twenty-four-hour pH monitoring showed pathological reflux in only three of 25 patients studied, and one of these was asymptomatic.
 This technique is effective, improving oesophageal symptoms and controlling long-term reflux.
",5
1020,"Gallstone pancreatitis. Choosing and timing treatment.
 Patients with gallstone pancreatitis are often seen initially by primary care physicians.
 Prompt diagnosis and timely intervention are crucial in reducing morbidity and mortality.
 Initial management should include supportive medical care and surgical consultation.
 The timing of surgery is then dictated by serum enzyme levels and liver function test results as well as by the patient's condition.
 The role of endoscopic intervention is currently evolving.
 Whether surgery or endoscopic sphincterotomy is preferable as primary therapy for gallstone pancreatitis remains unresolved.
 However, sphincterotomy with stone extraction is a viable option in selected cases, especially in patients who have severe gallstone pancreatitis.
",5
1021,"Endoscopy versus x-ray studies of the gastrointestinal tract: future health care implications.
 I did esophagogastroduodenoscopy in 147 patients and colonoscopy in 59 patients who had had gastrointestinal x-ray studies.
 The endoscopic procedure was done within 7 days after the x-ray study and/or while the patient was still symptomatic.
 The barium swallow findings were confirmed in only 40%; in the other 60%, the x-ray findings could not be confirmed.
 These unconfirmed x-ray findings were false-positive in 37.4%, false-negative in 16.3%, and suboptimal or nondiagnostic in 6.2%.
 The barium enema findings were confirmed in 32%.
 In the other 68%, the x-ray findings were false-positive in 42.3%, false-negative in 22%, and suboptimal in 3.3%.
 We conclude that in clinical or private practice, relying on x-ray studies alone may be associated with a high margin of diagnostic errors.
 When all factors are considered, the initial cost advantage of the x-ray studies appears to be lost.
 In future recommendations on the continuing dilemma of x-ray studies versus endoscopy, consideration should be given to factors other than the initial lower price of the x-ray studies.
",5
1022,"Neuroendocrine design of the gut.
 The enteric nervous system (ENS) can be thought of as the third component of the autonomic nervous system.
 It is a vast network of neurons widely dispersed throughout the gut.
 The ENS is a dominant regulator of gut function through the action of peptide and non-peptide neurotransmitters.
 The most intensively studied roles of the ENS have been the regulation of secretory processes, such as gastric acid secretion, and motility.
 It is clear, however, that the ENS plays a broader role in the regulation of other gut functions, including mucosal defense, the gut immune response, and sphincter function.
 Alterations in the regulation of gut function by the ENS are likely or suspected in a number of conditions, including achalasia, Hirschsprung's disease, inflammatory bowel disease, Chagas' disease, chronic intestinal pseudoobstruction, biliary dyskinesia, tachygastria, and irritable bowel syndrome.
 Improved knowledge of the pathophysiology of these troublesome conditions makes effective therapy more likely in the future.
",5
1023,"The Roux operation for postgastrectomy syndromes.
 The aim of this paper is to describe the technique, indications, and results of the Roux operation as used in the treatment of postgastrectomy syndromes.
 A Roux gastrojejunostomy with a 40-cm Roux limb is the procedure of choice for alkaline reflux gastritis, because it virtually eliminates reflux of bile and pancreatic juice into the stomach.
 The slow transit through a Roux limb can also be used to good advantage to slow gastric emptying in patients with dumping.
 Patients with delayed gastric emptying respond to the combination of near-total gastric resection, which removes the atonic gastric remnant and speeds emptying, and Roux-Y gastrojejunostomy, which prevents reflux esophagitis and provides a reservoir for ingesta in the upper gut.
 After all Roux operations, however, the Roux limb may slow emptying so much that pain, fullness, nausea, and food vomiting result, the so-called Roux stasis syndrome.
 Prevention of the Roux stasis syndrome with an ""uncut"" Roux limb and the treatment of the syndrome by using electrical pacing to suppress the ectopic pacemakers that emerge in the limb offer possible new solutions to this vexing problem.
",5
1024,"Functional comparison between double and triple ileal loop pouches.
 Ileal pouch function in 35 patients operated upon by the same surgeon were compared.
 Seventeen of the patients had a double loop (J) ileal pouch-anal anastomosis (IPAA) and 18 a triple loop (S) pouch.
 The patients were examined a mean of 27.9 months and 5.1 months, respectively, after ileostomy closure.
 Ten of the S-pouch patients were evaluated more than 6 months (S greater than 6 months), mean 9.1 after ileostomy closure.
 There were no differences in the mean maximum resting pressures or maximum squeeze pressures between the groups.
 The incidence of daytime and nocturnal leakage was lower in the S-pouch group, 22 and 29 percent, than in the J group 29, and 53 percent.
 Though the mean maximum tolerated volume (MTV) of the S-pouch group was greater than the J group, the difference was not statistically significant.
 The difference in the mean compliance between the J- and S-pouch groups and the J and S greater than 6 months group was statistically significant (P less than 0.01) and (P less than 0.008).
 All the patients could evacuate spontaneously.
 The difference in the 24-hour frequency of defecation between the S greater than 6 months and J group was significant (P less than 0.05), but not between the S and J groups.
 The median frequency of nocturnal defecation between the S greater than 6 months and J pouch groups was significant (P less than 0.005), but not between the S and J groups.
 The triple loop S-pouches were more compliant than the J-pouches and had a better functional result as shown by a lower incidence of nocturnal leakage, and a lower frequency of defecation during the day and night.
",5
1025,"Rectopexy is an ineffective treatment for obstructed defecation.
 The symptoms of obstructed defecation have been attributed to rectal intussusception, and thus rectopexy has been advocated in the surgical management.
 In this study, patients with obstructed defecation underwent manometry and proctography before and after rectopexy.
 Seventeen patients (16 females and one male, mean age 51.6 years) were studied.
 Eleven underwent anterior and posterior fixation of the rectum and six had posterior fixation only.
 Preoperatively five patients demonstrated rectoanal intussusceptions.
 Fifteen had significant pelvic descent.
 No significant change in maximum resting pressure, maximum voluntary contraction, pelvic descent, or anorectal angle was seen postoperatively.
 In the initial follow-up, many patients had significant amelioration of symptoms.
 However, on longer follow-up (mean 30.8 months) only two had long-term improvement.
 The remainder had a poor clinical result in spite of complete resolution of rectal intussusception.
 Many reported a worsening of symptoms as reflected by an increase in tenesmus and stool frequency.
 In the two cases with a satisfactory result, both could empty the rectum completely and demonstrated rectoanal intussusception on preoperative evacuation proctography.
 In those with poor results, four had complete emptying and three had rectoanal intussusception.
 In conclusion rectopexy is an ineffective treatment for obstructive defecation in most patients.
",5
1026,"Anal sphincter function after intersphincteric resection and stapled ileal pouch-anal anastomosis.
 This study was done to determine the effect of the direct ileal pouch-anal anastomosis upon pressure and sensory components of the anal canal and ileal pouch.
 These findings were related to postoperative continence.
 Thirty-three patients with ileal pouch-anal anastomosis (25 continent, eight with episodic minor incontinence) were studied 3 +/- 0.3 and 25 +/- 5 months after ileostomy takedown.
 The maximum resting pressure in the anal canal was significantly lower in patients with an imperfect result (35 +/- 5 mm Hg) than in continent patients (44 +/- 5 mm Hg) (P less than 0.05).
 Postoperatively the maximum squeeze anal pressure was slightly greater in continent than in incontinent patients (99 +/- 8 mm Hg vs.
 87 +/- 7 mm Hg) (P greater than 0.05).
 The postoperative recto-(ileo-)anal inhibitory reflex was present in 27 percent.
 The linear correlation between strength of rectal (ileal) distension and depth resp.
 duration of internal sphincter relaxation as preoperatively observed disappeared postoperatively in every group of patients.
 Simultaneous measurements of pouch and anal pressure in patients with imperfect results revealed a reduced positive pouch anal pressure gradient compared to the continent group.
 This low pouch-anal pressure gradient is thought to be responsible for the increased incidence of soiling in some of our patients.
",5
1027,"Studies on autoimmunity for initiation of beta-cell destruction. VII. Evidence for antigenic changes on beta-cells leading to autoimmune destruction of beta-cells in BB rats.
 The diabetic syndrome in BioBreeding (BB) rats is believed to result from the destruction of beta-cells by autoimmune responses.
 However, the initial events that cause the autoimmune destruction of beta-cells remain largely unknown.
 This investigation was initiated to see whether there are any antigenic changes on the beta-cells from neonatal to adult BB rats that may lead to the autoimmune destruction of beta-cells.
 Pancreatic grafts from neonatal BB rats remained largely intact without insulitis when transplanted into the renal subcapsular space of acutely diabetic BB rats.
 Similarly transplanted islet grafts from neonatal BB rats were also not subject to autoimmune destruction.
 In contrast, islet grafts obtained from adult BB rats, which had been treated with silica to prevent insulitis, were rapidly destroyed in diabetic recipients.
 These results indicate that beta-cells from neonatal BB rats are different from beta-cells from adult BB rats, at least regarding their recognition by immunologic effectors.
 Considering our observations and previous information on the initial role of macrophages/dendritic cells in the development of insulitis in BB rats, we suggest that beta-cell-specific antigenic changes that precede insulitis may result in the autoimmune destruction of beta-cells in BB rats.
",5
1028,"Minor papilla cannulation and dorsal ductography in pancreas divisum.
 Until recently, pancreas divisum represented a major technical barrier to a complete evaluation of pancreatic ductal anatomy.
 Technical refinements have now made it possible to achieve minor papilla cannulation and dorsal ductography in more than 90% of attempts.
 In 120 consecutive dorsal ductograms, structural pathology was demonstrated in 36 subjects (30%): chronic pancreatitis in 23, pancreatic stones in 10, pseudocyst(s) in 4, ductal ""cut-off"" in 7, pancreatic cancer in 3, and partial agenesis in 1 (some patients had more than one finding).
 For patients in whom alcohol abuse was excluded, ductal pathology was present in 25%.
 Abnormal ventral ductograms were present in only 8% of cases, demonstrating that dorsal ductography has an appreciable additional diagnostic yield.
 When the clinical situation indicates the need for pancreatography, minor papilla cannulation should be performed if major papilla cannulation fails or reveals only the ventral pancreatogram of pancreas divisum.
",5
1029,"Long-term follow-up in patients who have undergone balloon dilation for gastric outlet obstruction.
 Although balloon dilation for gastric outlet obstruction has supplanted vagotomy plus drainage or resective therapy in some institutions, there are no long-term data which demonstrate what percentage of patients ultimately requires surgical intervention.
 Of 23 evaluable patients treated with hydrostatic balloon dilation in our institution, 70% were asymptomatic at a mean follow-up of 2.5 years.
 Five patients required surgery--one for acute perforation and the other four for symptoms of continued obstruction, despite one to three additional attempts at dilation.
 Only three of seven patients with previous gastric resection had a satisfactory long-term result.
 Whereas endoscopic therapy initially cost one tenth to one fifth that of surgical intervention, such figures do not factor for loss of productivity, on the one hand, or potential need for chronic H2 blockade, on the other.
 Despite instruction to the contrary, only 6 of 15 (40%) active patients continue acid-suppressive therapy.
 We conclude that balloon dilation remains a viable alternative for selected patients with gastric outlet obstruction.
",5
1030,"Twelve hour overnight oesophageal pH monitoring in patients with reflux symptoms.
 Results of continuous 12 hour overnight pH monitoring (duration of pH less than 4) were reviewed in 112 patients with heartburn or regurgitation, or both, and in 56 normal subjects.
 Patients had more reflux than normal subjects.
 Medically controlled patients (n = 51) had less acid reflux than patients who subsequently underwent reflux surgery (n = 61), but there was a considerable overlap between those two groups.
 Surgery was followed by a reduction in acid reflux to a value similar to that in normal subjects.
 Patients in whom surgery was deemed to have failed had more reflux after the operation than those in whom it was successful, but no difference could be found in the preoperative reflux values of these two subgroups.
 Monitoring pH is not of value in selecting candidates for surgery since the results are not a good predictor of outcome, but it is useful in the objective evaluation of surgical results.
",5
1031,"Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations.
 It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells.
 To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients.
 After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours.
 During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01).
 This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration.
 The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05).
 On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration.
 In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin.
",5
1032,"Dissociation between systemic and mucosal humoral immune responses in coeliac disease.
 We examined humoral immunity in coeliac disease as expressed in serum (systemic immunity), and in saliva, jejunal aspirate, and whole gut lavage fluid (mucosal immunity).
 The aims were to define features of the secretory immune response (IgA and IgM concentrations and antibody values to gliadin and other food proteins measured by enzyme linked immunosorbent assay (ELISA)) in active disease and remission, and to establish whether secretions obtained by relatively non-invasive techniques (saliva and gut lavage fluid) can be used for indirect measurements of events in the jejunum.
 Serum, saliva, and jejunal aspirate from 26 adults with untreated coeliac disease, 22 treated patients, and 28 immunologically normal control subjects were studied, together with intestinal secretions obtained by gut lavage from 15 untreated and 19 treated patients with coeliac disease and 25 control subjects.
 Jejunal aspirate IgA and IgM and gut lavage fluid IgM concentrations were significantly raised in patients with untreated coeliac disease; the lavage fluid IgM concentration remained higher in patients with treated coeliac disease than in controls.
 Serum and salivary immunoglobulin concentrations were similar in the three groups.
 Patients with untreated coeliac disease had higher values of antibodies to gliadin compared with treated patients and control subjects in all body fluids tested; these were predominantly of IgA and IgG classes in serum, and of IgA and IgM classes in jejunal aspirate and gut lavage fluid.
 Values of salivary IgA antibodies to gliadin were significantly higher in untreated coeliacs, though antibody values were generally low, with a large overlap between coeliac disease patients and control subjects.
",5
1033,"Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis.
 Substantial amounts of phenols are produced in the human colon by bacterial fermentation of protein.
 In the colonic mucosa of animals, phenols are inactivated predominantly by conjugation with sulphate.
 The purpose of this study was to confirm sulphation of phenols by isolated colonocytes from man and to evaluate mucosal sulphation in inflammatory bowel disease using the phenol, paracetamol, in rectal dialysis bags.
 The incubation of paracetamol with colonocytes isolated from resected colon specimens (n = 7) yielded a mean (SE) value of 7.0 (0.9) mumols/g dry weight of paracetamol sulphate after 60 minutes but virtually undetectable values of paracetamol glucuronide.
 Paracetamol sulphate was detected in rectal dialysates from all control subjects, with a mean (SE) value of 4.2 (0.8) nmol/hour.
 Sulphation was significantly impaired (p less than 0.01) in 19 patients with active ulcerative colitis (0.6 (0.2) nmol/hour) and in 17 patients with ulcerative colitis in remission (1.1 (0.4) nmol/hour).
 Sulphation in eight patients with Crohn's colitis (4.3 (2.1) nmol/hour) was similar to that in control subjects.
 Impairment of the capacity of the mucosa to sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic burden on colonic epithelial cells, which are continuously exposed to endogenous phenols from the colonic lumen.
",5
1034,"5-Aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease.
 Interleukin 1 beta in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied.
 Compared with normal colonic mucosal biopsy specimens, a significantly greater amount of interleukin 1 beta was present in rectal mucosa before (median (range) 4.3 (2.0-11.8) v 119.2 (30.1-286.8) pg/mg; p less than 0.01) and produced during organ culture (39.1 (9.4-106.8) v 97.6 (28.2-991.6) pg/mg; p less than 0.01).
 Values of interleukin 1 beta after culture correlated with concentrations of thromboxane B2.
 Organ culture of inflamed biopsy specimens in the presence of 5 aminosalicylic acid and dexamethasone reduced the amount of interleukin 1 beta detected.
 At the doses studied, 5 aminosalicylic acid also reduced the amount of leukotriene B4 detected after culture.
",5
1035,"Candidacidal activity of Crohn's disease neutrophils.
 The ability of normal and Crohn's disease neutrophils to kill Candida albicans has been studied using neutrophils isolated from peripheral blood and suspended in phosphate buffered saline at 5 x 10(6) cells per ml.
 C albicans was grown to a stationary phase in broth culture and suspended in phosphate buffered saline at 10(7) organisms/ml.
 Neutrophils and Candida were then incubated together at 37 degrees C in a shaking water bath in the presence of fresh serum.
 At 30 and 60 minutes samples were withdrawn, neutrophils lysed, and Candida survival assessed by colony counting.
 Results were compared with control suspensions of Candida incubated with serum alone.
 After 30 and 60 minutes in the presence of autologous serum normal neutrophils had killed significantly more Candida than Crohn's disease neutrophils (mean (SD) 61.0 (16.7)% v 40.5 (16.2)% at 30 minutes, p less than 0.0001; 83.2 (7)% v 70.8) 16)% at 60 minutes, p less than 0.005).
 The results did not alter significantly when normal neutrophils were incubated with Candida in the presence of Crohn's disease serum instead of normal serum.
 When Crohn's disease neutrophils were incubated with Candida in the presence of normal serum instead of autologous serum there was some improvement in candidacidal ability at 30 minutes (48.9 (20.6)% v 40.5 (16.2)%, p less than 0.03) but not at 60 minutes.
 Phagocytosis, measured using a radiometric assay, was normal.
 Neutrophils from patients with Crohn's disease have an impaired ability to kill this granuloma provoking organism.
 It is not due to serum inhibitors or defective phagocytosis.
",5
1036,"How bad are the symptoms and bowel dysfunction of patients with the irritable bowel syndrome? A prospective, controlled study with emphasis on stool form.
 Since it is not known whether the symptoms and bowel function of patients with the irritable bowel syndrome are truly abnormal we used diaries and frequent telephone interviews over a 31 day period to assess symptoms, defecation, and stool types in 26 unselected female hospital patients with the irritable bowel syndrome, 27 women who admitted to recurrent colonic pain but had not consulted a doctor (non-complainers), and 27 healthy control subjects.
 Unexpectedly, abdominal pain and bloating occurred in most of the control subjects.
 Pain, however, was six times more frequent in the patients and was more often considered severe.
 Bloating occurred three times more often.
 Defecation was more frequent, more erratic in timing and stool form, and more likely to produce stools of extreme forms, indicating rapid fluctuations in intestinal transit time.
 Urgency was four times more prevalent in patients than control subjects.
 Straining to finish defecating was nine times more prevalent and was often accompanied by feelings of incomplete evacuation--a combination which could lead to the misdiagnosis of constipation.
 The normal relation between stool form and the above symptoms was distorted, possibly due to rectal irritability.
 Non-complainers were intermediate between patients and control subjects in almost every parameter but were closer to control subjects than to patients.
 Patients with the irritable bowel syndrome have real cause for complaint and their bowel function is truly abnormal.
",5
1037,"Provision of gastrointestinal endoscopy and related services for a district general hospital. Working Party of the Clinical Services Committee of the British Society of Gastroenterology.
 (1) The number of endoscopic examinations performed is rising.
 Epidemiological data and the workload of well developed units show that annual requirements per head of population are approaching: Upper gastrointestinal 1 in 100 Flexible sigmoidoscopy 1 in 500 Colonoscopy 1 in 500 ERCP 1 in 2000 (2) Open access endoscopy to general practitioners is desirable and increasingly sought.
 For a district general hospital serving a population of 250,000, this workload entails about 3500 procedures annually, performed during 10 half day routine sessions plus emergency work.
 (3) High standards of training and experience are needed by all staff, who must work in purpose built accommodation designed to promote efficient and safe practice.
 (4) The endoscopy unit should be adjacent to day care facilities and near the x ray department.
 There should be easy access to wards.
 (5) An endoscopy unit needs at least two endoscopy rooms; a fully ventilated cleaning/disinfection area; rooms for patient reception, preparation, and recovery; and accommodation for administration, storage, and staff amenities.
 (6) The service should be consultant based.
 At least 10 clinical sessions are required, made up of six or more consultant sessions and two to four clinical assistant, hospital practitioner, or staff specialist sessions.
 Each consultant should be expected to commit at least two sessions weekly to endoscopy.
 Extra consultant sessions may be needed to provide an efficient service.
 (7) A specially trained nursing sister (grade G or H) and five other endoscopy nurses are needed to care for the patients; their work may be supplemented by care assistants.
 (8) A new post of endoscopy department assistant (analogous to an operating department assistant) is proposed to maintain and prepare instruments, and to give technical assistance during procedures.
 (9) A full time secretary should be employed.
 Records, appointments, and audit should be computer based.
 (10) ERCP needs the collaboration of an interventional radiologist working with high quality x ray equipment in a specially prepared radiology screening room.
 This facility may need to serve more than one hospital.
 (11) A gastrointestinal measurement laboratory can conveniently be combined with the endoscopy unit.
 In some hospitals one or more gastrointestinal measurement technicians may staff this laboratory.
 (12) An endoscopy unit is a service department analogous to a radiology department.
 It needs an annual budget.
",5
1038,"The prevalence of gallstone disease in very old institutionalized persons.
 We present the results of a study that was undertaken at a large geriatric nursing home to assess the prevalence of gallstone disease in very old institutionalized persons.
 One hundred seventeen residents underwent ultrasound examination of the gallbladder.
 Two thirds of 82 women and half of 35 men had gallstone disease.
 When stratified for age, 80% of women and men over the age of 90 years were positive for the disease.
 In summary, the prevalence of gallstone disease in our very old nursing home population was found to be unexpectedly high.
",5
1039,"Self-management of dietary compliance in coeliac disease by means of ELISA ""home test"" to detect gluten.
 To improve compliance with a gluten-free diet in coeliac disease a simple prototype test kit was developed to detect gluten in foods for use at home.
 The test is based on monoclonal antibodies to heat-stable gluten proteins which crossreact appropriately with barley and rye proteins.
 It is suitable for use with a wide range of raw or cooked foods.
 The food is extracted with dilute hydrochloric acid and 1 drop of the extract transferred to an antibody-coated tube; enzyme-labelled gluten detection antibody is added and after 3 min the tube is washed and colour developer is added.
 The reaction is stopped after 2 min, stabilising the blue colour.
 The home kit was compared with a quantitative laboratory kit, and the qualitative agreement was very good.
 The kit could distinguish foods with trace gluten contents (acceptable for a ""gluten-free"" diet) from those with a slightly higher but unacceptable gluten content.
 In a trial of the prototype kit by 47 coeliac disease patients of diverse ages and educational backgrounds, 93% of tests correctly identified foods as acceptable or unacceptable.
",5
1040,"Evidence for role of prostacyclin as a systemic hormone in portal hypertension.
 The possibility that prostacyclin could be a systemic hormone and could mediate the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits in a normotensive state and in rabbits with chronic partial ligation of the portal vein.
 In rabbits with portal hypertension (PHT), 6-keto-prostaglandin F1 alpha (PGF1 alpha, a prostacyclin degradation product) was elevated twofold in all vascular beds (systemic arterial, systemic venous, and portal venous) when compared with levels in control animals.
 In PHT rabbits, exogenous prostacyclin infusion after cyclooxygenase blockade through the systemic arterial, systemic venous, or portal venous route resulted in an equal elevation of 6-keto-PGF1 alpha in the reciprocal vascular beds and restored the original precyclooxygenase blockade hemodynamics.
 These hemodynamic changes were of equal magnitude irrespective of site of infusion in PHT.
 In controls there was no significant change in 6-keto-PGF1 alpha or hemodynamics with intraportal infusion.
 We conclude that prostacyclin achieves systemic levels by escaping hepatic degradation resulting from portosystemic shunting in the animal with chronic portal hypertension.
",5
1041,"Nonpropulsive esophageal contractions and gastroesophageal reflux.
 Nonpropulsive esophageal contractions radiologically described as tertiary contractions or ""corkscrew"" esophagus suggest the presence of an underlying motility disorder and may lead to impaired acid clearance.
 The goals of this study were to determine the prevalence and role of gastroesophageal reflux (GER) in patients with tertiary contractions.
 Thirty-five consecutive patients with spontaneous, repetitive, nonpropulsive esophageal contractions noted on esophagography were studied with endoscopy, infusion esophageal manometry, and 24-h ambulatory pH monitoring.
 All patients had esophageal symptoms, mainly dysphagia, heartburn, and chest pain, but only three were found to have esophagitis by endoscopy and biopsy.
 Nineteen patients had repetitive, nonlumen-obliterating, nonperistaltic (tertiary) contractions, six had corkscrew esophagus, and 10 had forceful, lumen-obliterating simultaneous contractions (rosary bead esophagus).
 Twenty patients (58%) had GER by pH criteria with mean values: % time pH less than 4, 40.9; %upright pH less than 4, 41; %supine pH less than 4, 44.3%; number of episodes with greater than 5 min of pH less than 4, 12.
 Esophageal motility revealed ""nutcracker"" esophagus in eight, low LESP in two, and nonspecific esophageal motility disorder in 10.
 Symptoms or severity of nonperistaltic contractions did not correlate with GER.
 Radiologically demonstrable free reflux or the presence of heartburn did not predict GER.
 We conclude that 1) GER occurs in up to 58% of patients with nonpropulsive (tertiary) esophageal contractions on esophagography, and may play a role in the induction of abnormal peristaltic activity of the esophageal body; 2) GER is usually not associated with endoscopic evidence of esophagitis or characteristic symptoms, and is recognized by 24-h pH monitoring.
 We speculate that detection and treatment of GER may improve the symptomatic management of patients with nonpropulsive esophageal contractions.
",5
1042,"The symptom sensitivity index: a valuable additional parameter in 24-hour esophageal pH recording.
 Twenty-four-hour esophageal pH monitoring is useful for the quantitative measurement of gastroesophageal reflux and for the demonstration of a temporal relationship between symptoms and reflux.
 The symptom index, a numerical score, was developed to quantify the association between symptoms and reflux.
 Because the symptom index primarily assesses the specificity of a patient's reflux symptoms, we propose to refer to this score as the symptom specificity index.
 Because of certain limitations of this score, we developed and evaluated a new score, the symptom sensitivity index, that quantifies the subject's sensitivity for reflux.
 Fifty-two consecutive patients, referred to our laboratory for ambulatory 24-h pH recording were studied.
 Beside the conventional reflux variables, both indexes were calculated.
 Although a statistically significant correlation between the indexes was found, discordance between the specificity and sensitivity indexes was seen in 17 patients (33%).
 Based on the findings in this study we advocate that the symptom sensitivity index should be used, in addition to the symptom specificity index, and incorporated in future pH studies to optimalize the interpretation of the results.
",5
1043,"Radiographic evaluation of suspected small bowel obstruction.
 Plain abdominal radiographs and enteroclysis studies were reviewed blindly in 117 consecutive patients undergoing enteroclysis for suspected small bowel obstruction.
 Plain radiographs were unreliably predictive of the presence of obstruction as determined by enteroclysis and surgery.
 Among patients with normal or abnormal nonspecific plain radiographs, varying degrees of small bowel obstruction were demonstrated by enteroclysis in 22%.
 Conversely, of patients with obstruction on plain radiographs, 42% had either normal enteroclysis studies or only minor adhesions.
 Enteroclysis correctly predicted the presence of obstruction in 100%, the absence of obstruction in 88%, the level (proximal vs distal) of obstruction in 89%, and the etiology of obstruction in 86% of operated patients.
 Enteroclysis is advocated as the definitive study in patients with clinical uncertainty about the diagnosis of small bowel obstruction.
",5
1044,"Extracorporeal piezoelectric lithotripsy for complicated bile duct stones.
 Today, common bile duct stones are extracted endoscopically.
 After endoscopic sphincterotomy, nearly 90% of all stones can be removed with a Dormia basket or a mechanical lithotripter.
 Problems are encountered if there are larger stones or a duct stenosis.
 New conservative therapies do serve as an alternative to surgical intervention for those few patients in whom endoscopic measures have failed.
 Stone fragmentation can be achieved by extracorporeal shock wave lithotripsy, and remaining fragments can be removed endoscopically.
 So far, authors of most reports on the successful disintegration of common bile duct stones used the Dornier lithotripter.
 Stone localization is thus achieved with x-rays, and the shock waves are generated by an underwater spark discharge.
 We report on our experiences and results with extracorporeal piezoelectric shock wave lithotripsy (EPL) in 19 patients with complicated bile duct stones.
 With this lithotripter, stones are visualized by ultrasound, and shock waves are produced by a piezoelectric acoustic generator.
 Fragmentation was achieved in 84.2%, and complete stone removal in 78.9%.
 These results show that piezoelectric lithotripsy is also a useful method for the treatment of complicated bile duct stones, as has already been proved for the electrohydraulic- and electromagnetic-generated shock waves systems.
 However, the renunciation of general anesthesia and the need for analgesia or sedation in only 25% of the treatments render this lithotripter system attractive, especially for elderly and frail patients.
",5
1045,"Annular pancreas as a cause of extrahepatic biliary obstruction.
 Annular pancreas is a rare congenital abnormality that is increasingly diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) in the adult.
 In this population, it can present with duodenal or gastric ulceration, duodenal obstruction, pancreatitis, and, rarely, with associated congenital abnormalities.
 Although it has been suggested that biliary obstruction may result from associated pancreatitis, such cases have not been reported; primary extrahepatic biliary obstruction from a constricting annulus also has not been reported.
 We report such a case, and describe resolution of symptoms and a return to normal biochemical tests in a patient.
 The literature and embryology of annular pancreas are reviewed.
 We suggest that this entity be added to the differential diagnosis of extrahepatic biliary obstruction.
",5
1046,"Endoscopic management of retained cystic duct stones.
 The finding of residual common bile duct stones after cholecystectomy is a relatively frequently encountered problem for which effective nonoperative therapy exists.
 Retained stones in a cystic duct remnant are very rare.
 We present a case of multiple retained stones in a long variant cystic duct remnant following cholecystectomy and common duct exploration, which was successfully managed with endoscopic sphincterotomy and balloon extraction.
",5
1047,"Estrogen receptors in the external anal sphincter.
 Inasmuch as anal competence in women is reduced after the age of 50 years, it may be dependent on effects of estrogens.
 In this study, samples of the external anal sphincter were analyzed for the presence of estrogen receptors and were found to be present at a median concentration of 5.0 fmol per milligram of protein (range, 1.9 to 13) in women (n = 7), and 1.1 fmol per milligram of protein (range, 0 to 3.2) in men (n = 7).
 These findings are of interest with regard to the treatment of idiopathic anal incontinence.
",5
1048,"Alanine aminotransferase in clinical practice. A review.
 Alanine aminotransferase is an enzyme produced mainly in the liver.
 When serum activity is measured, it provides a marker of hepatic disease.
 This review explores the biochemistry and laboratory analysis of alanine aminotransferase in terms of its significance in human health and disease.
 Cut-off levels that define abnormality are rather arbitrary and this decreases the specificity of the test in apparently healthy patients.
 A small, but important, group of patients with alanine aminotransferase abnormality have underlying liver disease that may be treatable.
 Most can be diagnosed based on history, physical examination, and biochemical-serological profiles.
 Liver biopsy can complement the diagnostic process in selected circumstances.
 Literature pertaining to this is critically reviewed.
",5
1049,"The vagus nerve, gastric secretions, and their relationship to peptic ulcer disease.
 Although peptic ulcer disease was known to the ancients, the process by which the disease was produced remained a mystery.
 As advances were made in medicine and science, so too were advances made in the understanding of digestion and gastrointestinal disease.
 The treatment of peptic ulcer disease improved as our understanding of the digestive process grew.
 The current surgical treatment for peptic ulcer disease follows the principals articulated by Lester R.
 Dragstedt, MD, PhD, which he based on his observations in the research laboratory.
 We present a historical perspective of the role of the vagus nerve in the control of gastric secretions and its relationship to peptic ulcer disease, placing particular emphasis on Dragstedt's contributions.
",5
1050,"Water and electrolyte balance after ileoanal anastomosis.
 Water and electrolyte balance was studied in 30 patients with ileoanal anastomosis and J pouch, 10 patients with conventional ileostomy, and nine nonoperated patients with quiescent ulcerative colitis.
 Serum electrolyte concentrations, daily urinary volume, and daily losses of sodium, potassium, and chloride were measured in all patients.
 Daily fecal weight and daily losses of sodium and potassium were analyzed in patients with ileoanal anastomosis or conventional ileostomy.
 Serum chloride in patients with ileoanal anastomosis was significantly lower (P less than 0.05) than in those with conventional ileostomy or in nonoperated patients.
 Daily urinary loss of sodium in nonoperated patients was significantly higher than in patients with ileoanal anastomosis (P less than 0.01) or conventional ileostomy (P less than 0.05).
 Daily urinary loss of chloride in patients with ileoanal anastomosis was significantly lower (P less than 0.05) than in nonoperated patients.
 Daily fecal loss of potassium in patients with ileoanal anastomosis was significantly higher (P less than 0.05) than in those with conventional ileostomy.
 Daily urinary volume and fecal weight did not differ significantly in patients with ileoanal anastomosis or conventional ileostomy.
 The present study indicates that changes in water and sodium balance after ileoanal anastomosis are similar to those after conventional ileostomy but chloride balance is more altered after ileoanal anastomosis.
",5
1051,"""Mini-perforation"" of the colon--not all postpolypectomy perforations require laparotomy.
 In a 10-year experience with 4,784 consecutive colonoscopic polypectomies, the need for operative intervention in just two of seven perforations indicates that patients with specially defined, limited perforations can usually be treated nonoperatively.
 This specific complication, which has been termed ""mini-perforation,"" is generally detected within 6-24 hours of polypectomy, and is characterized by local pain and tenderness, without signs of diffuse or spreading peritoneal irritation.
 Free intra-abdominal or retroperitoneal air on x-ray documents the actual perforation.
 Complete resolution of symptoms within 24-48 hours confirms the diagnosis of ""mini-perforation."" Success depends on good bowel preparation for colonoscopy, and early recognition of perforation, with institution of bowel rest and intravenous antibiotics.
 The ""mini-perforation"" spontaneously closes, probably by omental adherence.
 Frequent serial clinical examinations are mandatory so that frank perforation with advancing peritonitis will be promptly recognized and treated surgically.
 An understanding of the three levels of cautery injury to the colon wall--""serosal burn,"" ""mini-perforation,"" and ""frank perforation"" are essential in managing the complications of colonoscopic polypectomy.
",5
1052,"Incarceration of colonoscope in an inguinal hernia. ""Pulley"" technique of removal.
 Because of its relative safety, colonoscopy has become an accepted diagnostic and therapeutic procedure in the evaluation of patients with colorectal disorders.
 Many unusual complications of colonoscopy have been described, but only anecdotal reports of hernial incarceration have been published.
 We present a case of a right-sided hernial incarceration of the colonoscope that would not permit reduction of the hernia nor removal of the instrument by conventional means.
 The mechanism of incarceration, which dictates the size of hernia at risk for incarceration, is explained.
 The ""pulley"" technique, which was used to remove the instrument without surgical intervention, is described.
",5
1053,"Gender differences in Manning criteria in the irritable bowel syndrome.
 The objective of this study was to determine if gender differences exist when using the Manning criteria for diagnosis of irritable bowel syndrome.
 In an outpatient setting, 61 women and 36 men with entry complaints of abdominal pain, altered bowel habits, or both underwent full evaluation by board-certified/eligible gastroenterologists who also systematically rated the presence or absence of the six Manning criteria.
 Irritable bowel syndrome was defined as the absence of an organic disease explanation for the entry complaints.
 This determination was made by two other board-certified gastroenterologists after patients had been in the study for 9 months.
 These raters were independent of the study and rated the transcripts of patients' clinic visits, all other available clinical data from this and other clinics, all laboratory data obtained during the 9-month study period, and the results of a 9-month telephone follow-up to patients and their physicians.
 Sixty-five percent of the study population had no organic disease explanation for the entry symptoms, thereby representing irritable bowel syndrome for this study.
 A similar proportion and type of organic disease and irritable bowel syndrome were experienced by men and women.
 For the total sample of 97 subjects, the correlation of the Manning criteria with irritable bowel syndrome was 0.22 (P less than 0.01).
 In the 61 women, correlation between the Manning criteria and irritable bowel syndrome was significant (r = 0.47; P less than 0.01).
 In the 36 men, however, the correlation was in the opposite direction, although it was not significant (r = -0.16).
 It was concluded that significant gender differences exist when using the Manning criteria for the diagnosis of irritable bowel syndrome and that the Manning criteria were not of diagnostic value in men.
",5
1054,"Impairment of esophageal emptying with hiatal hernia.
 Concurrent videofluoroscopy and manometry were used to analyze esophageal emptying during barium swallows in 22 patients with axial hiatal hernias and in 14 volunteers.
 Subjects were divided into three groups: (a) volunteers with maximal phrenic ampullary length less than 2 cm (controls); (b) patients or volunteers with maximal ampullary/hiatal hernia length greater than or equal to 2 cm that reduced between swallows (reducing-hernia group); and (c) patients with hernias that did not reduce between swallows.
 Complete esophageal emptying without retrograde flow was achieved in 86% of test swallows in the controls, 66% in the reducing-hernia group, and 32% in the nonreducing-hernia group (P less than 0.05).
 Impaired emptying in the reducing-hernia group was attributable to ""late retrograde flow,"" whereby barium squirted retrograde from the hernia during emptying.
 Impaired emptying in the nonreducing-hernia group was attributable to ""early retrograde flow"" that occurred immediately after LES relaxation.
 The nonreducing-hernia group also had longer acid clearance times than the controls (P less than 0.05).
 We conclude that gastroesophageal junction competence is severely impaired in patients with nonreducing hiatal hernias, suggesting a mechanism whereby this subgroup of hiatal hernia is involved in the pathogenesis of reflux disease.
",5
1055,"Small intestinal transit in the portal hypertensive rat.
 The purpose of this study was to determine the effects of portal hypertension on gastrointestinal transit.
 Portal hypertension was induced in a group of 15 rats by the staged portal vein ligation technique.
 A control group of 15 rats underwent a sham operation.
 Ten days later, a 51Cr-labeled Krebs' buffer solution was instilled into the duodenum and the distribution or radioactivity along the length of the small intestine was determined after 15, 30, and 60 minutes.
 Portal hypertension was consistently established in the study group; splenic pulp pressure (mm Hg, mean +/- SD, portal hypertensive vs.
 control) was 20.0 +/- 3.9 vs.
 12.7 +/- 3.9, P less than 0.002.
 Various measures of intestinal transit revealed delayed transit in the portal hypertensive group.
 Retention of radioactivity in the most proximal quartile of the intestine was greater [percentage retained (portal hypertensive vs.
 control) was 57.9 +/- 17.3 vs.
 31.2 +/- 15.3, P less than 0.02, 49.1 +/- 15.5 vs.
 28.3 +/- 4.8, P = 0.03, and 42.4 +/- 17.6 vs.
 29.0 +/- 8.8, P = 0.08, at 15, 30, and 60 minutes, respectively] and the geometric mean of transit was located more proximally (P less than 0.02) at each study interval in the portal hypertension group.
 It was concluded that portal hypertension is associated with delayed intestinal transit.
 This abnormality could predispose to bacterial overgrowth and contribute to altered digestion and absorption.
",5
1056,"Increased uptake of bromodeoxyuridine by hepatocytes from early stage of primary biliary cirrhosis.
 The relationship between DNA synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti-bromodeoxyuridine reaction and computed tomography.
 The mean bromodeoxyuridine (+/- SE) labeling index for 10 patients in an early histological stage (stage I, 4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly higher than that for 19 female patients with chronic aggressive hepatitis (0.9% +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001).
 The mean (+/- SE) liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3) was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001).
 These results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased DNA synthesis in hepatocytes.
",5
1057,"Glucose and fat metabolism during short-term starvation in cirrhosis.
 To evaluate the metabolic consequences of short-term (i.e., less than 24 hours) starvation, glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16-hour and again after 22-hour starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect calorimetry.
 Although patients and controls showed significant increases in free fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16- and after 22-hour starvation were higher in cirrhosis.
 Fat oxidation was enhanced in the patients, but did not increase during fasting in contrast to controls (increase 19% +/- 17%, P less than 0.05).
 Net glucose oxidation was decreased in postabsorptive cirrhotics (P less than 0.05).
 Although postabsorptive glucose turnover was not different from controls, starvation induced a greater decrease in glucose turnover in the patients (25% +/- 3% vs.
 10% +/- 3%, P less than 0.05).
 This was not reflected in plasma glucose concentrations.
 In conclusion, the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose.
 It remains to be established whether these changes are merely explained by defective liver function, per se.
",5
1058,"Ascites increases the resting energy expenditure in liver cirrhosis.
 The purpose of this study was to investigate the effect of ascites on the energy metabolism of patients with liver cirrhosis.
 The resting energy expenditure was determined in 10 patients with liver cirrhosis and ascites of moderate or large volume.
 The resting energy expenditure measurement was performed using indirect calorimetry and the resting energy expenditure predictive value was calculated with the Harris-Benedict equation, both before and after removal of ascitic fluid by paracentesis.
 Metabolic stress factors were absent in all cases.
 After an interval of 11.2 +/- 7.7 days between measurements, a weight loss of 16.6 +/- 10.3 kg was observed with paracentesis.
 The resting energy expenditure measured by indirect calorimetry showed a statistically significant decrease from 1682 +/- 291 to 1523 +/- 240 kcal/day (P less than 0.005) after removal of ascites.
 The repeatability of our indirect calorimetry method only allowed for the analysis of the results in 4 of 10 patients in whom ascites removal produced a consistent decrease in resting energy expenditure.
 There were no statistically significant differences between the measurements obtained by indirect calorimetry and those provided by the Harris-Benedict equation, but the latter had a moderate reliability in predicting the real resting energy expenditure of every patient.
 Our results suggest that, far from being an inert volume, ascites may be associated, at least in some patients, with an increased resting energy expenditure and therefore accelerate the appearance of protein energy malnutrition with corresponding complications.
",5
1059,"Incidence of gallstones in a Danish population.
 Five-year incidence of gallstone disease was assessed by ultrasonography in an age- and sex-stratified random population of Danish origin aged 30, 40, 50, and 60 years.
 The response rate was 82.8% (2987/3608).
 Nonrespondents did not differ from respondents regarding variables concerning gallstone disease.
 The 5-year incidence of gallstone disease in men aged 30, 40, 50, and 60 years was 0.3%, 2.9%, 2.5%, and 3.3%.
 Corresponding figures in women were 1.4%, 3.6%, 3.1%, and 3.7%.
 The incidence of gallstones was significantly higher in subjects aged 45 years or more compared with those aged 35 years.
 The sex difference in gallstone incidence decreased with increasing age.
 A significantly higher incidence of gallstone disease was found among subjects with former polyps in the gallbladder.
 Spontaneous disappearance of gallstones was seen in 4.5%.
",5
1060,"Prostaglandin E2-induced diarrhea in mice: importance of colonic secretion.
 The present study has investigated the basis for induction of diarrhea by prostaglandin (PG)E2 in mice.
 When given i.p., PGE2 induced a dose- and time-dependent diarrhea; the shortest post-treatment time for diarrhea onset was approximately 7 min, at a PGE2 dose of 200 micrograms/kg.
 At this dose, PGE2 also produced accumulation of fluid in the small intestine and in the colon (enteropooling).
 The enteropooling reached its maximum by 9 min and did not decrease until approximately 11 min (i.e., 2 to 4 min after the mean time for diarrhea onset).
 PGE2 treatment altered neither gastric emptying nor gastrointestinal propulsion, but strongly enhanced the expulsion of a glass bead from the colon (i.e., decreased the time to bead expulsion).
 The shortest time to expulsion of the glass bead was observed at 200 micrograms/kg i.p.
 The induction of diarrhea by PGE2 was unaffected by cecectomy, or sham-cecectomy, but the dose-response curve for time to onset of diarrhea by i.p.
 PGE2 was displaced to the right in animals with ligations of the ileo-ceco-colonic (ICC) junctions.
 The intraluminal fluid accumulation in the colon, evaluated in mice with ICC ligations, was increased by PGE2 administration within 2 min and remained greater than in vehicle-treated animals until the onset of diarrhea.
 The stimulation of colonic bead expulsion produced by i.p.
 PGE2 in control mice was not observed in animals with acute ICC ligations, even at i.p.
 doses up to 800 micrograms/kg.
",5
1061,"Enteroclysis and small bowel series: comparison of radiation dose and examination time.
 Respective radiation doses and total examination and fluoroscopy times were compared for 50 patients; 25 underwent enteroclysis and 25 underwent small bowel series with (n = 17) and without (n = 8) an examination of the upper gastrointestinal (GI) tract.
 For enteroclysis, the mean skin entry radiation dose (12.3 rad [123 mGy]) and mean fluoroscopy time (18.4 minutes) were almost 1 1/2 times greater than those for the small bowel series with examination of the upper GI tract (8.4 rad [84 mGy]; 11.4 minutes) and almost three times greater than those for the small bowel series without upper GI examination (4.6 rad [46 mGy]; 6.3 minutes).
 However, the mean total examination completion time for enteroclysis (31.2 minutes) was almost half that of the small bowel series without upper GI examination (57.5 minutes) and almost four times shorter than that of the small bowel series with upper GI examination (114 minutes).
 The higher radiation dose of enteroclysis should be considered along with the short examination time, the age and clinical condition of the patient, and the reported higher accuracy when deciding on the appropriate radiographic examination of the small bowel.
",5
1062,"Peptic ulcer disease: CT evaluation.
 The authors retrospectively describe the computed tomographic (CT) findings in 35 patients with peptic ulcer disease.
 Three of eight patients with gastritis or duodenitis had bowel-wall thickening.
 Ten of the remaining 27 patients had CT evidence of ulcer perforation (n = 2) or penetration (n = 8), four cases of which were unsuspected clinically.
 Both patients with acute free perforation had pneumoperitoneum, and one showed free extravasation of orally administered contrast material.
 The precise site of perforation could not be established in either case with CT.
 The eight patients with ulcer penetration had CT evidence of bowel-wall thickening (n = 3) and inflammatory changes in adjacent soft tissues and organs (n = 8), including the pancreas (n = 4), liver (n = 1), and lesser omentum (n = 1).
 Ulcer craters were seen in only two.
 The CT findings of penetration can mimic other disease processes.
 CT was not useful in detecting uncomplicated peptic ulcer disease.
",5
1063,"Diagnostic fine-needle puncture of the gallbladder with US guidance 
 From February 1988 to January 1990, 118 fine-needle diagnostic punctures of the gallbladder (DPG) were performed under continuous ultrasound (US) guidance on symptomatic patients with gallstones.
 The first attempt at gallbladder puncture and aspiration was successful in every patient with use of a 22-gauge needle and continuous US visualization of the needle tip.
 The aspirated volume varied between 3 and 88 mL (average +/- standard deviation, 25.0 mL +/- 15.3).
 Biliary analysis revealed an elevation of the cholesterol saturation index in patients with cholesterol gallstones (attenuation at computed tomographic examination of 50 HU or less) relative to that in patients with pigment stones (attenuation more than 50 HU) (1.3 +/- 0.2 vs 1.0 +/- 0.1, P less than .05).
 The nucleation time was prolonged in patients with pigment stones (19.3 days +/- 3.5 vs 1.8 days +/- 0.8 for patients with cholesterol stones, P less than .001).
 All patients remained hospitalized for 24 hours after DPG and were reexamined on an outpatient basis at 1 and 3 months thereafter.
 No complications were detected during either short-term observation or long-term follow-up.
 The authors conclude that DPG is a safe and valuable technique in the diagnostic work-up of gallstone patients to establish their suitability for nonoperative treatment.
",5
1064,"Asialoglycoprotein receptor function in benign liver disease: evaluation with MR imaging.
 An arabinogalactan-coated ultrasmall superparamagnetic iron oxide (AG-USPIO) preparation specific for asialoglycoprotein (ASG) receptors on hepatocytes was used as a magnetic resonance (MR) imaging contrast agent in the evaluation of a spectrum of benign liver diseases in animal models.
 The activity of hepatocyte ASG receptors, which directly reflects liver function, was directly assessed by measuring liver relaxation times in vitro and MR signal intensity in vivo.
 The following measurements allowed three-dimensional assessment of liver function: (a) liver relaxation time, (b) native MR signal intensities of liver, (c) response of liver to the AG-USPIO probe (percentage decrease of liver signal intensity after intravenous administration of 10 mumol/kg of AG-USPIO: normal liver 55%, fatty liver 57%, acute hepatitis 36%, chronic hepatitis 29%, and cirrhosis 46%), and (d) redistribution of hepatocyte-specific AG-USPIO to the spleen (present in hepatitis and cirrhosis but not in normal liver and fatty liver).
 The results of this study indicate that cellular hepatic abnormalities can be detected and quantitated with MR receptor imaging.
",5
1065,"Percutaneous rotational contact biliary lithotripsy: initial clinical results with the Kensey Nash lithotrite.
 The percutaneous rotary lithotrite introduces a new concept to fragmentation and percutaneous removal of gallstones.
 A fluid vortex is generated, pulling calculi into a high-speed blade that fragments stones to predominantly under 500 microns.
 The results of treating the first 10 patients with this instrument reveal that large stone burdens as well as small stones (2-3 mm) of any composition can be removed if the gallbladder is of sufficient size to accommodate the six-pronged basket.
 Rotation times of 7-39 minutes were required.
 Nine of 10 procedures were completed; access was lost in one case.
 One major complication occurred.
 At repeat oral cholecystography, the gallbladder was visualized after 3-6 weeks in eight of the nine patients.
 Ursodeoxycholic acid was administered from 3 to 12 months to five patients with either residual stones or aggregates.
 The hospital stay ranged from 48 to 72 hours.
 All patients (except the patient who underwent surgery) resumed light activity in 3-4 days and strenuous activity and full diet within 3 weeks.
",5
1066,"Sulphasalazine and prednisone compared with sulphasalazine for treating active Crohn disease. A double-blind, randomized, multicenter trial.
 OBJECTIVE: To determine whether sulphasalazine plus prednisone is more effective than sulphasalazine alone in treating active Crohn disease.
 DESIGN: Randomized, double-blind, placebo-controlled trial.
 SETTING: Multicenter trial in one university hospital and nine general hospitals.
 PATIENTS: Patients with active Crohn disease and a Van Hees Activity Index of 140 or more.
 Of 71 patients who were randomly assigned, 60 completed treatment and were analyzed.
 INTERVENTIONS: For 16 weeks, 30 patients received sulphasalazine, 6 g/d (or 4 g/d if adverse effects occurred) and prednisone, 30 mg/d initially.
 Prednisone therapy was tapered in increments of 5 mg/2 wk to 10 mg/d after 8 weeks.
 Thirty other patients received sulphasalazine and a placebo.
 MEASUREMENTS AND MAIN RESULTS: In the first 6 weeks of treatment, the Van Hees Activity Index decreased to a median of 70% (interquartile range, 57% to 81%) of the initial value in patients treated with sulphasalazine and prednisone and to a median of 87% (interquartile range, 70% to 94%) in patients treated with sulphasalazine alone (P = 0.001).
 In the last 4 weeks of treatment, the corresponding figures were 63% (interquartile range, 40% to 75%) and 70% (interquartile range, 54% to 90%) (P = 0.10).
 The Crohn's Disease Activity Index decreased in the first 6 weeks to a median of 65% (interquartile range, 57% to 86%) in patients receiving sulphasalazine and prednisone and to a median of 75% (interquartile range, 58% to 101%) in patients receiving sulphasalazine alone (P = 0.13).
 In the last 4 weeks of treatment, the corresponding figures were 65% (interquartile range, 42% to 90%) and 76% (interquartile range, 49% to 110%) (P = 0.19).
 CONCLUSIONS: The use of prednisone in addition to sulphasalazine in patients with active Crohn disease results in a significantly faster initial improvement, but not in a significantly better result after 16 weeks of treatment, when disease activity is measured by the Van Hees Activity Index.
",5
1067,"Management of an extensive tracheoesophageal fistula by cervical esophageal exclusion.
 Giant tracheoesophageal fistulae occurring in ventilator-dependent patients usually result in significant ventilatory embarrassment.
 Cervical exclusion of the fistula can safely control the fistula and quickly restore adequate ventilation to these critically ill patients.
",5
1068,"Medical treatment of esophageal achalasia. Double-blind crossover study with oral nifedipine, verapamil, and placebo 
 Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia.
 We performed a placebo-controlled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry.
 Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug.
 Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings.
 Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus.
 No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted.
 We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia.
",5
1069,"Management of dysphagia in suspected esophageal motor disorders 
 Fifty-three patients suffering from dysphagia because of suspected esophageal motor disorders were treated by pneumatic dilatation using the Rider-Moeller technique.
 Fifteen had achalasia demonstrated by manometric studies.
 Forty-nine of them had remarkable clinical improvement after the procedure.
 During the mean period of follow-up (average 5 years, range 1-11), 75% of the patients needed a new dilatation, with a delay of two years.
 The results of the dilatation were excellent or good in 80% of the cases.
 Early complications consisted in two esophageal perforations surgically treated.
 There was no mortality.
 We did not observe late complications of the procedure.
 We conclude that pneumatic dilatation should be the initial procedure in the treatment of dysphagia in suspected esophageal motor disorders.
",5
1070,"Reevaluation of manometric criteria for vigorous achalasia. Is this a distinct clinical disorder?
 Clinical and manometric data from 97 consecutive patients with idiopathic achalasia were analyzed to see if a distinct subset with vigorous achalasia could be identified.
 Statistical analyses failed to detect a unique group of subjects based on the distribution of contraction wave amplitudes alone.
 Because of this, patients falling above the 95th percentile (N = 4, mean wave amplitude greater than 100 mm Hg for each) were compared with those having mean amplitudes above the conventional threshold for the diagnosis of vigorous achalasia (mean amplitude 60-100 mm Hg, N = 4), and with the remainder (N = 89, mean amplitude less than 60 mm Hg).
 Subjects with mean amplitudes less than 60 mm Hg and with mean amplitudes 60-100 mm Hg closely resembled each other in all measured clinical features, whereas subjects with mean amplitudes greater than 100 mm Hg were all male, were older (67 +/- 4 years vs 47 +/- 2 years; P less than 0.01), and appeared to have somewhat longer duration of symptoms when compared with the remainder (82 +/- 41 vs 44 +/- 10 months; P = 0.4).
 Chest pain and other esophageal symptoms, basal and residual lower sphincter pressures, and response to first treatment did not differ among the three groups.
 These data indicate that high-fidelity manometry techniques identify a rare subset of achalasia patients with mean contraction amplitudes exceeding 100 mm Hg that, although older and possibly with greater duration of symptoms, presents similarly to others with idiopathic achalasia.
 Outcome from conventional treatment is also similar for the ""vigorous"" and ""nonvigorous"" patients, making the distinction of questionable value.
",5
1071,"Ulcerative colitis disease activity as subjectively assessed by patient-completed questionnaires following orthotopic liver transplantation for sclerosing cholangitis.
 To assess whether or not liver transplantation and subsequent immunosuppression with cyclosporine and prednisone affect ulcerative colitis symptomatology, we surveyed by questionnaire all 23 surviving patients with pretransplant colonoscopy-documented ulcerative colitis who were transplanted for primary sclerosing cholangitis between June 1982 and September 1985.
 At follow-up [89.8 +/- 7.6 weeks (mean +/- SEM], all six patients who had had asymptomatic colonoscopy-documented ulcerative colitis reported continued ulcerative colitis quiescence.
 Among the 17 patients who had had symptomatic colonoscopy-documented ulcerative colitis at time of liver transplantation, 88.2% reported improvement in overall ulcerative colitis severity (P less than 0.001), with significant improvement in the frequency of bowel movements reported by 100%, in crampy abdominal pain by 87.5%, in bowel urgency by 75%, in the occurrence of pus or mucus in stool by 87.5%, in the incidence of ulcerative colitis flares by 81.8%, and in the number of days unable to function normally due to ulcerative colitis symptoms by 78.6% (all at least P less than 0.01).
 These data demonstrate that ulcerative colitis symptom severity significantly improves following liver transplantation with immunosuppression with cyclosporine and prednisone.
",5
1072,"Carbon tetrachloride-induced alterations of hepatic calmodulin and free calcium levels in rats pretreated with chlordecone.
 Calmodulin, a low molecular weight Ca2+ binding protein, regulates a large number of cell activities including cell division.
 Previous studies from our laboratory indicated excessive accumulation of Ca2+ in hepatocytes succeeded by rapid glycogen breakdown and suppressed cell division in rats receiving CCl4 after previous dietary exposure to 10 ppm chlordecone.
 Since calmodulin plays a major role in Ca2(+)-regulated events and has been reported to be localized in mitotic apparatus during cell division, we have assessed subcellular distribution of calmodulin and estimated cytosolic phosphorylase a to indicate cytosolic free Ca2+ levels in livers of rats fed 0 ppm or 10 ppm (chlordecone) in the diet for 15 days before CCl4 (100 microliters/kg) administration to understand the role of Ca2(+)-calmodulin in chlordecone + CCl4 toxicity.
 Hepatotoxicity was assessed by determining serum AST and ALT succeeded by histopathological observations of liver sections.
 Serum aminotransferases were significantly elevated 6 hr after CCl4 administration to normal rats and returned to control level by 24 hr.
 However, serum AST and ALT elevations were severalfold higher, and progressive increase was observed starting 4 hr after CCl4 administration to chlordecone rats.
 Histopathological observations of liver sections for necrotic, swollen and lipid-laden cells provided findings commensurate with the serum enzyme data.
 These data indicate that normal rats do recover from CCl4 hepatotoxicity.
 However, the CCl4 hepatotoxicity is progressive in chlordecone rats without recovery.
 In normal rats, CCl4 administration resulted in a slight increase in phosphorylase a starting at 6 hr.
",5
1073,"Collagenous colitis as a cause of chronic diarrhea.
 When the usual workup for chronic diarrhea fails to provide a diagnosis and the endoscopic findings are normal, alternative etiologies must be considered.
 This case of collagenous colitis represents such an alternative diagnosis.
 The patient is a 65-year-old woman who complained of abdominal cramps and watery diarrhea for an 8-month span.
 The key element to her diagnosis was subepithelial collagen deposits of the mucosa of the colon.
 Her symptoms were resolved with supportive care, diet, and diphenoxylate.
 Essential features and treatment of collagenous colitis are reviewed.
",5
1074,"A simple score for the identification of patients at high risk of organic diseases of the colon in the family doctor consulting room. The Local IBS Study Group.
 In order to develop a scoring system for selecting patients at high risk of organic diseases of the colon, who would need a colonoscopy or a barium enema, we conducted a study with 14 GPs in the local health care district of Modena.
 Over one year, 254 consecutive patients who consulted their GP for chronic abdominal pain were asked to answer a guided questionnaire.
 A checklist of simple parameters suggestive of the presence of organic diseases of the colon was also registered by the GP.
 For the final diagnosis, the patients underwent either a colonoscopy or a barium enema.
 Data collected were analysed by means of a stepwise logistic regression analysis to obtain a weighted score for the diagnosis of either irritable bowel syndrome (score less than 0) or organic disease (score greater than 0).
 Out of the 25 parameters explored, six were significantly more common among patients with organic disease and weighted as positive score (namely ESR greater than 17 mm, first hour, history of blood in the stool, leukocytosis greater than 10,000 cm3, age greater than 45 years, slight fever and presence of neoplastic colonic diseases in first-degree relatives).
 On the contrary, five parameters were more frequent among patients with irritable bowel syndrome and weighted as negative score (namely visible distension of the abdomen, feeling of distension, presence of irritable bowel syndrome in first degree relatives, flatulence and irregularities of bowel movement).
 Our scoring system correctly classified 83.5% of the cases, and it was very sensitive (82.4%) for the diagnosis of organic disease.
",5
1075,"Breakdown of gastric mucus in presence of Helicobacter pylori.
 The potential of Helicobacter pylori to degrade gastric mucus was examined.
 Colonies of H pylori cultured from antral mucosal biopsy specimens of patients with non-autoimmune gastritis were washed with sterile saline, passed through a sterilisation filter, and the filtrate examined for urease, protease, and mucolytic activity.
 The filtrate failed to hydrolyse bovine serum albumin, or to degrade stable mucus glycoprotein structures of high particle weight that had been separated from human gastric mucus on Sepharose 2B.
 The high particle weight mucus glycoprotein was, however, extensively degraded when incubated with H pylori filtrate (which possessed urease activity) in the presence of 2 M urea, to release fragments of Mr approximately 2 X 10(6).
 The high particle weight mucus glycoprotein was also broken down to a comparable extent when incubated with Jack bean urease in the presence of 2 M urea, or 1 M ammonium carbonate, or 40 mM carbonate-bicarbonate buffer (pH 8.7), but not when treated with 4 M urea alone, or Jack bean urease alone.
 These results indicate that the loss of high particle weight mucus glycoprotein in gastric mucus from patients with gastritis and gastric ulcers is unlikely to be due to the mucolytic action of an extra-cellular protease produced by H pylori, but it may result from the destabilising effects of a carbonate-bicarbonate buffer, generated at the mucosal surface when H pylori urease hydrolyses transuded plasma urea.
",5
1076,"Valproate metabolism during hepatotoxicity associated with the drug.
 Plasma concentrations of valproate and certain of its metabolites and their patterns of excretion in urine are described in three adults who developed hepatotoxicity during treatment of epilepsy with sodium valproate.
 One patient also developed a degree of reversible renal insufficiency, whilst another may have had associated infectious mononucleosis.
 All three cases showed evidence of impaired mitochondrial beta-oxidation of valproate.
 In one the impairment was at the stage catalysed by fatty acyl-CoA dehydrogenase, in another at the stage catalysed by 3-hydroxyacyl-CoA dehydrogenase and in the third at the stage catalysed by enoyl-CoA hydratase and possibly also at the next stage catalysed by 3-hydroxyacyl-CoA dehydrogenase.
 The impaired beta-oxidation meant that valproate metabolism was diverted into various alternative pathways.
 Plasma concentrations of the suspected hepatotoxic metabolite 4-en-valproate were normal for the valproate-treated population in all cases.
 By analogy with certain spontaneous and acquired human disorders of branched chain amino acid metabolism, it is suggested that valproate-associated hepatotoxicity may represent the consequences of a valproate overload on a limited mitochondrial beta-oxidation capacity, causing accumulation of a toxic product of endogenous branched chain amino acid metabolism.
",5
1077,"Colon interposition for esophageal disease: histologic finding of colonic mucosa after a follow-up of 5 months to 15 years.
 Thirty-six patients, subjected to colon interposition for benign esophageal disease or carcinoma of the esophagus or gastric cardia, were studied by endoscopy for signs of mucosal disease in the interposed colon.
 Five months to 15 yr (mean 57 months) after the operation, endoscopic finding of the interposed colon was macroscopically normal in 28 patients.
 Signs of inflammation, including hyperemia or hyperemia and friability, were observed in seven patients.
 Histologic specimens obtained at endoscopy were examined microscopically, and the findings were compared with those seen in the preoperative graft.
 In two patients, chronic inflammatory changes were observed in the graft mucosa, consisting of mononuclear cell infiltration of the lamina propria accompanied by crypt dilatation and deformation.
 In one of these patients, the inflammation was in the proximal third of the graft, and it was also seen at the endoscopy.
 In the remaining 34 patients, the graft mucosa was microscopically comparable to normal.
 The alterations were unexpectedly few and mild considering the marked change in the location and function of the colonic segment.
",5
1078,"Gluten challenge in patients with celiac disease: evaluation of alpha 1-antitrypsin clearance.
 Our aim in this study was to monitor changes of the intestinal structure by alpha 1-antitrypsin clearance (alpha 1-ATCL) in order to offer an alternative to the gluten challenge biopsy.
 In addition, we evaluated the possibility of reducing the time of gluten challenge.
 Twelve patients had a presumptive diagnosis of celiac disease based on clinical and histological grounds.
 They were studied when the jejunal histology was normal after gluten-free diet and an alpha 1-ATCL was normal.
 The gluten was introduced by returning to a normal diet.
 The challenge lasted 4 wk.
 We measured alpha 1-ATCL at the end of the 1st and 4th wk, and a new jejunal biopsy was obtained at the end of the 4th wk.
 By wk 1, alpha 1-ATCL was abnormal in 11 patients but normal in one.
 By wk 4, alpha 1-ATCL was abnormal in 10 patients and still normal in one.
 The post-challenge biopsies showed atrophy in 11 and was normal only in the patient with normal alpha 1-ATCL at wk 1 and 4.
 One patient with abnormal alpha 1-ATCL had to stop the challenge at the first week.
 The patient with normal clearance at wk 1 and 4 and normal biopsy at wk 4 had abnormal results at 6 months.
 These data support our hypothesis that alpha 1-ATCL can be used as evidence of gluten toxicity after gluten challenge, and that this test can be abnormal as early as 1 wk after gluten is reintroduced.
",5
1079,"Gastric adaptive relaxation and symptoms after vagotomy.
 Gastric adaptive relaxation is reported to be impaired after vagotomy.
 This abnormality has been implicated in the pathogenesis of postvagotomy symptoms, but no association has previously been demonstrated between the two.
 Gastric adaptive relaxation was measured in 15 healthy volunteers and 33 patients more than 1 year after highly selective vagotomy or truncal vagotomy and drainage.
 Seventeen patients were asymptomatic.
 The remainder were symptomatic including seven patients with persistent diarrhoea.
 Fasted subjects were intubated with a Ryle's tube containing a pressure microtransducer within a flaccid (800 ml) plastic bag.
 Gastric corpus-fundus pressure was recorded during distension of the bag with air (15 ml/s) over 30 s.
 Pressure indices were derived from the areas under the pressure curves.
 Median (range) pressure indices were: healthy volunteers 12.7 (7.5-17.1) cmH2O, highly selective vagotomy 14.0 (9.8-15.9) cmH2O (n.s.), truncal vagotomy and drainage 14.5 (8.6-26.8) cmH2O (P = 0.04).
 All patients with diarrhoea had abnormally high pressure indices (P less than 0.001).
 Pressure indices in all other patient groups were within the normal range.
 We conclude that gastric adaptive relaxation remains abnormal in patients with postvagotomy diarrhoea but not in those who are asymptomatic or who have other symptoms.
",5
1080,"Advantages of a narrow-range, medium molecular weight hydroxyethyl starch for volume maintenance in a porcine model of fecal peritonitis 
 OBJECTIVE: To compare the effectiveness of two hydroxyethyl starch solutions of different molecular weight ranges for volume maintenance in a porcine model of fecal peritonitis.
 DESIGN: Randomized prospective trial.
 SETTING: Laboratory investigation.
 SUBJECTS: Adolescent female pigs weighing approximately 30 kg.
 INTERVENTIONS: We compared diafiltered 6% pentastarch with 6% high molecular weight hetastarch for volume maintenance in a porcine model of fecal peritonitis.
 The number average molecular weight of pentastarch is higher than hetastarch, although the weight average molecular weight is lower, i.e., a narrow range of medium weight molecules.
 The infusion rate of each agent was adjusted to maintain baseline arterial Hct for less than or equal to 7 hr after instrumentation and induction of fecal peritonitis.
 MAIN OUTCOME MEASUREMENTS: The volume of fluid required to maintain arterial Hct was compared along with comparisons of hemodynamic and histologic responses associated with the two agents.
 RESULTS: Significantly less pentastarch was required to prevent hemoconcentration than hetastarch (109 +/- 22.8 vs.
 150 +/- 10.3 mL/kg; p less than .05) while hemodynamics, colloid osmotic pressure, and oxygen transport responses were similar.
 Capillary patency was greater (21.99 +/- 3.68 vs.
 10.09 +/- 1.17%; p less than .05) and mean alveolar capillary barrier thickness was less (2.36 +/- 0.13 vs.
 3.06 +/- 0.17 microns; p less than .05) with pentastarch than with hetastarch, as judged by electron microscopy.
 CONCLUSIONS: These data suggest that pentastarch is better retained in the circulation in capillary leak syndromes compared with hetastarch.
",5
1081,"Incontinence and rectal prolapse: a prospective manometric study.
 A prospective, manometric study has been performed on 23 female patients with rectal prolapse and varying degrees of incontinence.
 Seven of the 14 incontinent patients regained continence after surgery, and a further two patients improved.
 Improvement in internal and external sphincter function follows correction of rectal prolapse.
 Preoperative resting anal pressure was significantly higher in continent patients than in incontinent patients (P less than 0.05), as was the maximum voluntary contraction pressure (P less than 0.027).
 Postoperatively there was a significant increase in the resting anal pressure (P less than 0.0001) and maximum voluntary contraction pressure (P less than 0.003) in the whole group.
 The preoperative resting anorectal angle was significantly more acute (P less than 0.028) in continent patients than in incontinent patients.
 There was no significant change in the resting anorectal angle following prolapse repair.
 Patients who remained incontinent had a significantly lower preoperative resting anal pressure (P less than 0.01) than patients who improved or regained continence.
 Similarly, maximum voluntary contraction pressure was lower preoperatively in these patients (P less than 0.02).
 Preoperative resting anal pressure below 10 mm Hg and maximum voluntary contraction pressure below 50 mm Hg are associated with persisting incontinence after surgery.
",5
1082,"Vascular responsiveness in obstructed gut.
 Multiorgan system failure due to hypotension and sepsis is an important cause of death in patients with bowel obstruction.
 We have investigated the pathophysiology of this entity in an animal model.
 After 5 days of bowel obstruction, blood flow in the superior mesenteric artery was measured with and without Pitressin and norepinephrine given in separate experiments.
 In controls, Pitressin in moderate dosages caused a substantial fall in gut blood flow, which was not seen in obstructed animals (blood flow reduction 52 percent vs.
 11 percent in sham and obstructed animals respectively, P less than 0.01).
 Similarly, norepinephrine infusion had less of an effect on gut blood flow in obstructed animals (blood flow reduction 79 percent vs.
 58 percent sham vs.
 obstructed animals (P less than 0.05).
 Thus, both agents had dose-related effects on gut blood flow, which was maintained at a higher level throughout the drug infusion periods in the bowel of obstructed animals, demonstrating that splanchnic flow is less responsive to vasoactive drug infusion under these experimental conditions.
 Because splanchnic vasoconstriction is an important feature of normal hemodynamic homeostasis, we suggest that these results may help explain some aspects of the pathophysiology of multiorgan failure caused or worsened by systemic hypotension seen in bowel obstruction.
",5
1083,"Development and application of an in vitro model for screening anti-hepatitis B virus therapeutics.
 The development of effective anti-hepatitis B virus agents has been hampered by the lack of reliable in vitro systems for the screening of new therapeutics.
 In an effort to circumvent this problem, we have developed an in vitro system for screening anti-hepatitis B virus drugs using hepatitis B virus DNA-transfected Hep G2 cells.
 The cell line designated 2.2.15 produces replicative viral DNA intermediates, mature Dane particles and high levels of viral antigens.
 Subconfluent 2.2.15 cells were treated with a variety of commonly used anti-hepatitis B virus therapeutics, and their efficacy was determined by analyzing changes in the replicative cellular or extracellular hepatitis B virus DNA content by Southern blotting or slot-blot hybridization.
 The slot-blot method was sensitive, reproducible and rapid and correlated well with Southern blotting.
 Analysis of the media for hepatitis B virus DNA was indicative of changes in intracellular, replicative hepatitis B virus DNA, permitting sampling of the media.
 Therefore 2.2.15 cells may provide a valuable method for identifying and monitoring effective anti-hepatitis B virus therapeutics.
 Using this system to test various agents, we confirm that 2'-deoxyguanosine strongly inhibited viral replication, whereas others tested were less effective.
 Correlation with in vivo systems is now needed.
",5
1084,"Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: a simplified method.
 The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass.
 The clinical feasibility of the test has so far been limited by methodological problems.
 A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis.
 The method was based on only four consecutive 2-hr urine collections and five blood samples.
 Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis).
 Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis.
 Urea-nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005.
 The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a well-established, quantitative, liver function measure.
 The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use.
 The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy.
",5
1085,"Autoantibodies in primary biliary cirrhosis: analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes.
 Six components of the mammalian 2-oxo acid dehydrogenase complexes have previously been identified as M2 autoantigens in primary biliary cirrhosis.
 In this report, we present data showing that both polypeptide-specific and cross-reacting antibodies are present in patients' sera.
 Antibodies reacting with E2 of the pyruvate dehydrogenase complex cross-react with protein X but not with any other mammalian antigen.
 The main immunogenic region on protein X has been localized to within its single lipoyl domain.
 Polypeptide-specific antibodies bind to E1 alpha and E1 beta of the pyruvate dehydrogenase complex.
 Antibodies reacting with the E2 polypeptides of the 2-oxoglutarate dehydrogenase complex and branched-chain 2-oxo acid dehydrogenase complex show some cross-reactivity but do not recognize any of the antigens of the pyruvate dehydrogenase complex.
 Antibodies against the E2 component of the mammalian pyruvate dehydrogenase complex cross-react effectively with the corresponding protein from yeast but not with E2 from Escherichia coli.
 Antibody titer against mammalian antigens is significantly higher than against the bacterial antigens, arguing against a bacterial origin for primary biliary cirrhosis.
",5
1086,"Quantitation of intrinsic drug-metabolizing capacity in human liver biopsy specimens: support for the intact-hepatocyte theory.
 Hepatic drug metabolism is decreased in patients with severe liver disease, but it is unclear to what extent this is due to altered hepatic blood flow or reduced intrinsic metabolic capacity.
 In this study we quantitated in needle-biopsy specimens the intrinsic capacity of liver tissue from 67 patients with mild liver disease (n = 36), chronic active hepatitis (n = 16) and cirrhosis (n = 15) to metabolize two model compounds in vitro.
 Hydroxylation of the low-extraction drug bufuralol resulted in the formation of 251 +/- 25 nmol 1'OH-bufuralol/gm wet wt/hr in mildly diseased liver tissue and was significantly (p less than 0.01) reduced in liver tissue exhibiting chronic active hepatitis (166 +/- 23 nmol/gm wet wt/hr) and cirrhosis (124 +/- 21 nmol/gm wet wt/hr).
 The formation rates of monoethylglycinexylidide, the main metabolite of the high-extraction drug lidocaine, varied widely and were not significantly different among the three groups.
 To relate the drug-metabolizing capacity to the hepatocyte content of liver tissue, morphometrical study was performed in the biopsy pieces originally submitted.
 The metabolic activity of each biopsy piece was then related to the fractional volume of hepatocytes it was calculated to contain.
 In mildly diseased liver tissue 355 +/- 35 nmol 1'OH-bufuralol/ml hepatocytes x hr or 12.4 +/- 1.0 mumol monoethylglycinexylidide/ml hepatocytes x hr- and in cirrhotic liver tissue 306 +/- 49 nmol 1'OH-bufuralol/ml hepatocytes x hr or 15.3 +/- 3.0 mumol monoethylglycinexylidide/ml hepatocytes x hr--were formed, respectively, and these differences were not significant.
",5
1087,"In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model.
 To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats.
 The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L.
 Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase.
 Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001).
 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats.
 No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005).
 Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005).
 Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone.
 Partial hepatectomy was also without effect on the activation of D3.
 Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers.
 The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
",5
1088,"Rapid induction of hepatic fibrosis in the gerbil after the parenteral administration of iron-dextran complex.
 The parenteral administration of iron-dextran complex to gerbils caused hepatic hemosiderosis and fibrosis after 6 wk.
 Type I and III collagen synthesis in the liver developed from perisinusoidal stellate cells that are often referred to as myofibroblasts.
 Immunohistologically these cells were shown to have large intracellular deposits of ferritin.
 The hepatic fibrosis appeared to be associated with aggregates of these cells rather than the aggregates of Kupffer cells, which also occur in hemosiderosis in the liver.
 No appreciable necrosis of hepatocytes to trigger the fibrotic response was found, so that the fibrosis appeared to be related to the accumulation of ferritin in the perisinusoidal stellate cells.
 In contrast, rats and mice did not accumulate ferritin in their perisinusoidal cells or develop hepatic fibrosis in response to parenterally administered iron, although they accumulated similar or greater amounts of total iron in their livers.
 The rapid induction of hepatic fibrosis in gerbils in response to parenterally administered iron will provide a model to investigate the mechanism of induction of collagen deposition in response to iron overload and a means of quickly evaluating therapeutic treatments for iron overload-induced fibrosis in vivo using iron-chelating drugs.
",5
1089,"Regulation of collagen production in freshly isolated cell populations from normal and cirrhotic rat liver: effect of lactate.
 Previous work has shown that lactic acid, and to a lesser extent pyruvic acid, is able to increase collagen synthesis significantly in liver slices of CCl4-treated rats but not normal rats.
 The purpose of this report is to document which cells in the cirrhotic liver are responsible for the lactate-stimulated increase in collagen synthesis.
 It was found that (a) incorporation of 3H-proline into protein-bound 3H-hydroxyproline is increased threefold to fourfold in hepatocytes from CCl4-treated rats as compared with normal rat hepatocytes; (b) neither the hepatocytes from normal nor those from CCl4-treated rats modify their collagen synthesizing capacity when 30 mmol/L lactic acid was added to the incubation medium; (c) nonparenchymal cells obtained from livers of CCl4-treated rats synthesize much less collagen than hepatocytes, but their synthesis is stimulated twofold by lactic acid; (d) from the different nonparenchymal cells, only fat-storing (Ito) cells increase collagen synthesis when lactic acid is present in the incubation medium.
 These results suggest that the increased lactic acid levels observed in patients with alcoholic hepatic cirrhosis may play an important role in the development of fibrosis by stimulating collagen production by fat-storing (Ito) cells.
",5
1090,"Apical secretion of lysosomal enzymes in rabbit pancreas occurs via a secretagogue regulated pathway and is increased after pancreatic duct obstruction.
 Lysosomal hydrolases such as cathepsin B are apically secreted from rabbit pancreatic acinar cells via a regulated as opposed to a constitutive pathway.
 Intravenous infusion of the cholecystokinin analogue caerulein results in highly correlated apical secretion of digestive and lysosomal enzymes, suggesting that they are discharged from the same presecretory compartment (zymogen granules).
 Lysosomal enzymes appear to enter that compartment as a result of missorting.
 After 7 h of duct obstruction is relieved, caerulein-stimulated apical secretion of cathepsin B and amylase is increased, but the ratio of cathepsin B to amylase secretion is not different than that following caerulein stimulation of animals never obstructed.
 These findings indicate that duct obstruction causes an increased amount of both lysosomal and digestive enzymes to accumulate within the secretagogue releasable compartment but that duct obstruction does not increase the degree of lysosomal enzyme missorting into that compartment.
 Pancreatic duct obstruction causes lysosomal hydrolases to become colocalized with digestive enzymes in organelles that, in size and distribution, resemble zymogen granules but that are not subject to secretion in response to secretagogue stimulation.
 These organelles may be of importance in the development of pancreatitis.
",5
1091,"Laparoscopic cholecystectomy 
 Laparoscopic cholecystectomy is a new endoscopic technique that has diffused throughout the surgical community with great rapidity.
 Although the DATTA panelists considered the procedure appropriate with respect to both its safety and effectiveness, recognition was made that there are no comparative trials of this technique vs open cholecystectomy and virtually no literature on complication rates.
 The Society of American Gastrointestinal Endoscopic Surgeons has developed minimal credentialing criteria for determining competence in laparoscopic surgery.
 This includes completion of an approved residency training in general surgery, training in laparoscopic technique either by a surgeon experienced in this procedure or by completion of an approved course in the technique requiring hands-on laboratory practice, and observation or proctoring of an actual surgical procedure.
 Many of the DATTA panelists (35 of 40 [87.5%]) reiterated the importance of requiring that the procedure be performed first with animals and that subsequent laparoscopic procedures on patients be done under the supervision of an expert in laparoscopic cholecystectomy.
",5
1092,"Abnormal liver enzyme levels. Evaluation in asymptomatic patients.
 Chronic elevation of serum aminotransferase levels, even in the absence of symptoms, often reflects chronic hepatitis or other significant underlying liver disease.
 Patients with persistently abnormal alkaline phosphatase levels may have extrahepatic biliary tract disease or a chronic cholestatic disorder.
 Physicians can discover unsuspected liver disease without undue risk, expense, or inconvenience to the patient by means of the following: a carefully taken history and thorough physical examination, appropriate timing of follow-up blood tests, and timely referral for percutaneous liver biopsy or endoscopic retrograde cholangiopancreatography.
",5
1093,"Pancreatic pseudocysts. When to drain, when to wait.
 Acute pain in the upper abdomen in a patient recovering from pancreatitis or abdominal trauma may herald a pancreatic pseudocyst.
 Although small cysts resolve spontaneously, those larger than 6 cm across usually require treatment to prevent such complications as rupture into adjacent structures and infection.
 The authors describe operative and nonoperative treatment methods and the success reported with each.
",5
1094,"Peptic ulcer disease. How to treat it now.
 Options for treatment of peptic ulcer disease are becoming more diverse.
 Most new agents are effective yet offer no real advantage over more traditional therapy.
 However, omeprazole (Prilosec) may be of benefit owing to its potent inhibition of acid secretion, but it is not yet approved for this purpose.
 Whether treatment of Helicobacter pylori infection will prove beneficial is not yet known, but the answer should be forthcoming.
 Finally, as with any disease process, alleviation of risk factors is always important.
 Appropriate counseling regarding use of nonsteroidal anti-inflammatory drugs and cigarette smoking is a necessity.
",5
1095,"Laparoscopic cholecystectomy.
 With more than 500,000 cholecystectomies performed per year, great interest has developed in laparoscopic cholecystectomy.
 The procedure offers the patient reduced hospital stay, faster return to work, less pain, and improved cosmetic results.
 In September 1988, we developed a technique of performing laparoscopic cholecystectomy that we have now performed in more than 800 cases with good results.
 The technique allows the surgeon to fully evaluate the common duct via operative cholangiography and has allowed us to use a laparoscopic approach in all patients who were candidates for cholecystectomy.
 The technique offers a minimally invasive alternative to open cholecystectomy.
",5
1096,"The Los Angeles experience with laparoscopic cholecystectomy.
 Surgeons should be competent in diagnostic laparoscopy before performing laparoscopic cholecystectomy (LC).
 Well-structured and endorsed courses with experienced faculty are important.
 Within 12 months, 418 LCs were performed in our hospital.
 The number of open cholecystectomies decreased to one third of all cholecystectomies performed.
 Cholangiography was attempted routinely and the duct was successfully cannulated in 90%.
 Inquiries were made at 6 other hospitals within a 5-mile radius where a total of 220 LCs were performed.
 The following gray areas need to be addressed: patients with slightly increased liver function tests but no jaundice, and unsuspected stones discovered by cholangiography.
 New projects are in progress to explore the common bile duct via the cystic duct or directly through the common bile duct with insertion of a T tube.
 The authors recommend proper training as well as caution and sound judgment before commencing with LC.
",5
1097,"Training, credentialling, and granting of clinical privileges for laparoscopic general surgery.
 Despite the lack of scientific data comparing it with traditional open operations, laparoscopic surgery has gained rapid acceptance and implementation by general surgeons.
 Individual hospitals, which have the responsibility for developing their own privileging criteria, are searching for guidance as to the amount and type of additional training required to grant clinical privileges in laparoscopic general surgery.
 Laparoscopic surgery involves techniques different from those learned during general surgery residency training.
 Therefore, until such techniques are regularly included in general surgery residency programs, additional training for and granting of separate privileges in laparoscopic surgery are appropriate.
 Adequate training for surgeons already experienced in abdominal and biliary tract surgery can be acquired through a preceptorship in diagnostic laparoscopy, attending a course in laparoscopic surgery that includes both didactic instruction and live animal experience, assisting with the procedures in humans, and being proctored and certified as competent by an experienced general surgeon.
",5
1098,"Atracurium decay and the formation of laudanosine in humans.
 Several groups of investigators have reported that the plasma concentrations of laudanosine, a metabolite of atracurium, are high immediately after administration of atracurium and thereafter decline.
 Such a time profile of a metabolite in plasma is very unusual.
 The authors describe a model of atracurium decay and laudanosine disposition that satisfactorily explains these data.
 The model reveals the following: 1) each atracurium molecule is degraded into two of laudanosine; 2) the generation of laudanosine occurs through two processes--a rapid one, involving approximately 31% of the atracurium dose and proceeding with a half-life of 0.25 min, and a slower one, involving the residual 69% and proceeding with a half-life of 51 min; 3) atracurium degradation by Hofmann elimination proceeds in the central and the noncentral compartments; 4) laudanosine formed from atracurium gains access to its central compartment and disappears from plasma in a biexponential pattern; 5) in cirrhotic patients, only 18% of the atracurium dose is degraded rapidly and laudanosine is disposed of more slowly.
 The authors propose that the rapid degradation of atracurium in plasma proceeds through a nucleophilic substitution reaction, with plasma nucleophiles substituting for the laudanosine moiety in atracurium.
 Because both laudanosine moieties in atracurium are required to establish and sustain plasma concentrations of laudanosine, excretion of atracurium or its degradation through pathways not generating laudanosine must be small.
",5
1099,"A comparative study of temporomandibular symptoms following mandibular advancement by bilateral sagittal split osteotomies: rigid versus nonrigid fixation.
 Rigid fixation to attach proximal and distal segments during bony healing of osteotomy sites has become increasingly popular.
 The effects of rigid fixation on the temporomandibular joints have been questioned.
 The purpose of this study was to evaluate the effects of rigid fixation after bilateral sagittal split osteotomies on temporomandibular dysfunction symptoms.
 Forty patients who had mandibular advancement surgery were evaluated for temporomandibular joint dysfunction.
 Twenty had received rigid fixation, and twenty had received nonrigid fixation.
 It was determined that there was no statistically significant difference in temporomandibular signs or symptoms between patients who were treated with rigid internal fixation for bilateral sagittal split osteotomies for mandibular advancement and those patients who were treated with nonrigid wire fixation.
",6
1100,"A retrospective evaluation of 301 TMJ Proplast-Teflon implants.
 A retrospective review of 301 meniscectomies with Proplast-Teflon implants was performed.
 Factors such as interincisal opening, occlusion, joint sounds, joint degeneration, and patient satisfaction were examined.
 The overall surgical success rate was 88.7%, with an average follow-up period of 33 months.
 Although many patients demonstrated significant condylar degeneration at 1-year follow-up, such change did not necessarily result in symptomatology or joint dysfunction.
 Only 10% of implants resulted in removal.
 Surgical and postoperative procedures are contrasted with those of other clinicians experiencing lower success rates.
",6
1101,"Microleakage associated with retrofilling of the apical two thirds with amalgam.
 In this investigation the effect of increasing the thickness of amalgam retrofilling on its sealing ability was studied and compared with the sealing ability of the laterally condensed gutta-percha with a sealer.
 The apical two thirds of the canals of 118 upper central incisors, filled with laterally condensed gutta-percha, were sealed with amalgam.
 Amalgam retrofills were also used to seal the apices of the roots of six teeth that had no other filling in their canals.
 The effectiveness of both techniques was determined by their ability to inhibit the penetration of methylene blue dye for the periods of 24 hours, 1 week, and 1, 3, and 6 months.
 At 24 hours both materials showed comparable sealing ability.
 However, the sealing ability of laterally condensed gutta-percha was significantly better than that of amalgam from the 1-week period until the end of the study.
 The depth of marginal penetration around both materials increased with time.
 The amount of the dye penetration increased acutely around amalgam, whereas its increase around gutta-percha was more uniform.
 At the end of the study, specimens retrofilled with amalgam exhibited total dye penetration that exceeded the full thickness of amalgam (6 mm) and spread into the root canal space.
 On the other hand, the mean value for marginal penetration of the dye around the laterally condensed gutta-percha was 2.6 mm at the end of the study.
 The present investigation proved beyond doubt that the use of any thickness of retrograde amalgam to seal the apex, with no other filling within the canal, invites failure.
",6
1102,"Prevalence of shovel-shaped incisors in Saudi Arabian dental patients.
 The prevalence of maxillary incisor shoveling was studied radiographically in 990 Saudi patients.
 According to the radiomorphologic characteristics, a new classification was developed and shovel teeth were categorized.
 The findings of this study showed 9% shovel-shaped incisors; among those, 4% were central incisors and 5% were lateral incisors.
 Frequency of dens invaginatus occurrence with the shovel-shaped incisors was also investigated.
 Eight percent of shovel-shaped incisors showed presence of dens invaginatus.
 Prevalence was found to be 4% in central shovel-shaped incisors, whereas that in lateral shovel-shaped incisors was 11%.
",6
1103,"One-stage closure of the entire primary palate.
 Timing of the closure of the anterior palate and alveolus is a subject of debate.
 Late repair of this defect is complicated by high fistula formation and subjects the patient to the problems of palate fistula for extended periods of time.
 We have utilized a single procedure performed when the child is 3 months of age that completely closes the anterior hard palate and alveolus along with the cleft lip.
 Our series consisted of 61 consecutive patients with unilateral clefts of the primary and secondary palate.
 Mucosal turnover flaps from the vomer along with lateral nasal mucosal flaps provide the nasal lining.
 A buccal sulcus flap with a Veau flap completes the oral repair.
 Ninety-five percent (58 of 61) of the patients had complete and stable closure of their anterior palate and alveolus after 1 year.
 The incidence of fistula formation in our series (3 of 61) is much lower than that reported with the utilization of other protocols.
 Excellent exposure of the anterior palate and alveolar defect during lip repair, early restoration of anatomic relationships, establishment of a good nostril floor and sill, and very low fistula formation are among the benefits of this procedure.
 The increase in operative time is considered minimal in light of aforementioned advantages.
",6
1104,"Congenital lateral cleft palate: a new anomaly?
 A case of atypical cleft palate abnormality that had not been identified before in a 9-year-old girl is presented.
 The cleft was localized laterally and in an oblique position at the soft palate.
 The patient had cleft palate repair.
 Finally, she had acceptable soft palate movements and speech.
",6
1105,"The surgical treatment of noma.
 Noma is a gangrenous stomatitis affecting children from developing countries.
 It may leave dreadful mutilations around the mouth, with amputation of the lips, cheek, nose, lids, maxilla, palate, or mandibula.
 Reconstruction should take into account the size of the defect, the presence of trismus or constriction of the mandible, the age of the child, and the child's general condition.
 During the last 3 years, eight patients were treated at the Unit of Plastic and Reconstructive Surgery of the Hopital Cantonal Universitaire.
 Except in one case, tracheostomy was avoided, thanks to intranasal intubation by fibroscopy.
 These children, aged 2 to 9 years, underwent 31 general anesthesias and complex reconstructive procedures, including latissimus dorsi musculocutaneous pedunculated and free flaps, cranial flaps with galea, cranial bone and skin grafts, and retroauricular temporal skin flaps.
 All patients were able to return to Africa with dramatic functional and cosmetic improvements.
 However, satisfactory mouth opening and mandibular function were not always obtained.
",6
1106,"Maintenance of condyle-proximal segment position in orthognathic surgery.
 Twenty patients underwent bilateral sagittal ramus osteotomy for the correction of mandibular retrognathia.
 A condylar positioning device (CPD) was used intraoperatively in 10 patients to maintain preoperative condyle-proximal segment position, while the CPD was not used in the other 10 patients.
 Postoperatively, the condyle-proximal segment positions in both groups were compared and evaluated for vertical, horizontal, and rotational changes.
 A significant improvement (P less than .05) was observed in the vertical and horizontal condylar position in the group in which the CPD was used.
 However, there was no significant difference in proximal segment rotation.
",6
1107,"The potential of periodontal pocket formation associated with untreated accessory root canals.
 Teeth that were to be extracted because of periodontic-endodontic involvement, in six patients, were treated by hemisection or root amputation.
 The roots were processed histologically.
 All cases showed the presence of accessory root canals with remnants of pulpal tissue, bacteria, and necrotic debris.
 It was demonstrated in the cases studied that residual necrotic tissue in untreated root canals can result in periradicular pathosis.
 We may speculate that if the inflammatory process persists and drainage results via the sulcus, in time, plaque and then concretions may develop.
",6
1108,"A retrospective clinical study of endodontically treated mandibular incisors in a selected Chinese population.
 Clinical studies of incidences of the number of canals in human teeth should correlate with the percentages obtained in laboratory samples.
 In this study the incidence of two canals in the mandibular incisors was compared with figures obtained from in vitro extracted teeth, as well as from one clinical study.
 A very low percentage was obtained from the examination of clinical records, and this could be due to racial differences in the samples examined.
",6
1109,"Cross-sectional tomography. A diagnostic technique for determining the buccolingual relationship of impacted mandibular third molars and the inferior alveolar neurovascular bundle.
 Twenty-two patients with 31 impacted mandibular third molars were examined with a new, precise, cross-sectional tomographic technique to assess the radiographic size, shape, branching pattern, location, and degree of cortication of the mandibular canal, and the inclination of impacted mandibular third molars in the buccolingual plane.
 The mandibular canal, including bifid canals, was accurately identified in 30 cases (96.8%).
 The cross-sectional appearance of the canal was an uncorticated, or partially corticated, radiolucent oval that measured on average (+/- SD) 2.9 +/- 0.7 x 2.5 +/- 0.6 mm in diameter.
 It was located more frequently (45.2%) on the buccal aspect of the impacted mandibular third molar.
 About 60% of the mandibular canals notched the inner cortical plate of the mandible or the third molar root surface.
 Cystic expansion and quantification of cortical bone destruction were readily assessed by this technique.
 It was concluded that diagnostic information obtained from cross-sectional tomograms significantly aids the oral and maxillofacial surgeon during the preoperative diagnostic workup and that the radiation risks are comparable to those of other accepted localization techniques.
",6
1110,"An assessment of salivary function in healthy premenopausal and postmenopausal females.
 The elderly represent the most rapidly growing segment of the U.S.
 population, and the majority of this group are females.
 The average woman can anticipate living about a third of her life beyond menopause, and many U.S.
 women undergo hormonal replacement in an attempt to relieve menopausal symptoms.
 Little is understood about the relationship between menopause, hormonal replacement therapy, and the oral structures, although oral discomfort, xerostomia, and salivary hypofunction have been associated with postmenopausal women.
 The effects of menopausal status and estrogen therapy on subjective reports of oral dryness and discomfort and objective measurements of major salivary gland output were assessed in 43 healthy premenopausal and postmenopausal females.
 No complaints of xerostomia or burning mouth and no alterations in the quantity of saliva occurred in this population.
 This study suggests that among healthy women salivary gland function is not significantly influenced by menopause or hormonal replacement therapy.
",6
1111,"Randomized, double-blind trial of mazindol in Duchenne dystrophy.
 There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy.
 We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy.
 Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo.
 The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05.
 Mazindol did not benefit strength at any point in the study.
 Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients.
 The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups.
 Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed.
 Mazindol doses not slow the progression of weakness in Duchenne dystrophy.
",6
1112,"Sensitivity restored of Class V abrasion/erosion lesions.
 The effectiveness of restorative treatment in reducing sensitivity associated with the Class V erosion/abrasion lesion was evaluated and the efficacy of three tooth-colored restorative materials in reducing sensitivity was compared.
 The 108 lesions were restored with either glass ionomer restorative material, composite resin with a dentin bonding agent, or composite resin with a dentin bonding agent and a glass ionomer liner.
 Composite resin with glass-ionomer liner restorations significantly reduced sensitivity to air and hot and cold water.
 Glass ionomer restorations and restorations with composite resin and a dentin bonding agent significantly reduced sensitivity but were also associated with increased sensitivity to air and cold respectively in 20% to 30% of the lesions restored when evaluated at 6 months.
",6
1113,"Microleakage at gingival dentin margins of Class V composite restorations lined with light-cured glass ionomer cement.
 This study compared the microleakage of light-cured and auto-set glass ionomer liners used in Class V composite laminated glass ionomer restorations by determining the amount of microleakage at the gingival cementum/dentin margins.
 Standardized nonundercut V-shaped Class V cavities with gingival margins below the cementoenamel junction were prepared on the mesial and distal surfaces of 40 molars, establishing a total of 80 cavities, which were randomly divided into four groups.
 Each was lined with glass ionomers: group 1, Ketac-Bond (ESPE-Premier), which served as the control; group 2, XR-Ionomer (Kerr); group 3, XR-Ionomer with polyacrylic acid (PAA) pretreatment (Kerr); and group 4, Vitrabond (3M).
 Specimens were thermocycled for 300 cycles in 0.5% aqueous solution of basic fuchsin between 4 and 55 C with a 1-minute dwell time, and individually embedded in an epoxy resin.
 Statistical analysis indicated no differences among groups using the light-cured glass ionomer (groups 2 to 4), and they showed significantly less leakage than the control (group 1) at P less than 0.00001).
 Removal of the smear layer using 10% polyacrylic acid solution did not influence microleakage in restorations with light-cured glass ionomer liners.
",6
1114,"Effect of endodontic access preparation on resistance to crown-root fracture.
 This investigation involved the creation of coronal-radicular fractures in vitro and compared the fracture resistance of intact human mandibular molars, with molars after varied tooth preparation.
 Forty freshly extracted, non-carious, nonrestored human mandibular molars were randomly divided into four treatment groups.
 The molars were subjected to constantly increasing occlusal load until coronal-radicular fracture occurred.
 Tooth preparations significantly diminished resistance to coronal-radicular fracture.
",6
1115,"Extraoral parotid sialolithotomy.
 The extraoral approach to duct surgery for the removal of parotid stones can be a simple procedure once the stone is accurately located in relation to the skin surface.
 The combination of sialography and sonography can provide this information.
 A case report demonstrates the step-by-step approach to diagnosis, localization, and surgery for the management of such extraglandular sialoliths.
",6
1116,"Indications for simultaneous orthognathic and septorhinoplastic surgery.
 Orthognathic and rhinoplastic surgery can be combined successfully when certain guidelines are understood.
 Relative indications and contraindications have been established that generally yield predictable results.
 Tip position (rotation and projection) may be the most difficult aspect to predict and, therefore, is best avoided during simultaneous surgery.
 Major deformities of the dorsum can be easily corrected in conjunction with maxillary surgery.
 Three cases demonstrating these guidelines are presented and discussed.
",6
1117,"The relationship between the indications for the surgical removal of impacted third molars and the incidence of alveolar osteitis.
 Six hundred forty-two impacted third molars were surgically removed in 412 patients.
 Before surgery, each patient was assessed clinically and radiographically, and the reason for the removal of each tooth was specifically recorded.
 One hundred eighty-two of the impacted teeth were removed for prophylactic reasons and 460 for therapeutic reasons.
 As much as possible, standardization of the operating procedure and environment, and of the preoperative and postoperative regimens was observed.
 After surgery, each case was followed to determine the absence or presence of signs and symptoms of alveolar osteitis.
 It was found that several factors seem to contribute to the development of alveolar osteitis; however, the most significant related finding was that the reason for the extraction, that is, whether the extraction was undertaken for therapeutic or prophylactic reasons.
",6
1118,"Location of abnormalities in panoramic radiographs of edentulous patients.
 A series of 308 panoramic radiographs of edentulous patients was examined for the presence of pathoses to determine whether any predictive basis could be found for occurrence of abnormalities by sex, age, or location.
 Radiolucencies, radiopacities, and retained roots and teeth were recorded by size and by anterior or posterior location in edentulous jaws.
 Radiopacities were the most frequently found abnormality (18% of subjects), followed by retained roots (8%), radiolucencies (3%), and retained teeth (3%).
 No significant correlation was found by chi-square test between type or location of abnormality and sex of the patient.
 There was, however, a significant relationship between location and type of abnormality.
 Radiopaque and radiolucent lesions were more frequently found in the mandible, and unerupted teeth and retained roots were more frequently seen in the posterior maxilla.
 Selective radiographs to detect retained roots and unerupted teeth in the posterior maxilla may be most productive in terms of prosthodontic treatment outcome.
 Otherwise, this study finds no basis for selection of intraoral sites for specific intraoral radiographs of asymptomatic edentulous patients.
",6
1119,"Pancreatic autoantibodies and pancreatic function in Sjogren's syndrome.
 Pancreatic autoantibodies were determined in 49 patients with Sjogren's syndrome and related to functional parameters.
 Pancreatic duct autoantibodies (PDA) were detected in the sera of three patients, and all showed abnormal exocrine pancreatic function.
 Islet cell antibodies (ICA) were not detected in the sera of the 49 patients, including two individuals with diabetes mellitus.
 In conclusion, PDA occur in patients with Sjogren's syndrome, and may be associated with exocrine pancreatic dysfunction.
",6
1120,"Medical and dental implications of cocaine abuse.
 With the ever-increasing supply of cocaine and use of ""crack,"" the potent and smokeable form of cocaine, the dangers of cocaine abuse, with its high morbidity and mortality, have become recognized.
 Oral and maxillofacial surgeons may frequently and unknowingly be treating patients who use cocaine, and, therefore, they must be educated about cocaine-related problems and be prepared to deal with the complications.
 This article discusses the nature of cocaine, its pharmacology, systemic affects, the oral manifestations of cocaine abuse, and recommended clinical management of the patient.
",6
1121,"Prevention of dry socket: an overview.
 Dentists, exodontists, oral surgeons, and now oral and maxillofacial surgeons have been plagued with a postextraction complication, commonly known as ""dry socket,"" since the inception of our profession.
 Other designations that have been attached to this malady over the years include alveolar osteitis, postextraction osteitis, osteomyelitic syndrome, alveolar sicca dolorosa, and, latterly, fibrinolytic alveolitis.
 Myriad attempts to eliminate this painful condition have been made, to no avail.
 Nonetheless, significant progress has been made in an endeavor to reduce its incidence.
 Perhaps it is time to take an inventory of the proven methods that will assist the practitioner in reducing the incidence of this complication in his/her practice.
 This article presents a review of past investigations that appear to have merit in this regard, with a summary of recommendations at the conclusion of the article.
",6
1122,"Effects of removing inferior alveolar neurovascular structures on mandibular growth and the eruption of permanent dentition in puppies.
 Investigation was performed on the effects of removing the inferior alveolar neurovascular structures on the permanent dentition and mandibular growth.
 Five puppies with erupted deciduous teeth had the inferior alveolar neurovascular structures removed unilaterally.
 When the test animals were 28 weeks old, examination revealed that the deciduous teeth on the side operated had exfoliated but permanent teeth did not replace them.
 On the other hand, the permanent teeth on the side not operated on replaced the exfoliated deciduous teeth.
 After a second period of 28 weeks, the germs of the permanent teeth on the side operated on were still buried in the mandibular bone, and the permanent teeth on the side not operated on erupted normally.
 Mandibular measurements demonstrated that translative and transformative growth and developmental processes were normal in both the sides operated on and the sides not operated on.
",6
1123,"Orofacial odontogenic infections: review of microbiology and current treatment.
 Orofacial odontogenic infections are common.
 Current evidence indicates that anaerobes play a major role in these infections and that the most common microbial isolates are Bacteroides, fusobacteria, peptococci, and peptostreptococci as well as some viridans streptococci.
 Drainage must be established where possible.
 Penicillin is still the drug of first choice for therapy, with metronidazole a good alternative.
 Nevertheless, not all clinicians are aware of current views and, therefore, this article is a state-of-the-art review for the practicing clinician of the microbiology and antimicrobial therapy of orofacial odontogenic infections.
",6
1124,"A comparison of the signs of temporomandibular joint dysfunction and occlusal discrepancies in a symptom-free population of men and women.
 To date, there has been no conclusive explanation for the predominance of female patients with temporomandibular joint (TMJ) dysfunction.
 The purpose of this study was to survey a normal population without symptoms for the presence of certain putative signs of TMJ dysfunction in association with certain signs of occlusal discrepancy and to determine the presence of any gender variation.
 The subjects (217 men and 217 women) were examined for the presence of three putative signs of TMJ dysfunction: limited mandibular opening (under 37 mm), deviation on opening, and joint sounds.
 The subjects were also examined for the presence of four signs of occlusal discrepancy: an anterior slide from centric relation (CR) to centric occlusion (CO), lateral slide from CR to CO, nonworking occlusal contacts, and working disclusive contacts distal to the canines.
 CR is the mandibular position at which the condyles are in their most superior position on the posterior aspect of the articular tubercles.
 CO is the mandibular position at which the mandibular and maxillary teeth are in maximum intercuspation.
 There were no significant differences in the prevalence of the putative signs of TMJ dysfunction and occlusal discrepancy between men and women.
 It was concluded that factors other than the presence of these signs of TMJ dysfunction and occlusal discrepancy are responsible for the high predominance of female patients with TMJ dysfunction.
",6
1125,"Intracoronal radiolucencies within unerupted teeth. Case report and review of literature.
 A panoramic radiograph obtained during orthodontic treatment revealed an intracoronal radiolucency within an unerupted permanent second molar.
 This unusual entity was successfully treated by surgical and endodontic intervention, followed by restorative and orthodontic treatment.
 These treatments enabled the tooth to maintain pulpal vitality, erupt, complete root formation, and function.
 This report will review the proposed etiologies for this condition, discuss the need for surgical intervention, and present the details of the case.
",6
1126,"A comparison of two temporary restorations: light-cured resin versus a self-polymerizing temporary restoration.
 Temporary restorative materials are an important component of endodontic therapy.
 They must both adequately seal the access preparation between visits and protect the obturated canal(s) from microleakage until a permanent restoration can be placed.
 The efficacy of Cavit and T.E.R.M.
 (a new light-cured composite product) was compared with the use of a carbon black coronal microleakage protocol.
 The teeth examined had previously received coronal restorations.
 After the teeth were accessed, restored with Cavit or T.E.R.M., and exposed to the dye, they were cleared.
 Three-dimensional assessment then revealed that Cavit more consistently provided an effective seal.
 In addition, a great deal of microleakage was observed around the permanent restoration-tooth interface.
 This indicates that perhaps leaking permanent restorations should be removed in their entirety before initiation of endodontic treatment.
",6
1127,"Primary parotid malignancies. A clinical and pathologic review.
 One hundred ninety-four patients with primary malignant tumors of the parotid gland who underwent surgery at the Mayo Clinic (1970 through 1987) are reviewed.
 Survival patterns were analyzed using the Kaplan-Meier product-limit method that separated histologic results into three significantly different groups.
 Survival rate was highest for patients with acinic cell, adenoid cystic, and low-grade mucoepidermoid carcinomas; intermediate for patients with high-grade mucoepidermoid carcinomas; and lowest for the remaining six histologic types encountered.
 Cox multiple linear regression was used to identify patient and tumor characteristics with greatest prognostic significance.
 In order of decreasing strength, regional metastatic involvement, pain, male gender, grade, stage, and advancing age all demonstrated independent prognostic significance.
 Fifty-three percent of patients requiring facial nerve sacrifice were asymptomatic at presentation.
 A high positive correlation was observed between advancing grade and stage.
",6
1128,"Dry mouth: diagnosing and treating its multiple causes.
 Dry mouth in the elderly is a common occurrence with multiple etiologies.
 It is not a normal phenomenon of aging and, therefore, an attempt at elucidating its cause should be made.
 Sjogren's syndrome may occur, and it is diagnosed by labial biopsy.
 Medications are also frequently associated with dry mouth, and dosages may need to be adjusted or the drug discontinued if symptoms are severe.
 Strategies for management of dry mouth are explored.
",6
1129,"Inhibition of fluorouracil-induced stomatitis by oral cryotherapy.
 Mucositis is a significant dose-limiting toxicity associated with fluorouracil (5FU), particularly when it is combined with leucovorin.
 We hypothesized that oral cryotherapy would cause local vasoconstriction and would temporarily decrease blood flow to the oral mucous membranes.
 If cryotherapy were used during the time of peak serum 5FU levels, then the oral mucous membranes would have less exposure to 5FU and thus develop less mucositis.
 To test this hypothesis, 95 patients scheduled to receive their first cycle of 5FU plus leucovorin were randomized to have oral cryotherapy at the time of chemotherapy administration or to serve as a control group.
 Subsequent mucositis was significantly reduced in the group assigned to receive cryotherapy as judged by the attending physicians (P = .0002) and by the patients themselves (P = .0001).
 We now routinely recommend this cryotherapy procedure for our patients receiving daily bolus 5FU plus leucovorin.
",6
1130,"Fine-needle aspiration biopsy of salivary glands.
 Between January 1, 1973, and December 31, 1988, the authors or their associates performed 552 fine-needle aspiration biopsies on patients with clinically significant masses of the salivary glands.
 All patients presented at the Medical College of Virginia Hospitals or Clinics of Virginia Commonwealth University; they were followed for periods ranging from 1 to 16 years.
 When available, the fine-needle aspiration diagnoses were correlated with histologic diagnoses and long-term patient outcomes.
 The sensitivity for a neoplasm was 93.3%; the specificity for the absence of a neoplasm was 99%.
 Diagnostic efficiency was 96.4%, and predictive value of a positive aspiration for a neoplasm was 98.3%.
 With fine-needle aspiration, surgical excision of salivary gland masses is often unnecessary.
 In patients with primary and metastatic neoplasms involving the salivary glands, fine-needle aspiration aids the surgeon in mapping the extent of the surgical procedure and in preoperatively preparing the patient.
 The procedure is cost-effective.
",6
1131,"Aerobic and anaerobic microbiology of peritonsillar abscess.
 Thirty-four aspirates of pus from peritonsillar abscesses that were studied for aerobic and anaerobic bacteria showed bacterial growth.
 A total 107 bacterial isolates (58 anaerobic and 49 aerobic and facultative) were recovered, accounting for 3.1 isolates per specimen (1.7 anaerobic and 1.4 aerobic and facultatives).
 Anaerobic bacteria only were present in 6 (18%) patients, aerobic and facultatives in 2 (6%), and mixed aerobic and anaerobic flora in 26 (76%).
 Single bacterial isolates were recovered in 4 infections, 2 of which were Streptococcus pyogenes and 2 were anaerobic bacteria.
 The predominant bacterial isolates were Staphylococcus aureus (6 isolates), Bacteroides sp (21 isolates, including 15 Bacteroides melaninogenicus group), and Peptostreptococcus sp (16) and S.
 pyogenes (10).
 beta-Lactamase-producing organisms were recovered from 13 (52%) of 25 specimens tested.
 This retrospective study highlights the polymicrobial nature and importance of anaerobic bacteria in peritonsillar abscess.
",6
1132,"S-100 protein antibodies do not label normal salivary gland myoepithelium. Histogenetic implications for salivary gland tumors.
 Neoplastically modified myoepithelial cells have a key role in developing the histologic characteristics of some salivary gland tumors.
 S-100 protein expressed in certain of these tumors is suggested to support this role, as the principal component in the human salivary gland reported to be S-100 protein-positive is myoepithelium.
 Confirmation of such an important aspect is required.
 Immunoperoxidase staining of parotid salivary gland shows considerably different patterns obtained with antibodies to S-100 protein, neuron-specific enolase, and neurofilaments compared with those for muscle-specific actin and cytokeratin 14; many more cells and their processes associated with acini and ducts are evident with the latter two antibodies.
 Double immunofluorescent staining with antibodies to either S-100 protein or neuron-specific enolase combined with muscle-specific actin does not reveal colocalization of these antigens in myoepithelial cells.
 The former localize only to nerve fibers adjacent to, but separate from, acini, and the latter only to myoepithelial cells.
 It is apparent that S-100 protein staining of the rich network of unmyelinated nerves in the interstitial tissues, evident ultrastructurally, has been misinterpreted as myoepithelium.
 This result has important implications for histogenetic classifications of salivary gland tumors.
",6
1133,"In vitro natural killer and lymphokine-activated killer activity in patients with bronchogenic carcinoma.
 The authors examined peripheral blood mononuclear cells from 45 patients with bronchogenic carcinoma to determine natural killer (NK) and lymphokine-activated killer (LAK) activity after in vitro incubation with media alone or media plus interferon gamma (IFN, 200 U/ml) and/or interleukin-2 (IL-2, 100 U/ml).
 Our results show that lymphocytes from patients with bronchogenic carcinoma can acquire LAK activity, but the level of activity acquired was significantly lower compared with lymphocytes from 25 control subjects when IL-2 cultures were supplemented with 10% autologous human serum (AHS) (15.6% +/- 2.1% specific release versus 26.0% +/- 2.9% specific release, P = 0.004).
 The LAK activity, defined as cytotoxicity of an NK-resistant cell line, of the patients' lymphocytes was augmented when cells were cultured with both IL-2 and IFN compared with IL-2 alone (P = 0.0001, paired t-test).
 Control subjects were unchanged (P = 0.09).
 There was no significant difference between groups of patients with different histologic types of tumor or different stages of disease.
 The NK activity, defined as killing of NK-sensitive K-562 target cells, of the patients' lymphocytes was not significantly different from that of the controls' lymphocytes (42.8% +/- 3.0% specific release versus 49.3% +/- 3.3% specific release, P = 0.16).
 These studies indicate the feasibility of IL-2 and IFN therapy in patients with bronchogenic carcinoma.
",7
1134,"Spirometric findings and mortality in never-smokers.
 The relation of ventilatory function to overall mortality has been studied in 662 male and 2048 female never-smokers who during the period 1976-1978 participated in the Copenhagen City Heart Study, a prospective community study of more than 14,000 men and women randomly selected from the general population of the City of Copenhagen.
 Until the end of 1986, 195 subjects who said they were never-smokers died.
 Mortality was analyzed using the proportional hazards model of Cox.
 In addition to measures of ventilatory function, the mortality analysis included age, sex, body-mass index, alcohol consumption, school education, diabetes mellitus, heart disease and bronchial asthma as confounding factors.
 Forced expiratory volume in 1 second (FEV1) as a percentage of that predicted, forced vital capacity (FVC) as a percentage of that predicted and the ratio of FEV1 to FVC were significant risk factors for mortality among both sexes.
 The relative risk of death associated with a 50% decrease in FEV1 and FVC as a percentage of a predicted value was 1.65 and 1.81, respectively.
 This study confirms that lowered ventilatory function is a strong risk factor for mortality among never-smokers of both sexes.
",7
1135,"The effect of sulindac on the abnormal cough reflex associated with dry cough.
 In order to determine the possible role of prostaglandins in the abnormal cough reflex in patients with dry cough, the effects of a cyclooxygenase inhibitor on cough symptoms were examined.
 This was measured by a cough symptom score and by the cough reflex sensitivity to inhaled capsaicin in a double blind, randomized, cross-over study comparing the effects of placebo with sulindac, 200 mg daily for 1 week.
 We studied six hypertensive patients with angiotensin converting enzyme inhibitor-associated cough and six patients with an idiopathic, dry, unproductive cough, all of whom had an increase in the sensitivity of the cough reflex.
 There was no change in blood pressure control in the hypertensive patients during sulindac therapy.
 The patients with the angiotensin converting enzyme-associated cough had a significant reduction in the cough symptom score and also a significant increase in the dose of capsaicin causing two or more coughs (threshold sensitivity) and that causing five or more coughs (near maximum response) during sulindac therapy as compared to placebo.
 In those patients with idiopathic, dry, unproductive cough, sulindac did not alter the symptom of cough or the cough reflex response to capsaicin.
 These results suggest that prostaglandins may be involved in cough associated with angiotensin converting enzyme inhibitor therapy, but are less likely to be important in the pathogenesis of more common dry coughs of unknown cause.
",7
1136,"Immune reactivity in bronchogenic carcinoma and its relation to 5-year survival rate.
 We performed a prospective study on the correlation of various parameters of the immune response with the 5-year survival rate in patients with bronchogenic carcinoma.
 Parameters were initially examined before starting treatment.
 Delayed hypersensitivity skin tests, lymphoblastogenesis, natural killer (NK) cell activity, and interleukin-2 (IL-2) production were employed to assess immune competence.
 Each reaction was classified into four or five grades in accordance with intensity; the 5-year survival rate of the patients showing each grade of the immune response was calculated.
 A correlation between response before treatment and the survival rate was most clearly noted for lymphoblastogenesis.
 The skin tests and the NK cell activity showed poorer correlations, and no exact correlation was noted between the IL-2 production and the immune response.
",7
1137,"Laryngeal mask airway and tracheal tube insertion by unskilled personnel 
 After a short training programme 11 naval medical trainees inserted a laryngeal mask airway (LMA) and a tracheal tube (ETT) in random order in a total of 110 anaesthetised patients.
 They were allowed 40 s for each attempt.
 Success was defined as the detection of expired carbon dioxide within 40 s of Guedel airway removal which subsequently rose to an end-tidal value of at least 4 kPa, together with satisfactory lung expansion and ventilation, without other airway intervention by the anaesthetist.
 104 LMA insertions were successful compared with 56 of ETTs (p less than 0.01).
 All first attempts at LMA insertion were successful, whereas satisfactory ETT placement was progressive.
 Insertion was also quicker with the LMA (20 s) than with the ETT (35 s) (p less than 0.01).
 Further studies are indicated to assess the value of the LMA in emergencies.
",7
1138,"A new method of needle-electrode placement in the posterior cricoarytenoid muscle for electromyography.
 In 1979 the authors developed a new method of needle-electrode placement in the posterior cricoarytenoid muscle (PCA) for electromyography.
 The PCA muscle is easily reached by inserting a needle electrode through the cricothyroid membrane at the midline and penetrating the lamina of the cricoid cartilage in the subglottic cavity.
 Access to the PCA muscle for electrode insertion was best afforded by a percartilaginous approach.
 This report details the new technique used at our laboratory.
 To our knowledge, this is the first report of needle-electrode placement in the PCA muscle by a percartilaginous approach.
 This new electrode insertion technique has been applied to more than 100 dogs for research purposes and to 1200 patients with laryngeal motor disorders for clinical diagnosis.
 This is a simple technique requiring the usual skills.
 Reliable electromyographic recordings have been obtained by this new method.
 No untoward effects, such as hematoma or infection from repeated placements were observed in approximately 3200 examinations performed to date.
 It is reasonable to assume that the percartilaginous route for electrode insertion in the PCA muscle is feasible in man.
 Techniques of electrode placement in the intrinsic laryngeal muscles are reviewed and compared.
",7
1139,"Serial Munchausen syndrome by proxy.
 Five cases of Munchausen syndrome by proxy (MSBP) are presented in which more than one child in the family was victimized.
 There was a high incidence of maternal psychiatric histories, marital difficulties, and Munchhausen syndrome in the mothers themselves.
 Seventy-one percent of the children in the families were known to be victims of MSBP; four of these children (31%) died.
 Multiple-child MSBP may reflect more significant maternal psychopathology than found in other cases of MSBP, or it may indicate the deteriorating consequences to the mother and other children in the family if this syndrome is not identified with the first child and effective interventions made.
",7
1140,"Acute respiratory infections during the first three months of life: clinical, radiologic and physiologic predictors of etiology.
 The usefulness of clinical, radiologic, and physiologic characteristics to identify pathogens was assessed in 90 infants aged two through 12 weeks, presenting to an outpatient clinic with an acute respiratory infection.
 Eighty-four cases had cultures or rapid diagnostic tests for RSV, of which 25 were positive.
 Eighty-two infants had cultures or rapid diagnostic tests for Chlamydia, of which 16 were positive.
 Additional respiratory pathogens identified included parainfluenza (6 cases), rhinovirus (3 cases), pertussis (2 cases), and CMV (1 case).
 Multiple pathogens were identified in four cases: Chlamydia and RSV (2 cases), Chlamydia and parainfluenza (1 case), and Chlamydia and CMV (1 case).
 Clinical characteristics other than the need for hospitalization were not useful predictors of specific pathogens.
 X-rays were obtained in 20 (80%) of the RSV infections, 13 (81%) of the Chlamydia infections, six of the parainfluenza infections, two pertussis infections, and 25 cases without identification of the pathogen.
 X-ray findings could not distinguish between patients with or without a pathogen or between the pathogens.
 Severe findings were present in 28% (11/40) of cases with a pathogen identified, compared to 12% (3/26) of cases without a pathogen identified (NS).
 Moderate findings were present in 58% (23/40) of cases with a pathogen identified compared to 62% (16/26) of cases without a pathogen identified.
 Slight/negative findings were present in 15% (6/40) of cases with a pathogen identified, compared to 27% (7/26) of cases without a pathogen identified.
 Pulse oximetry was done in 30 cases, 22 of which had a pathogen identified (RSV 14, Chlamydia 7, pertussis 1).
",7
1141,"Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis.
 Thirty-eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin (3 g) or matched placebo twice daily for 32 weeks in a double-blind study.
 Nine patients (four amoxycillin, five placebo) were withdrawn from the study treatment; the response of the two patients (both on amoxycillin) withdrawn within the first six weeks was not assessed.
 The pretreatment characteristics of the two groups were similar.
 Independent assessment of overall response based on patients' diary cards showed that a higher proportion improved in the amoxycillin group (11 of 17) than in the placebo group (four of 19; p = 0.02).
 Patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment.
 The frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group.
 There was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group (88 per cent of pretreatment volume, p = 0.008), although the concentrations of Haemophilus spp.
 in sputum between exacerbations was similar in the two groups.
 Adverse effects experienced were minor except in one patient (amoxycillin) withdrawn after developing a rash and in six patients (three amoxycillin, three placebo) who had diarrhoea lasting more than one week necessitating withdrawal of two patients (one amoxycillin, one placebo) from study treatment.
 Sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group.
 Prolonged higher-dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host (patient) inflammatory response to colonizing microorganisms and reduced morbidity.
",7
1142,"Hemoptysis: CT-bronchoscopic correlations in 58 cases.
 Computed tomographic (CT) and chest radiographic findings were retrospectively correlated with those found at fiberoptic bronchoscopy (FOB) in 58 patients presenting with hemoptysis.
 Abnormalities involving the airways were depicted by CT in a total of 28 cases (48%).
 In 18 of these (31% of the total group of 58), focal abnormalities involving the central airways were identified (17 were subsequently proved to be malignant) and in 10 (17% of the total), CT showed bronchiectasis.
 Focal airway abnormality was shown by FOB in 18 cases (31%); all of these were depicted with CT.
 Malignancy was diagnosed in 24 patients, including three in whom results of FOB were normal but malignant cells were identified at transbronchial biopsy.
 CT abnormalities were identified in all cases of malignancy.
 In 10 of 21 cases (48%) of non-small cell lung cancer, CT allowed definitive staging by documenting either direct mediastinal invasion and/or metastatic disease, while FOB allowed definitive staging in only three cases.
 CT studies provided no false-negative results.
 It is concluded that when carefully performed, CT may be an effective modality for evaluating patients presenting with hemoptysis.
",7
1143,"Coal worker's pneumoconiosis: CT assessment in exposed workers and correlation with radiographic findings.
 To study the signs of coal worker's pneumoconiosis (CWP) at computed tomography (CT), the authors obtained thoracic CT scans in 170 coal-dust-exposed workers who were concomitantly evaluated with conventional posteroanterior and lateral radiography.
 The profusion and extent of disease was assessed by means of CT in two groups of miners: group 1 (n = 86), miners with worker's compensation and radiographic evidence of CWP, and group 2(n = 84), miners who had applied for compensation without radiographic evidence of CWP.
 The CT signs of CWP consisted of micronodules, nodules, and progressive massive fibrosis.
 The comparative analysis demonstrates the superiority of an optimal CT technique over chest radiography in the evaluation of simple silicosis, with improved sensitivity in the detection of small parenchymal opacities.
 CT provides additional information on the stage of the disease but also clarifies some ambiguities of the ILO classification of small opacities.
 CT was equivalent to radiography for complicated silicosis, except in the identification of necrosis.
 CT evaluations are complementary to plain radiography in the assessment of CWP, and the addition of high-resolution CT is useful in achieving a more accurate evaluation of the small parenchymal opacities.
",7
1144,"Cross-sectional physiology of the lung.
 It is well known that gravity influences the physiology of the lung and thereby affects the intrapulmonary localization of disease processes.
 Less well known are the anatomic and physiologic differences in the axial or cross-sectional plane, which also affect the distribution of disease.
 Physiologic gradients in ventilation, perfusion, and lymph flow and stresses in the lung are present in the axial plane.
 Anatomic difference in branching patterns, interstitial design, and development of the secondary pulmonary lobules are also found.
 These regional disparities in anatomy and physiology can be applied to an old concept--the corticomedullary organization of the lung--and are used to consider why some diseases exhibit a propensity for the central or peripheral portions of the lung.
 The same analysis is applied to the anatomy and physiology in the secondary pulmonary lobule.
",7
1145,"Airway evaluation in children with use of ultrafast CT: pitfalls and recommendations.
 Ultrafast computed tomographic (CT) evaluation of the airway can be performed with either 50-msec low-resolution images (cine CT) or 100-msec high-resolution images (high-resolution CT).
 To determine the best imaging strategy for ultrafast CT of the pediatric airway, the authors prospectively compared ultrafast CT and endoscopy in 20 children.
 Both studies were performed in 11 patients; cine CT alone was performed in six and high-resolution CT alone in three.
 Six patients had normal anatomy.
 Six patients had focal tracheal stenoses, four had tracheomalacia or laryngomalacia, one had a laryngoesophageal cleft, one had irregularity and narrowing in the subglottic area, one had laryngeal papillomas, and one had focal stenosis with stoma granuloma.
 Cine CT results agreed with those of endoscopy in 10 of 17 cases.
 In five cases focal stenosis was misinterpreted with cine CT as tracheomalacia.
 High-resolution CT results agreed with those of endoscopy in 10 of 14 cases.
 The results of a technique that combined high-resolution CT for the entire airway and cine CT at selected areas agreed with those of endoscopy in 10 of 11 cases; only a tracheoesophageal cleft was missed with the combined technique.
 For the greatest diagnostic accuracy with ultrafast CT in evaluation of the pediatric airway, both cine and high-resolution modes should be used.
",7
1146,"A simple method for correcting single breath total lung capacity for underestimation.
 The single breath method underestimates total lung capacity by comparison with the multiple breath method (TLCmb) because of inhomogeneity of ventilation distribution.
 This study proposes a simple correction for the single breath TLC (TLCsb), using inert gas phase III slope to account for the effects of uneven ventilation distribution.
 A model of a non-uniform lung ventilation was designed, composed of a serial dead space and two alveolar compartments arranged in parallel, whose relative ventilations were determined from the phase III plateau.
 Before correction TLCsb was 104-44% of TLCmb in 64 subjects (17 with diffuse interstitial disease, 42 with chronic obstructive pulmonary disease, and five healthy subjects).
 The limit of acceptability for the correction (TLCcorr) was determined from the 95% confidence interval of TLCsb/TLCmb in the healthy subjects.
 The correction resulted in a significant increase in TLCsb (p less than 0.004).
 TLCcorr remained under the limit of acceptability for only 12 patients with emphysema, and all 12 showed a large improvement in the TLC estimate.
 The presence of poorly ventilated zones during a single breath in these patients may explain this partial correction.
",7
1147,"Lung fibrosis induced by Thorotrast.
 A 63 year old woman developed progressive shortness of breath, pulmonary hypertension, and respiratory failure and died from pulmonary fibrosis 45 years after thoracic fistulography with Thorotrast.
 Bouts of acute respiratory failure occurred with features of noncardiogenic pulmonary oedema.
 Lung tissue obtained by biopsy and at necropsy showed abundant radioactive particles of thorium dioxide in the lungs.
 The particles were congregated in the walls of blood vessels and in perivascular fibrous zones, consistent with a causal role of Thorotrast in the development of lung fibrosis.
 It is suggested that the fibrosis was due to the combined effects of alpha radiation on the interstitial perivascular zones and of recurrent pulmonary oedema due to endothelial damage.
",7
1148,"Effect of sulfurous (thermal) water on T lymphocyte proliferative response.
 We studied the effect of sulfurous water thermal therapy on the phenotype and the proliferative response of peripheral lymphoid cells from ten subjects affected by chronic upper respiratory disease and from six suffering from articular and periarticular disorders.
 Sulfurous water (S-H2O) therapy did not modify the phenotype and function of peripheral blood mononuclear cells (PBMC) nor did it modify systemic immunologic reactivity.
 A different result was obtained by analyzing the response to mitogens of peripheral blood mononuclear cells in cell cultures containing graduated amounts of S-H2O.
 These ""in vitro"" studies have shown an important dose-dependent inhibitory effect of S-H2O on mitogen induced T lymphocyte proliferation and on IL2 production.
 H2S present in S-H2O seems to be the primary component responsible for inhibition.
 Our results are consistent with a local immunosuppressive role of S-H2O, which may explain part of the observed therapeutic effect of inhalation therapy on upper respiratory allergic disorders.
",7
1149,"Human serologic response to envelope-associated proteins and adenylate cyclase toxin of Bordetella pertussis.
 The human serologic response to several envelope-associated proteins and adenylate cyclase toxin of Bordetella pertussis was examined using immunoblot techniques.
 Antigens recognized by sera from individuals with culture-confirmed pertussis and by sera from infants immunized with three doses of conventional whole-cell pertussis vaccine included a 63,000-Da protein that was shown to be antigenically related to a mycobacterial heat-shock protein.
 A 29,000-Da protein reacted with sera from convalescent individuals, whereas a 91,000-Da protein reacted with sera from vaccinated individuals.
 Antibodies to adenylate cyclase toxin were common in sera from individuals diagnosed with pertussis.
 B.
 pertussis lipooligosaccharide was also recognized by antibodies in some of these sera.
 These data suggest that some of these antigens may play a role in immunity to pertussis.
",7
1150,"Surfactant treatment of full-term newborns with respiratory failure.
 Surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full-term newborns.
 Fourteen full-term newborns with respiratory failure associated with pneumonia (7 patients) and meconium aspiration syndrome (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given intratracheally up to every 6 hours for a maximum of four doses.
 The group mean fraction of inspired oxygen (FI02) before treatment was 0.99 +/- 0.01 SEM, and the mean airway pressure (MAP) was 14.6 +/- 1.0 cm H2O.
 Patients showed significant improvement in oxygenation after initial surfactant treatment, with the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 +/- 0.01 before surfactant treatment to 0.22 +/- 0.05 by 15 minutes (P = .03) and remaining improved for 6 hours.
 The oxygenation index, incorporating MAP as well as oxygen variables, also improved significantly from 26.2 +/- 3.1 to 11.2 +/- 1.7 at 15 minutes (P less than .001), with improvement sustained for more than 6 hours.
 Chest radiographs were blindly scored from 0 (normal) to 5 (severe opacification), and these improved with marginal significance after initial surfactant treatment (from 2.9 +/- 0.2 to 2.5 +/- 0.2, P = .05).
",7
1151,"Intravenous streptomycin.
 Streptomycin is an effective drug for the treatment of tuberculosis.
 It is currently recommended for use only by the intramuscular route.
 This method of drug delivery is accompanied by considerable pain which is unacceptable to many patients.
 With the advent of many improvements in intravenous therapy that have occurred in the past 40 years, reevaluation of the intravenous use of this drug is warranted.
 We describe the short-term use of intravenous streptomycin in four patients with pulmonary tuberculosis.
",7
1152,"Central pulmonary embolism with normal ventilation/perfusion scan-diagnosis by nuclear pulmonary artery flow studies.
 Pulmonary embolism, although uncommon in children, occurs in as many as 104 per 100,000 pediatric patients.
 Undiagnosed and untreated pulmonary embolism has a high mortality rate; thus, a high index of clinical suspicion and reliable diagnostic modalities are necessary to ensure prompt and accurate diagnosis.
 We report the case of a patient with severe central pulmonary embolism with a normal ventilation-perfusion scan.
 The embolus was identified by a nuclear pulmonary flow study using dynamic imaging, which obviated the need for contrast pulmonary angiography.
 The traditional ventilation-perfusion scan may appear normal despite severe central pulmonary embolism.
 In this situation, early dynamic imaging is necessary to detect severe obstruction of the central pulmonary arteries.
 This approach may obviate the need for contrast pulmonary angiography in hemodynamically stable patients.
",7
1153,"Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease. A meta-analysis 
 PURPOSE: To evaluate the effectiveness of oral corticosteroid therapy in patients with stable chronic obstructive pulmonary disease.
 DATA IDENTIFICATION: An English-language literature search using MEDLINE (1966 to 1989) and a bibliographic review of all retrieved articles identified 33 original studies of oral corticosteroid use in chronic obstructive pulmonary disease published since 1951.
 STUDY SELECTION: We submitted a photocopy of each study's ""methods"" section to three nonstudy physician-investigators who used nine explicit criteria to independently assess study quality.
 Ten studies met all criteria and five studies met some of the criteria.
 DATA EXTRACTION: To compare outcomes across all qualifying studies, we defined response to therapy as a 20% or greater increase in the baseline forced expiratory volume in 1 second (FEV1); we defined the treatment effect size for each study as the proportion of patients who responded to corticosteroid therapy minus the proportion of patients who responded to placebo.
 Potential confounding variables as related to eligibility criteria and treatment protocols were also assessed for each study.
 RESULTS OF DATA SYNTHESIS: Among ten studies that met all nine criteria, we found no significant differences in eligibility criteria, treatment protocol, or study design.
 No association was found between treatment effect size and publication date, study size, mean patient age, or FEV1.
 These studies had reported effect sizes ranging from 0% to 56%; we calculated a weighted mean effect size of 10% (95% CI, 2% to 18%).
 When studies meeting only some of the criteria were included in the calculation, the weighted mean effect size was 11% (95% CI, 4% to 18%).
 CONCLUSIONS: Patients with stable chronic obstructive pulmonary disease receiving oral corticosteroid therapy have a 20% or greater improvement in baseline FEV1 approximately 10% more often than similar patients receiving placebo.
",7
1154,"Mechanism of bronchodilator effect in chronic airflow limitation.
 OBJECTIVE: To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities.
 METHODS: Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial.
 The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined.
 Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined.
 RESULTS: The two drugs proved to be beneficial the effects in general were additive rather than synergistic.
 The drugs improved the FEV1; theophylline significantly improved the MIPs.
 The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001).
 The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001).
 CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation.
 Changes in airway calibre may be of greater importance.
",7
1155,"Current status of etoposide in the management of small cell lung cancer.
 Etoposide is a schedule-dependent drug with excellent activity against small cell lung cancer (SCLC).
 Single-agent etoposide achieves overall response rates ranging from 15% to 84%, depending on the schedule of drug administration and the characteristics of the treated population.
 The route of etoposide administration (intravenous versus oral) has little impact on response rate, provided appropriate dose adjustments are made for oral therapy.
 In combination with other active agents, etoposide has proven particularly effective in the management of SCLC.
 Etoposide can be substituted for doxorubicin or vincristine in the cyclophosphamide, doxorubicin, and vincristine (CAV) regimen without loss of efficacy.
 The etoposide and cisplatin (EP) combination is thought to be synergistic and has proven to be an effective salvage regimen for CAV failures.
 A regimen that alternates CAV and EP has been found by some investigators to be modestly more effective against SCLC than CAV alone; however, EP alone may be as useful as an alternating regimen.
 Most studies to date have demonstrated that EP induction is at least as effective as any other standard induction regimen.
 However, EP has the potential advantage of being more easily integrated with thoracic radiation therapy (RT).
 This is particularly important in limited-disease patients: two recent pilot studies employing EP induction with hyperfractionated thoracic RT yielded 2-year survival rates of greater than 50%.
 These promising results are being evaluated further in an ongoing Phase III trial in the United States.
 The available data indicate that etoposide is one of the most active agents against SCLC and therefore should be included as a component of induction therapy in all patients.
 New schedules of etoposide administration warrant further study.
",7
1156,"A randomized trial to compare intravenous and oral etoposide in combination with cisplatin for the treatment of small cell lung cancer.
 In a randomized multi-center study, 83 patients with small cell lung cancer were randomly assigned to treatment with cisplatin 100 mg/m2 intravenously (IV) day 1 and etoposide 120 mg/m2 IV days 1, 2, and 3 or cisplatin 100 mg/m2 IV day 1 and etoposide 120 mg/m2 IV day 1 and 240 mg/m2 orally days 2 and 3.
 Both regimens were repeated every 4 weeks.
 Prior to randomization, patients were stratified by extent of disease, performance status, and gender.
 A total of 41 patients were randomly assigned to the parenteral treatment only regimen, and 42 patients received cisplatin and IV/oral etoposide therapy.
 Both treatment arms were comparable regarding patient characteristics.
 Limited disease (LD) patients constituted 52% and 49% of the patient population for the oral and IV etoposide regimens, respectively.
 The overall complete response (CR) and partial response (PR) rate was 50% (95% confidence interval [CI] 35% to 65%) for the oral etoposide regimen and 59% (95% CI 44% to 74%) for the IV etoposide regimen (P = 0.438).
 For both regimens, 55% of the LD patients achieved either CR or PR.
 Time to progression and survival were comparable for both treatment arms.
 Hematologic toxicity was comparable in both treatment arms, with 80% of patients experiencing grade 3 or 4 neutropenia or thrombocytopenia.
 Moderate to severe anemia and weight loss were more predominant with the IV than with the oral regimen.
",7
1157,"Target-flow inspiratory muscle training during pulmonary rehabilitation in patients with COPD.
 The effects of additional target-flow inspiratory muscle training (TF-IMT) on the performance of the inspiratory muscles, on general exercise capacity, and on psychologic parameters during a pulmonary rehabilitation program (PR) were studied in 40 patients with COPD selected for ventilatory limitation during exercise.
 The mean age of the patients was 59 years, and the mean FEV1 was approximately 50 percent of predicted.
 All patients participated in a ten-week PR program.
 They were randomized to receive either additional TF-IMT (PR + IMT) or not (PR).
 The TF-IMT was performed by means of a target-flow resistive device; the generated mouth pressure and the duration of inspiration and of the respiratory cycle were imposed.
 After the training period, maximal inspiratory mouth pressure and EMG-fatigability of the diaphragm were significantly better in the PR + IMT group than in the PR group.
 Maximal work load and psychologic symptoms increased to the same extent in both groups.
 The 12-minute walking distance also increased in both groups, but it increased significantly more in the PR + IMT group than in the PR group.
 We believe that additional TF-IMT during PR in a selected group of patients with COPD who have ventilatory limitation has an extra beneficial effect on the performance of the inspiratory muscles and on exercise performance.
",7
1158,"Combined thermodilution and two-dimensional echocardiographic evaluation of right ventricular function during respiratory support with PEEP.
 In ten patients requiring respiratory support for an episode of acute respiratory failure (ARF), the best therapeutic level of PEEP was determined by measurement of changes in lung and chest wall compliance (CT) during a PEEP challenge from 0 to 20 cm H2O.
 During this challenge, hemodynamic monitoring combined with thermodilution measurement of right ventricular (RV) ejection fraction (EF) and two-dimensional echocardiographic measurement of RV size permitted assessment of the effects of increasing levels of PEEP on RV function.
 RV preload, as reflected by RV end-diastolic volume (EDV) and two-dimensional RV end-diastolic area (EDA), remained unchanged and RV diastolic compliance progressively decreased.
 On the other hand, RV systolic function, as assessed by RVEF and two-dimensional RV fractional area contraction (FAC), was progressively depressed.
 Substantial deleterious effects of PEEP were noted at high levels of PEEP including reduced CT and augmented pulmonary vascular resistance.
 Inadequate increase in RV preload to compensate for increased RV afterload resulted in depressed RV systolic function and contributed to the reduction in cardiac output.
 Finally, two-dimensional echocardiography proved to be more sensitive than fast-response thermodilution to evaluate change in RV function.
",7
1159,"Natural killer cell activity in a rat model of amiodarone-induced interstitial lung disease.
 The role of lymphocytes in the pathogenesis of amiodarone-induced lung disease is controversial.
 Increases in the percentages of lymphocytes in bronchoalveolar fluid of both patients and animals with amiodarone pulmonary toxicity have been reported.
 To assess whether these lymphocytes are functionally activated, we measured natural killer cell activity in the lungs and blood of rats with amiodarone-induced pulmonary toxicity.
 Amiodarone treated rats exhibited pathologic evidence of amiodarone-induced lung disease after one week of treatment and this injury was sustained and more extensive during the remainder of the study period.
 Control rats had histologically normal lungs.
 Blood NK activity was equally present in both amiodarone-treated and control groups and was not significantly different over the course of the study (16 +/- 3 percent and 13 +/- 2 percent, respectively; p greater than 0.05).
 Thus, NK cells were activated only in the lungs of rats treated with amiodarone, suggesting a local immune response in the lung.
 These data support the concept that lymphocytes play an important role in the pathogenesis of amiodarone-induced lung disease.
",7
1160,"Fiberoptic bronchoscopy for refractory cough.
 Fiberoptic bronchoscopy (FB) has a low yield in the diagnosis of chronic cough (greater than 3 weeks) in unselected patients.
 We assessed the yield of FB for cough during a four-year period in patients with nonlocalizing chest roentgenograms who were refractory to diagnostic efforts and empiric bronchodilator or antitussive therapy.
 Seven (28 percent) of 25 patients undergoing FB for cough (of greater than 1,500 bronchoscopies) had diagnostic findings (broncholithiasis, two; tracheobronchopathia osteochondroplastica, two; and tuberculous bronchostenosis, laryngeal dyskinesia, and arytenoid polyp, one each).
 No tracheobronchial neoplasms were detected.
 Age greater than 50 years and female sex independently predicted positive results (p = 0.02 Fisher's exact test), while duration of cough (two to 240 months), airflow, and smoking status did not.
 When patients with prior pulmonary or extrathoracic neoplasms were excluded, seven (35 percent) of 20 studies were diagnostic.
 Diagnoses potentially could have been made by thoracic computed tomographic scanning in four patients and indirect laryngoscopy in two.
 Fiberoptic bronchoscopy has a respectable yield for diagnosis of refractory chronic cough and is a reasonable procedure in carefully selected patients.
",7
1161,"Comparison of incentive spirometry and intermittent positive pressure breathing after coronary artery bypass graft.
 Fifty-two patients were randomized to receive either incentive spirometry (IS) or intermittent positive pressure breathing (IPPB) in addition to conventional chest physical therapy following coronary artery bypass grafting.
 Slow vital capacity and peak expiratory flow readings decreased rapidly and to an equal extent in both groups after surgery, and partly recovered by the sixth postoperative day (POP).
 Arterial PO2 values were similar for the groups on the first three POPs.
 On the POPs 2, 3, and 6, the number of chest films showing atelectases as well as the number of individual patients having atelectases revealed no statistically significant differences between the two groups.
 Based on the three variables studied, we consider both devices equal in efficiency after coronary surgery.
",7
1162,"Managing lung disease in late life: a new approach.
 Advanced pulmonary disease (APD), a progressive, incurable condition, ultimately leading to death, is associated with significant, distressing symptoms.
 This paper reviews how the hospice approach to care, with its emphasis on treating those symptoms causing the patient the most distress, might be used by physicians in the outpatient setting to improve the patient's quality of life.
 Important aspects of care include management of hypoxia, malnutrition, osteoporosis, adverse drug reactions, and, especially, the symptomatic relief of dyspnea.
 Relief of emotional symptoms (depression, anxiety, panic) is also discussed.
",7
1163,"Compensation of respiratory alkalosis induced after acclimation to simulated altitude.
 Conscious intact rats previously acclimated for 3 wk to barometric pressure of 370-380 Torr (3WHx) were made alkalotic for 3 h by a decrease in inspired O2 fraction from 0.10 to 0.075 at ambient barometric pressure (730-740 Torr).
 Controls were normoxic littermates (Nx) in which inspired O2 fraction was lowered from approximately 0.21 to 0.10 for 3 h.
 Arterial PCO2 decreased progressively and similarly in both groups (65-70% of control at 15 min).
 Initially, arterial pH increased less in 3WHx (0.09 +/- 0.004 vs.
 0.15 +/- 0.008).
 As hypocapnia continued, delta[HCO3-]/delta pH (mmol.l-1.pH) became more negative in Nx, from -15.2 +/- 2.5 at 15 min to -37.0 +/- 2.9 at 3 h, indicating nonrespiratory compensation of alkalosis.
 In 3WHx, delta[HCO3-]/delta pH did not change during alkalosis.
 Cumulative renal excretion of base (mueq/100 g) during alkalosis increased by 73.2 +/- 11.1 in Nx and 25.4 +/- 7.3 in 3WHx.
 This difference was mainly due to a larger increase in HCO3- excretion in Nx.
 The data suggest that the smaller compensation of hypocapnic alkalosis in 3WHx is partly due to the smaller increase in renal base excretion.
 Because base availability limits renal base excretion, the smaller renal response of 3WHx may be secondary to the low plasma HCO3- concentration that accompanies altitude acclimation.
",7
1164,"Effects of ligation and embolization on Kf and multiple tracer measurements in dog lungs.
 In isolated blood-perfused dog lungs, the capillary filtration coefficient (Kf) and the permeability-surface area product of urea (PS) were measured to determine their responses to two different methods of altering filtration area: lobe ligation (LL, n = 5) and glass bead embolization (GBE, n = 4) during constant perfusion rates (700 +/- 45 ml/min).
 When two of three lobes were ligated, Kf decreased (1.36 +/- 0.13 to 0.58 +/- 0.23 g.min-1.cmH2O-1; P less than 0.05), but PS did not change (2.02 +/- 0.4 to 1.71 +/- 0.3 ml/s).
 Kf per gram of perfused blood-free dry lung weight was unchanged by LL (0.051 +/- 0.17 to 0.052 +/- 0.18 g.min-1.cmH2O-1), indicating that surface area per gram measured by Kf remained the same.
 However, PS per gram dry lung doubled (0.07 +/- 0.016 to 0.146 +/- 0.06 ml/s; P less than 0.05) after LL, suggesting that recruitment occurred in the remaining lobe.
 When three lobes were embolized with 200-microns glass beads (0.48 +/- 0.01 g beads/kg body wt), PS decreased (2.1 +/- 0.22 to 0.94 +/- 0.09 ml/s; P less than 0.05), but Kf was not altered (1.01 +/- 0.17 to 1.04 +/- 0.18 g.min-1.cmH2O-1).
 The constancy of Kf after GBE implies that the vascular pressure increase during the Kf measurement was transmitted to both blocked and flowing vessels and thereby measured the same filtration area before and after GBE.
 PS decreased significantly after GBE because of a loss of perfused surface area by the beads blocking flow in small arterial vessels.
",7
1165,"Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen.
 Rats were exposed to 100% oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema.
 The time course of development of increased solute flux was assessed by the clearance of 99mTc-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from the lung and the accumulation of 125I-labeled albumin (125I-albumin) in the lung.
 These end points were related to the development of pulmonary edema by the measurement of the wet-to-dry weight ratio of the lung and the weight of fluid in the pleural cavity.
 No significant changes occurred until 48 h of hyperoxia, when sharp increases in both indexes of lung permeability and wet-to-dry weight ratio occurred.
 By 60 h of exposure, pleural effusions had developed.
 The volume of this effusion was significantly correlated to both 99mTc-DTPA clearance and 125I-albumin flux.
",7
1166,"Stimulation of rat endothelial cell transforming growth factor-beta production by bleomycin.
 This study examines the hypothesis that mediators from lung endothelial cells could promote lung collagen synthesis in pulmonary fibrosis.
 Since bleomycin induces pulmonary fibrosis in humans and animals, the effects of this drug on endothelial cells were examined.
 Endothelial cell conditioned media were prepared in the presence of various doses of bleomycin, and tested for their ability to stimulate lung fibroblast collagen synthesis.
 The results show a dose-dependent stimulation of endothelial cell secretion of collagen synthesis stimulatory activity by bleomycin, which peaked at a dose greater than or equal to 100 ng/ml.
 Stimulation was selective for collagenous protein synthesis.
 Gel filtration analysis showed most of the activity to reside in fractions with an estimated molecular mass range of 10-27 kD.
 The activity was inhibited by anti-transforming growth factor-beta (TGF-beta)antibody, but not by nonimmune control IgG.
 The presence of TGF-beta was confirmed using the mink lung epithelial cell assay.
 Northern blotting revealed significant increases in TGF-beta mRNA in bleomycin-stimulated endothelial cells.
 Thus in vitro stimulation of endothelial cells by bleomycin upregulates TGF-beta production, presumably by increased transcription.
 In view of the chemotactic and matrix synthesis stimulatory properties of this cytokine, such an increase in TGF-beta production may play an important role in bleomycin-induced pulmonary fibrosis.
",7
1167,"Purification and characterization of a major human Pneumocystis carinii surface antigen.
 Previous studies of Pneumocystis carinii have identified the major surface antigen of rat and human isolates as proteins of 116,000 and 95,000 mol wt, respectively, that are antigenically not identical.
 In this study both rat and human P.
 carinii proteins were purified by solubilization with zymolyase followed by molecular sieve and ion exchange chromatography.
 The native proteins had an apparent mol wt of 290,000 or greater, based on molecular sieve studies as well as cross-linking studies.
 Both proteins were glycoproteins; treatment with endoglycosidase H resulted in a 9% decrease in mol wt.
 The carbohydrate composition of the rat P.
 carinii glycoprotein was distinct from the human isolate; glucose, mannose, galactose, and glucosamine occurred in approximately equimolar ratios in the human P.
 carinii protein, whereas glucose and mannose were the predominant sugars of the rat P.
 carinii protein.
 To evaluate humoral immune responses to the human P.
 carinii protein, an enzyme-linked immunosorbent assay using purified protein was developed.
 Some, but not all, patients who subsequently developed P.
 carinii pneumonia demonstrated a serum antibody response to the surface antigen.
 Nearly all subjects without a history of P.
 carinii pneumonia had no detectable antibodies.
 Purified P.
 carinii proteins will greatly facilitate the investigation of host-P.
 carinii interactions.
",7
1168,"A double-blind comparison of intranasal budesonide with placebo for nasal polyposis.
 Intranasal budesonide, 400 micrograms two times a day, was evaluated in 36 patients referred for treatment of nasal polyposis.
 The age range was 20 to 68 years.
 Polypectomy was done 5.6 (mean) times previously.
 After a 5-week, treatment-free, baseline period, patients were treated in a double-blind fashion with either budesonide or placebo during 4 weeks.
 After this treatment period, placebo-treated patients started receiving budesonide in an open trial for an additional 4 weeks.
 The patients rated their nasal symptoms daily.
 Nasal examinations and nasal inspiratory flow rate (IFR) measurements were done at clinic visits.
 After 3 and 4 weeks of treatment, the response to budesonide was significantly greater than response to placebo.
 The greater reduction in nasal blockage caused by polyps, observed on physical examination, p = 0.005, was mirrored by an increase in nasal IFR (p = 0.0001).
 Patient rating of the severity and frequency of nasal blockage were reduced more by budesonide than by placebo (p less than or equal to 0.0005).
 Switching placebo-treated patients to budesonide treatment resulted in a reduction of nasal blockage (p less than 0.001) and an increase in nasal IFR (p less than 0.001).
 The results demonstrate that topical nasal budesonide, 400 micrograms two times a day, is an effective treatment of nasal polyps.
",7
1169,"Expression of neurophysin-related precursor in cell membranes of a small-cell lung carcinoma.
 A monoclonal antibody (mAb L6) to a small-cell lung carcinoma surface antigen recognizes a common epitope of vasopressin-neurophysin and oxytocin-neurophysin in hypothalamic nuclei.
 We now report on the identification of a neurophysin-like precursor in human lung carcinoma (LX-1) cell membrane.
 mAb L6 immunoaffinity chromatography of solubilized membranes resulted in a single band of approximately 45 kDa.
 Western blot analysis demonstrated immunoreactivity of this band with mAb L6, anti-vasopressin, and an antibody to the vasopressin precursor, pro-pressophysin.
 N-terminal sequencing of this band demonstrated a 21-amino acid homology with the N terminus of human pro-pressophysin, and substitution of a Cys33 residue in the tumor antigen with Arg33.
 Absence of immunoreactivity with the antibodies described above in cytosolic extracts and culture medium suggests nonsecretion of processed or intact pro-pressophysin-like peptide.
 Northern analysis of LX-1 mRNA with a 30-mer to the C terminus of rat pro-pressophysin resulted in a band of approximately 1000 base pairs, 250 base pairs larger than hypothalamic message.
 In situ hybridization of LX-1 tumor-bearing nude rat brain with the same probe demonstrated specific hybridization in rat hypothalamus and xenografted tumor.
 These findings suggest expression of a pro-pressophysin-like protein in this tumor cell line that is preferentially targeted to the cell membrane.
",7
1170,"Laryngeal changes during exercise and exercise-induced asthma.
 Exercise-induced asthma is defined as bronchospasm within the distal airways initiated by exercise.
 Whether the larynx responds to produce an exacerbation or alleviation of symptoms during an attack has never been evaluated.
 Thirty subjects were tested, including 15 normals and 15 with exercise-induced asthma.
 Laryngeal response to exercise was determined by measuring the area of the glottic aperture before, during, and after exercise.
 The glottis was visualized with a flexible laryngoscope and video images were recorded during monitoring of respirations.
 Asthma was induced in subjects by having them exercise on an ergometer for 10 minutes while breathing dry air at 10 degrees C.
 Measurements were subsequently made from recorded images and relative glottic areas were compared between groups.
 Our data quantify the normal physiologic response of the larynx to exercise and demonstrate a substantial laryngeal contribution to asthma induced by exercise.
",7
1171,"Altered cellular immune function in the atelectatic lung.
 Pulmonary atelectasis is common and may predispose the lung to infection.
 We have previously shown that atelectasis impairs alveolar macrophage antibacterial function.
 This study examines the effect of atelectasis on the cytotoxic function of lymphocytes harvested from the bronchoalveolar space of atelectatic lung segments by bronchoalveolar lavage.
 Specifically, we studied natural killer and lectin-dependent cell-mediated cytotoxicity in peripheral blood and bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and contralateral normal lobes in a group of 8 dogs.
 We observed a decline of natural killer and lectin-dependent cell-mediated cytotoxicity to 62.7% and 61.5%, respectively, of preatelectasis control values in the affected lung lobes (p less than 0.01).
 Simultaneous measurements of cytotoxic activity of bronchoalveolar lavage lymphocytes harvested from the unaffected contralateral normal lungs were comparable with control values.
 On the other hand, natural killer and lectin-dependent cell-mediated cytotoxicity activities in peripheral blood lymphocytes were significantly increased in animals having right lower lobe atelectasis (166.7% and 154.7% of pretreated normal control, respectively, p less than 0.01).
 Atelectasis was also associated with an influx of polymorphonuclear leukocytes into the bronchoalveolar compartment.
 These findings confirm the presence of natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment and demonstrate an atelectasis-induced impairment of local bronchoalveolar lymphocyte function.
 Such a dysfunction of local lung cellular host defenses may render the atelectatic lung susceptible to infection.
",7
1172,"Hemoptysis. Indications for bronchoscopy.
 Indications for bronchoscopy in patients with hemoptysis and a normal or nonlocalizing chest roentgenogram continue to be controversial.
 We reviewed the records for 119 bronchoscopies performed for hemoptysis in patients with a normal (n = 75) or nonlocalizing (n = 44) chest roentgenogram.
 Bronchogenic carcinoma was identified in 2.5% of the bronchoscopies.
 Additional neoplasms were found in another 2.5%.
 The presence of nonlocalizing abnormalities was not associated with an increase in either the rate of bronchogenic carcinoma or in the diagnostic yield (specific anatomic diagnosis or bleeding site identified) at bronchoscopy when compared with patients with normal chest roentgenograms.
 The factors of male sex, age more than 40 years, and a more than 40 pack-year smoking history appear useful in identifying patients in whom the yield of bronchoscopy is likely to be high.
",7
1173,"Ultrasound assessment of the position of the tongue during induction of anaesthesia.
 Tongue position was assessed in 15 female patients at induction of anaesthesia with either thiopentone or propofol.
 A video recording of a midline sagittal section of the tongue was made using an ultrasound transducer placed below the chin, and representative figures analysed by an observer who was not aware of the patient's state.
 In 11 satisfactory recordings, the tongue movement was inconsistent in direction and not more than 8 mm in the anterior tongue and 6 mm in the posterior tongue.
 The movements detected did not suggest that the tongue is likely to be an important cause of airway obstruction on induction of anaesthesia.
",7
1174,"Factor analysis in difficult tracheal intubation: laryngoscopy-induced airway obstruction.
 We have studied eight patients with a history of difficult tracheal intubation, using x-ray laryngoscopy and local anaesthesia, a curved Macintosh blade and a standard intubating position.
 The view obtained was better than recorded previously during general anaesthesia in two patients, and in a third the x-ray showed that positioning the blade tip beneath the epiglottis would have improved vision, suggesting that reproducibility of the assessment may not be consistent.
 The ""ease of intubation"" and ""complementary"" angles may be helpful in the assessment of such patients.
 A ""peardrop"" effect is described whereby during laryngoscopy, the epiglottis became pressed against the posterior pharyngeal wall as a result of tongue compression.
 In the absence of muscle paralysis, removal of the blade caused immediate correction.
 However, during anaesthesia with neuromuscular block it is suggested that this not only occurs more readily but, may not correct when the blade is removed.
 Iatrogenic airway obstruction during moderately difficult tracheal intubation may be common and should be anticipated.
",7
1175,"Diagnostic sensitivity of different techniques in the diagnosis of lung tumors with the flexible fiberoptic bronchoscope. Comparison of brush biopsy, imprint cytology of forceps biopsy, and histology of forceps biopsy.
 Brush and forceps biopsies were done consecutively in 186 cases of pulmonary neoplasia with a flexible fiberoptic bronchoscope guided by x-ray television fluoroscopy.
 Imprint and histologic sections were prepared from all forceps biopsy specimens.
 The three techniques were compared for their diagnostic sensitivity.
 As a result 84.9% of all imprints, 80.6% of brush biopsy specimens, and 62.9% of histologic sections were positive for malignancy.
 The sensitivity of brush biopsy specimens was independent of the location and morphology of the tumors, but the sensitivity of forceps biopsy specimens was lower in neoplasms unidentified by bronchoscopy.
 The sensitivity of the diagnostic accuracy when all three methods were used jointly was 97.3%, and the specificity was 100%.
 Agreement in the final morphologic tumor type was found in 130 of 150 cases (86.7%) by positive brush biopsy specimens, in 136 of 158 cases (86.1%) by positive imprint cytology, and in 104 of 117 cases (88.9%) by positive histology from forceps biopsy specimens.
 For routine bronchoscopy, all three methods should be used in combination to obtain the highest diagnostic yield.
",7
1176,"Prolonged venous infusion of cisplatin and concurrent radiation therapy for lung carcinoma. A feasibility study.
 Fifty patients with non resectable and/or inoperable bronchogenic carcinoma were entered into a feasibility study of cisplatin (CDDP) given in continuous infusion with concurrent radiation therapy.
 The radiation therapy regimen consisted of 2 Gy given 5 days a week in the first 3 and last 2 weeks of a 7-week split course (50 Gy of total dose).
 The CDDP (daily dose of 4 to 6 mg/m2) was administered to cover the days of radiation treatment by means of a central venous catheter and a portable pump.
 Less than 1% of predicted duration of infusion was lost due to complications related to venous access and pump.
 Toxicity was moderate.
 The overall probability of a locoregional major response (complete + partial) within 1 month after treatment completion was 86%.
 Twenty-three patients underwent resection.
 The 1-year actuarial probability of survival was 64%.
 The high response and survival rates warrant further studies on concurrent CDDP continuous infusion and radiation therapy in inoperable lung carcinoma.
",7
1177,"Life-threatening airway obstruction at the presentation of Hodgkin's disease.
 Mediastinal involvement from Hodgkin's disease is common.
 Significant symptoms resulting from disease at this site are less common and only rarely does severe airway obstruction occur.
 The authors report six cases of Hodgkin's disease in which life-threatening airway obstruction was a major feature of the clinical presentation and early clinical course.
 The literature describing this complication is reviewed.
 General anesthesia with endobronchial intubation should be avoided if at all possible in patients with airway obstruction and alternative methods of diagnosis and management are discussed.
",7
1178,"Vocal fold sulcus.
 Vocal fold sulcus is a cause of dysphonia which has not been recognized until recently.
 Awareness of its existence combined with use of laryngostroboscopy would enhance the management of this group of patients.
 Five such cases were treated initially by voice therapy and subsequently combined with microlaryngeal Teflon injections of the vocal cord.
 Representative photomicrographs and the end results of treatment are presented.
 A good voice, subjectively and objectively, was obtained in three patients, with satisfactory improvement in the other two.
",7
1179,"Tracheostomy closure in restrictive respiratory insufficiency.
 A retrospective study is presented of 31 patients who required ventilatory support via a tracheostomy for periods of one month to 27 years whilst in a tertiary referral centre for the care of patients with restrictive respiratory insufficiency.
 All patients underwent closure of a long-standing tracheostomy.
 Post-operative follow-up periods of up to 16 years are documented.
 The indications for and the complications of tracheostomy closure in patients with severe chronic restrictive respiratory insufficiency requiring long-term respiratory support are discussed.
 It is concluded that the benefits of operative tracheostomy closure outweigh the disadvantages in this unusual type of patient.
",7
1180,"Differential diagnosis of lung tumor with positron emission tomography: a prospective study.
 To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F-fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET).
 Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001).
 The ratios indicate that malignant tumors have higher metabolic demand than benign lesions.
 Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution.
 Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24).
 The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively.
 No significant differences were observed between the two tracers.
 This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors.
",7
1181,"Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial.
 We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment.
 There were no differences among the three study groups in the proportion of children considered ""better"" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53).
 There were no differences among groups in individual or composite symptom score changes.
 Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms.
 In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused.
 Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment.
 We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.
",7
1182,"Prognosis of idiopathic pulmonary fibrosis in patients with mucous hypersecretion.
 In order to determine the prognosis of patients with chronic idiopathic pulmonary fibrosis (IPF), we evaluated clinical, laboratory, and bronchoalveolar lavage (BAL) data at the onset of IPF in 25 patients who survived beyond 1 yr (nine women and 16 men, 59 +/- 3 yr of age, mean +/- SE).
 When the patients were divided into two groups according to whether they had or did not have mucous hypersecretion, 11 patients with hypersecretion (Group A) had a poorer survival rate (6 yr) than did 14 patients without hypersecretion (Group B) (10 yr) (p less than 0.01).
 Further, there was a significant negative correlation between sputum volume and the duration of survival in 25 patients (r = -0.55, p less than 0.01).
 Before glucocorticoid treatment, we also found significantly larger numbers of neutrophils (17%) and eosinophils (5%) in differential cell counts of bronchoalveolar lavage fluid (BALF) in Group A than in Group B (neutrophils, 1%; eosinophils, 0.6%) (p less than 0.05 each).
 Chest radiographic findings and other laboratory data including pulmonary function tests did not correlate with the survival rate.
 These findings suggest that mucous hypersecretion as well as neutrophils and eosinophils in BALF are among the determinants of prognosis in patients with chronic IPF.
",7
1183,"Serum and lavage lactate dehydrogenase isoenzymes in pulmonary alveolar proteinosis.
 Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of lipoproteinaceous material in the alveolar space.
 Serum lactate dehydrogenase (LDH) has been noted to be elevated in patients with PAP in previous studies.
 We sought to extend this observation in a series of patients with PAP by looking at total serum LDH concentrations and LDH isoenzyme fractions measured before and after whole lung lavage.
 Total LDH and LDH isoenzymes were also determined in the lavage effluent.
 Total serum LDH was elevated before lavage in 10 of 16 patients.
 Prelavage serum LDH and prelavage alveolar-arterial O2 gradient showed a significant correlation (r = 0.62, p less than 0.05).
 A decrease in serum LDH was found after lavage in all patients in whom postlavage data was available (paired t test, p less than 0.01, n = 11), although the magnitude of this decrease varied considerably.
 The isoenzyme pattern before lavage was isomorphic, and this pattern was unchanged after whole lung lavage.
 This was in marked contrast to the LDH isoenzyme pattern observed in the lavage effluent, which showed a lower percent LDH1 and LDH2 and a higher percent LDH3, LDH4, and LDH5 when compared with the corresponding prelavage isoenzyme percentages for serum (unpaired t test, p less than 0.001).
 There was no correlation between the total serum LDH concentration and the total lavage LDH concentration.
 These data confirm that elevated serum LDH is a common finding in PAP.
 Furthermore, the LDH elevation found consistently in the alveolar fluid points to this as the source of the serum LDH.
",7
1184,"Breathing circuit respiratory work in infants recovering from respiratory failure.
 OBJECTIVE: To compare cardiopulmonary function during spontaneous breathing with three continuous-flow breathing circuits.
 The major difference between these circuits was the degree of flow resistance offered by the exhalation valve.
 DESIGN: Randomized crossover trial.
 PATIENTS: Twelve infants less than 12 months of age recovering from respiratory failure of variable etiology.
 Only patients weighing 3 to 10 kg were studied.
 INTERVENTIONS: The patients were connected to each respiratory circuit in a random sequence, with 15 min allowed for equilibration before assessment of cardiopulmonary function.
 Airway pressure (Paw) and FIO2 were maintained unchanged.
 MEASUREMENTS AND MAIN RESULTS: Ventilation, gas exchange, or circulatory function were not altered significantly by changing the breathing circuit.
 However, Paw and esophageal pressure fluctuations were altered and were largest during breathing with the circuit that had an exhalation valve with high-flow resistance.
 The Paw fluctuation recorded while the patient was breathing with the flow-resistor circuit increased with weight and exceeded 2 cm H2O in all patients weighing greater than 4.5 kg.
 Paw fluctuation could be decreased by greater than 2 cm H2O in ten of 12 patients by using the threshold-resistor circuit.
 CONCLUSIONS: The results indicate a need for evaluating the characteristics of respiratory circuits used for spontaneous breathing in infants and children, to avoid unnecessary equipment-related increase in respiratory work.
",7
1185,"The reliability of magnitude estimation for dyspnea measurement.
 The reliability of magnitude estimation with an open scale was evaluated in a physiologically stable population of adults with chronic respiratory disease who experienced chronic dyspnea.
 Magnitude estimation was used to measure one dimension of dyspnea, perceptual sensitivity.
 The relationship between external inspiratory resistive loads (stimuli) and numbers that reflected the perceived intensity of the breathing effort (response) as expressed by a power function was measured on three visits 3 to 5 days apart.
 The correlations of the exponent of the power function between visits were high and stable.
",7
1186,"Lung abscess: CT-guided drainage.
 Lung abscesses were drained by means of catheters guided by computed tomography (CT) in 19 patients who still had sepsis despite standard medical therapy; all patients had received antibiotics for at least 5 days, and 11 of the 19 patients had undergone bronchoscopy.
 The abscess was cured (by clinical and radiographic criteria) in all 19 patients (100%), and surgery was avoided in 16 of the 19 patients (84%).
 Three patients underwent surgery for removal of organized tissue or decortication after the lung abscess was evacuated.
 Complications included a hemothorax that required a chest tube in one patient and three minor complications (a clogged catheter in two patients and transient elevation of intracerebral pressure in one patient).
 The hemothorax occurred in one of two patients in whom the catheter traversed normal lung.
 The percutaneous drainage catheters traversed juxtaposed abnormal pleura on route to the abscess in 17 of the patients.
 CT-guided drainage of lung abscess is an effective method to treat lung abscesses that are refractory to conventional therapy; the procedure should obviate major operation in most patients.
 A catheter route through abscess-pleural syndesis is preferable, and CT is useful for planning this route.
",7
1187,"Respiratory rate greater than 50 per minute as a clinical indicator of pneumonia in Filipino children with cough.
 The diagnosis and epidemiology of acute respiratory tract infection (ARI) in 199 children less than 5 years old were investigated in Manila.
 As part of this study, children who were treated at one of two outpatient clinics for cough of less than 3 weeks' duration were studied to test the validity of the use of a respiratory rate (RR) of greater than 50/minute for identifying ARI of a severity necessitating treatment with antibiotics.
 In the first population, in which 69% of the children had radiologically confirmed pneumonia, the sensitivity of a RR of greater than 50/minute was 54%, the specificity was 84%, the false-positive rate was 16%, and the false-negative rate was 46%.
 In the second population, in which 29% of the children had pneumonia, the sensitivity and positive predictive values were low.
 The validity of a RR of greater than 50/minute may vary in populations with different prevalences of ARI.
",7
1188,"Aspiration pneumonitis: risk factors and management of the critically ill patient.
 Pulmonary aspiration of gastric contents is a significant source of patient morbidity, mortality, and increased healthcare costs.
 Prevention by identifying patients at risk for aspiration and initiating prophylaxis is the most effective method of reducing complications associated with aspiration pneumonitis.
 H2-receptor antagonists are among the best prophylactic agents because of their efficacy in reducing gastric acidity and their convenience of administration.
",7
1189,"Diagnosis of Pneumocystis carinii pneumonia from non-invasive sampling of respiratory secretions.
 An infant infected with HIV presented with fever, tachypnoea, hypoxia, and radiological evidence of bilateral pneumonitis.
 Fluorescent antibody technique identified Pneumocystis carinii within 24 hours from secretions obtained by nasopharyngeal aspiration.
 This rapid, non-invasive method should be the first line investigation of suspected P carinii pneumonia in immunocompromised patients.
",7
1190,"Air pollution and fatal lung disease in three Utah counties.
 A unique situation found in two Utah counties has made it possible to estimate the fraction of respiratory cancer and nonmalignant respiratory disease (NMRD) deaths, which are attributable to community air pollution (CAP) in one county.
 The two counties were very similar in many ways, including low smoking rates, until a steel mill constructed during WW II caused substantial CAP in one of them.
 Subsequent differences in mortality rates from both respiratory cancer and NMRD are striking.
 A third county, similar to many counties outside Utah, was included in the analysis for comparison.
 In one county, 30-40% of the respiratory cancer and NMRD deaths were attributable to CAP.
 In this county, NMRD deaths (but not respiratory cancer deaths) were slightly more frequent than in Salt Lake County where smoking rates were twice as high.
",7
1191,"Health effects of volcanic ash: a repeat study.
 The Mount Sakurajima volcano in Kyushu, Japan, is proximal to a large residential area, and it emits an enormous amount of volcanic ash during frequent eruptions.
 In our previous study, we investigated, for the first time, respiratory effects of chronic exposure to volcanic ash.
 The study demonstrated a low prevalence of respiratory symptoms, even in the area of highest exposure; only a slight excess prevalence of symptoms appeared to be associated with exposure to volcanic ash.
 To confirm the findings of our previous study, the prevalence study of chronic respiratory symptoms for residents was repeated in Kanoya and Tashiro, which are located 25 and 50 km, respectively, from the crater of Mt.
 Sakurajima.
 The concentration of suspended particulate matter in Kanoya frequently exceeded the national environmental quality standards and, during summer and winter, was 2-3 times higher than that found in Tashiro.
 Women who were 30-59 y of age and who had resided in Kanoya or Tashiro for more than 3 y completed a modified ATS-DLD questionnaire.
 The prevalence of nonspecific respiratory disease was low, i.e., 6.5% in Kanoya and 6.2% in Tashiro; similar prevalences were found in women who had never smoked.
 When we restricted the analysis to individuals without a history of occupational exposure to dusts and who had no exposure to passive smoking, there was a slightly higher prevalence of nonspecific respiratory disease in Kanoya than Tashiro, but the difference was not significant.
 Eye symptoms were equally prevalent in the two areas.
",7
1192,"Interaction of chemical and high vascular pressure injury in isolated canine lung [published erratum appears in J Appl Physiol 1991 Mar;70(3):964]
 Because both chemical and mechanical insults to the lung may occur concomitantly with trauma, we hypothesized that the pressure threshold for vascular pressure-induced (mechanical) injury would be decreased after a chemical insult to the lung.
 Normal isolated canine lung lobes (N, n = 14) and those injured with either airway acid instillation (AAI, n = 18) or intravascular oleic acid (OA, n = 25) were exposed to short (5-min) periods of elevated venous pressure (HiPv) ranging from 19 to 130 cmH2O.
 Before the HiPv stress, the capillary filtration coefficient (Kf,c) was 0.12 +/- 0.01, 0.27 +/- 0.03, and 0.31 +/- 0.02 ml.min-1.cmH2O-1 x 100 g-1 and the isogravimetric capillary pressure (Pc,i) was 9.2 +/- 0.3, 6.8 +/- 0.5, and 6.5 +/- 0.3 cmH2O in N, AAI, and OA lungs, respectively.
 However, the pattern of response to HiPv was similar in all groups: Kf,c was no different from the pre-HiPv value when the peak venous pressure (Pv) remained less than 55 cmH2O, but it increased reversibly when peak Pv exceeded 55 cmH2O (P less than 0.05).
 The reflection coefficient (sigma) for total proteins measured after pressure exposure averaged 0.60 +/- 0.03, 0.32 +/- 0.04, and 0.37 +/- 0.09 for N, AAI, and OA lobes respectively.
 However, in contrast to the result expected if pore stretching had occurred at high pressure, in all groups the sigma measured during the HiPv stress when Pv exceeded 55 cmH2O was significantly larger than that measured during the recovery period.
",7
1193,"Cough-enhanced mucus clearance in the normal lung.
 We studied the effectiveness of cough for clearing mucus in 12 nonsmoking subjects with normal lung function.
 On 2 separate study days, each subject breathed 6-microns Mass Median Aerodynamic Diameter 99mTc-labeled iron oxide particles under controlled breathing conditions while they were seated in front of a gamma camera.
 Retention (R) of lung activity was measured over the initial 2 h and again at 24 h after particle inhalation.
 On the control day the subject sat quietly in front of the camera, while on the cough day each subject performed 60 controlled coughs during the 1st h of retention measurements.
 By paired analysis, retentions at both 1 and 2 h (R1 and R2, respectively) for the cough measurements were significantly less than control (mean control R1 = 85% vs.
 mean cough R1 = 72%, P less than 0.002; mean control R2 = 75% vs.
 mean cough R2 = 65%, P less than 0.02).
 Retention at 24 h (R24) was not significantly different between cough and control measurements (mean cough R24 = 35% and mean control R24 = 32%).
 Thus coughing increased the rate at which the radiolabeled particles were cleared from the bronchial airways in these individuals.
 Follow-up experiments with subjects performing rapid inhalations rather than cough showed similar enhanced particle clearance to that seen with cough.
 These results suggest that the observed enhancement of mucus clearance by cough (and rapid inhalation) in the normal lung may be due to a stimulation of the mucociliary apparatus rather than via a two-phase gas-liquid flow mechanism.
",7
1194,"Intensive weekly chemotherapy for good-prognosis patients with small-cell lung cancer.
 A weekly, intensive chemotherapy regimen has been used to treat 70 patients with small-cell lung cancer (SCLC).
 Forty-five patients had limited disease (LD) and 25 extensive disease (ED) with good prognostic features.
 The regimen consisted of cisplatin 50 mg/m2 intravenously (IV) day 1 and etoposide 75 mg/m2 IV days 1 and 2, alternating weekly with ifosfamide 2 g/m2 IV day 8 and doxorubicin 25 mg/m2 IV day 8, for a total of 12 weeks.
 Dose modifications were made according to defined hematologic criteria.
 Responding patients with limited disease subsequently received mediastinal radiotherapy.
 Overall response to chemotherapy was 91% with a complete response (CR) rate of 50%.
 Forty-five patients with limited disease (LD) achieved an overall response rate of 91% with a CR rate of 51%, and 25 patients with extensive disease (ED) achieved an overall response rate of 92% with a CR rate of 48%.
 Median survival for the whole group was 54 weeks (LD, 58 weeks; ED, 42 weeks).
 Hematologic toxicity was predictable, without the wide fluctuations in WBC count seen in conventional 3-weekly regimens.
 In all, one quarter of treatment courses were delayed, most frequently because of leukopenia.
 Dose reductions were required in 63% of cases.
 The average delivered dose intensity was calculated and shown to be 73% of projected.
 Nonhematologic toxicity was mild with nausea and vomiting being the most common.
 This weekly schedule of chemotherapy has proved to be active and well tolerated and is currently being compared with conventional 3-weekly chemotherapy in a randomized study.
",7
1195,"At the water's edge: where obstetrics and anesthesia meet 
 Conflict exists between satisfying the parturient's desire for oral intake and traditional restrictive standards of obstetric and anesthesia departments.
 Surveys of institutions providing obstetric services reveal greatly varying oral intake policy.
 There is neither evidence of benefit in withholding fluids nor evidence of risk in allowing them.
 Prolonged fasting has potential liabilities.
 Maternal mortality is rare, and anesthesia-related causes are not among the common etiologies.
 Aspiration is not a significant factor in the modern era.
 Higher risk for anesthesia morbidity is associated with general anesthesia, particularly difficult intubation.
 Instead of implicating oral intake as a risk factor for pulmonary aspiration, the literature consistently emphasizes the critical role of properly trained and dedicated obstetric anesthesia personnel.
 Unless parturients are not candidates for regional anesthesia, a nonparticulate diet should be allowed.
 Liberal use of regional anesthesia as well as antacid prophylaxis is recommended.
",7
1196,"Lung scanning for pulmonary embolism: clinical and pulmonary angiographic correlations.
 A group of 78 patients with suspected pulmonary embolism was studied by both ventilation perfusion lung scanning and pulmonary angiography.
 Symptoms and clinical signs were analysed using Bayesian techniques to produce pre-test odds for pulmonary embolism in individual patients.
 While, as a group, those with embolism could be discriminated from those without on this basis, major overlap existed between the groups, invalidating the use of this approach for individual patients.
 Strict diagnostic criteria for interpretation of lung scans were accurate using pulmonary angiography as the 'gold standard', but at the expense of a significant number of patients (38 per cent) in the indeterminate (non-diagnostic) group.
 In the 48 patients in whom the test yielded a diagnostic result, there was a sensitivity of 100 per cent (15/15) and a specificity of 97 per cent (32/33).
 In the series as a whole, the likelihood of lung scanning correctly diagnosing pulmonary embolism was 55 per cent (15/27) and of correctly excluding embolism, 63 per cent (32/51).
 By the use of strict criteria for interpretation of lung scanning, reliable information can be obtained on the presence or absence of pulmonary embolism in a large proportion of patients suspected of having the condition.
 Such information is more discriminating than clinical signs and symptoms.
",7
1197,"The ""natural history"" of the transplanted lung: rates of pulmonary functional change in long-term survivors of heart-lung transplantation.
 Long-term pulmonary function in HLT is well preserved with no evidence of functional decline as a result of transplant ""aging,"" providing the allografts remain free of complications.
 Long-term survivors with OB appear to be able to maintain adequate oxygenation despite the marked alterations of pulmonary function.
 The ability to preserve gas exchange at reasonable levels of oxygenation may be the factors permitting extended survival with OB for mean periods of 36.0 months or greater.
 Preliminary studies suggest that a declining FEF50/FVC, at a time when pulmonary function is normal, may be an index of impending airway disease.
 Physiologically, from a long-term point of view, HLT remains a viable option for selected patients with end-stage cardiopulmonary disease.
",7
1198,"Single-lung transplantation for pulmonary vascular disease.
 Six patients with end-stage pulmonary vascular disease received right SLTs.
 Though patients generally had difficult early postoperative courses, four of the six have survived from 3 to 23 months and have achieved good recovery of right ventricular function and good functional results.
 SLT is a viable option in selected patients with severe pulmonary hypertension even when right ventricular function is severely impaired.
",7
1199,"Body composition by bioelectrical-impedance analysis compared with deuterium dilution and skinfold anthropometry in patients with chronic obstructive pulmonary disease.
 Body composition is an important measure of nutritional status in patients with chronic obstructive pulmonary disease (COPD).
 We generated a regression model for bioelectrical impedance (BI) by using deuterium dilution (2H2O) as a reference method in 32 COPD patients, aged 63 +/- 9 y (mean +/- SD), in stable pulmonary and cardiac condition.
 Height squared divided by resistance (Ht2/Res) correlated well with total body water (TBW) as measured by 2H2O (r = 0.93, P less than 0.001, SEE = 1.9 L).
 The best-fitting regression equation to predict TBW comprised Ht2/Res and body weight (r2 = 0.89, SEE = 1.8 L, P less than 0.001).
 BI-predicted TBW was used to estimate BI-fat-free mass (FFM) that was compared with skinfold-thickness-based FFM predictions (Anthr-FFM).
 Relative to BI-FFM a significant overestimation of 4.4 +/- 0.8 kg was found by Anthr-FFM.
 Our results suggest that BI is a useful measure of body composition in patients with severe COPD.
",7
1200,"Pulmonary embolectomy: a 20-year experience at one center 
 Between 1968 and 1988, 96 consecutive patients with acute massive pulmonary embolism underwent pulmonary embolectomy under cardiopulmonary bypass.
 The operative mortality rate was 37.5%.
 We analyzed 12 clinical and hemodynamic variables by univariate and multivariate analyses to assess the predictive factors of postoperative outcome.
 Multivariate analysis disclosed that cardiac arrest and associated cardiopulmonary disease were independent predictors of operative death.
 Long-term follow-up (range, 2 to 144 months; mean, 56 months) information was available for 55 of the 60 discharged patients: 6 had died, and 5 complained of persistent mild or severe exertional dyspnea (New York Heart Association class II).
 These results help assess the preoperative risk in patients undergoing pulmonary embolectomy.
 They also show that, in the few patients who do not benefit from optimal medical therapy, pulmonary embolectomy remains an acceptable procedure in view of the long-term results.
",7
1201,"Improved outcomes from tertiary center pediatric intensive care: a statewide comparison of tertiary and nontertiary care facilities 
 OBJECTIVE: To compare outcomes from pediatric intensive care in hospitals with different levels of resources.
 DESIGN: Prospective, blinded comparison of outcome and care.
 SETTING: Tertiary (n = 3) and nontertiary (n = 71) hospitals in Oregon and southwestern Washington.
 PATIENTS: All critically ill children admitted with respiratory failure and head trauma for 6 months.
 MEASUREMENTS AND MAIN RESULTS: Severity of illness adjusted mortality rates were determined using admission day, physiologic profiles (Pediatric Risk of Mortality score) and care modalities were assessed daily.
 The crude mortality rate of the tertiary patients was four times higher than for the nontertiary patients (23.4% vs.
 6.0%, p less than .0001).
 In the tertiary patients, the numbers of outcomes were accurately predicted by physiologic profiles (observed: 30 deaths and 98 survivors; predicted: 29.3 deaths and 98.7 survivors, z = -.25, p greater than .4).
 However, for the nontertiary patients, the number of the deaths were significantly different than predicted (observed: 20 deaths and 315 survivors; predicted: 14.4 deaths and 320.6 survivors, z = -2.08, p less than .05).
 The odds ratios of dying in a nontertiary vs.
 a tertiary facility were about 1.1, 2.3, and 8 (p less than .05) for mortality risk groups of less than 5%, 5% to 30%, and greater than 30%.
 Patients in tertiary facilities received more (p less than .05) invasive (e.g., arterial catheters) and complex (e.g., mechanical ventilation) care, whereas patients in nontertiary facilities received more (p less than .05) labor-intensive care (e.g., hourly vital signs).
 CONCLUSIONS: Care of the most seriously ill children in tertiary pediatric ICUs could improve their chances of survival.
",7
1202,"Inhibition by methylprednisolone of leukocyte-induced pulmonary damage.
 BACKGROUND AND METHODS: The purpose of this study was twofold: the development of a chronic model of leukocyte-mediated pulmonary injury and the evaluation of the protective effects of methylprednisolone.
 Rabbits were inoculated ip with zymosan.
 Blood gases and circulating leukocytes were evaluated.
 Survivors were killed on day 10 for microscopic studies and for the evaluation of lung lipid peroxidation through the by-product malondialdehyde.
 RESULTS: Intraperitoneal zymosan resulted in a marked decrease of Pao2 and circulating leukocytes, and increased cellularity of alveolar septa, interstitial edema, and increased lung malondialdehyde.
 Pulmonary damage was partially prevented when methylprednisolone was administered before zymosan inoculation, but not when methylprednisolone was given 24 hr later.
 CONCLUSIONS: The authors conclude that a local nonseptic inflammatory stimulus may provoke remote changes to the lungs and that methylprednisolone may counteract the process only if it is administered before or very early after the onset of inflammation.
",7
1203,"Use of a biotinylated DNA probe specific for the human Y chromosome in the evaluation of the allograft lung.
 A cloned 3.4 kilobase DNA probe derived from the heterochromatin of the Y chromosome was used to investigate the regeneration and reepithelialization of allograft lungs of nine recipients who received sex mismatched donor organs.
 Patients were monitored for varying periods of time, up to four years, by transbronchial biopsy.
 In situ hybridization on paraffin-embedded biopsies utilizing the Y probe revealed that bronchial and alveolar epithelium and arterial and venous endothelium of the peripheral lung retained a donor phenotype, irrespective of episodes of acute or chronic rejection (obliterative bronchiolitis) which are known to injure these cellular subsets.
 In contrast, migratory cells, lymphocytes and macrophages, gradually, at varying rates, infiltrated the allografted lungs, replacing preexisting donor elements.
 Cases of active OB were manifested by infiltration of bronchioles by sex-mismatched lymphocytes; however, in some instances, quiescent recipient lymphocytes colonized the allograft and were unassociated with histologic rejection.
 Macrophages of similar sex seemed to cluster together within air spaces.
 Use of a DNA probe for the Y chromosome and in situ hybridization techniques allow monitoring of cellular alterations over time in recipients with sex mismatched allografts.
",7
1204,"Lymphokine-activated killer cell activity in lung cancer.
 This study evaluates local pulmonary immune effector cell lytic activity.
 Purified lymphocyte populations were isolated from BALF obtained from 18 patients with bronchogenic carcinoma, six patients with lung disorders other than cancer, and ten normal control volunteers matched for age and smoking history.
 These cells were evaluated for NK and LAK cell lytic activity against NK-resistant LAK-sensitive tumor targets (A549 pulmonary tumor and Daudi tumor cells) and an NK-sensitive tumor (K562); LAK activity was detected in BALF from 6 of the 18 patients with cancer.
 The remaining patients with cancer, the subjects with pulmonary disease other than cancer, and the normal volunteers had no detectable lytic activity.
 Peripheral blood lymphocytes from all subjects had only NK lytic activity and did not kill the pulmonary tumor target; AMs were not tumoricidal.
 Interleukin-2, which is required for LAK cell activation, was detected only in BALF recovered from the six patients with pulmonary LAK lytic activity.
 These results demonstrate that activated LAK cells, capable of killing pulmonary tumor cells, are present in BALF of some patients with bronchogenic carcinoma.
 This lytic LAK cell population represents a local pulmonary response against the lung cancer in the absence of systemic tumoricidal activity.
 The functional status of pulmonary immune effector cells, as well as the type and quantities of cytokines in the lung determine local responsiveness to bronchogenic carcinoma and may well control the course of this disease.
",7
1205,"Magnetic resonance imaging in the diagnosis of pulmonary infarction.
 We report for the first time, to our knowledge, MRI features which could differentiate noninvasively pulmonary infarction from pneumonia.
 Three subjects with angiographically proven pulmonary infarction showed high T1 weighted MRI signals located in the embolic territory.
 Three patients with pneumonia and one patient with emboli, but without infarction, did not have these T1 weighted images.
",7
1206,"Amiodarone-induced pulmonary toxicity. Immunoallergologic tests and bronchoalveolar lavage phospholipid content.
 Amiodarone (A) is a widely-used antiarrhythmic drug.
 Pulmonary toxicity is the most serious adverse effect with an estimated mortality of 1 to 33 percent.
 In order to determine an element helpful for diagnosis, we examined four patients with amiodarone-induced pulmonary toxicity, three patients treated with A, without evidence of pulmonary toxicity but with a main underlying pulmonary disease, and four healthy volunteers.
 Daily and cumulative doses or duration of treatment were similar in the first two groups.
 Pulmonary function tests (spirometry, CO-diffusing capacity, arterial blood gases), roentgenographic examinations, pulmonary biopsies or immunoallergologic tests (skin reaction, lymphoblastic transformation test and human basophile degranulation test) did not provide any discriminatory element.
 In APT+, we observed an increased cellularity of the bronchoalveolar lavage.
 Neither the differential cell count nor the presence of foamy macrophages were distinguishable between APT+ and APT-.
 The phospholipid composition of BAL fluid showed a decreased total phospholipid and phospholipid/protein ratio in all patients compared to normal subjects.
 These changes reflect more the severity of pulmonary disease than the specificity of the causative agent.
 However, we observed that the unique PL which decreases in APT- and remains normal in APT+ is phosphatidyl-serine + phosphatidylinositol (PS + PI).
 This has to be confirmed and should be evaluated at different stages of the disease to determine an eventual specific element.
 We conclude that there are no data currently available to establish the diagnosis of APT except perhaps for the analysis of BAL PL content.
",7
1207,"Effect of fast vs slow intralipid infusion on gas exchange, pulmonary hemodynamics, and prostaglandin metabolism.
 Intralipid (20 percent, 500 ml) was infused fast (5 h) or slow (10 h) randomly in patients with lung injury to relate changes in plasma prostaglandin (PG) concentrations to gas exchange and pulmonary hemodynamics.
 Data were collected at baseline, midpoint of infusion, and 2 h following infusion.
 Vasodilator and vasoconstrictor PG metabolites, 6-keto-PGF1 alpha, and thromboxane B2, respectively, were measured in radial arterial blood samples.
 Slow Intralipid infusion increased shunt fraction (QS/QT) without changing mean pulmonary artery pressure (MPAP), whereas fast Intralipid infusion increased MPAP without changing QS/QT.
 Prostaglandin levels did not change significantly during either infusion.
 However, in both groups when the PG substrate was removed, hemodynamic and metabolite values decreased in parallel.
 In conclusion, we were unable to demonstrate a cause and effect relationship between plasma levels of 6-keto-PGF1 alpha and thromboxane B2 and the observed pulmonary hemodynamic response to slow or fast Intralipid infusion.
",7
1208,"Treatment of atelectasis with selective bronchial suctioning. Use of a curved-tipped catheter with a guide mark.
 We applied our technique of selective bronchial suctioning (SBS) for the treatment of atelectasis (AT) of middle and lower lobes; nine patients with refractory ATs were successfully treated.
 We considered that SBS using a curve-tipped catheter with a guide mark (CTCGM) is the technique of choice for the treatment of refractory AT when conventional respiratory therapy is not effective and a bronchoscopist is not available.
",7
1209,"Giant cell interstitial pneumonia.
 Giant cell interstitial pneumonia is a distinctive and uncommon form of interstitial pneumonia.
 It is distinguished by the prominence of large, actively phagocytic alveolar giant cells of histiocytic origin in the presence of chronic interstitial pneumonia.
 Multinucleated type 2 granular pneumocytes are also identified.
 The multinucleated cells lack viral intranuclear inclusions of the type seen in measles pneumonia.
 Giant cell interstitial pneumonia may be idiopathic or it may occur with occupational exposure to hard metals or cobalt.
 We report this case to give recognition to an uncommon interstitial pneumonia.
",7
1210,"Return of tuberculosis: screening and preventive therapy 
 Approximately 25 percent of individuals exposed to Mycobacterium tuberculosis become infected.
 Of those, about 10 percent will develop clinically active tuberculosis at some time in their lives.
 The tuberculin skin test should be used to screen all patients, especially those at greatest risk of contracting the disease, such as the young and the old, and those with weakened immune systems from poor nutrition, alcohol and drug abuse, chronic illness and human immunodeficiency virus infection.
 Depending on the characteristics of the local population and individual medical risk factors, a reaction (induration) between 5 and 15 mm (or more) generally represents infection.
 Isoniazid therapy in persons with positive skin tests will decrease the risk of disease by 60 to 80 percent.
 Family physicians will play a critical role in efforts to eliminate tuberculosis from the United States by the year 2010.
",7
1211,"Adult respiratory distress syndrome.
 Basic scientists and clinicians have written numerous articles on the diverse causes of adult respiratory distress syndrome (ARDS).
 There is no specific diagnostic test for ARDS; the condition is characterized by interstitial lung edema, reduction in lung compliance, alveolar and small airway closure, decrease in functional residual capacity, and persistent hypoxia with increasing amounts of pulmonary blood flow coursing through nonventilated or poorly ventilated alveoli.
 Recent studies have emphasized the roles of macrophages and polymorphonuclear neutrophils in lung defense and injury.
 Advances in understanding the pathophysiology of ARDS have produced little significant change in the clinical management of the syndrome.
 There is no specific treatment for ARDS.
 The cornerstone of therapy is the early recognition and elimination of initiating factors such as sepsis.
 ARDS is not a single disease process, but appears to represent a final common pathway for the manifestation of a variety of lung injuries.
 The goal of therapy is to eliminate the predisposing condition and support the patient.
 New modes of ventilatory and pharmacologic therapy are presented.
",7
1212,"Quantitation of abnormal 67Ga uptake in pulmonary interstitial vascular disease--a new test to detect diffuse lung disease.
 Gallium 67 has been used as a modality to diagnose and follow the clinical course of diseases such as tumors, infections, inflammatory disorders, and interstitial lung disease.
 It has been appreciated, however, that mild to moderate changes in scan activity, when these disorders are followed over time, are less than optimal.
 SPECT (single-photon emission computed tomography) scanning is a new technique designed to obviate this problem.
 SPECT scanning utilizes computer acquisition to provide three-dimensional scanning and the additional benefit of colorization to aid in discerning differences of uptake.
 SPECT scanning was performed on 22 patients with interstitial lung disease of various etiologies.
 Additionally, 7 patients had follow-up SPECT scanning to determine their response to treatment.
 Two patients are presented as examples.
",7
1213,"Immunoglobulin G antineutrophil cytoplasmic antibodies are produced in the respiratory tract of patients with Wegener's granulomatosis.
 Wegener's granulomatosis (WG) is a small-vessel vasculitis of unknown etiology that usually involves the upper and lower respiratory tract and the kidneys.
 Recently, an association has been made between the presence of serum antineutrophil cytoplasmic antibodies (ANCA) and WG.
 Because WG frequently involves the lung, we sought to evaluate bronchoalveolar lavage (BAL) fluids obtained from 14 patients with WG for the presence of ANCA.
 Immunoglobulin (Ig) G ANCA was found in the BAL with the same staining patterns as observed in the serum.
 Patients with active disease had the highest serum and BAL IgG ANCA titers.
 IgA or IgM ANCA was not detected in the serum or BAL of these patients.
 Protein analysis of BAL fluid revealed that patients with active, untreated WG had approximately a fourfold elevation in total protein (41.3 versus 10.5 mg/dl), with a disproportionately greater increase in the ratio of IgG to albumin (BAL IgG index = 1.49, normal = 0.74; p = 0.027).
 The increase of the IgG index in patients with active WG suggests that local production of IgG ANCA occurs in the lungs.
",7
1214,"Size distribution of human lung elastin-derived peptide antigens generated in vitro and in vivo.
 The protease-antiprotease hypothesis of emphysema development suggests that degradation of elastin in the lung interstitium may give rise to abnormal quantities of circulating elastin-derived peptides (EDP) during periods of inflammation.
 Recent studies have shown a relationship between emphysema and high levels of EDP in human plasma.
 This report characterizes elastin digests on the basis of antigenicity, size, and method of preparation, as well as the size distribution of EDP found in the plasmas of nonsmokers, smokers, and emphysema patients.
 Gel filtration of elastin digests prepared by hydrolysis of human lung elastin using a low (1:500) ratio of neutrophil elastase to elastin generated a broad protein peak of approximately 70,000 daltons.
 In contrast, a high (1:25) ratio of neutrophil elastase to human lung elastin gave a broad protein peak, with a size distribution in the 10,000 to 30,000 dalton range.
 This digest showed distinct immunochemical properties.
 A polyclonal antibody directed against the low-ratio digest showed a minimum detection of 2 ng/ml for the homologous antigen but required 1,000 ng/ml of the high-ratio digest for detectable inhibition in an indirect ELISA assay.
 Gel filtration of plasmas from normal nonsmokers and the majority of normal smokers revealed a single immunoreactive EDP fraction of approximately 70,000 daltons.
 Plasmas from selected normal smokers and emphysema patients with high levels of circulating EDP (greater than 90 ng/ml) fractionated into a complex pattern of peptides in which the 70,000 dalton component represented 50% of the immunoreactive material and several lower molecular weight peptides represented the remaining circulating elastin antigens.
",7
1215,"A ten-year follow-up study of cotton textile workers.
 A follow-up study of respiratory function in cotton textile workers was performed 10 yr after the original cross-sectional study (1975 to 1985).
 There were 35 nonsmoking female and 31 smoking male textile workers restudied from the original group of 116.
 The majority of those lost to follow-up had left the industry.
 The prevalence of byssinosis among the female workers at the time of follow-up was 15/35 (42.9%) compared with 8/35 (22.9%) at the time of the initial study (p = 0.063).
 For men the byssinosis prevalence at follow-up was 16/31 (51.6%) compared with 8/31 (22.9%) at the time of the initial study (p = 0.03).
 Similarly, the prevalence of almost all other respiratory symptoms was significantly higher at the follow-up than at the time of the initial study.
 Significant across-shift decrements in FEV1 and FVC were documented at both surveys.
 The mean annual decline in ventilatory capacity was greater than expected for both female (FVC: -0.036 +/- 0.005 L/yr; FEV1: -0.059 +/- 0.009 L/yr) and male workers (FVC: -0.059 +/- 0.008 L/yr; FEV1: -0.068 +/- 0.006 L/yr) (Mean +/- SE).
 The mean total airborne dust concentration measured at the time of the follow-up study was 3.95 mg/m3 with an average respirable dust concentration of 0.97 mg/m3.
 We conclude that continued exposure to high dust concentrations in the cotton textile industry is associated with an increasing prevalence of respiratory symptoms and progressive impairment of lung function.
 The increase in respiratory impairment was seen both in smokers and nonsmokers.
",7
1216,"Relationship of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide yield of cigarettes.
 The data from consecutive surveys of the Tucson Epidemiologic Study (1981-1988) were used to evaluate the relationship in cigarette smokers of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide (CO) yields of the cigarette.
 There were 690 subjects who reported smoking regularly in at least one survey, over age 15.
 After adjustment for intensity and duration of smoking and for depth of inhalation, the risk of chronic phlegm, cough, and dyspnea were not related to the tar and nicotine yields.
 In 414 subjects with pulmonary function tested in at least one of the three surveys the spirometric indices used were significantly related to the daily dose of tar, nicotine, and CO (product of the cigarette yield and daily number of cigarettes smoked).
 The effects were more pronounced for past than for current doses.
 However, the differentiation of pulmonary function due to various yields of cigarettes was small in comparison to the difference in pulmonary function between smokers and nonsmokers.
",7
1217,"Protective effect of theophylline on bronchial hyperresponsiveness in patients with allergic rhinitis.
 Disorders of the upper respiratory tract, particularly allergic rhinitis are commonly associated with bronchial hyperresponsiveness.
 The latter may be responsible for chronic cough, a common symptom in patients with allergic rhinitis, which, as previously shown, can be the sole presenting manifestation of bronchial hyperresponsiveness.
 Theophylline is widely used in patients with asthma for its bronchodilator effect, whereas its action on bronchial reactivity is controversial.
 The aim of this study was to determine the effect of theophylline administration on bronchial hyperresponsiveness in patients with allergic rhinitis complaining of chronic cough.
 Fourteen patients were studied.
 All of them were judged atopic on the basis of positive skin tests to common allergens.
 During control, spirometry, flow-volume curves and specific airway conductance (SGaw) were measured.
 Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed.
 The concentration of carbachol, which decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve.
 After control measurements patients received in a randomized, double-blind crossover fashion either theophylline 10 mg/kg/day orally or placebo for 30 days.
 Measurements were then redone.
 After a washout period of 8 days the measurements were repeated, and patients received theophylline or placebo for a second period of 30 days.
 Measurements were again performed at the end of this last study period.
 During control all patients had normal baseline lung function data and showed marked bronchial hyperresponsiveness, PD35 amounting to 26 +/- 7 micrograms of carbachol (normal value greater than 160 micrograms).
 No significant changes in PD35 were noted after placebo and washout when compared with control values.
",7
1218,"Lymphokine-induced airway hyperresponsiveness in the rat.
 We evaluated the potential role of the lymphocyte in chronic airway inflammation and responsiveness by repeated administration to rats of interleukin-2 (IL-2), the principal lymphokine responsible for lymphocyte proliferation.
 Lewis rats (mean weight, 184 +/- 2 g) received either 120,000 units of IL-2 (n = 10) or vehicle (n = 7) subcutaneously twice a day for 4.5 days.
 Animals were anesthetized with urethane and intubated for measurements of pulmonary resistance (RL) and airway responsiveness to aerosol methacholine (MCh).
 Lung lavage was performed, the animals were exsanguinated, and the lungs were fixed in 10% formalin.
 Histologic edema and the extent of infiltration of the bronchi, pulmonary veins, and arteries by cells was scored blindly.
 IL-2 increased airway responsiveness to MCh; the concentrations of MCh causing a doubling of RL were 0.14 versus 1.39 mg/ml (geometric mean) for the IL-2 and vehicle group, respectively (p = 0.001).
 IL-2 significantly increased total cellular return and the percentage of lymphocytes, neutrophils, and eosinophils in lavage.
 IL-2 caused edema and a mixed cellular infiltration of the bronchovascular tree.
 Lymphocytes predominated around the airways and veins.
 A correlation (r = 0.50) was present between airway responsiveness and airway inflammation but not with edema or vascular infiltration.
 Release of IL-2 by lymphocytes in the airways may be an important mediator of airway hyperresponsiveness.
",7
1219,"Acute effects of interleukin-2 on lung mechanics and airway responsiveness in rats.
 We studied the acute effects of interleukin-2 (IL-2), the principal lymphokine responsible for lymphocyte proliferation, on lung mechanics and airway responsiveness to methacholine (MCh) in rats.
 Lewis (n = 12) and Fisher 344 (n = 13) rats were anesthetized and intubated, and intravenous and intra-arterial lines were inserted.
 IL-2 (750,000 U/kg) was infused intravenously over 2 to 4 min into seven Lewis and seven Fisher rats, and vehicle alone was administered to five Lewis and six Fisher rats.
 Blood pressure, heart rate, respiratory frequency (f), tidal volume (VT), minute ventilation (VE), and lung resistance (RL) were measured before and every 5 min for 45 min after the infusion of IL-2.
 Lung compliance was measured before and 30 min after IL-2.
 Bronchial provocation testing with MCh was performed 45 min after the infusion of IL-2.
 Subsequently, the animals were exsanguinated, and the lungs were removed for histologic examination.
 Infused IL-2 did not alter heart rate or blood pressure, VT, f, VE, and RL increased significantly by 15 min (p less than 0.05), but they returned to baseline by 45 min.
 Lung compliance decreased significantly in both rat strains.
 IL-2 increased airway responsiveness only in Lewis rats; the concentration of MCh that caused a doubling of RL (EC200RL) was 0.6 mg/ml and 4.3 mg/ml (p = 0.003) in IL-2-treated and control rats, respectively.
 The airway responsiveness did not change significantly in Fisher rats; EC200RL was 0.13 and 0.35 mg/ml for IL-2-treated and control rats, respectively (p = 0.09).
",7
1220,"Morphometric analysis of the lung in bronchopulmonary dysplasia.
 We studied lung development in children with or without bronchopulmonary dysplasia (BPD) using light microscopic morphometry and thick lung sections stained for elastic fibers.
 One lung was obtained at autopsy from each of eight patients with BPD (ages, 2 to 28 months) and six children (ages, 5 days to 51 months) who died without lung disease.
 Patients with BPD demonstrated severe somatic growth retardation and had reduced lung volumes with abnormal lobar volume proportions.
 In the central bronchi mean volume proportion of glands and smooth muscle was increased in BPD.
 Bronchiolar density was also increased, but it tended to normalize with advancing age.
 Mean bronchiolar diameter was slightly smaller in BPD, and bronchiolar smooth muscle hypertrophy was a constant histologic feature.
 The most striking change, however, was noted in alveolar structure and development.
 Total alveolar number was severely decreased in patients with BPD compared with that in control subjects, and there was little evidence of compensatory alveolar development with increasing age.
 Lung internal surface area was correspondingly reduced, and mean linear intercept was increased.
 Sections stained for elastic tissue demonstrated in the patients with BPD a simplified acinar structure with thickened, tortuous, and irregularly distributed alveolar elastic fibers.
 We conclude that in severe, fatal BPD there is marked impairment of lung development with alveolar hypoplasia and reduced internal surface area.
 In addition, bronchial and bronchiolar smooth muscle hypertrophy and bronchial gland hyperplasia may be important contributing factors to airflow limitation.
",7
1221,"The characteristics of children with epiglottitis who develop the complication of pulmonary edema.
 A review was performed of 234 consecutive cases of epiglottis that occurred during a 20-year period to delineate the rate of, and clinical characteristics associated with, the complication of pulmonary edema.
 As a result of the prior utilization of a ""dual"" management protocol, there were 170 children who received endotracheal intubation, and 64 children managed without placement of an artificial airway.
 In all, five children (2.1%) of varying ages developed this complication--all experienced severe airway obstruction progressing to respiratory arrest, with evidence of pulmonary edema developing shortly after endotracheal intubation.
 Two of these five children died due to complications resulting from upper airway obstruction-induced cardiorespiratory arrest.
 By contrast, no child with milder degrees of airway obstruction managed without an artificial airway exhibited clinical evidence of pulmonary edema.
 Several possible mechanisms for the development of this complication are described.
 Pulmonary edema associated with epiglottitis is an uncommon complication that can occur following endotracheal intubation in those patients with marked respiratory insufficiency.
 An artificial airway should be instituted in all cases of pediatric epiglottitis--the potential complication of pulmonary edema should be anticipated before placement of an artificial airway, especially in those patients with a severe degree of upper airway obstruction.
",7
1222,"Screening for lung cancer. A critique of the Mayo Lung Project.
 The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer.
 The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic.
 Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer.
 Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer.
 In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months.
 The control population was offered yearly chest radiography only.
 In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage.
 The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year.
 This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group.
 However, there was no significant difference in lung cancer mortality rate between the two groups.
 The statistical power of these trials was somewhat limited.
 Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.
",7
1223,"The applications of imaging in lung cancer.
 The applications of imaging to the lung cancer patient have become more focused recently.
 Screening of high risk patients is not recommended even though intuition and clinical judgment prevail in practice to justify the use of chest radiographs in this patient category.
 Cross-sectional imaging procedures should be tailored to the staging process in the individual with a large central primary or to confirm an abnormality noted on the chest radiographs.
 The patient at high risk for thoracotomy is generally also subjected to radiologic staging.
 The radiologic staging process is reviewed and critiqued, emphasizing our role in identifying the disease sites that would suggest nonrespectability.
",7
1224,"Differentiation between the intensity of breathlessness and the distress it evokes in normal subjects during exercise.
 1.
 This study was designed to examine whether normal subjects could differentiate between the 'intensity' of their breathlessness and the amount of 'distress' it evoked, by specific wording of the instructions.
 2.
 A preliminary study showed no significant difference between 'distress' score during exercise measured on two separate occasions (P = 0.3).
 3.
 Ten subjects each performed two identical incremental cycle-ergometer exercise tests on separate occasions during which they were asked to quantify either 'intensity' or 'distress' by using modified Borg scales.
 4.
 In all subjects there was a significant correlation (P less than 0.001) between 'intensity' and minute ventilation.
 In eight subjects there was a significant correlation (P less than 0.05) between 'distress' and minute ventilation.
 One subject displayed no significant correlation and one registered no distress.
 5.
 Mean 'intensity' was greater than the mean 'distress' (P = 0.0001).
 The slope of 'intensity'/minute ventilation was greater than the slope of 'distress'/minute ventilation (P = 0.0001).
 6.
 Within individuals there was a significant correlation between 'intensity' and 'distress' (P less than 0.05).
 There was a wide scatter in the slope of this relationship between subjects and maximum 'intensity' and 'distress' did not correlate.
 7.
 Different elements of the breathlessness sensation could be identified and selectively measured depending on the wording of the instructions given to the subject.
 8.
 There was a wide intersubject variation in the magnitude of both breathlessness 'intensity' and 'distress' estimates, but the differences between subjects in these two components of the sensation did not appear to follow a common pattern.
",7
1225,"Pneumonia: update on diagnosis and treatment.
 Pneumonia is the most common infectious disease necessitating hospitalization of elderly patients.
 A number of misconceptions exist regarding the clinical and radiological features of pneumonia in elderly patients.
 Early recognition and appropriate therapy can reduce morbidity and enhance survival.
 This article explores the manifestations of pneumonia in the elderly, as well as the diagnostic approach and contemporary therapy.
",7
1226,"Is there ever a role for salvage operations in limited small-cell lung cancer?
 Combined modality treatment with chemotherapy and radiation produces tumor regression in most patients with small-cell lung cancer, but the impact on survival has been small, and less than 20% of patients with limited disease survive 2 years.
 Survival time is extremely short after failure to respond or relapse after treatment.
 Local control remains a problem, with one third of patients having recurrence only at the primary site.
 In an attempt to prolong survival and perhaps achieve cure, we undertook surgical resection in 28 patients with limited small-cell lung cancer who did not have complete remission with standard treatment or who had only local recurrence after treatment.
 There were 28 patients, 22 male and six female, median age 61 years (range 41 to 76).
 All patients had been treated with chemotherapy and 13 had received preoperative radiotherapy to the primary site and mediastinum.
 Eight patients underwent an operation for relapse after complete remission.
 Five patients had had no response to treatment, three had had a slight response followed by progression during chemotherapy, and 12 had achieved partial response but had greater than 3 cm residual masses.
 Twelve patients required pneumonectomy, 15 lobectomy, one patient had unresectable disease, and two had bulky residual masses after the operation.
 Three others had microscopic residual disease.
 Pathologic examination showed only small-cell lung cancer in 18 patients, mixed small-cell and non-small-cell in four, and only non-small-cell lung cancer in six.
 There were only four patients with stage I disease, 10 with stage II, and 14 with stage III.
 The median survival from the date of diagnosis for the entire group is 105 weeks and from the date of operation, 74 weeks.
 The projected 5-year survival rate is 23%.
 The two patients with residual masses died with local progression, and distant metastatic disease developed in 17 others.
 One patient died at 6 years without recurrent disease.
 Eight patients are alive 2 to 5 years after diagnosis.
 Seven of these patients required only a lobectomy, four had stage I disease, two had stage II, and two had stage III disease.
 Five had pure small-cell lung cancer and three had mixed small-cell and non-small-cell tumors.
 All of the patients with pathologic stage I disease remain alive compared with one of 10 with stage II disease and two of 14 with stage III.
 In summary, relapse or failure to respond to chemotherapy may be due to non-small-cell lung cancer or a mixed tumor.(ABSTRACT TRUNCATED AT 400 WORDS).
",7
1227,"Radon and health 
 Radon and its daughter decay products are thought to be the cause of 5% of lung cancer in the UK.
 This assessment has been made by the National Radiological Protection Board (NRPB) after a national survey of radon levels in homes, when more houses than anticipated were found to have high levels, and after a reappraisal upwards of the effectiveness of radon and its daughter products in causing lung cancer.
 A review of the scientific evidence reveals no direct evidence to incriminate radon or its decay products at the levels found in our homes in lung cell carcinogenesis.
 The issue involves different scientific disciplines and is highly complex.
 Debate between scientists is required and more epidemiological studies of lung cancer and low radon exposure are necessary.
 Meanwhile the indirect evidence linking low levels of radon exposure to lung cancer is insufficient to warrant the remedial action proposed by the NRPB and accepted by the UK government.
",7
1228,"Modified muscle sparing posterolateral thoracotomy.
 A modified posterolateral thoracotomy is described that combines the advantages of complete muscle sparing through a thoracolumbar fascial slide with excellent exposure.
 The technique is easy to perform.
 The procedure was associated with relatively little postoperative pain, coughing was effective, and early ambulation was achieved.
 Experience with this approach in the first 49 patients suggests that it offers an attractive alternative to the standard muscle cutting posterolateral thoracotomy approach for elective procedures.
",7
1229,"Inhaled micronised gentamicin powder: a new delivery system.
 Forty patients undergoing routine bronchoscopy were randomised to receive inhaled micronised gentamicin powder (180 mg) or nebulised gentamicin solution (160 mg) one hour before the procedure.
 Similar levels of gentamicin were detected in bronchoalveolar lavage fluid in the two groups (micronised powder (n = 20) 9.3 (SD 9.3) mg/l, nebulised solution (n = 20) 8.0 (7.8) mg/l).
 The micronised gentamicin powder preparation caused cough in half the patients but this did not stop their receiving a full dose.
 Dry powder gentamicin may be a convenient formulation for long term inhaled treatment if the problem of cough can be overcome.
",7
1230,"Selective differences in macrophage populations and monokine production in resolving pulmonary granuloma and fibrosis.
 Alveolar macrophages (AM) and their production of interleukin-1-like activity (IL-1) and macrophage-derived growth factor for fibroblasts (MDGF) were examined during chronic inflammatory reactions leading to either granuloma formation or fibrosis.
 Groups of five rats each received, respectively, a single transtracheal injection of xonotlite, attapulgite, short chrysotile 4T30, UICC chrysotile B asbestos, or saline.
 One month later, such treatments induced either no change (xonotlite), granuloma formation (attapulgite and short chrysotile 4T30), or fibrosis (UICC chrysotile B).
 By 8 months, however, the granulomatous reactions had resolved or greatly diminished, whereas the fibrosis persisted irreversibly.
 Parallel examination of cell populations obtained by bronchoalveolar lavage revealed that multinucleated giant macrophages (MGC) were present in lavage fluids of animals with resolving granulomatous reactions but absent in those obtained from animals with lung fibrosis.
 Evaluation of monokine production by inflammatory macrophages also revealed significant differences.
 Enhanced production of IL-1-like activity was seen in both types of lung injury, although especially during the early stage (1 month) and decreased thereafter (8 months).
 By contrast, augmentation of MDGF production was observed in animals with lung fibrosis only and persisted up to 9 months.
 Taken together, these data indicate that production of selected cytokines, as well as AM differentiation along a given pathway, may modulate the outcome of a chronic inflammatory response.
",7
1231,"Treatment of intractable aspiration using a laryngeal stent or obturator.
 Twenty-five patients were treated with a laryngeal stent for potentially reversible chronic aspiration of life-threatening magnitude.
 The causes of the intractable aspiration were diverse and included chronic neurologic disease, extensive head and neck surgery, and severe gastroesophageal reflux.
 The advantages of this technique are noted in comparison to those of more invasive procedures.
 Disadvantages of the laryngeal stent and complications encountered are also covered.
 The long-term results show that all but one patient had a significant improvement in their chronic aspiration with the stent in place.
 However, only eight patients achieved adequate oral deglutition without aspiration following stent removal.
",7
1232,"Surgical applications of ultrathin flexible bronchoscopes in infants.
 Ultrathin flexible bronchoscopes with controlled distal angulation allow the conventional diagnostic examination of the lower airways of even the smallest infants.
 These instruments may be passed through small endotracheal or tracheostomy tubes while ventilation is maintained.
 It is thus possible, under direct visualization, to control the manipulation of surgical instruments where they could not otherwise be seen, or to study airway dynamics and anatomy intraoperatively without extubating the patient.
",7
1233,"Radiological abnormalities among sheet-metal workers in the construction industry in the United States and Canada: relationship to asbestos exposure.
 We investigated the possible adverse health effects to sheet-metal workers who had past exposure to asbestos.
 A cross-sectional medical examination of 1,330 workers was conducted during 1986 and 1987 in seven cities in the United States and Canada.
 A total of 1,016 workers had been employed for at least 35 y in the industry, and the mean duration from onset of asbestos exposure was 39.5 y (SD = 7.41 y).
 Chest x-ray abnormalities were found in more than half of the group.
 Pleural fibrosis, the most frequently found abnormality, was present in 47.0% of the cases and was the only abnormality found in 27.8% of cases; parenchymal interstitial fibrosis, found in 33.1% of cases, was the only abnormality found in 16.2% of cases.
 Radiologic abnormalities increased as duration of exposure increased.
 A positive smoking history was associated with a higher prevalence of radiologically detectable parenchymal abnormalities, a finding confirmed by us and others.
 Dyspnea on exertion was graded by a Medical Research Council questionnaire, the examinee's self-assessment, and a more detailed 12-point scale questionnaire.
 Few persons had marked shortness of breath, and approximately one-third had slight dyspnea.
 Individuals who had radiologic abnormalities experienced more shortness of breath than did those who had no radiologic abnormalities.
 Cigarette smoking also resulted in a higher prevalence of dyspnea.
 The results indicate that during the past, construction sheet-metal workers have been significantly exposed to asbestos on the job.
 Every effort should be made to minimize the anticipated serious health consequences, and further asbestos exposure for those who continue in this trade should be avoided.
",7
1234,"Lymphocytes and nonlymphoid cells in human nasal polyps.
 Immunohistochemical stainings were performed on polyp specimens of 48 patients and on mucosal biopsy specimens of the middle and inferior turbinates of 23 and 28 patients, respectively.
 Significantly more CD8+ (suppressor/cytotoxic) than CD4+ (helper/inducer) cells were found in the polyps.
 The number of CD2+, CD4+, and CD8+ lymphocytes in nasal polyps were very similar to the number in the macroscopically unaffected mucosa of the middle turbinates, whereas scores in the inferior turbinates were lower.
 In healthy subjects, the differences were smaller.
 CD22+ B cells were detected in varying numbers in the polyps in more or less organized clusters.
 Significantly more HLA-DR+ cells were found in polyps and middle turbinates than in the inferior turbinates.
 Eosinophils were found in moderate to large numbers in polyps of 77% of the patients.
 Mast cells and plasma cells were detected in moderate numbers, whereas neutrophils were found in 35% of the patients.
 In the middle and inferior turbinates varying but small numbers of eosinophils, mast cells, plasma cells, and neutrophils were found.
 In considering these findings, the role of chronic inflammation with T cell-dependent disturbances is discussed with regard to the pathogenesis of nasal polyps.
",7
1235,"Bronchopulmonary dysplasia: improvement in lung function between 7 and 10 years of age.
 To evaluate the natural history of bronchopulmonary dysplasia, we studied the same 32 patients at a mean age of 7 and 10 years.
 The group as a whole had normal height and weight percentiles, and each child grew along his or her established somatic growth curve.
 Although some children had abnormal values, the group maintained a normal mean total lung capacity and functional residual capacity.
 The mean residual volume and the residual volume/total lung capacity ratios were elevated at both ages.
 At age 7 years the 19 patients (59%) who had a forced expiratory volume in 1 second (FEV1) of less than 80% had ""catch up"" improvement by 10 years of age (65 +/- 11% to 72 +/- 16% of predicted value; p less than 0.05).
 All the children who had a normal FEV1 at 7 years of age continued to have a normal FEV1 at age 10 years.
 Resting single-breath carbon monoxide uptake by the lung was normal when measured at age 10 years.
 The majority of patients had a positive methacholine challenge test result at both ages, although there was a low incidence of clinically diagnosed asthma.
 This study demonstrates that patients with bronchopulmonary dysplasia who have normal lung function at age 7 have had normal lung growth and that those with evidence of mild to moderate lung disease have continued lung growth or repair, or both, during their school years.
",7
1236,"Pulmonary atelectasis: signal patterns with MR imaging.
 To assess the signal characteristics of different types of pulmonary atelectasis on magnetic resonance (MR) images, the authors studied obstructive atelectasis (OA) in 17 patients and nonobstructive atelectasis (NOA) in 25 patients.
 All patients underwent electrocardiographically gated MR imaging studies of the thorax with standard spin-echo sequences.
 No signal differences were observed between either type of atelectasis on T1-weighted images.
 Conversely, OA and NOA appeared significantly different on spin-density-weighted images (P less than .001) and on T2-weighted studies (P less than .0001).
 On T2-weighted images, all 17 cases of OA appeared hyperintense, whereas 22 of 25 cases of NOA demonstrated a very low signal intensity.
 Differences in the pathophysiology of OA and NOA presumably account for this observation.
 In OA, alveolar air is totally resorbed and secretions accumulate in the obstructed lung.
 The resulting increase in free fluid prolongs the T2 relaxation times and leads to high signal intensity on T2-weighted images.
 In NOA, the short T2 relaxation time of lung tissue in the absence of secretions and potential magnetic susceptibility effects due to residual air are likely to be responsible for the low T2 signal pattern.
",7
1237,"Apical opacity associated with pulmonary tuberculosis: high-resolution CT findings.
 To elucidate the nature of the apical opacity that is commonly seen in patients with tuberculosis--usually referred to as an ""apical cap"" or ""apical pleural thickening""--18 patients with upper lobe tuberculosis were studied with high-resolution computed tomography (HRCT).
 All had a homogeneous apical opacity at least 1 cm thick on chest radiographs.
 Fifteen of the 18 had a history of pulmonary tuberculosis of more than 5 years duration, and nine showed evidence of ipsilateral pleurisy.
 HRCT scans at the apex of the thorax in all nine patients scanned at this level showed that extrapleural fat with interspersed vessels accounted for most of the plain radiographic opacity.
 Scans obtained at a level slightly above visible aerated lung showed extrapleural fat 3-25 mm thick peripherally and atelectatic lung centrally.
 At more caudal levels, at which both aerated lung and ""thickened pleura"" were visible on plain radiographs, HRCT showed extrapleural fat (3-20 mm thick), thickened pleura (1-3 mm thick), and atelectatic lung peripherally and areas of emphysematous bullae, bronchiectasis, and atelectatic lung centrally.
",7
1238,"Interstitial lung disease: impact of postprocessing in digital storage phosphor imaging.
 The ability to resolve the fine linear structures of interstitial lung disease is one measure of the limiting performance characteristics of an imaging system.
 Conventional screen-film radiography was compared with six algorithms of isodose storage phosphor digital radiography (0.2-mm x 10-bit pixel matrix) in the detection of interstitial lung abnormality documented by means of computed tomography in 40 patients with abnormalities and 25 healthy control subjects.
 Performance was evaluated with an analysis of variance (the Fisher paired comparison test; P less than .05) of the average receiver operating characteristic area of 2,730 observations by six readers.
 The moderately and the more markedly high-frequency edge-enhanced algorithms of storage phosphor digital radiographs were equivalent in performance to screen-film radiography.
 The default mode, low- and medium-frequency edge-enhanced algorithms, and gray scale reversed mode of storage phosphor digital radiography were inferior to screen-film radiography.
 The authors conclude that high-frequency edge-enhanced algorithms can perform as well as screen-film radiography in the detection of interstitial disease.
",7
1239,"Outpatient assessment of infants with bronchiolitis.
 Two hundred thirteen infants younger than 13 months with bronchiolitis were prospectively followed up to identify the historical, physical, and laboratory clues at initial emergency department evaluation that would help to predict disease severity.
 Based on their total course of illness, the patients were classified as having mild (139 patients) or severe (74 patients) disease, and the initial emergency department evaluation findings of these two groups were compared.
 Six independent clinical and laboratory findings were identified that were strongly associated with more severe illness: (1) ""ill"" or ""toxic"" general appearance; (2) oxygen saturation less than 95%, as determined by pulse oximetry; (3) gestational age, younger than 34 weeks; (4) respiratory rate, 70/min or greater; (5) atelectasis on a chest roentgenogram; and (6) age, younger than 3 months.
 The infant's oxygen saturation as determined by pulse oximetry was the single best objective predictor of more severe disease.
",7
1240,"The role of passive immunity in bovine respiratory syncytial virus-infected calves.
 The role of passive immunity in bovine respiratory syncytial virus (BRSV) infections in neonatal calves was evaluated.
 Calves were divided into groups as follows: colostrum-deprived, sham-inoculated; colostrum-deprived, BRSV-inoculated; and colostrum-fed, BRSV-inoculated.
 Calves were inoculated with a low-passage field isolate of BRSV for 4 consecutive days by a combined respiratory tract route and were euthanized 6 days after receiving the last inoculation.
 Arterial oxygen tension (Pao2) decreased significantly over time in colostrum-deprived, BRSV-inoculated calves (P less than .01) and was significantly different among treatment groups (P less than .05).
 A significant decrease in arterial oxygen saturation was observed in this same group over time (P less than .01).
 Mean percentage of pneumonic lung volume (determined by computer data digitalization) was significantly greater in infected, colostrum-deprived calves compared with the other groups (P less than .01), and BRSV antigen was detected in these calves by avidin-biotin immunoperoxidase staining.
 Thus, passive immunity derived from colostrum feeding decreased the severity of BRSV infections in calves.
",7
1241,"Immune responses to Bordetella pertussis infection and vaccination.
 To assess antibody and cellular immune responses, 156 healthy children were immunized at approximately 18 months of age with acellular diphtheria-tetanus-pertussis vaccine.
 Changes in antibody responses to filamentous hemagglutinin (FHA) and to pertussis toxin (PT) were similar in pattern, and antibody titers reached values equal to those from patients with convalescent-stage pertussis.
 The FHA-induced DNA synthesis in peripheral blood mononuclear cells was maximum at 4 weeks after the primary series, and these levels were equal to those of patients with pertussis.
 High amounts of PT-induced DNA synthesis were observed in both immunized and nonimmunized children; thus, PT seemed to act mainly as a nonspecific mitogen.
 Almost the same responses to several mitogens that activate different subsets of lymphocytes were observed in young infants compared with older children.
 Furthermore, young infants who had Bordetella pertussis infection responded by FHA stimulation almost as well as older children.
",7
1242,"No detection of characteristic fungal protein elongation factor EF-3 in Pneumocystis carinii.
 The taxonomic status of Pneumocystis carinii is uncertain, and P.
 carinii has been categorized both as a fungus and as a protozoan.
 Recent comparisons of RNA sequence homologies between P.
 carinii and several genera of fungi and protozoa suggest that P.
 carinii has closer affinities with the ascomycetes than with the protozoa.
 The translatory systems of the fungi, however, require three soluble protein factors for peptide chain elongation rather than the two necessary in other eukaryotic systems; to date the additional protein elongation factor (EF-3) appears to be unique to fungi.
 Western blot analysis of cell-free extracts of P.
 carinii, derived from rat, was done using a polyclonal antibody raised in rabbits to Saccharomyces cerevisiae EF-3.
 Anti-EF-3 cross-reacting material was detected only in lysates of Candida albicans and S.
 cerevisiae included as fungal controls; no cross reaction was detected in lysates of P.
 carinii, P.
 carinii-infected rat lung, or a protozoan control (Trichomonas vaginalis).
",7
1243,"Meta-analysis in epidemiology, with special reference to studies of the association between exposure to environmental tobacco smoke and lung cancer: a critique 
 Meta-analysis, a set of statistical tools for combining and integrating the results of independent studies of a given scientific issue, can be useful when the stringent conditions under which such integration is valid are met.
 In this report we point out the difficulties in obtaining sound meta-analyses of either controlled clinical trials or epidemiological studies.
 We demonstrate that hastily or improperly designed meta-analyses can lead to results that may not be scientifically valid.
 We note that much care is typically taken when meta-analysis is applied to the results of clinical trials.
 The Food and Drug Administration, for example, requires strict adherence to the principles we discuss in this paper before it allows a drug's sponsor to use a meta-analysis of separate clinical studies in support of a New Drug Application.
 Such care does not always carry over to epidemiological studies, as demonstrated by the 1986 report of the National Research Council concerning the purported association between exposure to environmental tobacco smoke and the risk of lung cancer.
 On the basis of a meta-analysis of 13 studies, 10 of which were retrospective and the remaining 3 prospective in nature, the Council concluded that non-smokers who are exposed to environmental tobacco smoke are at greater risk of acquiring lung cancer than non-smokers not so exposed.
 In our opinion, this conclusion in unwarranted given the poor quality of the studies on which it is based.
",7
1244,"Monoclonal immunofluorescence compared with silver stain for investigating Pneumocystis carinii pneumonia.
 Two hundred and eighty two specimens from 220 patients positive for HIV with respiratory tract symptoms, or febrile illness, or both, were examined for the presence of Pneumocystis carinii.
 Specimens were either induced sputum samples or bronchoalveolar lavage fluids.
 To establish the optimal method for laboratory diagnosis a comparison was made of detection of the organism by use of monoclonal antibody and immunofluorescence with conventional silver staining methods.
 Three commercially available reagents for immunofluorescence were also compared.
 Immunofluorescence was significantly more sensitive than the silver stain and the best results for immunofluorescence were obtained using.
 Northumbria Biologicals Ltd reagents.
",7
1245,"Pneumothorax in a patient with Wegener's granulomatosis during treatment with immunosuppressive agents.
 We present the case of a 16-year-old woman with Wegener's granulomatosis, who developed a pneumothorax while receiving treatment with cyclophosphamide and glucocorticoids.
 The lung was re-expanded by tube drainage, and the patient recovered completely while the immunosuppressive treatment was continued in combination with sulphamethoxazole-trimethoprim.
 A possible role for this antimicrobial drug in the treatment of Wegener's granulomatosis is briefly discussed.
",7
1246,"Upper respiratory tract infections.
 Upper respiratory tract infections are among the most common acute infections in humans.
 This review discusses the clinically important aspects of the epidemiology, etiology, clinical presentation, diagnosis, management, complications, and prevention of the common cold, pharyngitis, otitis media, and sinusitis.
 Most episodes of the common cold and pharyngitis are of viral origin, and curative therapy is not available.
 Streptococcal pharyngitis, acute otitis media, and sinusitis are secondary to bacterial infections, and antibiotic therapy is important.
",7
1247,"Pharmacokinetics of cefepime in patients with respiratory tract infections.
 The steady-state pharmacokinetics of cefepime were evaluated in 10 middle-aged and elderly patients with acute lower respiratory tract infections who were receiving 1 g intravenously every 12 h.
 One preinfusion and 15 postinfusion serum samples and total urine output were collected over one dosing interval between days 3 and 8 of therapy.
 Cefepime concentrations in serum over time exhibited a multicompartmental profile.
 Peak and trough concentrations in serum determined by a validated high-performance liquid chromatography method were 71.2 +/- 17.2 (mean +/- standard deviation) and 6.0 +/- 4.9 mg/liter, respectively.
 The steady-state volume of distribution was 0.22 +/- 0.05 liter/kg.
 Elimination half-lives ranged from 1.93 to 6.04 h (3.92 +/- 1.28 h), and total body clearances ranged from 36.9 to 102 ml/min per 1.73 m2 (73.0 +/- 19.7 ml/min per 1.73 m2).
 The disposition of cefepime at steady state in patients was comparable to previous observations in healthy elderly volunteers.
 The predictive performance of regression equations derived from single-dose studies in volunteers relating creatinine clearance with total body and renal clearances of cefepime exhibited slight biases (mean predictive errors, -9.7 and 2.1 ml/min per 1.73 m2, respectively) and similar precisions.
 Predicted and observed total body clearances (63.3 +/- 25.1 versus 73.0 +/- 19.7 ml/min per 1.73 m2, respectively) and renal clearances (51.3 +/- 24.4 versus 49.3 +/- 19.6 ml/min per 1.73 m2, respectively) were not significantly different.
 The pharmacokinetics of cefepime in infected patients appeared to be unaltered by illness, and the steady-state disposition of cefepime was predictable from data derived from single-dose studies in volunteers.
",7
1248,"Computed tomography-guided minithoracotomy for the resection of small peripheral pulmonary nodules.
 Small peripheral pulmonary nodules ranging in size from 1 mm to 20 mm were excised in 58 patients.
 Computed tomography was used to mark the skin overlying the nodules to minimize the surgical exposure needed for operative identification.
 The nodules were 1 cm or less in maximum diameter in 76% of the patients.
 Twenty-six patients had single nodules and 32 patients had multiple nodules.
 The preoperative diagnosis was inaccurate in 67% of the patients.
 In 61% of the patients in whom malignancy was suspected, no tumor was demonstrated.
 Conversely, of the 20 patients in whom a malignant nodule was excised, the preoperative diagnosis was correct in only 50%.
 Thirty-one patients required no further treatment apart from their biopsy and 27 required additional intervention.
 Small peripheral pulmonary nodules require biopsy for diagnosis.
 When percutaneous needle aspiration biopsy is unsuccessful, or technically difficult, a computed tomography-guided thoracotomy is an effective and minimally invasive surgical alternative.
",7
1249,"Bilateral iliac vein filtration. An effective alternative to caval filtration in patients with megacava.
 Greenfield filters were placed bilaterally in the iliac veins in five of 250 patients undergoing percutaneous filter placements.
 Four of the five patients had megacava (inferior vena cava diameter greater than 28 mm).
 In all patients, the filters were effective in preventing pulmonary embolism.
 Follow-up at 9 months in two patients revealed no changes of chronic venous insufficiency or venous stasis.
 Iliac filtration should be considered in patients in whom a caval filter cannot be placed because of large caval size or because it is technically difficult due to iliac vein tortuosity.
",7
1250,"Exercise testing in the assessment of pulmonary disease.
 In this chapter, the different types of exercise tests and the indications for requesting a particular type of test have been discussed.
 The normal physiological responses to exercise have been reviewed and examples of the abnormal responses seen in a variety of disease states that have been discussed.
 The relatively small number of these responses limits the specificity of exercise tests in actually establishing a diagnosis, but can be helpful in narrowing the differential diagnosis.
 Perhaps exercise tests are most valuable in cases where the patient's symptoms are mainly limited to exercise and where investigations done at rest have failed to resolve a diagnostic question.
 When exercise testing is used under these circumstances, it serves a unique function in the diagnosis and management of pulmonary disease.
",7
1251,"Bronchoalveolar lavage.
 The technique of BAL performed through the fiberoptic bronchoscope has, in two decades, provided clinicians and researchers with the ability to safely sample the inflammatory-immune cell milieu of the human lung.
 Standardized BAL and processing of the lavage constituents provides assistance in determining the optimal care of patients with a variety of lung diseases, and renders diagnosis in selected cases.
 It has become indispensable in the diagnosis of pulmonary infiltrates in immunocompromised patients, and plays an important role in improving clinical management.
 Finally, it continues to yield an ever increasing amount of data for the researchers studying the mechanisms and pathogenesis of lung disease.
 It is likely that BAL will become an even more valuable tool with increasing relevance to the practice of chest medicine in the 1990s.
",7
1252,"Stable and reproducible porcine model of acute lung injury induced by oleic acid.
 BACKGROUND AND METHODS: Previous studies on acute lung injury induced with oleic acid did not attempt to limit the influence of secondary changes on pulmonary circulation, and cardiopulmonary variable data were only collected and processed intermittently.
 Our study was designed to continuously monitor the following variables in five swine: systemic and pulmonary pressure; mixed venous oxygen saturation (SVO2) and arterial oxygen saturation (SaO2); minute oxygen consumption and CO2 production before, during, and for 4 hr after the infusion of oleic acid.
 A personal computer was programmed to produce 20-sec updates of deadspace ratio (VD/VT), venous admixture (Qsp/Qt), pulmonary (PVR) and systemic vascular resistance (SVR), and cardiac output (Qt) from these data.
 RESULTS: During the oleic acid infusion, there were increases in PVR, SVR, heart rate (HR), mean pulmonary arterial pressure (MPAP), Qsp/Qt, and VD/VT, and a decrease in Qt, SaO2, and SVO2.
 Thirty minutes after the oleic acid infusion, there was a further increase in HR, Qsp/Qt, and VD/VT, while MPAP, PVR, and SVR gradually decreased to pre-oleic acid infusion levels.
 No further decrease in SaO2, SVO2, and Qt was observed during that time.
 After the 30-min period, there was no further change in the cardiopulmonary variables.
 CONCLUSION: Our method of continuous monitoring was able to demonstrate in swine both the dynamic changes during, and stability after, the oleic acid infusion.
",7
1253,"A target feedback device for ventilatory muscle training.
 In a previous study, we successfully used a target feedback device, together with an external resistor, to train the ventilatory muscles of patients with chronic obstructive pulmonary disease.
 In this article, we describe the details of the design and function of the target feedback device.
 When used in conjunction with an external resistance, the target feedback device provides timing and pressure targets, together with feedback information, on whether these targets are achieved.
 The target feedback device consists of readily available electronic components and is relatively simple to construct.
 Adjustment of an external pressure knob permits setting of pressure targets.
 Adjustment of internal components is possible and allows control of breathing frequency, inspiratory time, and breathing waveform.
",7
1254,"Treatment of limited small-cell lung cancer with concurrent etoposide/cisplatin and radiotherapy followed by intensification with high-dose cyclophosphamide: a Southwest Oncology Group study.
 Between March 1986 and May 1988, the Southwest Oncology Group enrolled 58 previously untreated patients with limited small-cell lung cancer on a treatment program that administered high-dose cyclophosphamide (150 mg/kg) as late intensification.
 Treatment consisted of induction chemo-radiotherapy, (weeks 1 to 11), consolidation chemotherapy (weeks 11 to 18), and intensification (week 18).
 Median age was 61.5 years.
 Eighty-nine percent of patients had a Southwest Oncology Group (SWOG) performance status of 0-1.
 Twenty-one patients completed all prescribed treatments.
 There were seven treatment-related deaths, four as a result of intensification.
 Fifty-six patients are available for response analysis.
 Thirty-two patients achieved a complete remission (CR) (57%) and fifteen achieved a partial remission (PR) (26%).
 Median survival for all patients is 11.1 months.
 Among the 21 patients who received intensification, nine remain alive in a CR with a median survival of 27 months.
 This sequence of treatments was not associated with a survival advantage for the group as a whole, possibly because of the toxicity of induction and consolidation treatment and the delayed administration of high-dose cyclophosphamide.
",7
1255,"Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung.
 To determine if chemotherapy dose intensity (DI) influences treatment outcome, 60 published studies in limited- and extensive-stage small-cell carcinoma of the lung (SCCL) were retrospectively analyzed for relationship between intended DI and response (complete response [CR] or partial response [PR]) or median survival (MS).
 Agents used in the regimens included cyclophosphamide (C), doxorubicin (A), vincristine (V), etoposide (E), and cisplatin (P).
 Relative DI (RDI) of each study regimen was calculated against a reference regimen, and weighted regression analysis was used.
 Additionally, analysis of individual drug RDI within combinations was performed.
 For CAV, increasing RDI of the regimen showed no correlation with outcome.
 For the individual drugs, C RDI correlated positively, while A RDI correlated negatively with attainment of CR in limited disease, but both only after unduly influential observations were eliminated.
 In extensive-stage disease, A RDI correlated positively with CR+, PR but only in randomized trials, and this correlation lost statistical significance after unduly influential observations were eliminated.
 For CAE and CAVE, the RDI of the regimens correlated positively with MS in extensive-stage disease as did the C RDI.
 In limited disease, the C RDI correlated negatively with MS.
 For EP, no significant correlations were seen.
 We conclude that DI-outcome correlations are not consistent for these chemotherapy regimens in SCCL.
 Meta-analysis of retrospective data can generate hypotheses for testing in prospective clinical trials, but study sample and method of analysis can appreciably affect conclusions.
",7
1256,"Surgical treatment for limited small-cell lung cancer. The University of Toronto Lung Oncology Group experience.
 Since 1977, 119 patients with limited small-cell lung cancer have undergone combined modality therapy including surgery at our institution.
 Seventy-nine patients (58 male, 21 female; median age 63 years) had surgery first, and 67 of these had adjuvant chemotherapy.
 Forty (27 male, 13 female; median age 59 years) had chemotherapy first, and 94% had a complete or partial response before the operation.
 Pretreatment staging revealed 69 stage I, 27 stage II, and 23 stage III tumors.
 Twenty-six patients required pneumonectomy, 88 lobectomy, and five had no resection.
 Four patients had gross and six had microscopic residual disease.
 Postoperative pathologic examination showed small-cell lung cancer only (n = 95), non-small-cell lung cancer (n = 3), mixed (n = 17), and no residual tumor (n = 4).
 Postoperative staging revealed 35 stage I, 36 stage II, and 48 stage IIIa tumors.
 The median survival of the entire group is 111 weeks and the projected 5-year survival rate is 39%.
 No survival difference was seen between patients treated with chemotherapy before the operation and those undergoing an initial operation followed by chemotherapy (p = 0.756).
 The median survival for patients with pathologic stage I disease has not been reached, and the projected 5-year survival rate is 51%.
 This is significantly better than for the patients with stage II (median 82 weeks, p = 0.001) or stage III (median 83 weeks, p = 0.001) disease, who have projected 5-year survival rates of 28% and 19%, respectively.
 Seven of the 12 patients who had no adjuvant chemotherapy remain alive at 6 to 48+ months.
 Sixty-seven patients have died (11 had no evidence of disease).
 Only 10 patients had a relapse in the primary site alone, seven at the primary and distant sites, and 39 only in distant sites.
 In summary, resection improves control at the primary site, and a significant proportion of patients with stage I (N0) disease achieve long-term survival and cure with combined modality therapy including surgery.
 Stage II and IIIa patients have survival predictions similar to stage IIIa non-small-cell lung carcinoma treated surgically.
",7
1257,"Surfactant apoprotein-A concentration in sputum for diagnosis of pulmonary alveolar proteinosis.
 Pulmonary alveolar proteinosis (PAP), a disease characterised by accumulation of surfactant in alveoli, is diagnosed on the basis of invasive biopsy procedures.
 We have measured apoprotein A (SP-A) concentrations in sputum to see if this is useful for the diagnosis of PAP.
 Sputum samples from three patients with PAP and twenty patients with other pulmonary disease were assayed using monoclonal antibodies to SP-A.
 SP-A concentrations were 400 times higher in patients with PAP than in the controls, suggestions that this measurement is useful for the diagnosis of PAP especially where lung biopsy is contraindicated.
",7
1258,"Origin of nasal polyps.
 The nasoethmoid complexes from 6 patients with nasal polyps were systematically examined.
 First, the location and place of the origin of the polyps were recorded and photographed.
 The polyps and their places of origin were removed, serial sectioned, and examined.
 In all 6 patients, the polyps originated from the nasal mucosa.
 Most of the polyps extended laterally from the mucosa into the anterior part of the middle meatus.
 Several polyps originated from the mucosa near the ethmoid cell ostium or directly from the mucosa lining the edge of the ostium.
 The ostia themselves were not blocked by the polyps, and there was no indication of polyp formation in the ethmoid cells.
",7
1259,"Perioperative effect of methylprednisolone given during lung surgery on plasma concentrations of C3a and C5a.
 Methylprednisolone or saline (placebo) solution was infused intravenously in 28 patients undergoing elective lobectomy for lung cancer.
 The state of the complement system during and after surgery and the effects of methylprednisolone on biologically active products of complement were studied by measurements of plasma C3a and C5a anaphylatoxins and leukocyte counts in peripheral blood perioperatively.
 In the placebo group plasma concentrations of C3a were significantly increased on postoperative days 1 and 2, whereas C5a had risen significantly 6 hours after surgery and on days 1 and 2.
 Methylprednisolone infusion during surgery eliminated the postoperative elevation of C3a and C5a.
 The postoperative leukocyte count in peripheral blood was higher in the methylprednisolone group than in the controls.
 The observations indicated that methylprednisolone may reduce the influx of leukocytes from peripheral blood into the airways by attenuating production of biologically active complements.
",7
1260,"The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation.
 Endotoxin, a lipopolysaccharide (LPS) component of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1).
 Lipopolysaccharide and IL-1 both cause severe acute neutrophilic inflammation in the lung after intratracheal injection, suggesting that LPS-induced IL-1 expression contributes to the pathogenesis of LPS-induced acute inflammation.
 In the present study, the role of IL-1 in LPS-induced acute pneumonia was investigated by quantitating the acute inflammation occurring at 6 hours after the intratracheal injection of LPS as compared to the same timepoint after the intratracheal coinjection of LPS and IL-1 receptor antagonist (IL-1ra).
 The IL-1ra was found to inhibit LPS-induced acute inflammation (P greater than 0.0001) as measured by the number of neutrophils recovered in bronchoalveolar lavage.
 The LPS-induced emigration of neutrophils was inhibited by as much as 45%.
 Recombinant IL-1 beta-induced neutrophil emigration into the lung was inhibited by 95% when IL-1ra was coinjected intratracheally with IL-1 beta.
 Coinjection of recombinant IL-1 beta and LPS increased the neutrophilic exodus as compared to the intratracheal injection of either agent alone.
 Intratracheal injection of LPS induces a progressive increase in IL-1ra mRNA expression in whole-lung RNA preparations, suggesting that endogenous IL-1ra may play an important role as a negative feedback mechanism to downregulate LPS initiated IL-1-mediated acute inflammation.
 In conclusion IL-1ra inhibits both LPS- and IL-1-induced neutrophilic inflammation and may therefore prove clinically useful as an anti-inflammatory agent for the therapy of either septic or aseptic IL-1-mediated acute inflammation.
",7
1261,"Contrasting roles for tumor necrosis factor in the pathogeneses of IgA and IgG immune complex lung injury.
 Recent studies suggest that development of acute gamma G immunoglobulin (IgG) immune complex lung injury is partially dependent on a tumor necrosis factor (TNF)-dependent mechanisms of neutrophil (PMN) recruitment.
 The authors have sought to further define the role of intrapulmonary TNF in IgG alveolitis and to examine its role in IgA immune complex alveolitis, a neutrophil-independent model of acute lung injury.
 IgG immune complex lung injury resulted in a marked rise in intrapulmonary TNF activity accompanied by progressive pulmonary PMN accumulation.
 Intratracheal instillation of neutralizing concentrations of anti-TNF markedly reduced PMN influx measured at 4 hours but had no effect on PMN recruitment quantitated at 2 hours.
 IgA immune complex deposition resulted in acute lung injury accompanied by increased numbers of intrapulmonary mononuclear phagocytes but few neutrophils.
 Lung lavage fluids obtained from IgA immune complex-injured rats contained both neutrophil and monocyte chemotactic activities, albeit at twofold to fourfold lower concentrations than observed in IgG-mediated alveolitis.
 In contrast to IgG complex-mediated alveolitis, lung lavage fluids from IgA-injured rats contained no TNF activity.
 Intratracheal administration of anti-TNF antibodies had no effect on the development of IgA lung injury as assessed by morphology and measurements of vascular permeability.
 In vitro exposure of isolated alveolar macrophages to performed IgG immune complexes resulted in dose-dependent TNF secretion, while exposure to IgA complexes resulted in very low levels of TNF secretion.
 These data suggest that TNF-mediated pulmonary neutrophil recruitment (in IgG lung injury) is manifest chiefly in the late phase (approximately 4 hours) of developing alveolitis.
 The virtual absence of intrapulmonary TNF activity in evolving IgA immune complex alveolitis may in part account for the limited PMN recruitment observed in this model.
",7
1262,"The role of bacterial adherence in otitis media with effusion.
 Adherence of nontypable Haemophilus influenzae and Streptococcus pneumoniae to nasopharyngeal epithelial cells was investigated in vitro.
 Both strains had higher affinity to the epithelial cells of children than to those of adults.
 In children, the adherence was significantly greater in patients with otitis media with effusion than in normal subjects.
 Secretory IgA in nasopharyngeal secretions was found to have antibody activity against the bacteria.
 Adherence of both bacteria was significantly smaller in the group having secretory IgA antibody activity than in the group having no activity.
 These results suggest that bacterial adherence to the nasopharynx may play an important role in the pathogenesis of otitis media with effusion in children, and that secretory IgA in nasopharyngeal secretions may be related to the decrease of adherence.
",8
1263,"Lidocaine in the middle ear.
 Anesthesia of the ear canal is produced by injection of lidocaine hydrochloride into the skin of the lateral external ear canal.
 Ear canal, tympanic membrane, and middle ear surgeries are performed with this injection.
 The fluid found in the middle ear during tympanotomy was collected and analyzed.
 The percentage of lidocaine in the fluid was calculated by an enzyme immunoassay technique.
 Fifteen surgical cases were undertaken in which perilymphatic fluid in the middle ear would not be suspected, such as tympanotomy for otosclerosis.
 Lidocaine was found in all middle ears in which there was sufficient fluid to collect.
 The authors question the validity of using the presence of clear fluid in the middle ear, even with reaccumulation, as the sole criterion for identifying perilymph and cerebrospinal fluid.
",8
1264,"Stapedotomy technique and results: ten years' experience and comparative study with stapedectomy.
 Fifty of the 810 patients who underwent stapedotomy for otosclerosis from 1969 through 1988 were randomly chosen for follow-up of at least 5 years.
 Most of the patients (65%) had follow-up of 10 years after stapedotomy, but another 50 patients who underwent stapedectomy had follow-ups of longer than 10 years.
 In 50 patients, stapedectomy under local anesthesia was performed by removal of the footplate of the stapes, using an endaural incision, and covering the oval window with Gelfoam.
 In the other 50 patients, stapedotomy was performed under general anesthesia, using an endopreauricular incision, making a small hole in the footplate, and covering the hole only with blood from the surgical area.
 Although both groups showed improvement in hearing after the operation, the air-bone gap in the stapedotomy group was significantly better than that in the stapedectomy group.
 The use of the endopreauricular incision under general anesthesia was preferable to endaural incision under local anesthesia because the operative field was wider, more convenient for the surgeon, and conducive to patient safety.
 There were no significant complications in either group.
",8
1265,"An improved stent method for choanal atresia repair.
 Short intranasal stents secured sublabially have a number of advantages.
 They provide secure fixation without an external ligature across the columella.
 The short length of the stents allows them to sit only in the operative area where the atretic plate had been removed.
 This lessens the chance of intranasal syechiae formation and eliminates the possibility of erosion in the anterior septal and nasal alar region from pressure exerted by a stent.
 Since the stents do not protrude from the nose, they cannot be grasped by infants or young children and are not visible externally.
 School-aged children who have undergone repair of a unilateral choanal atresia can attend school without having to suffer the embarrassment of being teased about a tube protruding from the nose.
 When compared with other stenting methods, the posterior stent is more secure and less likely to become dislodged.
",8
1266,"Fat myringoplasty in the guinea pig.
 Fat myringoplasty is a simple office technique for repairing tympanic membrane perforations.
 It involves wedging a piece of fat from the ear lobule into the perforation.
 A search of the literature failed to reveal any controlled studies on the efficacy of this method, which may allow patients to avoid more invasive procedures.
 Controlled perforations in guinea pig tympanic membranes were treated with fat myringoplasties, paper patches, or no intervention.
 Four weeks following the procedures, ears were examined and photographed under the microscope and studied histologically.
 The fat myringoplasty healing rate exceeded the rates of both the control and paper-patch groups.
 Results were stratified with respect to location and size of perforations.
 The results and histological studies suggest that controlled studies in humans are warranted.
",8
1267,"Monothermal differential caloric testing in patients with Meniere's disease.
 The monothermal differential caloric test allows determination of vestibular recruitment and decruitment, variables which may help discriminate peripheral from central vestibular lesions.
 Previous reports indicated a strong association between vestibular recruitment and Meniere's disease.
 This study examined patients having unilateral Meniere's disease.
 Nystagmus beat frequency (NBF) and slow-component velocity (SCV) responses were recorded by electronystagmography (ENG).
 Electronystagmographic findings showing unilateral dysfunction were present in 54% of patients by slow-component velocity and in 31% by nystagmus beat frequency.
 Unilateral hypofunction was the most frequent lateralizing ENG finding.
 Absolute vestibular recruitment occurred in less than 10% of patients but relative recruitment was found in nearly 20% of patients.
 Slow-component velocity had higher sensitivity than nystagmus beat frequency, with excellent clinical concordance.
 Monothermal caloric testing as described in this study best detects peripheral vestibular disease in Meniere's patients using slow-component velocity to determine unilateral hypofunction and relative vestibular recruitment.
",8
1268,"Paranasal sinus bony anatomic variations and mucosal abnormalities: CT analysis for endoscopic sinus surgery.
 Coronal plane computerized tomographic (CT) scanning has dramatically improved the imaging of paranasal sinus anatomy as compared to sinus radiographs.
 Increasingly, subtle bony anatomic variations and mucosal abnormalities of this region are being detected.
 Data regarding the ""background"" prevalence of these findings are needed to determine their clinical relevance.
 A detailed analysis of coronal plane CT scans of the paranasal sinuses obtained in 202 consecutively imaged patients was conducted.
 Special attention was directed toward identifying bony anatomic variations and mucosal abnormalities.
 Anatomic variations studied included pneumatization of the middle turbinate, paradoxical curvature of the middle turbinate, Haller's cells, and pneumatization of the uncinate process.
 Such bony anatomic variations were detected in 131 (64.9%) of 202 patients and were found with a similar frequency in patients scanned for sinus complaints and in those scanned for nonsinus reasons.
 Mucosal abnormalities were detected in 168 (83.2%) of 202 patients.
 For those patients scanned during the evaluation of sinus-like complaints, mucosal abnormalities were noted in 153 (92.2%) of 166 cases, and were predominantly detected in the anterior ethmoid region.
 For patients scanned during nonsinus evaluations, mucosal abnormalities were detected in 15 (41.7%) of 36 cases, without predilection for the anterior ethmoid region.
 Discussion regarding the prevalence and clinical significance of paranasal sinus bony anatomic variations and mucosal abnormalities is included as a guide to assist the otolaryngologist and/or radiologist in the evaluation of coronal sinus CT scans.
",8
1269,"Whole-blood filterability in sudden deafness.
 Sixteen patients with sudden deafness (SD), diagnosed on the basis of a battery of audiometric tests, but with no other medical or surgical pathology requiring drug treatment, underwent monitoring of their hemorheological profiles to see whether disturbances in the microcirculation could be linked to SD.
 Plasma viscosity, the filterabilities, (using a low-shear positive pressure system) through 5-microns-diameter pore Nuclepore filters, of whole blood and red and unfractionated white cells were monitored in 16 SD patients and 32 controls matched for age, sex and socioeconomic status.
 Whole blood filterability and the filterability of the red blood cells were significantly impaired in the SD patients, which suggests that alterations in the microcirculation are linked, in some way, to sudden deafness.
",8
1270,"Conservative management of epistaxis.
 A retrospective study to assess the clinical usefulness of non-surgical management of epistaxis was performed on 340 patients requiring hospitalisation at the ENT Department of La Paz Hospital (Madrid).
 The previous history, type of management, hospitalisation time, and volume of transfusion were considered.
 Nasal packing was employed in 94.1 per cent of the patients.
 Most patients (82.9 per cent) were hospitalised less than seven days, and 84.1 per cent of the patients required no transfusion.
 There was one death.
 This study supports the clinical usefulness of conservative management in the treatment of patients with epistaxis.
",8
1271,"Improved technique for inserting a T tube in patients with subglottic stenosis.
 An improved method for inserting a silicone T tube through a tracheostomy stoma in patients with subglottic stenosis is presented.
 A silicone T tube is pulled into the trachea with a catheter that is inserted into the tracheostomy stoma, advanced through the stenotic subglottic space, and pulled out the mouth.
 A cone-shaped dilator is placed beforehand at the proximal end of the vertical limb of the T tube to facilitate the passage of that end through the stenotic subglottic space.
 This method was used in 4 patients with good results.
 We suggest this technique be tried when attempts to insert a T tube by the usual method fail, as it can be performed under local anesthesia without special instruments and is technically easy.
",8
1272,"Acoustic reflectometry for assessment of hearing loss in children with middle ear effusion.
 We sought associations between acoustic reflectometry and hearing loss in ears with and without middle ear effusion in 137 New Zealand children ages 3 to 16 years.
 Reflectometry was significantly associated with conductive hearing loss.
 These associations were present in the entire sample; correlation coefficients varied between 0.31 at 2000 Hz (P less than 0.001) and 0.55 for a three frequency pure tone average (P less than 0.001).
 The associations persisted for the sample of ears deemed to be filled entirely by effusion; correlation coefficients varied between 0.27 at 4000 Hz (P = 0.026) and 0.47 at 500 Hz (P less than 0.001).
 Using a reflectivity of 6.0 or greater to detect a three frequency pure tone average loss of 30 dB or more, the sensitivity was 88% and the specificity was 44%.
 The technique of acoustic reflectometry should be explored and extended to permit rational decisions about management of middle ear effusions.
",8
1273,"Quantitation of DNA ploidy in squamous intraepithelial neoplasia of the laryngeal glottis.
 The DNA contents in 56 laryngeal glottic biopsy specimens with a spectrum of squamous intraepithelial neoplastic (SIN) changes were evaluated by image analysis.
 A combination of DNA histogram features were used to define abnormal DNA-containing cell populations that were interpreted as representing intraepithelial neoplastic transformation.
 Eighteen biopsy specimens were classified as dysplasia/keratosis and graded SIN I, six (33%) of which were aneuploid.
 Eighteen (78%) of 23 biopsy specimens graded SIN II were aneuploid, and all 15 biopsy specimens graded SIN III had abnormal quantities of nuclear DNA.
 Twelve biopsy specimens (six of SIN II grade and six of SIN III grade) were considered to represent keratinizing forms of dysplasia, and all 12 (100%) were found to contain increased (aneuploid) quantities of DNA.
 We conclude that the proposed SIN-grading scheme for laryngeal epithelial abnormalities exhibits strong correlations with nuclear DNA content.
 In addition, aneuploidy was observed in all SIN II- and SIN III-graded biopsy specimens with prominent keratinization.
",8
1274,"Modification of the fluorescent allergosorbent test as an inhibition assay for determination of cross-reactivity among aeroallergens.
 The fluorescent allergosorbent test was adapted as an inhibition assay to determine cross-reactivity between aeroallergens.
 With this method, similar antigenic determinants were found between short ragweed and giant ragweed, cocklebur, lamb's-quarter, rough pigweed, marsh elder, and goldenrod.
 Cocklebur and giant ragweed were highly potent in their ability to competitively bind to short ragweed IgE.
 The other pollens demonstrated lower potency of cross-reacting antigens.
 The fluorescent allergosorbent test-inhibition assay appears to be a useful method to determine cross-reactivity among aeroallergens.
",8
1275,"Point and period prevalence of otitis media with effusion evaluated by daily tympanometry.
 Previous studies on daily tympanometric screening using an automatic impedance tympanoscope indicated relatively high incidences of type B tympanograms of one day's duration, which is contrary to our conceptions of the pathogenesis and pathology of otitis media with effusion.
 We therefore repeated the study in 51 otherwise healthy children (100 ears) attending kindergarten.
 Tympanometry was performed daily for one month using both the conventional impedance apparatus AZ7 and the automatic impedance tympanoscope ZS 331.
 The impedance apparatus did not indicate any one-day type B tympanograms and only a few short-lasting episodes occurring either in the beginning or end of the study period.
 Several ears had type B tympanograms on all days examined.
 The point prevalence was 15 per cent and the period prevalence 17 per cent, which accord well with findings of previous epidemiological studies of secretory otitis.
 The impedance tympanoscope indicated 16 cases of B-curves lasting only one day and considerably higher point and period prevalences, which make the impedance tympanoscope unsuited for both scientific and clinical purposes.
",8
1276,"Cochlear otosclerosis: statistical analysis of relationship of spiral ligament hyalinization to hearing loss.
 This paper presents an analysis of the relationship of the amount of hyalinization of the spiral ligament, secondary to cochlear otosclerosis (spongiosis), to the amount of hearing loss.
 This relationship was previously studied by Parahy and Linthicum.
 It was found that the larger the amount of hyalinization, the greater the hearing loss.
 This hyalinization is a measure of the amount of toxic enzymes being excreted into the inner ear fluid.
 These enzymes are suspected to affect the metabolic function of the hair cells.
",8
1277,"Isolated congenital round window absence.
 An adult with unilateral round window atresia is presented.
 With care, CT scanning may be used to demonstrate round window occlusion.
 Cochlear fenestration resulted in only a modest hearing improvement.
 Previously reported cases are reviewed.
",8
1278,"Burkitt's lymphoma of the tonsil.
 A case of Burkitt's lymphoma involving the tonsil in a 10-year-old Bedouin boy, is presented.
 The biological behaviour and the clinical presentation of this unusual neoplasm are discussed and the English language literature is reviewed.
 The diagnosis was made by histological examination, electron microscopy and confirmed by immunohistochemistry.
 The patient showed an excellent symptomatic response to surgery and chemotherapy.
",8
1279,"The Glasgow Benefit Plot: a new method for reporting benefits from middle ear surgery.
 Conventionally, the results of middle ear surgery are reported in terms of postoperative closure of the air-bone gap or the improvement in air-conduction thresholds.
 While these are relevant in that they assess the technical success of the procedure and the lessening of monaural disability, they do not necessarily assess whether the patient has benefited.
 This is determined by many factors, not least of which is the hearing in the nonoperated ear.
 In this paper, we suggest that preoperative and postoperative plots of the air-conduction thresholds in both ears be used as an additional method of presenting the results.
 First, the proportion of patients that fall into each of three main preoperative impairment groups are identified.
 This is important, as the potential benefits from surgery are not the same in each group.
 Thereafter, the percentages of patients that achieve various postoperative hearing categories can be calculated, allowing surgeons to audit their results and make comparisons between series.
",8
1280,"Ototoxic reaction to erythromycin.
 We report a case of bilateral hearing loss in a patient treated with intravenous erythromycin lactobionate.
 The ototoxic reaction occurred despite the patient's having normal renal and hepatic function and the fact that serum erythromycin levels were within the predicted normal range.
 In addition to hearing loss, a marked labyrinthic hyporreflexia was also observed.
 Hearing loss improved after the treatment was discontinued, but labyrinthic abnormalities persisted suggesting that erythromycin had caused a permanent vestibular damage.
",8
1281,"Microdrill versus perforator for stapedotomy.
 The purpose of this study was to compare the hearing results of performing stapedotomy using either a microdrill or a perforator.
 Two groups of patients, otherwise similar, were followed up for at least 2 years after the stapedotomy.
 It was possible to create 0.8 mm fenestra in 91.6% of our patients.
 There was no significant difference between the two groups in hearing results.
 The results showed a continuous improvement in the first 6 post-operative months after which the hearing stabilized.
 In our hands, the microdrill has not proved to be more traumatic than the perforator to the inner ear.
",8
1282,"A pilot study of pemirolast in patients with seasonal allergic rhinitis.
 Pemirolast is a potent, long-acting, orally effective antiallergic agent evaluated for clinical activity in prevention of symptoms of seasonal allergic rhinitis.
 It was evaluated in a randomized, double-blind, placebo-controlled parallel group in season trials to test its safety, tolerance, and prophylactic activity.
 Thirty-one patients with a history of fall seasonal allergic rhinitis were treated for 6 weeks with pemirolast, 50 mg bid, or placebo beginning approximately 2 weeks before the onset of the ragweed season in Atlanta.
 Daily evaluation of symptom scores disclosed statistically significantly less sneezing, rhinorrhea, and stuffy nose during treatment with pemirolast.
 There was, however, no difference for other evaluated symptoms or for the use of rescue medicines.
 There were no side effects during this short study.
 This preliminary study indicates that pemirolast may warrant further evaluation for the treatment of allergic rhinitis.
",8
1283,"Loracarbef concentrations in middle ear fluid.
 Loracarbef concentrations in plasma and middle ear fluid (MEF) were measured in specimens obtained approximately 2 h after doses of 7.5 or 15 mg/kg.
 The mean +/- standard deviation concentrations in MEF were 2.0 +/- 2.6 mg/liter (48% of the concentration in plasma) after the smaller dose and 3.9 +/- 2.6 mg/liter (42% of the concentration in plasma) after the larger dose.
 With the larger dose, the concentrations in MEF were greater than the MIC for 90% of strains of the usual pathogens of acute otitis media tested in 16 of 17 specimens.
",8
1284,"Noncongenital hereditary hearing loss in children. Prospective documentation.
 Younger siblings of children with sensorineural hearing loss of possible hereditary cause underwent interval audiologic examination.
 Seven siblings (in unrelated families) were found to have progressive sensorineural hearing loss despite early audiograms documenting normal hearing levels for age.
 Continued testing of these children allowed for early identification and intervention.
 We advocate regular otolaryngologic and audiologic follow-up even after normal audiologic assessments are made for younger siblings of children with documented sensorineural hearing loss, unless a definite nongenetic origin of the hearing loss in the older child is known.
 Recessive sensorineural hearing loss with onset in infancy or childhood may present with no antecedent family history and with normal behavioral audiograms early in life.
",8
1285,"Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs 
 OBJECTIVE--To evaluate the efficacy and safety of immunotherapy (hyposensitisation) in patients with severe summer hay fever.
 DESIGN--A randomised, double blind, placebo controlled study of a biologically standardised depot grass pollen extract.
 SETTING--Allergy clinic, Royal Brompton and National Heart Hospital, London.
 PATIENTS--40 adults (mean age 35 years) with a history of severe grass pollen allergy uncontrolled by standard antiallergic drugs.
 Patients with perennial asthma were specifically excluded.
 INTERVENTION--Patients were randomised to receive either an active preparation (Alutard SQ, a grass pollen (Phleum pratense) extract) or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached.
 This maintenance dose was given once a month.
 MAIN OUTCOME MEASURES--Clinical efficacy was evaluated by symptom and drug diary cards, visual analogue scores during the grass pollen season, and a postseasonal assessment by the patients and a doctor.
 Conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment.
 RESULTS--There was a highly significant decrease (median Alutard SQ v median placebo (95% confidence interval for difference between medians] in total symptom scores (p=0.001) in the Alutard SQ treated group (360 v 928 (238 to 825].
 Significant differences were also found in total drug use (p=0.002, 129 v 627 (178 to 574].
 Visual analogue symptom scores were also reduced in the active group (p=0.02, 2.2 v 5.5 (-4.8 to -0.5].
 The postseasonal assessment, by either the doctor or the patients, showed a large improvement (p less than 0.001) in favour of Alutard SQ.
 Provocation tests showed a greater than 10-fold reduction for the active group in immediate conjunctival allergen sensitivity (p=0.001), a 40% decrease in early phase response (p=0.02), and a 57% decrease in the late phase (p=0.001) cutaneous response after intradermal allergen.
 A total of 523 active injections were given.
 There was one systemic reaction at 10 minutes after injection, which was rapidly reversed with intramuscular adrenaline.
 There was one mild delayed urticarial reaction at 2 1/2 hours.
 CONCLUSION--Immunotherapy is effective in patients with severe summer hay fever, but immediate anaphylactic reactions limit its use to specialised centres.
 Patient selection is extremely important, and chronic perennial asthma should be specifically excluded.
 As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary.
",8
1286,"Management of posterior epistaxis with the use of the fibreoptic nasolaryngoscope.
 Posterior epistaxis is usually treated by repeated nasal packing and in failed situations by ligation of feeding arteries with considerable morbidity and mortality.
 The most logical approach should be location of the bleeding site and arrest of haemorrhage by local treatment.
 The exact location of the bleeding area can be identified in actively bleeding noses with the fibreoptic naso-laryngoscope and the bleeding arrested by chemical, or thermal cautery and in failed situations by using small nasal packs confined to the bleeding site.
 This approach to the management of posterior epistaxis is effective and reduces the duration of hospital stay.
 It significantly reduces the discomfort to the patient.
 The current practice of indiscriminate blind nasal packing in the hope of arresting nasal haemorrhage by incidental pressure on the bleeding site should be re-evaluated.
",8
1287,"Argon laser stapedotomy.
 Lasers have been used in otology for 10 years.
 There have been reports of excellent hearing results using laser energy in surgery for otosclerosis.
 We used the argon laser in 75 consecutive primary stapedotomy procedures.
 The postoperative air-bone gap was 10 dB or less in 87% of patients and 20 dB or less in 95%.
 One ear (1.5%) had no postoperative hearing secondary to a granulomatous reaction.
 Complications were otherwise uncommon and mild.
 Most patients were treated on an outpatient basis.
 Our results compare favorably with other reports of laser surgery for otosclerosis.
 We conclude that excellent hearing results can be obtained using the argon laser for stapedotomy procedures.
",8
1288,"The response to human rIL-1, rIL-2, and rTNF in the middle ear of guinea pigs.
 Human recombinant interleukin 1 (rIL-1), interleukin 2 (rIL-2), or tumor necrosis factor (rTNF) were injected transtympanically into the middle ear of normal guinea pigs.
 Effusion volume and cellular content were determined after sacrifice and rapid dissection of the ear.
 By 24 hours, rIL-2 (100 U) had produced a cellular effusion (77% to 92% polymorphonuclear neutrophil leukocytes), which cleared by 72 hours.
 rTNF (10 U) yielded a cellular effusion (12% to 67% lymphocytes) at 24 hours, which cleared by 48 hours.
 rIL-1 (100 U) did not produce significant effusion when compared to control.
 rIL-2 and rTNF cause an inflammatory effusion in the middle ear.
 To the extent they are generated in the middle ear during otitis media, these cytokines have the potential to contribute to the pathogenesis of otitis media with effusion.
",8
1289,"Age-related balance changes in hearing-impaired children.
 This study compared balance skills of hearing-impaired children with those of hearing children in order to determine whether a deficit in balance exists in hearing-impaired children and to ascertain whether this deficit is age-related.
 Twenty-eight hearing-impaired subjects were chosen as a sample of convenience from the Pennsylvania School for the Deaf and placed into one of three age groups.
 Ten subjects were in the 4.5 to 6.5-year-old age group, 8 in the 8- to 10-year-old age group, and 10 in the 12.5 to 14.5-year-old age group.
 Selection criteria included bilateral sensorineural hearing loss of greater than or equal to 65 dB and normal intelligence (IQ greater than or equal to 80).
 Balance was measured by the use of the Balance subtest of the Bruininks-Oseretsky Test of Motor Proficiency.
 For each age group, a z test was used to compare the subjects' scores with the Balance subtest standard scores.
 The results showed that for each age group, the mean score for the hearing-impaired children was lower than the standard score.
 Both older groups had significantly higher scores than the youngest group, but the mean scores of the older groups were not significantly different.
 No difference between the subjects' balance scores and the Balance subtest standard scores was found among the age groups, suggesting that the balance deficit was not age-related.
 Gender differences were not found for balance scores.
",8
1290,"Botulinum toxin treatment in spasmodic torticollis.
 Botulinum toxin A was administered to 19 patients in a double-blind placebo controlled trial.
 Toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments.
 Following the controlled trial, treatment with botulinum toxin was continued in an open fashion.
 A total of 60 patients with torticollis received toxin in a total of 117 treatment periods.
 The mean follow up period was 8.4 months.
 In 39 patients with pain there was benefit in 77% of treatment periods.
 Some improvement in neck posture occurred in 83% of the treatment periods with a mean duration of 12 weeks.
 Side effects were frequent with dysphagia being the most common (28% of treatment periods).
 Botulinum toxin is an effective treatment for toticollis but treatment should be initiated with doses at the lower end of the range used in this study (400-600 mouse units).
",9
1291,"Bimanual simultaneous motor performance and impaired ability to shift attention in Parkinson's disease.
 The ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with Parkinson's disease (PD) and 19 age- and intelligence-matched controls.
 The task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand.
 Motor performance was measured using the variables: amplitude of squeezing, frequency of squeezing and velocity of drawing triangles.
 After eliminating variance due to baseline differences in single-handed performance, the bimanual simultaneous performance of PD and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles.
 The amplitude of squeezing, however, differed between the two groups: it was significantly reduced in PD.
 Arguably the disturbance in the bimanual performance of PD patients was not due to a disorder of time sharing, but to a decreased ability to shift attention from the visually cued task to the non visually cued task.
 The results agree with current evidence that PD patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available.
",9
1292,"Misperceptions of comprehension difficulties of stroke patients by doctors, nurses and relatives.
 Doctors, nurses and relatives involved with 30 recently aphasic stroke patients were asked to predict how the patient would perform on a comprehension test.
 Results show that not only do doctors, nurses and relatives underestimate the receptive disability of these patients, but they also illustrate a lack of agreement between health professionals.
 Implications for management are considered.
",9
1293,"Practice effects on the preprogramming of discrete movements in Parkinson's disease.
 The effects of practice on the simple and choice reaction times (RTs) of Parkinson's disease (PD) and control subjects in a discrete aiming task were analysed.
 For controls, practice led to a selective decrease in choice RTs, as has been reported previously.
 An opposite effect was seen in the PD group, with little change in choice RTs and substantial reduction in simple RTs.
 The results suggest that PD subjects can use advance information to initiate discrete movements more rapidly, but that this ability to ""preprogramme"" movements requires practice.
 Reconciliation of these results with studies reporting an inability to preprogramme in PD are made in a discussion of task characteristics which may allow or preclude preprogramming.
",9
1294,"Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood.
 Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumors.
 The clinical presentation correlated with age: infants under 1 year of age presented with macrocephaly, failure to thrive, and severe visual failure; children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits; and older children (greater than 5 years old) had slowly progressive loss of vision.
 All three infants had biologically aggressive tumors in spite of low-grade histology, and died from progressive tumor growth.
 Eleven of the 13 children aged 1 year or over are alive and well, without clinical or radiographic evidence of disease progression, 4 months to 4 1/2 years following surgery.
 Six of these patients, with a follow-up period of 10 months to 4 1/2 years (mean 27 months), have had no adjuvant therapy following radical surgical resection.
 The authors conclude that: 1) radical surgical resection of chiasmatic-hypothalamic tumors can be performed with minimal morbidity; 2) radical resection may delay the time to disease progression in older children and postpone the need for irradiation; 3) resection of postirradiation recurrent tumors may provide neurological improvement and long-lasting clinical remission; and 4) chiasmatic-hypothalamic tumors of infancy are aggressive neoplasms that require multimodality therapy.
",9
1295,"Long-term follow-up review of 31 children with severe closed head trauma.
 Thirty-one children aged 3 to 15 years were followed for 5 to 11 years after suffering severe closed head trauma which caused coma for 1 week or more (median duration of coma 3 weeks).
 One patient remained in a persistent vegetative state until his death 9 years later.
 The other 30 recovered consciousness and were discharged.
 All suffered diminution of their abilities, and 24 of them had major permanent disability.
 The most common motor disabilities were pure spastic hemiparesis (seven cases), basal ganglia syndromes (four cases), ataxia (three cases), and a combination of hemiparesis and ataxia (five cases).
 Of the 30 patients, 26 regained independent ambulation, seven were epileptic, and 14 were dysarthric in various degrees.
 Only 10 had the cognitive ability to profit from the normal educational system, and none had attempted postsecondary education.
 Social problems were common.
 The worst outcomes were associated with intracranial bleeding and/or brain contusion seen on computerized tomography (CT) scans at the acute stage; the best were associated with normal CT scans.
 The degree of residual disability in these children seems no less than that of adults with trauma of similar severity.
",9
1296,"Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank.
 The outcome 1 year after they had sustained a severe head injury was investigated in patients who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank (TCDB).
 Of 300 eligible survivors, the quality of recovery 1 year after injury was assessed by at least the Glasgow Outcome Scale (GOS) in 263 patients (87%), whereas complete neuropsychological assessment was performed in 127 (42%) of the eligible survivors.
 The capacity of the patients to undergo neuropsychological testing 1 year after injury was a criterion of recovery as reflected by a significant relationship to neurological indices of acute injury and the GOS score at the time of hospital discharge.
 The neurobehavioral data at 1 year after injury were generally comparable across the four samples of patients and characterized by impairment of memory and slowed information processing.
 In contrast, language and visuospatial ability recovered to within the normal range.
 The lowest postresuscitation Glasgow Coma Scale (GCS) score and pupillary reactivity were predictive of the 1-year GOS score and neuropsychological performance.
 The lowest GCS score was especially predictive of neuropsychological performance 1 year postinjury in patients who had at least one nonreactive pupil following resuscitation.
 Notwithstanding limitations related to the scope of the TCDB and attrition in follow-up material, the results indicate a characteristic pattern of neurobehavioral recovery from severe head injury and encourage the use of neurobehavioral outcome measurements in clinical trials to evaluate interventions for head-injured patients.
",9
1297,"Intracarotid hydroxyethyl methacrylate solution causing stroke in dogs.
 Hydroxyethyl methacrylate (HEMA) has been advocated as a polymerizing solution with which to prevent deflation of detachable balloons in interventional neuroradiology.
 It is pertinent to know if unpolymerized HEMA would have untoward effects if accidentally released into the carotid artery by balloon rupture or deflation.
 Seven mongrel dogs underwent transfemoral catheterization of the common carotid artery and subsequent injection of HEMA solution in volumes of 1 cc in five dogs, 2 cc in one, and 4 cc in one.
 Angiography performed at the time of injection revealed evidence of intravascular thrombosis as well as possible spasm.
 Three surviving animals were sacrificed at 48 hours; the brains were fixed and examined histopathologically.
 One brain was normal and one was autolyzed and could not be examined.
 Five of the seven animals had histopathologically documented cerebral infarctions of varying size.
 No foreign substance was seen within the blood vessels to suggest intravascular polymerization.
 The animals injected with 2 or 4 cc HEMA solution did not survive 48 hours.
 Literature review reveals little documentation of the toxicology of intravascular HEMA.
 With its increasing popularity as a compound for polymerization in detachable balloons introduced into the brain, further investigations are warranted to understand the physical properties of the compound and potential risks of its use.
",9
1298,"Hemiparkinsonism as a complication of an Ommaya reservoir. Case report.
 The authors describe the case of a 28-year-old woman who developed the following symptoms in her right hand: a lasting resting tremor, transient focal rigidity, and paresthesia.
 These deficits occurred following treatment with intrathecal methotrexate via an Ommaya reservoir which was placed too deeply, resulting in trauma to the contralateral mesencephalon.
",9
1299,"Stereotactic investigation of limbic epilepsy using a multimodal image analysis system. Technical note.
 A methodology has been developed for stereotactic investigation of limbic epilepsy using an image-analysis system that simultaneously displays different structural and functional images of the brain.
 The validity and accuracy of this system were established with phantom studies.
 Surgical planning and electrode implantation are guided by stereotactic magnetic resonance imaging, digital subtraction angiography, and position emission tomography.
 This methodology provides the spatiotemporal relationship of cerebral structure and function necessary to identify seizure onset and propagation in human limbic system epilepsy.
",9
1300,"An evaluation of sensory changes and pain relief in trigeminal neuralgia following intracranial microvascular decompression and/or trigeminal glycerol rhizotomy.
 Nineteen patients with trigeminal neuralgia were treated with either trigeminal ganglion glycerolysis or glycerolysis and intracranial microvascular decompression.
 All had a good degree of pain relief.
 Of those receiving glycerol alone (group A), 50% subjectively reported a mild reduction of fine tactile sensation.
 A similar response was reported by those treated with both glycerol and decompression (group B).
 The degree of sensory loss was so mild that thermal testing was useless as a discriminatory tool.
 The degree of sensory loss was not greater when both surgical procedures were performed than when the less-invasive trigeminal ganglion glycerolysis alone was used.
",9
1301,"Transcranial Doppler ultrasonography: clinical applications in cerebrovascular disease.
 Transcranial Doppler ultrasonography was introduced in 1982 as a noninvasive procedure for assessment of the intracranial cerebral circulation.
 The lightweight and portable equipment used for transcranial Doppler examination facilitates its use in the bedside assessment of critically ill hospitalized patients and outpatients.
 Clinical applications include the diagnosis of vasospasm in patients with subarachnoid hemorrhage, assessment of intracranial collateral flow in patients with extracranial arterial occlusive disease, detection of intracranial arterial stenosis, identification of the feeding arteries of arteriovenous malformations and monitoring the hemodynamic effects of their treatment, confirmation of the clinical diagnosis of brain death, intensive-care unit monitoring of brain-injured patients, and intraoperative and postoperative monitoring of neurosurgical patients.
 Transcranial Doppler technology is also providing new insights into the pathophysiologic mechanisms of a variety of cerebrovascular conditions.
 Clinicians will find transcranial Doppler technology most helpful if they have a specific question about the status of the intracranial circulation.
 Further investigations may expand the clinical and research utility of this technology.
",9
1302,"Arterial responses during migraine headache.
 The superficial temporal artery has been thought to be the main focus of pain during migraine attacks, but its diameter has never been measured directly.
 The use of a new, high-resolution ultrasound machine to measure arterial size in 25 migraine patients with unilateral head pain showed that the lumen was wider on the painful than on the non-painful side during a migraine attack.
 The diameters of both radial arteries and the temporal artery on the non-painful side were smaller during than between attacks.
 The generalised vasoconstriction was not shared by the temporal artery on the affected side, which suggests a local vasodilatory response.
 The findings suggest that cephalic arteries may play a role in migraine pathogenesis.
",9
1303,"Evoked potentials in assessment and follow-up of patients with Wilson's disease.
 Treatment of 9 patients with Wilson's disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI).
 Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively.
 ABP and SEP were normal in 3 other symptom-free patients.
 MRI showed cerebral lesions in 4 of 7 patients.
 Quantified indices of brain atrophy were unaffected by treatment.
 ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy.
",9
1304,"Effects of uvulopalatopharyngoplasty on sleep architecture and patterns of obstructed breathing.
 In this retrospective study, 72 obstructive sleep apnea patients with polysomnograms taken before and after uvulopalatopharyngoplasty were evaluated.
 Postoperatively, there was a significant improvement of sleep architecture and respiratory indices.
 In addition, a second group of 17 patients also had position recordings with their polysomnograms.
 Time spent in supine and lateral sleep positions changed postoperatively.
 There was significant decrease of the apnea plus hypopnea index in the lateral position.
 This study indicates that there is significant improvement of sleep architecture and respiratory indices in the majority of patients after uvulopalatopharyngoplasty, particularly in the lateral sleep position.
",9
1305,"The molecular biology of occlusive stroke in childhood.
 It is very likely that many of the same factors involved in occlusive disease in the adult are operative in the child.
 The major difference may be in the factors that damage endothelium in these two age groups and thereby initiate this catastrophe (atherosclerosis versus ""other"" causes of endothelial changes).
 Our task in this next decade is the rational exploration of the effects of endothelium-mediated kinins, endothelial secretory products, angiospasm, platelet aggregration, prostaglandins, and lipoproteins on pediatric stroke.
",9
1306,"Infantile spasms.
 Infantile spasms are a seizure disorder in young infants with diverse etiologies, suggesting that they arise from any disturbance of central nervous system function during susceptible periods of development.
 The prognosis for normal intellectual and neurologic development parallels that of the underlying etiology.
 Early and appropriate treatment with ACTH may lead to seizure control in a majority of patients.
 The treating physician must anticipate the side effects of this modality.
",9
1307,"Rett syndrome and the autistic disorders.
 Rett syndrome is a disorder noted to date only in females and characterized by a pervasive developmental disability following apparently normal early infancy.
 In addition to gait difficulties, stereotypic hand movements, and loss of communication and purposeful hand skills, autistic-like behavior is an early sign that often results in misdiagnosis.
 Despite these significant clinical abnormalities, neuropathologic features are modest, and no consistent laboratory abnormality or diagnostic marker has been identified.
 The current status of research in RS is considered within the context of autism and other disorders in which autistic features may occur, such as the fragile X syndrome.
 The concept of autism as neurobiologically based behavior is developed.
 As such, autism is regarded as an umbrella category containing an ever-expanding list of specific disorders.
",9
1308,"Tourette syndrome: recent advances.
 Clinical and genetic studies have allowed the limits of Tourette syndrome to be broadened.
 There is now strong evidence that chronic motor tics and Tourette syndrome are different manifestations of an autosomal dominant gene with high penetrance.
 A genetic link with obsessive-compulsive disorder also appears to have been established.
 Up to 10% of cases of Tourette syndrome may be nongenetic phenocopies, however.
 There is also an association between Tourette syndrome and attention deficit hyperactivity disorder.
 This complicates therapy, as psychostimulant drugs may precipitate or exacerbate tics in some individuals.
 A high proportion of patients with Tourette syndrome also has neuropsychological deficits and learning disabilities.
 The pathophysiology is incompletely understood.
 The best supported hypothesis is that there is dopamine receptor supersensitivity, although there are strong suggestions of abnormalities in serotonin metabolism.
 The possibility of abnormalities in neuropeptide systems is being explored.
 Treatment of tics relies primarily on neuroleptics with dopamine receptor blocking activity.
 Clonidine may be useful in some patients, especially those with behavior problems.
 Obsessive-compulsive symptoms can be treated using appropriate pharmacologic agents.
 The treatment of attention deficit disorder in patients with tics should begin with behavioral strategies.
 Clonidine can be tried as the first-line drug, and psychostimulants should be used only if necessary and with great caution.
 In rare instances it may be necessary to combine a psychostimulant and a neuroleptic.
",9
1309,"The floppy infant: recent advances in the understanding of disorders affecting the neuromuscular junction.
 The clinician is often asked to evaluate the floppy infant.
 Numerous conditions that cause hypotonia in infancy are briefly outlined in this article.
 These conditions may affect the brain, spinal cord, or motor unit.
 Several disorders of neuromuscular transmission, including four distinct and recently described congenital myasthenic syndromes and infant botulism, are discussed thereafter.
",9
1310,"Rehabilitation of the pediatric patient with a neuromuscular disease.
 A rehabilitation program for a patient with a neuromuscular disease can be developed only after an accurate diagnosis has been established.
 The diagnosis and its ramifications should suggest a natural course of disease which, it is hoped, can be improved upon with a rational and realistic program.
 The program is best developed by an interdisciplinary team, including a pediatric neurologist, who should have the greatest understanding of the patient's problem and should ultimately be responsible for the implementation and monitoring of the program.
 A child with cerebral palsy commonly requires the services of physical and occupational therapists as well as knowledgeable orthopedists.
 Is the program appropriate? Does it consider the child's potential as well as his limitations? A child with a traumatic brain injury requires, in addition to the above, psychological intervention and an intensive educational program.
 Will the child and family need help from mental health professionals? A child with a motor unit disease such as Duchenne's muscular dystrophy requires, in addition to the above services, a ""philosophy"" of care.
 Will the child ever ambulate independently? If so, at what cost? What will be necessary for the child to reach this potential, including items such as orthoses and adaptive equipment? Will respirator care become necessary? What issues must be addressed for this form of care to be established? There is no one program for all children.
 The programs must be individualized to meet the needs of the patient and the family.
 This point cannot be overemphasized.
",9
1311,"The use of ultrasound in evaluating neurologic diseases of childhood.
 Real-time cranial sonography, intracranial Doppler, and neuromuscular sonography are the sonographic techniques that are applicable to the neurologic evaluation of infants and children.
 Although limited by age, specificity, and operator skill and experience, the advantages of real-time cranial and intracranial Doppler sonography make them useful techniques in the evaluation of the young infant, particularly in the serial assessment of ventricular size and in the study of the critically ill infant.
 The use of neuromuscular sonography in the assessment of the floppy infant and in the guidance of biopsy makes this an increasingly valuable tool.
",9
1312,"Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1.
 Mutations at the mouse dwarf locus (dw) interrupt the normal development of the anterior pituitary gland, resulting in the loss of expression of growth hormone, prolactin and thyroid-stimulating hormone, and hypoplasia of their respective cell types.
 Disruptions in the gene encoding the POU-domain transcription factor, Pit-1, occur in both characterized alleles of the dwarf locus.
 The data indicate that Pit-1 is necessary for the specification of the phenotype of three cell types in the anterior pituitary, and directly link a transcription factor to commitment and progression events in mammalian organogenesis.
",9
1313,"Tonic contraversive ocular tilt reaction due to unilateral meso-diencephalic lesion.
 We studied 4 patients with tonic contraversive ocular tilt reactions due to unilateral, paramedian, mesodiencephalic lesions.
 This is in contrast to the only 2 previously reported patients with ocular tilt reactions due to unilateral mesodiencephalic lesions, each of whom had a paroxysmal ipsiversive ocular tilt reaction.
 This new finding is considered in the context of previous clinical and experimental data on the various types of ocular tilt reactions that follow stimulation or destruction of the peripheral and central vestibular system.
 Otolithic inputs to the interstitial nucleus of Cajal from the contralateral vestibular nucleus and motor outputs from the interstitial nucleus of Cajal to cervical and ocular motoneurons could be involved in the ocular tilt reaction.
 We propose that in patients with unilateral meso-diencephalic lesions, a tonic contraversive ocular tilt reaction could be due to persistently decreased resting activity of ipsilateral interstitial nucleus neurons, whereas a paroxysmal ipsiversive ocular tilt reaction could be due to transiently increased activity of the same interstitial nucleus neurons.
 Cases of ocular tilt reaction due to unilateral meso-diencephalic lesion point to the existence of a crossed graviceptive pathway between the vestibular nucleus and the contralateral interstitial nucleus of Cajal.
",9
1314,"An estimate of the incidence of dementia in idiopathic Parkinson's disease.
 The proportion of patients with idiopathic Parkinson's disease (PD) who are considered demented ranges from 10% to 15%.
 Because dementia may affect survival in PD, the incidence rate of dementia, rather than proportion, would be a more accurate measure of disease frequency.
 We previously estimated the proportion of patients with PD and dementia to be 10.9% from the records of a cohort with the idiopathic form of PD in a major medical center.
 We reviewed the clinical records of this cohort after 4 years and 9 months to estimate the incidence rate of dementia.
 We identified 65 new cases of dementia from the 249 patient-records available.
 Using the number of person-years of follow-up for each case as the denominator, we estimated the overall incidence rate to be 69 per 1,000 person-years of observation.
 The mean age of this cohort was 71.4 years.
 The cumulative incidence of dementia increased with age.
 By 85 years of age, over 65% of the surviving members of the cohort were demented.
 The age-specific incidence rates for dementia in this cohort of PD were significantly greater than for a similarly aged cohort of healthy elderly people.
 The age-specific standard morbidity ratios indicated that, compared with people of similar ages, patients with PD have the highest increase in risk for dementia between ages 65 and 75.
",9
1315,"Antemortem diagnosis of diffuse Lewy body disease.
 Using the presence of widespread cortical Lewy bodies (LB) as the pathologic criteria of diffuse Lewy body disease (DLBD), we describe serial neurologic and mental status examinations in 6 patients with DLBD, 3 patients with Alzheimer's disease (AD), and 1 patient with Parkinson's disease (PD).
 The 6 patients with DLBD included 3 with neocortical neurofibrillary tangles (NFT) consistent with coincident AD.
 Most patients with DLBD had gait impairment concurrent with mild to moderate dementia.
 Abnormalities of tone or resting tremor were also prominent early symptoms in the subjects with DLBD, but not AD.
 Patients with DLBD frequently had abnormal EEGs with background posterior slowing and a frontally dominant burst pattern at the time of mild to moderate dementia.
 Agitation, hallucinations, and delusions were frequent early symptoms in DLBD patients.
 Patients with DLBD without concomitant AD had numerous Alz-50 negative cortical plaques.
 Patients with DLBD have a distinct clinical syndrome that can be differentiated from AD.
 Pathologic features, including the absence of Alz-50 immunoreactivity, also differentiate DLBD from AD.
",9
1316,"Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy: relationship to laterality and nature of paroxysmal discharges.
 We compared the pulsatile secretion of luteinizing hormone (LH) between 13 men with clinically and electrographically documented temporal lobe seizures and 8 age-matched controls.
 Serum for LH measurement was drawn every 15 minutes during 8 hours of EEG telemetry in both groups.
 The 2 groups did not differ significantly in average mean baseline LH secretion, total LH secretion, or average pulse amplitude.
 The group with seizures, however, showed a significantly greater (p less than 0.05) variability of baseline LH secretion and pulse frequency.
 Among the men with unilateral paroxysmal EEG findings, pulse frequency was significantly greater (p = 0.05) with right epileptiform discharges or left slowing (6.4 +/- 0.4) than with left epileptiform discharges or right slowing (3.0 +/- 1.3).
 The relationship of pulse frequency to the nature and laterality of paroxysmal discharges makes it unlikely that endocrine abnormalities can be attributed to medication alone and strengthens the notion that temporal lobe epileptiform discharges may disrupt hypothalamic regulation of pituitary secretion.
",9
1317,"Neuroexcitatory plasma amino acids are elevated in migraine.
 To investigate the role of glutamic (Glu) and aspartic acid (Asp) in migraine, we measured the plasma amino acids in migraine patients with and without aura, between and during attacks, and compared the profiles with the plasma amino acid profiles of tension headache patients and healthy controls.
 Between attacks, migraineurs (notably with aura) had substantially higher plasma Glu and Asp levels than did controls and tension headache patients.
 In addition, patients with migraine without aura showed low plasma histidine levels.
 During migraine attacks, Glu (and to a lesser extent Asp) levels were even further increased.
 The results suggest a defective cellular reuptake mechanism for Glu and Asp in migraineurs, and we hypothesize a similar defect at the neuronal/glial cell level, predisposing the brain of migraineurs to develop spreading depression.
",9
1318,"Borderzone hemodynamics in cerebrovascular disease.
 To investigate the possible existence of chronic selective hemodynamic impairment in the arterial borderzone regions of the brain, we used positron emission tomography (PET) to measure regional mean vascular transit time (rt, equal to the ratio of regional cerebral blood volume to cerebral blood flow) and regional oxygen extraction fraction (rOEF) in 32 patients with either severe internal carotid artery stenosis or occlusion and 11 normal controls.
 Twenty-four of the patients had had TIAs or amaurosis fugax from 1 to 60 days before PET; all had normal brain CT.
 We used a stereotactic localization method to locate the anterior and posterior borderzone regions of the middle cerebral artery (MCA) territory.
 We then calculated ratios of each borderzone to the ipsilateral MCA territory for both rt and rOEF.
 There was no significant difference from control ratios in any patient subgroup including those with greater than or equal to 75% stenosis or occlusion, those with or without contralateral greater than or equal to 50% stenosis, or those with abnormal hemodynamics in the MCA territory.
 We therefore found no evidence for selective borderzone hemodynamic impairment in this group of patients with severe carotid artery disease.
",9
1319,"Comparison of algorithms of testing for use in automated evaluation of sensation.
 Estimates of vibratory detection threshold may be used to detect, characterize, and follow the course of sensory abnormality in neurologic disease.
 The approach is especially useful in epidemiologic and controlled clinical trials.
 We studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy.
 Appearance thresholds obtained by linear ramps increasing at a rate less than 4.15 microns/sec provided accurate and repeatable thresholds compared with thresholds obtained by forced-choice testing.
 These rates would be acceptable if only sensitive sites were studied, but they were too slow for use in automatic testing of insensitive parts.
 Appearance thresholds obtained by fast linear rates (4.15 or 16.6 microns/sec) overestimated threshold, especially for sensitive parts.
 Use of the mean of appearance and disappearance thresholds, with the stimulus increasing exponentially at rates of 0.5 or 1.0 just noticeable difference (JND) units per second, and interspersion of null stimuli, Bekesy with null stimuli, provided accurate, repeatable, and fast estimates of threshold for sensitive parts.
 Despite the good performance of Bekesy testing, we prefer forced choice for evaluation of the sensation of patients with neuropathy.
",9
1320,"Right-left disorientation in dementia of the Alzheimer type.
 We demonstrated that right-left orientation (R/L-O) on a confronting subject is more impaired in patients with dementia of the Alzheimer type than in patients with multi-infarct dementia of comparable degree of dementia.
 The impairment in R/L-O is independent of aphasia and spatial disorientation.
",9
1321,"Dopamine beta-hydroxylase activity in cerebrospinal fluid of idiopathic torsion dystonia.
 Since a postmortem biochemical study and a genetic linkage study of idiopathic torsion dystonia suggested possible involvement of dopamine beta-hydroxylase (DBH), we determined CSF DBH activities of Jewish and non-Jewish patients with childhood-onset idiopathic torsion dystonia and found no differences from a control population.
",9
1322,"Inconsistent response to divalproex sodium in hemichorea/hemiballism.
 We report 6 patients with hemichorea/hemiballism of vascular origin who were treated with divalproex sodium (Depakote).
 Four of 6 responded initially.
 Marked improvement was seen in 2 patients only and in 1 of these hemiballism recurred despite continuing therapy.
 Divalproex sodium is not uniformly effective in the treatment of hemichorea/hemiballism.
",9
1323,"Oxidation reactions in Parkinson's disease.
 Free radicals generated from oxidation reactions may contribute to the pathogenesis of Parkinson's disease (PD).
 Free radicals are capable of reacting almost instantaneously with membrane lipids and causing lipid peroxidation, membrane injury, and cell death.
 Dopamine is metabolized by oxidation reactions capable of generating free radicals.
 Recent evidence indicates that the substantia nigra of patients with PD contains increased iron, which enhances oxidation, and decreased glutathione, which protects against the formation of free radicals.
 Further, the end products of lipid peroxidation are increased in the substantia nigra of patients with PD, supporting the notions that free radicals are being generated and may contribute to dopamine neuronal death.
 This hypothesis suggests that antioxidant therapies may slow the rate of progression of PD and raises concern that metabolites of levodopa therapy may accelerate the rate of neuronal degeneration.
",9
1324,"Levels of mRNA for a putative kainate receptor are affected by seizures.
 In situ hybridization and RNA blot-hybridization techniques were used (i) to examine the regional distribution of mRNA for a putative kainate receptor in adult rat brain and ii) to test the possibility that seizures affect expression of the receptor gene.
 The highest densities of hybridization were distributed within hippocampal pyramidal and granule cells, medial habenula, Purkinje cells and the molecular layer of cerebellum, and olfactory bulb.
 Recurrent limbic seizures caused a massive, delayed, and reversible reduction in levels of the kainate receptor mRNA in dentate gyrus; lesser decreases were found in pyramidal cell fields of hippocampus and superficial cortex.
 These findings provide evidence that unusual patterns of physiological activity can alter genomic expression for a subclass of glutamate receptors in brain.
",9
1325,"Immunodominant regions for T helper-cell sensitization on the human nicotinic receptor alpha subunit in myasthenia gravis.
 In myasthenia gravis an autoimmune response against the nicotinic acetylcholine receptor (AChR) occurs.
 The alpha subunit of the AChR contains both the epitope(s) that dominates the antibody response (main immunogenic region) and epitopes involved in T helper cell sensitization.
 In this study, overlapping synthetic peptides corresponding to the complete AChR alpha-subunit sequence were used to propagate polyclonal AChR-specific T helper cell lines from four myasthenic patients of different HLA types.
 Response of the T helper lines to the individual peptides was studied.
 Four immunodominant sequence segments were identified--i.e., residues 48-67, 101-120, 304-322, and 419-437.
 These regions did not include residues known to form the main immunogenic region or the cholinergic binding site, and they frequently contained sequence motifs that have been proposed to be related to T-epitope formation.
",9
1326,"Conditioning of the spinal stretch reflex: implications for rehabilitation.
 The purpose of this article is to describe a new technique that can potentially be applied to patients with hyperactive spinal stretch reflexes (SSRs).
 The progression of clinical research from conditioning of individual muscles or muscle groups (electromyographic biofeedback) to conditioning SSRs is explained.
 Research data from subhuman primates in addition to the first human experiments are reviewed.
 Potential applications of SSR conditioning are discussed, as are the issues requiring further delineation and research before the specificity of a training effect can be ascertained.
",9
1327,"Wilson's disease: 35 years' experience.
 Thirty-seven Chinese patients fulfilling the criteria for Wilson's disease seen during a 35-year period were reviewed.
 Males and females were equally affected.
 Twenty-two patients were symptomatic and 15 asymptomatic; most of them presented before the third decade.
 Thirty-one per cent of the relatives screened showed evidence of disease, and parents were rarely affected (13 per cent).
 Half of the adult symptomatic females presented with primary amenorrhoea.
 Liver laboratory tests were abnormal in only 50 per cent of patients, with gamma-glutamyltranspeptidase being the most sensitive index.
 Renal disease was infrequent.
 Serum caeruloplasmin level was the single biochemical parameter of prognostic significance (p = 0.0001).
 Seventy per cent of the symptomatic patients showed an improvement after treatment with penicillamine.
",9
1328,"Bicarbonate-buffered lidocaine-epinephrine-hyaluronidase for eyelid anesthesia.
 A double-masked, randomized clinical trial was conducted to determine if subcutaneous eyelid injections of a bicarbonate-buffered lidocaine-epinephrine-hyaluronidase mixture were less painful than unbuffered injections.
 Twenty-one patients received both buffered (pH = 7.4) and unbuffered (pH = 4.6) injections.
 After each injection, patients recorded pain on a scale of 0, ""no pain,"" to 10, ""severe pain."" Mean pain score for buffered injections was 2.0 versus 4.1 for unbuffered injections (P = 0.0003).
 Seventeen (81%) of 21 patients ranked the buffered injection less painful.
 Use of a bicarbonate-buffered lidocaine-epinephrine-hyaluronidase mixture is effective in making ophthalmic anesthesia less painful.
",9
1329,"Optic nerve sheath meningoceles. Clinical and radiographic features in 13 cases with a review of the literature 
 Thirteen patients with dilated intraorbital optic nerve sheaths with an expanded, patulous cerebrospinal fluid (CSF) space were studied with high-resolution computed tomography (CT) or magnetic resonance imaging (MRI).
 Eleven patients had bilateral findings.
 Headache or visual complaints, or both, were present in all patients.
 Signs of optic nerve dysfunction were present in eight patients.
 Three patients had visual acuity worse than 20/200.
 Cerebrospinal fluid pressure was mildly elevated in two patients.
 Three patients underwent a surgical procedure; visual acuity improved in one.
 The authors propose the term meningocele for this condition and suggest MRI with fat-suppression techniques and off-axis sagittal views as the radiographic procedure of choice.
",9
1330,"Strategies underlying the control of disordered movement.
 The purpose of this article is fourfold.
 First, a theory of motor control--the dual-strategy hypothesis--is outlined.
 Second, the methodologies and theoretical framework that are used to develop this theory are examined.
 Third, motor dysfunction is discussed in the context of this theory.
 In particular, Down syndrome, Parkinson's disease, cardiovascular accidents, and spasticity are discussed.
 Finally, potential applications of the theory to physical therapy are considered.
",9
1331,"A new challenge--robotics in the rehabilitation of the neurologically motor impaired.
 Rehabilitation robotics is a research area, originating in engineering, that has emerged in the last decade.
 Its broad aim is to use robot technology to assist people with movement dysfunction.
 The neurologically impaired population might gain considerably from the provision of robots as ""assistants"" or ""therapy aides,"" but the interface with the machine must match both the physical and intellectual abilities of the user.
 We therefore consider a multidisciplinary approach, encompassing both behavioral and engineering perspectives, to be essential in achieving this aim.
 However, to date, published reports have been largely restricted to engineering journals or conference reports, and relatively little has appeared in the therapy literature.
 This article seeks to introduce physical therapists to robotics, describe possible applications to the rehabilitation of neurologically impaired patients, and suggest issues deserving further investigation.
",9
1332,"Brain potentials associated with movement in traumatic brain injury.
 Brain potentials may be used to assess the functional abnormalities that underlie impairments of movement.
 The purpose of this article is to illustrate the usefulness of examining these potentials.
 In addition to an overview of the topic, the article includes a report of a study demonstrating that there were differences between the brain potentials of five patients with traumatic brain injury and those of four healthy control subjects.
 All five patients were in the postacute phase of hemiplegia.
 Slow cortical potentials associated with simple goal-directed forearm and finger movements were recorded from frontal and parietal electrodes.
 Two seconds of movement-related electroencephalographic activity (movement-related potential) were recorded.
 The patients showed reduced brain potentials for movements associated with their paretic limb and, to a lesser extent, reduced brain potentials for movements associated with their nonparetic limb.
 The waveforms obtained from the patients were unusual, with uncharacteristic cross-cortical movement-related potential correlations associated with specific electrode configurations, as well as with specific movement conditions.
 Brain potentials associated with the fore-period interval of a simple reaction time paradigm were later recorded in two of the patients with traumatic brain injury and in a control subject to help determine the functional significance of the relative positivity apparent in their movement-related potential data.
 This preliminary study indicates that electroencephalographic potentials obtained during the preparation for and execution of movement can provide information regarding the basis for motor dysfunction.
",9
1333,"Movement disorders--limb movement and the basal ganglia.
 The primary concern of this article is to review experimental methods that may lead to a better understanding of the functional role of the basal ganglia in the control of movement.
 Two models of basal ganglia impairment are considered: Parkinson's disease and Huntington's disease.
 The review focuses primarily on akinesia and bradykinesia because they are key abnormalities of basal ganglia dysfunction.
 In general, through electromyography and kinematic analysis of movement, it may be possible to characterize specific movement disorders.
 Specifically, if damage sustained by the central nervous system is traced to a certain structure, it may provide insight on the extent of involvement and functional role of that structure in the control of movement.
 Much of the data reviewed suggests that the basal ganglia may play a specific role in the initiation and regulation of force control.
",9
1334,"Return to work for persons with traumatic brain injury: a supported employment approach.
 Supported employment was used to place 41 persons into competitive employment during 30 months.
 All individuals had experienced severe head injuries; almost 70% of injuries were due to motor vehicle accidents.
 A mean of seven years had passed since injury for all referred clients, who had been unconscious a mean of 53 days.
 Only 36% of referred clients had achieved any competitive postinjury employment, compared with 91% of the same group who were competitively employed before injury.
 A job retention rate of 71% was reported, with most jobs in warehouse, clerical, and service-related occupations.
 A mean of 291 hours of job coaching was required to place and maintain all clients in supported employment.
",9
1335,"Functional evaluation of quadriplegic patients using a hand neuroprosthesis.
 The objective of this retrospective study was to compare the abilities of quadriplegic patients to complete activities of daily living with and without the use of a portable hand neuroprosthesis.
 The neuroprosthesis provided synthetic hand grasp through functional neuromuscular stimulation of paralyzed forearm and hand muscles.
 Data were obtained from telephone interviews, patient records, and videotapes.
 Twenty-two quadriplegic patients were included in the study; 15 were functional at a C5 spinal cord injury level and seven at a C6 level.
 The median success rate (ie, the percentage of patients who could complete each activity) across the ten activities was 89% with the hand neuroprosthesis but was only 49% without the hand neuroprosthesis.
 All patients could perform more tasks when the neuroprosthesis was used, although the relative improvement of C5 patients was larger than that of C6 patients.
",9
1336,"Impaired awareness of behavioral limitations after traumatic brain injury.
 Sixty-four traumatically brain injured patients were divided into three groups.
 Patients in Group I overestimated their behavioral competencies.
 Patients in Group II showed behavioral ratings similar to relatives' reports concerning behavioral competencies.
 Patients in Group III underestimated their behavioral competencies.
 Group I patients had greater evidence of bilateral and multiple-site lesions than group II and III patients.
 Speed of left-hand finger tapping was also worse in Group I than groups II and III, but other standard neuropsychologic test findings failed to separate the groups.
 Specific brain lesion sites were not related to group membership.
 Impaired awareness of behavioral limitations after traumatic brain injury may be related to neuropsychologic changes not measured by standard tests.
 Bilateral impairment of heteromodal cortex may be important to this phenomenon when it exists several months or years postinjury.
",9
1337,"Maximal exercise testing of mentally retarded adolescents and adults: reliability study.
 Few data are available regarding maximal exercise testing of mentally retarded individuals.
 No data are available on the reliability of maximal exercise testing of mentally retarded individuals.
 The purpose of this study was to determine the reliability of graded exercise testing of mentally retarded adolescents and adults.
 The testing was conducted at two geographically different centers.
 At Center A, 14 mentally retarded adolescents (11 boys, three girls) with Down syndrome, who were educable or trainable, were recruited from a nonresidential school.
 The subjects completed two Balke-Ware treadmill protocols until exhaustion.
 The treadmill time and heart rate (HR) were recorded.
 The time between tests was approximately one week.
 At Center B, 21 mentally retarded adults (14 women, seven men means IQ = 56) were recruited from local workshops and group homes.
 These subjects completed a treadmill walking protocol, with metabolic measurements, until exhaustion.
 The time between tests varied from one to four months.
 At Center A, the subjects achieved a mean treadmill time of 8.72min on test one and 8.84min on test two (means HR = 174 and 175bpm, respectively).
 The reliability coefficient between the two tests was .94.
 At Center B, the subjects achieved a mean V0(2)max of 27.2mL.kg-1.min-1 on test one and 26.9mL.kg-1.min-1 on test two.
 The reliability coefficient was .93.
 These data show that maximal exercise testing is reliable for these populations of mentally retarded individuals, exhibiting similar values to their nonretarded peers.
",9
1338,"Familial trigeminal anesthesia.
 Familial congenital trigeminal anesthesia as an isolated abnormality is an unusual disorder.
 To our knowledge, only one family has previously been reported.
 We report here a family with three affected members demonstrating facial anesthesia, bilateral corneal changes, and nasal septal damage secondary to self-traumatization.
 Magnetic resonance imaging demonstrated hypoplasia of gasserian ganglia and trigeminal nerves in the affected father of two affected sons.
 The pathogenesis of this disorder appears to be congenital hypoplasia of the trigeminal nerves and gasserian ganglia that is inherited in a dominant fashion.
",9
1339,"Enhanced in vitro uptake and retention of 3H-tetraphenylphosphonium by nervous system tumor cells.
 Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells.
 Certain lipophilic cationic compounds, such as tetraphenylphosphonium (TPP), are selectively taken up by a variety of carcinomas.
 Although preferential retention of TPP has been demonstrated for the breast carcinoma cell line MCF-7, this compound had not been tested previously on cells derived from nervous system tumors.
 In the present study, tritiated-TPP (3H-TPP) uptake and retention for eight different cell cultures of three histologically different types of nervous system tumors was measured and the data were compared to a positive control (MCF-7) and negative controls (normal African Green monkey kidney epithelium (CV-1) and the normal human fibroblast (WI-38) cell lines).
 Uptake and retention characteristics could be grouped by specific pathological tumor types, but individual tumor variability was notable.
 Malignant astrocytoma (grade III/III glioblastoma) and malignant neurofibrosarcoma cells showed preferential uptake and retention of 3H-TPP relative to meningioma cells and normal controls.
 A clonogenic assay utilizing the cytotoxic lipophilic cationic compound dequalinium showed strong retainers of 3H-TPP to be more susceptible to the effects of dequalinium than weak retainers.
 These data demonstrate that certain human and experimental animal nervous system tumor cell lines retain lipophilic compounds possessing a delocalized positive charge.
 Lipophilic cationic compounds may be useful in the intraoperative delineation of tumor margins and in the photodynamic therapy of certain nervous system tumors.
",9
1340,"Tension pneumocephalus: treatment with controlled decompression via a closed water-seal drainage system. Case report.
 The successful treatment of a patient with tension pneumocephalus by controlled decompression via external drainage is described.
 The advantage of the technique includes the immediate release of high pressure and the capability of maintaining constant low pressure to enable and facilitate sealing of dural tears.
 The method has been used in three other patients, leading to resolution of the tension pneumocephalus without recurrence or other complications.
",9
1341,"Cerebrospinal fluid rhinorrhea following acoustic neurinoma surgery. Technical note.
 The authors describe a method of preventing cerebrospinal fluid (CSF) rhinorrhea following surgery for acoustic neurinoma.
 Mastoid air cells exposed during craniectomy are skeletonized and packed with bone dust, then covered with Surgicel soaked with Tisseel fibrin glue.
 The use of this technique has reduced the number of acoustic neurinoma cases requiring secondary mastoidectomy for CSF leakage from 16% to 5%.
",9
1342,"The effect of glucose administration on carbohydrate metabolism after head injury.
 The role of intravenous infusion of glucose in limiting ketogenesis and the effect of glucose on cerebral metabolism following severe head injury were studied in 21 comatose patients.
 The patients were randomly assigned to alimentation with or without glucose.
 Systemic protein wasting, arterial concentrations of energy substrates, and cerebral metabolism of these energy substrates were monitored for 5 days postinjury.
 Both groups were in negative nitrogen balance, and had wasting of systemic proteins despite substantial protein intake.
 Blood and cerebrospinal fluid (CSF) glucose concentrations were highest on Day 1, but remained higher than normal fasting levels on all days of study, even in the patients who received no exogenous glucose.
 Although there were no differences in blood or CSF glucose concentrations in the two groups of patients, the glucose group had higher plasma insulin levels, with a mean +/- standard deviation of 14.8 +/- 7.3 microU/ml compared to 10.3 +/- 4.2 microU/ml in the saline group.
 The blood concentrations of beta-hydroxybutyrate, acetoacetate, pyruvate, glycerol, and the free fatty acids were higher in the saline group than in the glucose group.
 Cerebral oxygen consumption was similar in the two groups, while the cerebral metabolism of glucose and of the ketone bodies was dependent on whether glucose was administered.
 In the glucose group, glucose was the only energy substrate utilized by the brain.
 In the saline group, the ketone bodies beta-hydroxybutyrate and acetoacetate replaced glucose to the extent of 16% of the brain's total energy production.
 Cerebral lactate production and CSF lactate concentration were lower in the saline group.
 These studies suggest that administration of glucose during the early recovery period of severe head injury is a major cause of suppressed ketogenesis, and may increase production of lactic acid by the traumatized brain by limiting the availability of nonglycolytic energy substrates.
",9
1343,"Management of meralgia paresthetica 
 Meralgia paresthetica is a syndrome of pain or dysesthesia, or both, in the anterolateral thigh caused by entrapment or neurinoma formation of the lateral femoral cutaneous nerve.
 Conservative treatment was successful in relieving symptoms in 91% of 277 patients with this syndrome; however, 24 patients required surgical treatment for intractable symptoms.
 Although neurolysis with transposition is the most common procedure, sectioning of the lateral femoral cutaneous nerve was performed in 24 cases and was successful in 23.
 One patient had early symptomatic relief, but subsequently developed different neurological signs and symptoms because of an undetected pelvic neoplasm.
 Anatomical variations of the nerve and neurinomas, which occur frequently, are easily handled with sectioning but may lead to recurrence with neurolysis and transposition.
",9
1344,"Post-traumatic intracerebral pneumatocele: case report.
 Pneumocephalus occurs in 0.5 to 1.0% of head trauma, but may also occur after neurologic surgery, or as a result of eroding infection or neoplasm.
 The pathophysiology involves the presence of craniodural fistula allowing ingress of air.
 A ball-valve mechanism may allow air to enter but not exit the cranium, or CSF leak permits air entrance as fluid leaves the intracranial space.
 While a ""succession splash"" is considered diagnostic of pneumocephalus, most patients have nonspecific signs and symptoms such as headache.
 Therefore, a high index of suspicion in a patient with recent head trauma is necessary.
 The diagnosis is made radiographically by CT scan.
 This is generally performed to rule out intracranial hematoma or cerebral contusion in head trauma, but will reveal even very small quantities of air to the unsuspecting physician.
 Therapy is often noninvasive, allowing the craniodural defect to heal spontaneously.
 Selected situations require immediate operative repair of the fistula.
",9
1345,"Headache. Public health problem.
 Headache is, and apparently always has been, a frequent pain syndrome.
 It is reported in American and Western European societies in very high percentages of the population.
 Headache, and specifically severe headache, have also been reported as prevalent from a variety of societies worldwide, although prevalence rates have varied (they are very low, for example, in the People's Republic of China).
 Whether prevalence varies with different socioeconomic groups remains uncertain.
 Severe headache and specifically migraine is, for reasons still unknown, much more common in women, and, in most studies, is reported to decrease in prevalence in older age groups.
 Positive family histories are common, but the precise role of genetics is unknown.
 A major problem in the epidemiologic studies remains the difficulty of uniform definition of headache syndromes.
",9
1346,"The classification and diagnosis of headache disorders.
 Headache disorders recently have been reclassified, and new operational diagnostic criteria assist in making the correct diagnosis.
 These diagnostic criteria have been accepted worldwide.
",9
1347,"Basic mechanisms in vascular headache.
 To better understand and treat painful conditions, one needs to identify the cause, discover the source, and develop knowledge of peripheral and central pain transmission; headaches are no exception.
 The development of appropriate animal models is important.
 Accordingly, we have reviewed the anatomy, neurochemistry, electrophysiology, and pharmacology of the trigeminovascular system in experimental animals and emphasized whenever possible the relevance of this final common pathway to migraine, cluster, and other headache syndromes in humans.
 For example, based on recent anatomic dissections, the pericarotid cavernous sinus plexus was suggested as an important focus to investigate cluster headache pathophysiology.
 This plexus is an anatomic point of convergence for the nerves giving rise to the signs of sympathetic and parasympathetic activity and sensory symptoms that develop in cluster patients.
 As in other nociceptive systems, trigeminovascular axons assume at least two important roles.
 One concerns the transmission of nociceptive information.
 Electrophysiologic evidence supports the trigeminal nucleus caudalis as an important site for the convergence of visceral (vessel) and somatic (forehead) inputs to mediate the referral of vascular pain to superficial tissues.
 A second important role concerns the initiation of local increases in blood flow and enhanced protein permeability (sterile inflammation) via the axonal release of vasoactive neuropeptides.
 Plasma extravasation develops within the dura mater following trigeminal stimulation.
 Extravasation can be blocked by the administration of ergot alkaloids or sumatriptan, a new serotonin-like agonist, and a prejunctional (neuronal) mechanism of action for these drugs (such as blockade of release) was suggested based on experimental evidence.
 Whether vasoconstriction also relates to the therapeutic efficacy remains to be determined.
 As in other organ systems, real or threatened tissue injury provides an important stimulus for depolarizing sensory fibers.
 The stimulus may come from external conditions such as reduced blood flow or hypoglycemia.
 The brain may also possess intrinsic neuronal mechanisms by which nociceptors may be synthesized (e.g., glutamate-induced neurotoxicity, seizures).
 Molecules of relevance include bradykinin, prostaglandins, leukotrienes, and potassium.
 Experimental evidence was presented demonstrating that the trigeminal nerve mediates hyperemia within cortical gray matter by axon-reflex like mechanisms.
 An important role for this nerve was established during the hyperemic period of recirculation after ischemia or during severe hypertension above the limits of autoregulation.(ABSTRACT TRUNCATED AT 400 WORDS).
",9
1348,"The concept of migraine as a state of central neuronal hyperexcitability.
 This article explores the hypothesis that migraine with aura is associated with a state of central neuronal hyperexcitability.
 The authors propose that this central neuronal hyperexcitability involves overactivity of the excitatory amino acids, glutamate, and possibly aspartate.
 Stimuli that activate the migraine attack evoke neuronal depolarization, slow depolarization shifts, and spreading suppression of spontaneous neuronal activity possible by glutamate and K+ dependent mechanisms.
 A low brain Mg2+ and consequent reduced gating of glutamatergic receptors may provide the link between the physiologic threshold for a migraine attack and the mechanisms of the attack itself by promoting glutamate hyperactivity, neuronal hyperexcitability, and susceptibility to glutamate-dependent spreading depression.
",9
1349,"Developments in 5-hydroxytryptamine receptor pharmacology in migraine.
 Because a satisfactory animal model for migraine does not exist, attempts to determine a common mechanism of action for effective antimigraine agents may be of benefit in elucidating the pathogenesis of this neurologic syndrome.
 The present review demonstrates that the clinical data that has developed over the past 30 years may allow for the elucidation of the role of specific 5-HT receptor subtypes in the pathophysiology of migraine.
 A large number of both acute and prophylactic antimigraine agents share an ability to interact with 5-HT receptor subtypes in human brain.
 As summarized in Table 3, acute antimigraine drugs (e.g., ergots, sumatriptan) share high affinity for 5-HTID receptors and somewhat lower affinity for 5-HT1A receptors.
 These receptors are present in certain intracranial blood vessels.
 5-HT1D receptors are also located on nerve terminals where they act to inhibit the release of 5-HT and other neurotransmitters.
 Theoretically, 5-HTID receptor agonists may acutely inhibit the release of vasoactive or pain-inducing substances in the perivascular space.
 Conceivably, drugs acting at this receptor would stop the progression of this perivascular process.
 In addition, a number of prophylactic antimigraine drugs display a relatively high affinity for both 5-HT2 and 5-HT1C receptors in human brain.
 Although these receptors are also found in certain blood vessels, they are present throughout the nervous system.
 The receptors appear to mediate neuronal depolarizations at the cellular level.
 Moreover, the 5-HT2 receptor appears to play a key role in the development of inflammation in certain smooth muscle systems.
 Theoretically, the ability of 5-HT2 antagonists to protect perivascular inflammation may account for their efficacy in the prophylactic treatment of migraine.
 These data offer a novel approach to the analysis of antimigraine agents.
 Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype.
 For example, an agent that displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated.
 Its effectiveness, or lack thereof, would indicate the importance of this specific 5-HT receptor site in the pathogenesis of migraine.
 Future attempts to determine a common mechanism of action for effective antimigraine agents should facilitate the elucidation of the pathogenesis of this neurologic syndrome.
",9
1350,"Manifestations of migraine.
 Migraine is a disorder with multiple manifestations affecting the circulation, gastrointestinal tract, and the central nervous system.
 Involvement of the autonomic nervous system is responsible for many of the clinical features.
 An attack of migraine can vary from a fragment of the clinical spectrum to one with several phases and potentially permanent sequelae.
",9
1351,"Modern pharmacotherapy of migraine.
 Rectal ergotamine and naproxen are the major candidates for the ad hoc treatment of migraine attacks; for particularly dramatic episodes, intravenous DHE with prochlorperazine is the author's preference.
 For long-term stabilization, after simpler measures fail, valproate appears to be a major addition to migraine therapy.
",9
1352,"Advances in cluster headache.
 The physician may have to combine the art and science of medicine in the management of this most fascinating of human ailments.
 The choice of drugs and the length of treatment prescribed are greatly influenced by the individual physician's experience, convictions, and reasoning.
 Needless to say, chronic use of narcotics should be avoided.
 The author's own regimen is to use combinations of ergotamine prophylaxis with either verapamil or prednisone in episodic cluster headache and with lithium for chronic cluster headache.
 Management of the treatment-resistant patient remains problematic, but a carefully performed trigeminal radiofrequency thermocoagulation procedure may be worthwhile.
",9
1353,"Drug-induced headache.
 Headache induced by medications used for nonheadache conditions, and more importantly, headache perpetuated by symptomatic medications used for primary headache disorders are discussed in detail in this article.
 The clinical features and mechanisms of drug-induced headaches are reviewed.
 Ergotamine and analgesic rebound phenomena are described.
 Management strategies for drug-induced headaches are outlined.
",9
1354,"Oromandibular disorders and headache. A critical appraisal.
 Oromandibular disorders are functional disorders and associated pains in the anatomic region of the temporomandibular joint.
 Their diagnosis and treatment are controversial because of the lack of conformity concerning these disorders among health care providers.
 This article provides a clear classification of these disorders and critically reviews their evaluation and treatment.
",9
1355,"Psychologic and behavioral aspects of chronic headache.
 It is important for physicians to be aware of the expectations and psychologic needs patients have, to understand how psychologic and personality variables can impact care, to realize the importance of patient education, and to be cognizant of how environmental factors can influence headache pain behaviors.
 Empirical data indicate that the nonpharmacologic treatments of biofeedback, relaxation, and stress coping training can serve as useful adjunctive or alternative procedures, and that the combined use of medication and nonpharmacologic treatments yields the greatest clinical outcome.
 Certain headache types show minimal response to nondrug therapies alone (cluster, menstrual, and post-traumatic headache).
 Age and personality variables have a bearing on nondrug treatment outcome as well.
",9
1356,"Surgical decompression without transposition for ulnar neuropathy: factors determining outcome.
 Fifty-one surgical decompressions without nerve transposition for ulnar neuropathy were performed in 46 patients.
 All of the patients were men with an average age of 59 years at the time of surgery.
 The follow-up range was between 5 and 32 months (average, 17.8 months).
 The disease involved the nondominant arm in 24 patients (52%) and was bilateral in 5 (11%).
 In 23 cases (50%), no predisposing condition could be identified, whereas 15 patients (33%) abused alcohol and 8 patients (17%) had diabetes mellitus.
 Fifty-seven percent of the patients helped by surgery had symptoms for less than 1 year, whereas only 30% of patients with symptoms for more than 1 year had symptomatic improvement.
 The relative magnitude of the slowing of ulnar nerve conduction velocity across the elbow was not significantly correlated with the success of decompression in relieving symptoms.
 Ulnar nerve conduction velocities across the elbow were 36.13 +/- 11.76 m/s in those responding to surgery and 38.97 +/- 13.91 m/s in those not responding (c = 0.06, dF = 50, P less than 0.3).
 A total of 37 patients showed symptomatic improvement after decompression.
 Simple decompression of the ulnar nerve was performed under local anesthesia without transposition of the nerve.
 In all of these cases, compression of the nerve occurred predominantly in the epicondylar groove.
 Narrowing of the nerve in the groove was present in 28 cases (55%); scar tissue was found adhering to the nerve in 21 cases (41%); and two pseudoneuromas were found (4%).
 Forty-one operations (80%) resulted in symptomatic improvement, typically noted by the patient within the first month postoperatively.
",9
1357,"Blood flow direction in the lumbar nerve root.
 The effect of clipping on lumbar nerve root blood flow rates in the region of the nerve root canal was studied experimentally in the hog.
 Blood flow rate was measured using the hydrogen washout technique.
 When the entrance zone was clipped with a microvascular clip, blood flow rate of the nerve root was decreased by 37% in comparison with the initial control rate; clipping at the exit zone reduced blood flow rate by 69%.
 Blood flow direction in the lumbar nerve root within the nerve root canal was found to be predominantly proximal.
 The current data indicate that the more lateral the impingement of the nerve root occurs, the more ischemic changes are induced.
",9
1358,"Preventing stroke by the modification of risk factors.
 Epidemiologic research has revealed the major risk factors in cerebrovascular disease.
 This review will concentrate on three important risk factors: elevated blood pressure, the most common and important, since it is responsible for up to 70% of all strokes; raised cholesterol; and smoking.
 These factors are important not only because they increase the risk of stroke, but also because they are amenable to modification by drugs, diet, or other interventions.
 Strategies to avoid stroke can either 1) try to produce substantial reductions, usually with drugs, in the level of the risk factor in the few individuals in the population with high levels (the ""high-risk"" approach), or 2) try to produce modest reductions in the level of the risk factor in every individual in the population, usually not with drugs but with lifestyle modification (the ""mass"" approach).
 The prevention of stroke could best be achieved through continuing medical efforts to deal with high-risk individuals and through political strategies to encourage a healthier lifestyle in the population as a whole.
",9
1359,"Cytosolic free calcium during focal cerebral ischemia and the effects of nimodipine on calcium and histologic damage.
 The role of calcium as a mediator in neuronal death during ischemia is now quite strong.
 Evidence supporting this link includes studies in cell cultures and measurements of calcium accumulation in the mitochondria during ischemia, as well as direct measurements of shifts in extracellular calcium using microelectrodes.
 Since it is dangerously high concentrations of the intracellular free calcium that have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important.
 A technique for the measurement of intracellular free calcium is described, along with data from studies that dramatically demonstrate the time course of changes in intracellular free calcium induced by focal ischemia.
 Additional data are also presented that indicate that cellular damage can be attenuated by the use of agents that block calcium channels (nimodipine, which blocks voltage-sensitive calcium channels, and MK-801, which blocks receptor-operated channels) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium.
",9
1360,"Effect of nimodipine on acute ischemic stroke. Pooled results from five randomized trials.
 In a review of pooled data from five double-blind, placebo-controlled studies of nimodipine in acute ischemic stroke, we compared the effect of 120 mg nimodipine given orally with that of placebo.
 In the five studies, 871 patients were followed, and 781 adhered to entry and inclusion criteria.
 End points were mortality and outcome at the end of the treatment period (21 or 28 days).
 Outcome was assessed with Mathew's scale and the physician's clinical judgement.
 The treatment and control groups were well matched with respect to demographic data, risk factors, and baseline Mathew scores.
 In the treatment group, 34 patients (7.9%) died during the treatment period, whereas 54 (12.3%) in the control group died, corresponding with a mortality reduction of 36%.
 Significantly less neurologic impairment at the end of the treatment period was documented under nimodipine treatment, and this impairment improved more in patients with moderate-to-severe stroke (baseline Mathew score less than 66) if administration of nimodipine occurred within 12 hours after stroke onset or if the patient was more than 65 years old.
 The overall incidence of adverse reactions was relatively modest, and these were of minor severity; only a few appeared to have more than a remote relation to the study medication.
",9
1361,"Sleep disturbances in survivors of the Nazi Holocaust.
 OBJECTIVE AND METHOD: Sleep disturbances are commonly reported by victims of extraordinary stress and can persist for decades.
 This study was designed to test the hypothesis that survivors of the Nazi Holocaust would have significantly more and different sleep problems than depressed and healthy comparison subjects and that the severity of the survivors' problems would be correlated with length of time spent in a concentration camp.
 Forty-two survivors, 37 depressed patients, and 54 healthy subjects of about the same age, all living in the community, described their sleep patterns over the preceding month on the Pittsburgh Sleep Quality Index, a self-rating instrument that inquires about quality, latency, duration, efficiency, and disturbances of sleep, use of sleep medication, and daytime dysfunction.
 RESULTS: The survivors had significantly greater sleep impairment than the healthy comparison subjects, as measured by all subscales of the index, but had less impairment than the depressed patients except on the sleep disturbances and daytime dysfunction subscales.
 However, for specific items within these subscales, survivors had significantly more frequent awakenings due to bad dreams and had less loss of enthusiasm than the depressed subjects.
 Sleep disturbances and frequency of nightmares were significantly and positively correlated with the duration of the survivors' internment in concentration camps.
 CONCLUSIONS: These findings suggest that for some Holocaust survivors, impaired sleep and frequent nightmares are considerable problems even 45 years after liberation.
",9
1362,"Large-scale neurocognitive networks and distributed processing for attention, language, and memory.
 Cognition and comportment are subserved by interconnected neural networks that allow high-level computational architectures including parallel distributed processing.
 Cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved.
 The resultant texture of mental activity is characterized by almost infinite richness and flexibility.
 According to this model, complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites, giving rise to brain-behavior relationships that are both localized and distributed.
 Each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone.
 This approach provides a blueprint for reexploring the neurological foundations of attention, language, memory, and frontal lobe function.
",9
1363,"Impairment of sequences of memory-guided saccades after supplementary motor area lesions.
 Different paradigms of saccades were recorded electro-oculographically in 2 patients with infarction affecting the left supplementary motor area.
 Saccades made toward visual targets (visually-guided saccades) or away from them (antisaccades) were normal in both patients.
 Memory-guided saccades, made to the remembered position of a flash occurring 2 seconds before, were preserved in 1 patient and only slightly impaired in the other.
 However, sequences of two or three memory-guided saccades were severely impaired in both patients.
 It has previously been reported that the supplementary motor area plays an important role in programming sequential limb movements.
 Our data suggest that this area plays a similar role in the control of sequential eye movements.
",9
1364,"Brain pH in head injury: an image-guided 31P magnetic resonance spectroscopy study.
 It has been suggested that brain acidosis may follow head trauma, and therapies aimed at correcting acidosis have been proposed.
 Direct measurements of intracellular pH, however, have thus far not been possible in clinical situations.
 We have studied the intracellular brain pH in 22 patients after head injury (mean Glasgow Coma Score 6.1).
 Patients were investigated by a combined approach of phosphorus 31 magnetic resonance spectroscopy and magnetic resonance imaging (overall examination time 50-75 min) at a mean time of 11 days after injury (36 hours to 24 days).
 31P spectra were obtained in 11 patients on assisted ventilation and in 11 patients on spontaneous ventilation.
 These spectra were analyzed to yield the pH in the regions studied in all the patients.
 All pH values were in the normal or alkalotic range when compared with 6 age-matched normal controls.
 No differences were found between patients on assisted ventilation and patients on spontaneous ventilation.
 When analyzed as a group, the brain pH in the focal lesions appeared to increase in the first days, to reach a peak in the alkalotic range in the second week, and to return toward normal within 3 weeks from acute injury.
 Our results suggest that there is no evidence of posttraumatic intracellular brain acidosis in recent human head injury, and therefore, therapies aimed at alkalinizing brain cells need to be reconsidered.
",9
1365,"Magnetic motor-evoked potentials in epilepsy: effects of the disease and of anticonvulsant medication.
 Magnetic motor-evoked potentials were recorded in 53 patients with medically intractable, mainly temporal lobe epilepsy and compared with potentials of 110 healthy volunteers.
 The motor-evoked potentials were reevaluated in 16 of the 53 patients after substantial reduction of antiepileptic drug doses.
 The objective was to assess the effect of epilepsy and of anticonvulsant medication on the central motor system.
 In subjects receiving antiepileptic treatment, cortical threshold intensities were markedly elevated and peripheral latencies were prolonged.
 Cortical threshold intensities and peripheral latencies decreased to approach control values after anticonvulsant medication was reduced but were increased in patients treated with 2 or 3 anticonvulsant agents instead of 1.
 Additionally, high levels of interictal epileptiform activity and a high frequency of seizures significantly decreased the central motor conduction time and, in part, threshold intensities.
 The central motor conduction time was further diminished after reduction of anticonvulsant treatment and increased when several drugs were administered.
 The duration of epilepsy, the location of the epileptic focus, and the type of the epileptic seizure did not affect motor-evoked potentials.
 Conclusively, central motor pathways are endogenously facilitated by epileptiform activity even if clinical signs of their involvement are absent.
 Anticonvulsant medication exerts major reversible effects on magnetic motor-evoked potentials.
",9
1366,"A follow-up study of intractable seizures in childhood.
 One hundred forty-five children with seizures that were refractory to medical therapy for at least 2 years were followed 5 to 20 years after onset.
 The majority of children with uncontrollable seizures (61%) were mentally retarded, and most of these (73%) had onset of seizures at younger than 2 years of age.
 Age of onset was significantly later (mean 5.0 +/- 0.5 yr [SEM]) in the group of children with borderline to normal intelligence.
 Follow-up data showed remission of seizures in a significant proportion of children with borderline or normal intelligence, with a linear decrease of the percentage with persistent seizures at a rate of about 4% per year.
 Remission of seizures was much less frequent (1.5%/yr) in the group with mental retardation.
 Seizure type had some effects on outcome.
 Children with focal atrophic brain lesions did no worse than those without definable pathology on brain-imaging studies.
",9
1367,"Relationship of clinical features with psychological status in primary fibromyalgia.
 Clinical features and psychological status determined by the Minnesota Multiphasic Personality Inventory (MMPI) in 103 patients with primary fibromyalgia syndrome (PFS) were analyzed by univariate and multivariate techniques to determine if clinical features were related to psychological status or were intrinsic to PFS per se.
 The central features of PFS, e.g., number of pain sites, number of tender points, fatigue, and poor sleep, were independent of psychological status.
 However, discriminant analysis identified 4 variables--patient-reported depression, anxiety, stress, and pain severity--which together predicted 3 MMPI subgroups with an accuracy of 55% (P less than 0.001); the only musculoskeletal feature--pain severity--alone provided an accuracy of only 34% (P greater than 0.05).
 These data suggest a new concept, that the central features of fibromyalgia are independent of the psychological status and are more likely related to the PFS itself.
 However, pain severity may be influenced by psychological factors.
",9
1368,"Brain death and organ donation in a neurosurgical unit: audit of recent practice 
 OBJECTIVE--To assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit.
 DESIGN--Retrospective review of all deaths for 1986, 1987, and 1988 and prospective data for 1989.
 SETTING--A regional neurosurgical unit serving 2.7 million population.
 RESULTS--Of 553 deaths, 35% (191) patients died while on a ventilator and 17% (92) after discontinuation of ventilation.
 Medical contraindications to donation were found in 23% (32) of 141 patients tested for brain death, in 38% (19) of 50 patients who died while being ventilated who were not tested, and in 12% (11) of 92 patients no longer being ventilated.
 Consent for donation was sought in 88% (96) of 109 medically suitable brain dead patients and granted in 70% (67) of these.
 Half those with permission for multiorgan donation had only the kidneys removed.
 CONCLUSIONS--More organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients.
 The estimated size of the pool of potential donors depends on what types of patients might be considered.
 Ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors.
 Ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues.
",9
1369,"Treatment of fulminant hepatic failure with insulin and glucagon. A randomized, controlled trial.
 Insulin and glucagon are among the therapeutic modalities that have been investigated in the treatment of fulminant hepatic failure (FHF).
 We have completed a randomized, controlled trial of insulin and glucagon in 38 patients with FHF from either viral or toxin exposure.
 The control and treatment groups consisted of 21 and 17 patients, respectively, and did not differ significantly in etiology or admission laboratory values.
 Mortality was not significantly different between control and treatment groups and was 67% and 82%, respectively.
 Time from randomization to death or discharge was not significantly different between the two groups.
 Peak levels of alpha-fetoprotein were statistically higher in survivors than in nonsurvivors (P less than 0.01).
 We conclude that even though a type-2 error may exist, the combination of insulin and glucagon is not useful in the treatment of FHF.
",9
1370,"Analgesic use: a study of treatments used by patients for migraine prior to attending the City of London Migraine Clinic.
 Eighty-three unselected patients attending the City of London Migraine Clinic for the first time were asked about their drug intake and use of alternative treatment.
 Thirty-one of those questioned took regular daily doses of medication.
 Fifteen were taking a combination of drugs bought 'over the counter' (OTC) and drugs prescribed by their GP; eleven took OTC drugs only; and 5 took prescription drugs only.
 It was noticeable that those taking drugs prescribed both by the GP and obtainable over the counter were more likely than the other groups to be taking several drugs rather than a single type.
 Thirty five of the 83 (42.2%) had tried alternative treatments for their attacks.
",9
1371,"Vasospasm contributes to monosodium glutamate-induced headache.
 Consumption of monosodium glutamate has long been considered to precipitate headaches in susceptible patients.
 In this study the direct effects of glutamate and its metabolite, glutamine, on arterial contractility were examined using rings of rabbit aorta.
 In a high concentration glutamate caused significant concentration-dependent contractions (EC50, 10(-1)M; maximum tension, 188.4 +/- 33.3 mg wt tension/mg tissue).
 Agonists and antagonists for alpha-adrenergic, histaminergic, serotonergic, cholinergic, and GABA-nergic receptors as well as inhibition of prostaglandin synthesis failed to influence glutamate contractions.
 At high concentrations (10(-5)M) the calcium channel blocker, verapamil, inhibited the glutamate response.
 Glutamate and glutamine both exhibited concentration dependent relaxation of norepinephrine (NE), phenylephrine (PE), histamine, serotonin (5-HT), and prostaglandin F2 alpha (PGF2 alpha)-induced contractions.
 Kainic acid (10(-4)M), an agonist of one subpopulation of central glutamate receptor, potentiated glutamate-induced vasoconstriction; a higher concentration (10(-3)M) produced an irreversible inhibition of glutamate contractility.
 Only the central glutamate receptor antagonist, ketamine (10(-4)-10(-2)M), induced a reversible, concentration dependent inhibition of glutamate-induced contractions.
 Glutamate contractility was not dependent on extracellular calcium, an intact endothelium or neuronal function.
 These results demonstrate a direct effect of glutamate on peripheral arterial tone.
 Dietary consumption of large quantities of MSG may represent a serious health hazard to certain individuals with pre-existing vascular disease.
",9
1372,"The blink reflex in cluster headache.
 To investigate the involvement of the trigeminal system in cluster headache, in twelve subjects the electrically-elicited blink reflex during a symptomatic period was examined.
 In eleven cases, the amplitude of the contralateral R2 response on the symptomatic side was significantly lower, at the same stimulus intensity, than on the asymptomatic side (p = 0.005).
 The blink reflex can be useful to evaluate biological and drug-induced phenomena in cluster headache.
",9
1373,"Assessment and treatment of children's headaches from a developmental perspective.
 Childhood headache is a common pediatric problem.
 Clinical researchers have evaluated several behavioral treatment, such as biofeedback and relaxation training, that may be viable interventions.
 Adding a developmental perspective to the evaluation and treatment of childhood headache is a likely way to increase the effectiveness of these strategies.
 This paper presents developmental issues related to the assessment and treatment of childhood headache.
 Three major areas of development are examined and the impact of these areas on the treatment and assessment of headache are discussed.
 The three major areas are cognitive development, self-regulation and psychosocial development.
 Provided are practical suggestions for the application of child development principles to assessment and intervention practices that may be more developmentally appropriate.
",9
1374,"Health status in patients with tension headache treated with acupuncture or physiotherapy.
 Sixty-two female patients with chronic tension headache were randomly divided into two treatment groups--acupuncture and physiotherapy.
 Their overall function (Sickness Impact Profile), and mental well-being (Mood Adjective Check List) and the intensity and frequency of headache were assessed before and after treatment.
 Before treatment the patients showed significantly more dysfunction and less positive mental well-being than a general population sample.
 Both treatment groups improved in overall function, the physiotherapy group somewhat more.
 The mental well-being increased only in the physiotherapy group.
 The intensity and frequency of headache was significantly reduced in both the physiotherapy group and the acupuncture group.
 The intensity of headache was significantly more improved in the physiotherapy group.
 The improvement of headache intensity persisted unchanged 7-12 months after treatment.
",9
1375,"Nocturnal sleep recording with cassette EEG in chronic headaches.
 Many headache patients complain of poor sleep, and sleep disturbance has been shown to play a role in chronic pain.
 We recorded nocturnal sleep with a 4-channel cassette EEG monitoring device in 10 common migraine patients, 10 individuals with muscle contraction (tension) headache, and 10 chronic tension-vascular headache sufferers.
 Migraine patients had essentially normal sleep, although rapid eye movement (REM) sleep and REM latency were increased.
 Patients with tension headache had reduced sleep time and sleep efficiency, decreased sleep latency but frequent awakenings, increased nocturnal movements, and marked reduction in slow wave sleep, without change in REM sleep or latency.
 Mixed-element headaches with both tension and vascular features were associated with reduced sleep, increased awakening, diminished slow wave sleep, and REM sleep that was decreased in amount and reduced in latency.
 The findings suggest that patients with intermittent migraine may have minimal sleep disturbance, while chronic headache may be worsened by chronically poor sleep.
 Muscle contraction headache may be associated with frequent awakenings and decreased slow wave sleep similar to the sleep changes of fibrositis, while chronic tension-vascular headache may have a depressive substrate.
 Four-channel sleep recording may miss contributory sleep apnea, but nonetheless cassette EEG may facilitate outpatient evaluation of refractory headaches.
",9
1376,"Contingent Negative Variation in migraine.
 The Contingent Negative Variation (CNV) is an event-related slow potential.
 It was recorded in healthy volunteers (n = 8) and in patients suffering from migraine without (n = 12) or with (n = 5) aura, during one (CNV1) and three second (CNV3) foreperiods in a forewarned reaction time task.
 CNV1 was recorded at the vertex while CNV3 was recorded at multiple electrode sites to assess topographical differences.
 Seven out of twelve migraine patients without aura had increased CNV1 amplitudes.
 CNV3 amplitudes were increased as well, but only at electrode positions C3 and C4 and not at Fz.
 CNV3, which allows for analysis of both an early and a late CNV component, could improve the discrimination of migraine without aura beyond that of CNV1.
 In migraine with aura all CNV parameters were at control levels, confirming previous results.
 The data obtained are discussed in terms of arousal, activation and stress and the ""biobehavioral model of migraine"" (Welch, 1986).
",9
1377,"Centrifugal intensity and duration as countermeasures to soleus muscle atrophy.
 Mechanical acceleration is a countermeasure that may be employed to prevent atrophy of slow-twitch muscle during non-weight bearing.
 In the present study, daily centrifugation of rats for different durations (1 or 2 h) and at different gravitational intensities (1.5 or 2.6 G) was used to test whether mechanical acceleration could ameliorate the atrophy of the soleus muscle induced by non-weight bearing (tail-traction model).
 The soleus muscle atrophied 32% during 7 days of non-weight bearing without countermeasures.
 Centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle.
 Non-weight-bearing groups receiving 2-h daily treatments of 1, 1.5, or 2.6 G had 48, 56, and 65%, respectively, of the atrophy observed in the non-weight-bearing-only group compared with the precontrol group.
 No evidence was obtained that centrifugation at 2.6 G was more effective than exposure to 1 or 1.5 G as a countermeasure to non-weight-bearing-induced atrophy of the soleus muscle.
",9
1378,"Effects of carotid denervation and decerebration on ventilatory response to CO.
 To clarify the mechanisms involved in the ventilatory response to the inhalation of low concentrations of CO (0.18-0.22% in air), the roles of the arterial chemoreceptors and the forebrain structures have been investigated in unanesthetized adult cats.
 The ventilatory response was observed in conscious animals intact, after carotid denervation (CD), and after midcollicular decerebration.
 The results show that the initial small ventilatory depression was unaffected by CD but that the subsequent characteristic tachypnea was blunted after CD even after more prolonged exposure to CO.
 The CO tachypnea was not observed after decerebration, but a residual hyperventilation was noted with the higher concentration used.
 It may be concluded that carotid chemoreceptors do not mediate the CO tachypnea, which may then originate in suprapontine structures as shown by comparison of intact and decerebrate animals.
 The blunting of the tachypnea after CD may be caused by the relative hypercapnia observed in CD animals.
 The residual hyperventilation observed in decerebrate animals may be caused by central acidosis and/or some peripheral potentiation of chemoreceptor activity resulting from the decrease in arterial blood pressure that accompanied CO inhalation in decerebrate animals.
",9
1379,"Florid refractory schizophrenias that turn out to be treatable variants of HLA-associated narcolepsy.
 Narcolepsy in which the hallucinatory component is unusually prominent may lead to the development of an illness indistinguishable from the schizophrenic syndrome.
 Psychotic symptoms dominate the symptomatology, so that the primary illness is obscured.
 Five patients are described for whom conventional antipsychotic drugs were ineffectual, but for whom treatment with stimulants produced substantial improvement.
 The diagnosis of narcolepsy was confirmed by Human Leukocyte Antigen typing and sleep laboratory testing.
 These results support the ""REM intrusion"" hypothesis of the causation of schizophrenia in as many as 7% of a series of schizophrenic patients.
 Implications for diagnosis and treatment are discussed.
",9
1380,"Neurotoxic action of veratridine in rat brain neuronal cultures: mechanism of neuroprotection by Ca++ antagonists nonselective for slow Ca++ channels.
 The effect of various Ca++ antagonists and local anesthetics on neuronal cell degeneration induced by veratridine was studied in primary rat brain neuronal cultures.
 Cell death was quantified by measuring lactate dehydrogenase (LDH) released in the culture medium.
 The neuronal cell degeneration was Ca+(+)-dependent because, in the absence of extracellular Ca++, 16 hr of exposure to 30 microM veratridine failed to produce release of LDH.
 Ca++ antagonists, nonselective for slow Ca++ channels (flunarizine, cinnarizine, lidoflazine, prenylamine and bepridil) inhibited veratridine-induced release of LDH with IC50 values between 0.11 and 0.47 microM.
 Ca++ antagonists selective for slow Ca++ channels were less potent and inhibited veratridine-induced release of LDH at concentrations in the following order of potency: nicardipine greater than gallopamil and verapamil greater than niludipine greater than nitrendipine greater than nifedipine greater than nimodipine greater than diltiazem.
 Tested local anesthetics were incomplete inhibitors of veratridine-induced release of LDH.
 A good correlation was found between the potency of the drugs to inhibit released LDH induced by 30 microM veratridine in neuronal cultures and their binding affinity for the batrachotoxin binding site of Na+ channels in rat cortex synaptosomal preparation.
 It is concluded that protection against veratridine-induced neurotoxicity can be mediated by blocking a veratridine-sensitive Na+ channel.
 It is a property of certain nonselective Ca++ antagonists.
 There is apparently no direct relationship with Ca++ antagonistic activity.
 The effect is unrelated to local anesthetic activity.
",9
1381,"Central adenosinergic system involvement in ethanol-induced motor incoordination in mice.
 To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v.
 adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as well as enprofylline on ethanol-(i.p.)-induced motor incoordination was evaluated by rotorod.
 Adenosine agonists and antagonists dose dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, thereby suggesting a central mechanism of adenosine modulation of this effect of ethanol and confirmed our previous reports in which adenosine agonists and antagonists were given i.p.
 Enprofylline, a weak adenosine antagonist but potent inhibitor of cyclic AMP phosphodiesterase, did not alter ethanol's motor incoordination, further supporting involvement of brain adenosine receptor mechanism(s) in ethanol-adenosine interactions.
 Results from R-PIA and N6-(S-phenylisopropyl)adenosine experiments showed nearly a 40-fold greater potency of R-vs.
 S-diastereoisomer, suggesting predominance of adenosine A1 subtype.
 However, 5'-(N-cyclopropyl)-carboxamidoadenosine data indicate complexity of the mechanism(s) and point toward an additional involvement of a yet unknown subtype of adenosine A2.
 No effect of ethanol on blood or brain levels of [3H]R-PIA was noted and sufficient amount of the latter entered the brain to suggest adenosine receptor activation adequate to produce behavioral interaction with ethanol.
 There was no escape of i.c.v.-administered [3H]R-PIA from brain to the peripheral circulation ruling out a peripheral and supporting a central mechanism of ethanol-adenosine interaction.
",9
1382,"Interactions between N-methyl-D-aspartate and CGS 19755 administered intramuscularly and intracerebroventricularly in pigeons.
 Behavioral effects of N-methyl-D-aspartate (NMDA) and the competitive NMDA antagonist cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) were studied in pigeons.
 NMDA decreased responding under a fixed-ratio schedule of food presentation and was 8000 times more potent administered intracerebroventricularly (i.c.v.) as compared to intramuscularly (i.m.).
 CGS 19755 was 870 times more potent in producing catalepsy when administered i.c.v.; however, the duration of catalepsy was similar by the two routes of administration.
 Administered i.m.
 CGS 19755 decreased response rates only at doses that also produced catalepsy; administered i.c.v.
 some doses of CGS 19755 decreased responding without producing other behavioral effects.
 Rate-decreasing effects of i.m.
 NMDA were attenuated by i.m.
 CGS 19755; however, when CGS 19755 was administered i.c.v., there was little or no antagonism of NMDA.
 Rate-decreasing effects of i.c.v.
 NMDA were not attenuated by i.m.
 or i.c.v.
 CGS 19755 up to doses that produced catalepsy or eliminated responding.
 The large difference in potency between i.m.
 and i.c.v.
 administration for NMDA and for CGS 19755, as well as the slower onset of catalepsy when CGS 19755 was administered i.m., suggests these compounds do not readily cross the blood-brain barrier when administered parenterally.
 The inability of CGS 19755 to attenuate the rate-decreasing effects of NMDA when CGS 19755 or NMDA was administered i.c.v.
 suggests NMDA might decrease responding by different mechanisms when administered i.m.
 or i.c.v.
 in pigeons.
 Together these results indicate antagonism of NMDA in this study, and perhaps in other studies, when both NMDA and CGS 19755 were administered parenterally, might result from a peripherally mediated interaction.
 Moreover, this agonist-antagonist interaction is not a simple, competitive antagonism.
",9
1383,"Mechanical restraint use among residents of skilled nursing facilities. Prevalence, patterns, and predictors 
 The patterns of and risk factors for mechanical restraint use were determined in 12 skilled nursing facilities.
 Restraints were being used for 59% of residents at the beginning of the study; 31% of remaining residents were restrained during the follow-up year.
 No facility characteristic was associated with restraint use.
 The resident characteristics independently associated with initiation of restraints were older age, disorientation, dependence in dressing, greater participation in social activities, and nonuse of antidepressants.
 Unsteadiness (72%), disruptive behavior such as agitation (41%), and wandering (20%) were the most frequently cited reasons for initiation of restraints.
",9
1384,"Response to treatment with antihistamines in a family with myotonia congenita.
 In a family in which myotonia congenita was found in five generations, both great-grandparents of the index case were affected.
 In subsequent generations mild and severely affected cases were clearly segregated down parallel lines of this family.
 The grandmother of the index case had noted improvement with an antihistamine.
 When the index case was prescribed trimeprazine, she showed a striking reduction in severity of symptoms.
 Antihistamines seem to deserve further evaluation as a safe and effective treatment for myotonia congenita.
",9
1385,"Transcranial Doppler in acute hemispheric brain infarction.
 We studied cerebrovascular anatomy using intra-arterial digital angiography, and blood flow velocity in the middle cerebral artery (MCA) using transcranial Doppler (TCD) ultrasonography in 42 patients with acute hemispheric ischemic brain infarction.
 We compared angiography with TCD and the clinical findings within 6 hours of the onset of symptoms.
 The location and extent of the chronic ischemic brain damage was assessed by CT performed 1 to 3 months after the ictus.
 Abnormal TCD, as manifested by either an unobtainable MCA flow signal or a significantly depressed MCA flow velocity, was highly associated with proximal MCA occlusions demonstrated by angiography.
 Abnormal TCD predicted both larger chronic CT lesions and more extensive ischemic change within the MCA territory.
 These data demonstrate that early TCD conveys useful information concerning cerebral tissue prognosis following hemispheric ischemia.
",9
1386,"""Pseudospasticity"" in Guillain-Barre syndrome.
 We report a woman with Guillain-Barre syndrome who developed a flexion posture of the right arm and hand resembling upper motor neuron dysfunction.
 EMG demonstrated that involuntary peripherally generated continuous motor unit discharges caused the posture.
",9
1387,"Suppression of carbamazepine-induced rash with prednisone.
 We report our experience with 20 patients who developed a rash shortly after the introduction of carbamazepine and were treated with prednisone and an antihistamine.
 Sixteen patients were successfully continued on carbamazepine while 4 had to discontinue the drug.
",9
1388,"Handcuff neuropathies 
 Compressive neuropathy due to tight application of handcuffs occurred in 5 patients.
 The superficial radial nerve was affected in 8 hands and the median nerve in two.
 Neurologic deficits persisted as long as 3 years after handcuffing.
 Nerve conduction studies helped to exclude malingering and other diagnoses.
 All patients had been intoxicated when handcuffed or had been arrested with force.
 The handcuff mechanism, which allows accidental overtightening after application, is an unrecognized factor in these neuropathies.
",9
1389,"Mesencephalic cholinergic nuclei in progressive supranuclear palsy.
 Using an antibody against choline acetyltransferase (ChAT), mesencephalic cholinergic cell nuclei were studied in autopsy material from 3 cases of progressive supranuclear palsy (PSP) and 4 controls.
 ChAT-immunoreactive neurons were quantified in sections that spanned the rostrocaudal extent of each nucleus.
 In PSP, there was a significant decrease in the number of neurons with detectable immunoreactivity for ChAT in and adjacent to the central gray substance in the following nuclei: the nucleus of Edinger-Westphal (69%); the rostral interstitial nucleus of the medial longitudinal fasciculus (97%); the interstitial nucleus of Cajal (78%).
 A cell loss was also evident in a group of neurons found in the deep layers of the superior colliculus (93%).
 In contrast, the estimated number of ChAT-immunoreactive cell bodies in cranial nerves III and IV, in the mesencephalic reticular formation, and in the parabigeminal nucleus was not different from that of controls.
 The results are compatible with the notion that, in PSP, there is a regionally selective destruction of cholinergic neurons.
",9
1390,"Central nervous system involvement in Von Hippel-Lindau disease.
 Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency and distribution of CNS lesions.
 The associated clinical features were also reviewed.
 Thirty-six (72%) of the 50 had 1 or more CNS tumors.
 The most frequently affected sites in the CNS excluding the retina were the cerebellum (52%), spinal cord (44%), and brainstem (18%).
 New regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study.
 Forty-one percent of all VHL patients with CNS tumors were neurologically asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem tumors (44%) were often without clinical signs or symptoms.
 Multiple lesions were common.
 The mean age of all VHL patients (34.5 years) was similar to the mean age of all CNS VHL patients (34.4 years), suggesting a lack of age association.
 CNS lesions commonly occurred in the 2nd decade of life.
 All patients at risk for VHL should be evaluated using gadolinium-enhanced MRI after 10 years of age, although ophthalmic examination should be initiated within the 1st 2 years of life.
 Enhanced MRI is particularly useful in the detection of CNS tumors in patients with the VHL gene.
",9
1391,"Prognosticating study for cervical myelopathy using evoked spinal cord potentials.
 One hundred twenty-three cases of cervical spondylotic and ossification of the posterior longitudinal ligament (OPLL) myelopathy cases with long tract signs subjected to surgical treatment were studied to identify the most important factors having an influence on postoperative outcome using evoked spinal cord potentials (ESCP).
 Disappearance and positive wave changes of these potentials at the level of responsible lesions and slow conduction velocity under 40 m indicated an unsatisfactory outcome.
 Localized-lesion cases diagnosed by ESCPs had excellent results, significantly more so than extensive-lesion cases, regardless of operative methods.
 In 123 cases, 76% were found to have localized lesions, while the other 24% showed extensive lesions.
 Concerning the difference between CSM and OPLL, 54% of OPLL and only 14% of CSM demonstrated extensive lesions.
",9
1392,"Cerebral blood flow and oxygen metabolism in patients with vascular dementia of the Binswanger type.
 We performed clinical and neuroradiologic studies, including positron emission tomography, in five patients with vascular dementia of the Binswanger type.
 The clinical features of these cases consisted of slowly progressive dementia, together with vascular risk factors such as hypertension and often a history of minor stroke, and characteristic white matter lesions on brain computed tomograms or magnetic resonance images.
 Digital subtraction angiography of the cervical and intracranial arteries demonstrated no occlusive lesion in any patient.
 Both cerebral blood flow and the cerebral metabolic rate for oxygen were markedly reduced in the white matter (54-77% of control values), and both were decreased in the parietal (73% of control), frontal (74-80%), and temporal (74-83%) cortices, where no abnormalities were detected by brain computed tomography or magnetic resonance imaging.
 We conclude that vascular dementia of the Binswanger type may be caused by disconnection between the cerebral cortex and subcortical structures due to ischemic damage in the white matter.
",9
1393,"An open trial of high-dosage antioxidants in early Parkinson's disease.
 High dosages of tocopherol and ascorbate were administered to patients with early Parkinson's disease as a preliminary open-labeled trial for the eventual controlled double-blind study evaluating antioxidants as a test of the endogenous toxin hypothesis of the etiology of Parkinson's disease.
 The primary endpoint of the trial was the need to treat patients with levodopa.
 The time when levodopa became necessary in the treated patients was compared with another group of patients followed elsewhere and not taking antioxidants.
 The time when levodopa became necessary was extended by 2.5 y in the group taking antioxidants.
 The results of this pilot study suggest that the progression of Parkinson's disease may be slowed by the administration of these antioxidants.
 A large multicenter, controlled clinical trial currently underway in North America evaluating tocopherol and deprenyl has the potential to confirm these results.
",9
1394,"Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA).
 We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA).
 Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA.
 Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic.
 The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs.
 The combined informativeness of these two probes is 30%.
 We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity).
 This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS).
 The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel.
 We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families.
 This establishes that DXS296 is distal to FRAXA.
 The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304.
 Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA.
 The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications.
",9
1395,"Identification of a highly polymorphic microsatellite VNTR within the argininosuccinate synthetase locus: exclusion of the dystonia gene on 9q32-34 as the cause of dopa-responsive dystonia in a large kindred.
 Dopa-responsive dystonia is a clinical variant of idiopathic torsion dystonia that is distinguished from other forms of dystonia by the frequent occurrence of parkinsonism, diurnal fluctuation of symptoms, and its dramatic therapeutic response to L-dopa.
 Linkage of a gene causing classic dystonia in a large non-Jewish kindred (DYT1) and in a group of Ashkenazi Jewish families, to the gelsolin (GSN) and arginino-succinate synthetase (ASS) loci on chromosome 9q32-34, respectively, was recently determined.
 Here we report the discovery of a highly informative (GT)n repeat VNTR polymorphism within the ASS locus.
 Analysis of a large kindred with dopa-responsive dystonia, using this new polymorphism and conventional RFLPs for the 9q32-34 region, excludes loci in this region as a cause of this form of dystonia.
 This provides proof of genetic heterogeneity between classic idiopathic torsion dystonia and dopa-responsive dystonia.
",9
1396,"Sudden cervical pain: spontaneous cervical epidural hematoma.
 Three cases of cervical epidural hematoma are reported.
 Acute neck pain usually associated with a mild effort, closely followed by radicular pain and a neurologic deficit below the lesion is the typical presentation of this extremely rare and difficult diagnosis.
 As prognosis depends on preoperative neurologic state, the authors emphasize the importance of prompt identification of this lesion.
 The diagnosis is confirmed by computed tomography, and emergency neurosurgical laminectomy is mandatory.
",9
1397,"Unconsciousness associated with midazolam and erythromycin.
 An 8-yr-old boy suffering from an asymptomatic ventricular septal defect was given erythromycin for antibiotic prophylaxis before adenoidectomy.
 Sixty minutes after premedication with oral midazolam 0.5 mg kg-1 and oral atropine 0.03 mg kg-1, an infusion of erythromycin 400 mg was started.
 When 200 mg of erythromycin had been infused, the patient lost consciousness, but other vital functions remained normal.
 After 45 min, he awakened spontaneously.
 At the time the plasma concentration of midazolam was 134 ng ml-1.
 In order to investigate possible interactions between midazolam and erythromycin, we studied the pharmacokinetics of midazolam in six children of the same age undergoing minor otolaryngological surgery.
 The plasma concentration of midazolam in the patient who lost consciousness was significantly greater than in six other children without concomitant administration of erythromycin.
 The altered pharmacokinetics of midazolam may result from reduced hepatic clearance of midazolam caused by an enzyme inhibiting drug, erythromycin.
",9
1398,"Radiosurgery of acoustic neurinomas.
 Eighty-five patients with acoustic neurinomas underwent stereotactic radiosurgery with the gamma unit at the University of Pittsburgh (Pittsburgh, PA) during its first 30 months of operation.
 Neuroimaging studies performed in 40 patients with more than 1 year follow-up showed that tumors were smaller in 22 (55%), unchanged in 17 (43%), and larger in one (2%).
 The 2-year actuarial rates for preservation of useful hearing and any hearing were 46% and 62%, respectively.
 Previously undetected neuropathies of the trigeminal (n = 12) and facial nerves (n = 14) occurred 1 week to 1 year after radiosurgery (median, 7 and 6 months, respectively), and improved at median intervals of 13 and 8 months, respectively, after onset.
 Hearing loss was significantly associated with increasing average tumor diameter (P = 0.04).
 No deterioration of any cranial nerve function has yet developed in seven patients with average tumor diameters less than 10 mm.
 Radiosurgery is an important treatment alternative for selected acoustic neurinoma patients.
",9
1399,"Effects of discontinuation of phenytoin, carbamazepine, and valproate on concomitant antiepileptic medication.
 We report a prospective, controlled study of the effects of the reduction and discontinuation of phenytoin (PHT) (22 patients), carbamazepine (CBZ) (23 patients), and valproate (VPA) (25 patients) with concomitant antiepileptic drugs (AEDs).
 The principal changes in the serum concentrations of concomitant AEDs were (a) phenobarbital (PB) concentrations decreased by a mean of 30% on discontinuation of PHT; (b) total CBZ concentrations increased by a mean of 48% and free CBZ concentrations increased by a mean of 30% on discontinuation of PHT, with no change in CBZ-10, 11-epoxide (CBZ-E) concentrations; (c) VPA concentrations increased by a mean of 19% on discontinuation of PHT; (d) VPA concentrations increased by a mean of 42% on discontinuation of CBZ; (e) ethosuximide (ESM) concentrations increased by a mean of 48% on discontinuation of CBZ; (f) PHT concentrations decreased by a mean of 26% on discontinuation of CBZ; (g) PHT free fraction decreased from a mean of 0.11 to 0.07 on discontinuation of VPA; and (h) the mean concentrations of total and free CBZ increased by a mean of 10 and 16%, respectively, on VPA discontinuation, with a concomitant mean 24% decrease in total CBZ-E and a 22% decrease in free CBZ-E.
 Apart from the decrease in PB concentrations on PHT discontinuation, all significant changes had occurred by 1 week after the end of AED discontinuation.
 The implication for clinical practice is that a serum AED concentration at this time reflects the new steady state.
 Free concentrations did not add any clinically useful information to that gained from analysis of total serum concentrations.
",9
1400,"Cognitive function and time-of-day variation in serum carbamazepine concentration in epileptic patients treated with monotherapy.
 Different parameters of antiepileptic drug (AED) treatment have been shown to affect cognitive function.
 The drug, dose, and duration of treatment have been studied.
 The present study assessed cognitive function in relation to time-of-day variation in serum carbamazepine (CBZ) concentration in epileptic patients treated with monotherapy.
 We studied 10 males and 12 females with a mean age of 36 years and a mean duration of CBZ-therapy of 4.4 years.
 Patients had been seizure-free for at least 1 month and took two daily CBZ doses.
 The test battery included tests of motor speed, reaction time, attention, and memory.
 In the experimental design, the subjects were tested twice at times close to expected daily maximum and minimum serum CBZ concentration.
 They were studied in two balanced blocks (block 1 tested at 8 a.m.
 and noon, block 2 tested at noon and 8 p.m.).
 Blood samples were collected every 2 hr from 8 a.m.
 to 8 p.m.
 The subjects showed significant differences in serum CBZ concentration between testing times, with suggested maximum concentration between 10 a.m.
 and noon.
 The test battery showed no consistent differences between performance at times of high versus low serum concentration.
 A supplementary analysis of correlations between mean performance level on cognitive tests and variables related to CBZ treatment did not show consistent trends.
",9
1401,"Immunologic aspects of carbamazepine treatment in epileptic patients.
 Immune abnormalities have been found in epileptic patients receiving antiepileptic drugs (AEDs).
 Phenytoin (PHT) produces a decrease in serum IgA and IgM levels and a decrease in blastic transformation of circulating lymphocytes stimulated with phytohemoagglutinin (PHA).
 The effects of carbamazepine (CBZ) on the immune response are still conflicting.
 To elucidate the effects of CBZ on some immunologic parameters, serum concentrations of IgA, IgG, IgM, the phagocytosis and killing properties of polymorphonuclear leukocytes (PMNs), the cytotoxic activity of natural killer cells and the response of lymphocytes to mitogenic agents were studied.
 Forty healthy individuals and 39 epileptic patients treated with carbamazepine (CBZ) monotherapy (age range 18-40 years) entered the study.
 Student's t test was used to evaluate the data.
 CBZ had no effect on the serum immunoglobulin concentrations or on lymphocytic reactivity to phytohemoagglutinin (PHA) mitogen.
 CBZ produced a significant enhancement of phagocytosis and killing properties of PMNs and an increase in natural killer (NK) cell activity.
 Therefore, a negative effect of CBZ therapy on the immune system was not observed in this study.
",9
1402,"Effect of felbamate on plasma levels of carbamazepine and its metabolites.
 Felbamate (FBM) is a novel antiepileptic drug (AED) currently undergoing clinical evaluation in the United States.
 During a controlled clinical trial conducted at the National Institutes of Health Clinical Center, FBM was added to constant carbamazepine (CBZ) monotherapy.
 CBZ total concentrations were reduced during active FBM treatment (mean reduction 25%, range 10-42%, p less than 0.001).
 The effect was evident after the first week of treatment and reached a plateau in 2-4 weeks.
 To clarify the interaction mechanism, free and total concentrations of CBZ and its plasma metabolites were determined by high-performance liquid chromatography (HPLC) and ultrafiltration in four patients.
 In these patients, FBM treatment reduced CBZ concentrations and increased CBZ-epoxide (CBZ-E) concentrations (p less than 0.01).
 Free fractions of all compounds were unmodified.
 FBM appears to be capable of inducing CBZ metabolism.
 CBZ-FBM interaction may be clinically relevant.
",9
1403,"Double-blind, placebo-controlled, cross-over trial of progabide as add-on therapy in epileptic patients.
 In a double-blind, cross-over trial, progabide (PGB) and placebo were compared as add-on therapy in 59 patients with moderate to severe epilepsy.
 Eight patients did not complete the study, 4 because of adverse drug reactions (elevation of liver transaminases, 2; gastritis, 1; and acute psychosis, 1) and 4 because of administrative reasons.
 Among the remaining 51 patients, seizure frequency was reduced greater than 50% in 18 patients with PGB treatment and in 8 patients with placebo (p less than 0.05).
 The number of days with seizures was significantly (p = 0.034) reduced during PGB treatment.
 Both patients' and physicians' preferences at the end of the trial were in favor (p less than 0.01) of PGB.
 Mild clinical side effects were present in 54.7% of the patients treated with PGB and in 37.7% with placebo.
 Increase in liver transaminases was observed in 2 patients during the double-blind study and in 1 during the follow-up period.
 Our data show that PGB, as previously reported, is useful in 30-40% of patients who are not responding completely to other antiepileptic drugs (AEDs).
 The compound is well tolerated, but liver function must be monitored.
",9
1404,"Development and reversal of contingent inefficacy and tolerance to the anticonvulsant effects of carbamazepine.
 The relationship of the timing of drug administration to anticonvulsant efficacy against amygdala kindled seizures was studied.
 During kindling development, rats received carbamazepine (CBZ, 15mg/kg) before (CBZ-before) or after each amygdala stimulation (CBZ-after).
 After kindling to full seizures, when all animals were given CBZ before the stimulation, only the CBZ-after group showed a good anticonvulsant response.
 The rats that had received CBZ before (during development of kindled seizures) remained unresponsive to CBZ treatment (contingent inefficacy).
 When drug-naive or CBZ-after animals repeatedly received CBZ before electrical stimulation, they developed tolerance to its anticonvulsant effects (contingent tolerance).
 The tolerance could be reversed by a period of treatment with CBZ-after or by kindling the animal drug-free, but not by CBZ administration alone or by time off from both drug and seizures.
 These findings suggest that inefficacy and tolerance to CBZ may be affected by the temporal contingencies of drug administration and that responsiveness can be reinstated by altering these contingencies.
",9
1405,"Kindling susceptibility and genetic seizure predisposition in inbred mice.
 Olfactory bulb kindling rates were studied in two inbred strains of genetically seizure-prone mice (DBA/2 and El) and in three non-epileptic inbred strains [C57BL/6 (B6), ddY, and C3H/He (C3H)].
 None of the DBA/2 mice had been stimulated to seizure before or during the kindling and all mice were studied at 4-6 weeks of age, before development of spontaneous or movement-induced seizure activity in the El strain.
 The audiogenically seizure-susceptible DBA/2 mice required the fewest number of stimulations to reach stage 5 seizure (mean +/- SE = 4.0 +/- 0.6).
 The nonepileptic C3H mice required the most stimulations to reach stage 5 seizures (22.6 +/- 1.4).
 Kindling rates for B6 (9.6 +/- 0.6), El (14.8 +/- 1.1), and ddY (18.5 +/- 1.0) strains were intermediate, and the kindling rate for each strain was significantly different from that of the other strains.
 These findings show that the seizure-susceptible El mouse kindles more rapidly than the genetically similar but nonepileptic ddY control and suggest that an inherited seizure susceptibility accelerates the kindling rate.
 Nonepileptic B6 mice kindled more rapidly than El mice, however, suggesting that genetic factors other than those that influence seizure susceptibility are of primary importance in the determination of the kindling rate.
",9
1406,"Changes of hippocampal glucose utilization subsequent to amygdaloid-kindled generalized seizures.
 Local changes in cerebral glucose utilization during the postictal phase of amygdaloid-kindled generalized seizures were studied with the quantitative autoradiographic 2-[14C]deoxyglucose method in conscious rats.
 Measurement was initiated either just after termination of a behavioral seizure (GS-I) or 30 s after seizure termination (GS-II) to determine dynamic metabolic changes in the postictal phase.
 Although glucose utilization of the neocortex was remarkably depressed in both GS-I and GS-II, that of the hippocampus significantly increased in GS-I and then decreased in GS-II as compared with control.
 These changes of hippocampal glucose utilization were observed in all sectors of the pyramidal cell layer (CA 1-4) and in the molecular layer.
 Because metabolic changes associated with development of amygdaloid-kindled seizures begin in the limbic structures including the hippocampus, the transient increase in hippocampal glucose utilization observed in the early postictal phase indicates that the hippocampus is one of the key structures not only for initiating and maintaining but also for terminating kindled seizures.
",9
1407,"Panic disorder in seizure patients: a diagnostic pitfall.
 Panic disorder is a psychiatric diagnosis whose main feature is paroxysmal attacks of anxiety that strike suddenly without apparent provocation.
 Physicians explain the attacks as an ictal phenomenon in patients with known seizures because of their similarities to complex partial seizures.
 We report eight patients with seizures and panic disorder.
 Recognition of a second diagnostic entity resulted in a beneficial change in treatment in six of the eight.
 We did not find an increased incidence of panic disorder in our seizure clinic population as compared with the general population.
",9
1408,"Effect of epilepsy and sleep deprivation on the rate of benign epileptiform transients of sleep.
 Seventy-eight individuals with EEG records containing benign epileptiform transients of sleep (BETS) were identified among 7,400 records reviewed in our laboratory in a 6-year period.
 The records contained no other abnormality in 51 patients (65%).
 Genuine epileptiform discharges were found in the records of 19 patients; 14 had a history of epilepsy.
 Thirty-five patients (45%) had a proven history of epilepsy with antiepileptic drug (AED) therapy.
 In the records of these patients, the mean number of BETS per unit of time was significantly higher (11.88 +/- 2) than in the record of the rest of the laboratory population with BETS (6.89 +/- 0.9) (p less than 0.02).
 Among five conventional surface montages, ipsilateral ear referential montage (IERM) showed a significantly higher number of BETS per unit of time than did any other surface montage used in the study.
 Thirty-nine records (50%) were performed after sleep deprivation (SD).
 When only IERM was considered, SD records showed a significantly higher number of BETS per unit of time (7.36 +/- 1.1) than did non-SD records (3.89 +/- 0.69) (p less than 0.01).
 Our findings support the general consensus that individual BETS may be normal variants, but a high occurrence of BETS in the record should raise suspicion of underlying epilepsy.
",9
1409,"Dreams and epilepsy.
 The relationship between dreams and epilepsy is illustrated by two patients whose awake epileptic seizures and recurrent dreams during night sleep had similar content.
 In both of our cases the EEG showed right anterior temporal spike discharge, suggesting a role for the temporal lobe in the association between dreams and seizures.
",9
1410,"Epilepsy with continuous spike-waves during slow sleep and its treatment.
 Five children with epilepsy with ""continuous spike-waves during slow sleep"" (CSWS) are reported.
 The main clinical features of CSWS include (a) onset between 5 and 7 years of age, (b) the occurrence of several types of seizure (i.e., partial motor, generalized motor, and atypical absence), and (c) the presence of language disturbances and abnormal behavior based on emotional impairment.
 The EEG findings were characterized by sleep tracings showing almost continuous (greater than 95%), diffuse slow spike and wave activity.
 After treatment with valproate (VPA) (or ethosuximide, ESM) and clonazepam (CZP), the spike and wave complex status disappeared.
 Symptoms and signs of the CSWS also decreased.
 We suggest that combined treatment is an appropriate treatment for CSWS.
",9
1411,"Sexual behavior of a sample of females with epilepsy.
 A sample of 700 female epileptic outpatients was examined between 1985 and 1987.
 The incidence of psychosexual disorders was 18%.
 Epileptic females with psychosexual disorders were compared with epileptic females without sexual disorders and with normal female controls on selected clinical and EEG parameters.
 Epileptic females with sexual disorders showed: lower marriage rates, a longer duration of illness, sexually colored prodromata, predominance of partial complex seizures (83%) and a higher incidence of menstrual abnormalities.
 Hyposexuality and exhibitionism were the psychosexual disorders most frequently noted.
 Temporal lobe EEG abnormalities were significantly higher.
",9
1412,"Attitudes of major employers toward the employment of people with epilepsy: a 30-year study.
 Beginning in 1956, major San Francisco Bay area employers were sampled at 10-year intervals for a 30-year period to assess attitudes toward the employment of epileptic workers.
 In this time, we documented a trend of sustained positive change that appears to validate the efforts of organizations that have focused on raising public awareness of this disorder.
",9
1413,"Antiepileptic drug monitoring at the epilepsy clinic: a prospective evaluation.
 To assess the value of on site therapeutic drug monitoring at the epilepsy clinic, management decisions were recorded before and immediately after antiepileptic drug (AED) concentrations became available.
 In the first year of this prospective study, 632 [277 carbamazepine (CBZ), 170 phenytoin (PHT), 113 valproate (VPA), and 72 phenobarbital (PB)] assays were performed during 488 clinic attendances in 182 actively managed epileptic patients.
 The results of drug analysis led to alterations in management at 114 patients visits, i.e., 23% of those monitored.
 Dosage was increased in response to the circulating AED concentration in 12% of consultations and decreased in another 7.5%.
 Unsuspected poor compliance was uncovered in eight patients, and in three others an AED was added or discontinued on the basis of the assay result.
 The time of the next appointment was rearranged in 58 attendances.
 Only 50% of results were in the ""therapeutic"" ranges for the four major AEDs.
 Dosage was adjusted (50 up, 16 down) after 54% of low results.
 ""Therapeutic"" levels were followed by a change in AED dose (52 up, 31 down) in 26%.
 Only 29% of concentrations above the ""therapeutic"" range persuaded the doctor to alter the dosage regimen, and in 20% of these an increase in dose was recommended.
 On-site AED monitoring had an immediate impact on clinical decision-making in greater than 23% of consultations but in a form more subtle than the simple quest for a therapeutic result.
",9
1414,"Effects of lactulose and lactitol on protein digestion and metabolism in conventional and germ free animal models: relevance of the results to their use in the treatment of portosystemic encephalopathy.
 Protein digestion and metabolism have been studied in laboratory rats and miniature pigs to investigate the mechanisms of action of lactulose and lactitol when used in the treatment of patients with portosystemic encephalopathy.
 Lactulose (beta-D-galactopyranosyl-(1----4)-beta-D-fructofuranose) and lactitol (beta-D-galactopyranosyl-(1----4)-D-glucitol) increased the excretion of nitrogenous material in the faeces and decreased nitrogen excretion in the urine in a similar degree to that reported for human patients.
 In studies with germ free rats given lactulose no such effect was observed, suggesting that, for lactulose at least, these effects are mediated by the gut flora.
 Measurement of the alpha-, epsilon-diaminopimelic acid content of the faeces confirmed that the enhancement of faecal nitrogen was due to an increased contribution from bacteria.
 The similarity in the results for lactulose and lactitol suggests that, from the perspective of protein metabolism, lactitol acts in a similar way to lactulose in the treatment of portosystemic encephalopathy.
",9
1415,"The relation of pain to depression among institutionalized aged.
 Nursing home and congregate apartment residents (N = 598) were classified on the basis of a DSM-IIIR symptom checklist as suffering possible major, minor, or no depression; they also completed the Geriatric Depression Scale (GDS) and the Profile of Mood States (POMS).
 Possible major depressives reported more intense pain and a greater number of localized pain complaints than did minor depressives; nondepressed individuals reported the least intense pain and fewest localized complaints.
 The effect remained strong even when functional disability and health status were controlled statistically.
 Both pain intensity and number of localized complaints were correlated with GDS and POMS factor scores, but strength and direction of associations varied with level of depression.
 Item-by-item examination of localized complaints again indicated that more depressed individuals were more likely to report pain, particularly where physicians had identified a physical problem that might account for the pain.
 Results are compared with previous research on pain among younger individuals.
 Implications for treatment of depressed elderly are discussed.
",9
1416,"Oestrogen and progesterone receptors in acoustic neuroma.
 Tissue samples from fourteen consecutive (8 male: 6 female) acoustic neuromas were assayed for hormone receptors using either a monoclonal antibody (MA), dextran coated charcoal (DCC) or isoelectric focusing (IEF) technique.
 In this series there were no unequivocally positive results, a finding at variance with previously published results.
",9
1417,"Effect of nicardipine on somatosensory evoked potentials in patients with acute cerebral infarction.
 We evaluated the effect of nicardipine, a calcium channel blocker, on somatosensory evoked potentials (SEP) in 26 patients with acute cerebral infarction.
 Post treatment, 58% (15/26) of the N20 and P25 latencies were prolonged in the affected hemispheres; 8% (2/26) were shortened; and 35% (9/26) did not change.
 The mean N20 and P25 latencies were significantly prolonged two hours post treatment in the affected hemisphere (N20, P less than 0.01, P25 P less than 0.01).
 Nicardipine (Ni) had no effect on SEP components in the intact hemispheres.
 Seventy five per cent of the 12 patients with hypertension had a decrease in blood pressure (BP) after taking nicardipine, but there were no undesirable side effects or worsening of neurological signs.
 Our study demonstrates that nicardipine prolongs the latencies of short-latency components of SEP in the affected hemisphere after acute ischaemic stroke and also decreases BP.
 These observations suggest that nicardipine therapy might impair neuronal function in the ischaemic zone.
",9
1418,"Platelet monoamine oxidase B activity in parkinsonian patients.
 Monoamine oxidase B (MAO B) plays a pivotal role in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinsonism.
 An increased MAO B activity in platelets of patients with idiopathic Parkinson's disease (PD) is reported in this study.
 The possibility that high MAO B activity may represent a trait of vulnerability for PD by enhancing the neurotoxic effects of environmental compounds is discussed.
",9
1419,"Specificity of affective and autonomic symptoms of depression in Parkinson's disease.
 Previous investigators have suggested that numerous symptoms used to diagnose depression, such as sleep or appetite disturbance, are non-specific in medically ill patients, and alternative diagnostic criteria should be developed.
 In the study this hypothesis was tested in Parkinson's disease (PD) by comparing patients with PD who reported a depressive mood with patients having PD but without a depressive mood.
 Depressed patients showed a significantly higher frequency of both autonomic and affective symptoms of depression.
 Depressed patients with PD reported a significantly higher frequency of worrying, brooding, loss of interest, hopelessness, suicidal tendencies, social withdrawal, self-depreciation, ideas of reference, anxiety symptoms, loss of appetite, initial and middle insomnia, and loss of libido when compared with non-depressed patients.
 No significant between-group differences, however, were observed in the frequency of anergia, motor retardation, and early morning awakening.
",9
1420,"Neurophysiological observations on corticospinal projections to the upper limb in subjects with Rett syndrome.
 The aim of the present study was to investigate the excitability of corticospinal neurons and the integrity of their projections to the alpha motor neurons through the corticospinal tract in subjects of different ages with Rett syndrome.
 Electromagnetic stimulation of the motor cortex and cervical motor roots was used to evoke motor action potentials in the biceps brachii and hypothenar muscles.
 The phasic stretch reflex in the biceps brachii was also recorded to study the excitability of spinal alpha motor neurons.
 Motor cortex stimulation evoked motor action potentials at low threshold and with abnormally short latencies and prolonged durations.
 In contrast cervical motor root stimulation resulted in responses of normal latency and duration.
 The phasic stretch reflex had a low threshold, short latency and prolonged duration.
 It is concluded that in Rett syndrome the corticospinal pathway is intact.
 The results suggest disordered synaptic control of the Betz cell of the motor cortex and/or the spinal alpha motor neuron, although the involvement of the latter might be a consequence of dysfunction in supraspinal descending motor pathways.
",9
1421,"Stroke rehabilitation: Australian patient profile and functional outcome.
 A prospective, multi-institutional, population based study identified 1274 non-surgical stroke admissions to all hospitals in a major Australian city during 1984.
 The demographic and diagnostic profile and the nature of functional recovery of all 258 first stroke survivors who were referred for inpatient rehabilitation are presented.
 The median duration of rehabilitation stay was 49 days.
 The mean functional independence score, as measured on a modified Barthel Index at admission was 44, compared with 78 on discharge, a mean improvement of 34.
 Stair climbing had the lowest mean value on admission (12), while bowel control had the lowest residual deficit on discharge (95).
 The stroke study group was representative of the unimpaired aged population in all respects except ethnicity, where differences are attributed to age.
 The variables identified as significant are; side and severity of paralysis, age and sex, marital status and ethnicity.
 Stroke rehabilitation outcome was not influenced by etiology, site of lesion, arterial distribution, occupation or education.
",9
1422,"Status of cochlear implantation in children. American Academy of Otolaryngology-Head and Neck Surgery Subcommittee on Cochlear implants.
 The cochlear implant is a medical device, part of which is placed surgically, that uses electrical stimulation to provide hearing.
 For almost a decade, investigational studies have been ongoing to define its safety and efficacy in profoundly deaf children.
 During this period, more than 500 children aged 2 through 17 years have been implanted with either a single-electrode or multielectrode device.
 Extensive auditory, speech, educational, and psychologic testing has been performed before and after implantation.
 Results show that the cochlear implant provides auditory detection over much of the speech signal.
 Compared with the preimplant period, there is significant improvement in auditory discrimination and speech production skills.
 Limited open-set word and sentence recognition is possible for at least some children.
 Complications with the device have been minimal.
 The cochlear implant can provide sound to deaf children unable to benefit from hearing aids.
 The complex assessment, rehabilitation, and parent counseling should be performed by centers with the multidisciplinary staffs necessary to provide effective care for patients with this specialized auditory prosthesis.
",9
1423,"Phenotypic variability in glutaric aciduria type I: Report of fourteen cases in five Canadian Indian kindreds.
 We describe 14 patients with glutaric aciduria type 1 in five Canadian Indian kindreds living in Manitoba and northwest Ontario.
 The patients had marked clinical variability of the disease, even within families.
 Eight followed the typical clinical course of normal early growth and development until the onset of neurologic abnormalities, often precipitated by infection, between 6 weeks and 7 1/2 months of age.
 Five patients had early developmental delay; one was thought to be normal until 8 years of age.
 Three patients died, seven are severely mentally and physically handicapped, and four have only mild mental retardation or incoordination.
 Six patients had macrocephaly in the neonatal period.
 Computed tomography was done for 12 patients, and findings were abnormal in 11.
 Glutaric acid and 3-hydroxyglutaric acid were detected in increased amounts in the urine of all patients, but the concentrations were much lower than those in most other reported patients.
 Glutaryl coenzyme A dehydrogenase activity in skin fibroblasts, interleukin-2-dependent lymphocytes, or both, ranged from 0% to 13% of control values.
 There was no correlation between clinical severity and urine glutaric acid concentration or level of residual enzyme activity.
 We recommend that organic acid analysis of the urine be done in patients with unexplained cerebral palsy-like disorders, especially if the computed tomographic scan is abnormal.
 If there is suspicion of glutaric aciduria, glutaryl-coenzyme A dehydrogenase should be measured in fibroblasts or lymphocytes even if glutaric acid is not increased in the urine.
",9
1424,"The management of mid-face fractures with intracranial injury.
 Recent advances have radically changed the management of facial fractures.
 CT scanning, extensive exposure, and rigid plate fixation in the setting of the trauma center have permitted early operation with improved results.
 A subset of patients with facial fractures will also have intracranial injuries (ICI).
 We sought to identify parameters associated with an increased risk for ICI.
 We also sought to examine the safety and limits of early craniofacial repair in patients with intracranial injuries.
 Of 114 mid-face fractures treated over a 1-year period, 43 (38%) had a concomitant ICI.
 The majority, 36 (84%), were from motor vehicle accidents (MVA).
 Frontal sinus and orbitoethmoid fractures were at the highest risk for ICI, although orbitozygomatic fractures caused by MVAs also had a surprisingly high incidence of ICI.
 Our results show that early craniofacial repair can be performed safely with appropriate general surgical and neurosurgical support.
",9
1425,"Feasibility of reversing benzodiazepine tolerance with flumazenil 
 To examine whether the benzodiazepine antagonist flumazenil can reverse tolerance to benzodiazepines but without precipitating withdrawal seizures, the antiepileptic effect of flumazenil itself and its ability to reverse tolerance at a dose that would leave sufficient receptors free for the binding of benzodiazepines were investigated.
 Electroencephalographic studies in 6 patients with partial and 6 with generalised seizures showed that flumazenil had a short (20 min) non-dose-dependent suppressant effect on epileptic discharges in those with partial seizures.
 Receptor occupancy studies in 12 patients showed that 1.5 mg flumazenil given intravenously occupied 55% receptors, whereas 15 mg occupied nearly all receptors.
 When 3 patients with partial seizures who had become tolerant to clonazepam were given 1.5 mg flumazenil, they were seizure-free for 6-21 days after the injection.
 The value of intermittent therapy with a benzodiazepine antagonist for preventing or reversing tolerance to benzodiazepine agonists ought to be investigated further.
",9
1426,"Carpal tunnel syndrome: correlations between pressure measurement and intraoperative electrophysiological nerve study.
 In 19 carpal tunnel syndrome (CTS) patients and 4 control subjects a catheter was introduced into the carpal tunnel and slowly retracted in 5 mm steps.
 Pressure was measured with the continuous infusion technique.
 In the same group of patients and controls, median nerve antidromic sensory action potential (aSAP) was detected intraoperatively stimulating proximally (S1), in the center (S2), and distally (S3) to the carpal tunnel and recording from the third finger (R).
 Sensory conduction velocity (SCV) and aSAP amplitude were considered in S1-S2, S2-S3 and S3-R segments.
 The intracarpal tunnel pressure was significantly higher in CTS patients than in controls, with the highest values located between 25 and 35 mm distal to the proximal border of the flexor retinaculum.
 SCV and aSAP amplitude were also decreased most often in the distal part (S2-S3) of the carpal tunnel.
",9
1427,"Vector short-latency somatosensory-evoked potentials after median nerve stimulation.
 A new method has been developed for recording short-latency somatosensory-evoked potentials after median nerve stimulation.
 Negative electrical forces recorded with three orthodiagonal bipolar electrodes in the neck had a direction opposite to that of impulse conduction in the proximal peripheral and cervical somatosensory pathway.
 Sequential tracings of vectors opposite the electrical forces were made in three-dimensional display, thus reproducing the actual time sequence of electrical events in those structures.
 Fixed generators such as the subcortical nuclei were also analyzed with this technique, and multiple generators of N13 potential (N13a and N13b) were visualized.
 This technique may be useful in the functional evaluation of the somatosensory pathway in the cervical cord.
",9
1428,"The painful shoulder: Part I. Extrinsic disorders.
 Shoulder disorders are most commonly manifested by pain and limited function.
 Careful history and examination help the physician localize the problem to the shoulder joint, the surrounding tissues or adjacent sites that can cause referred pain to the shoulder.
 Common extrinsic causes of shoulder pain include postural problems and cervical spine disorders.
",9
1429,"Tables for estimation of individual risks of fetal neural tube and ventral wall defects, incorporating prior probability, maternal serum alpha-fetoprotein levels, and ultrasonographic examination results.
 Tables are provided for estimation of the risk of open spina bifida in patients who have elevated maternal serum alpha-fetoprotein levels but normal results on detailed anatomy ultrasonographic scan.
 Risks are provided for various prior population risks, for various levels of elevated maternal serum alpha-fetoprotein, and for various assumptions about the sensitivity of ultrasonographic examination.
 The formula used is based on sequential multiplication of odds with the use of Bayes' theorem, but an arbitrary reduction (to the power of 0.5) in the degree to which ultrasonographic information modifies the odds has been made to allow for the nonindependence of ultrasonography and maternal serum alpha-fetoprotein tests.
 The wide range of resulting risks shows that the decision to offer amniocentesis after a negative scan should be individualized.
",9
1430,"Relationship of laparoscopic findings to self-report of pelvic pain.
 An assessment battery including standardized measures of behavioral and psychosocial factors associated with other chronic pain conditions was administered to 102 women scheduled for laparoscopic surgery.
 Surgeons who were blinded to the patient's self-reported pain data completed the American Fertility Society classification for endometriosis and adhesions on the basis of observed physical disease.
 Although American Fertility Society classification scores were significantly related to self-assignment into pain or no-pain groups, the extent of physical disease evaluated by this procedure was not significantly correlated with ratings of pain levels or a number of indexes of impairment.
 The group of patients with laparoscopically diagnosed pathologic conditions reported higher pain levels and greater interference than the group who reported pain and had negative laparoscopic results; however, some women with observable pathologic conditions reported no pain symptoms.
",9
1431,"Acute tolerance in morphine analgesia: continuous infusion and single injection in rats.
 This study aimed to determine whether the decline of the analgesic effect of morphine with a continuous infusion or that after a single injection correlates with the changes in brain concentration of morphine.
 The analgesic effect of morphine and its brain and serum concentrations were determined with a continuous 8-h infusion at a constant rate and after a single subcutaneous injection of the agent.
 The analgesic effect was determined by measuring the threshold of motor response to noxious stimulation.
 Brain and serum concentrations of morphine were detected by radioimmunoassay with the use of 125I-labeled morphine.
 With the constant-rate (4 mg.kg-1.h-1, intravenous) morphine infusion, the peak of analgesia could not be maintained: the increase in the pain threshold at 2 h was 1,003 g and at 8h was 286 g (a decrease in analgesia by 72%, P less than 0.0002).
 At the same time, the brain morphine concentration tended to increase, to 278 ng/g at 2 h and 329 ng/g at 8 h.
 After the single morphine injection (6 mg/kg, subcutaneous), recovery from analgesia occurred at a much faster rate than did the decrease in morphine brain concentration; the decrease in pain threshold was 79% at 90 vs.
 30 min after the injection (P less than 0.0001), and the corresponding decrease in brain concentration was 28% (NS).
 The absence of correlation between analgesia and morphine brain concentration both with the constant-rate morphine infusion and after the single injection suggests the development of acute tolerance, which is pharmacodynamic in nature.
",9
1432,"Effect of systemic medetomidine, an alpha 2 adrenoceptor agonist, on experimental pain in humans.
 The effect of systemic (intravenous) medetomidine, an alpha-2 adrenoceptor agonist, on pain thresholds was studied in healthy human subjects (n = 6).
 Medetomidine produced a dose-dependent (cumulative doses: 25 and 50 micrograms) sedative effect evaluated by visual analog scale.
 Also, a dose-dependent decrease of blood pressure but not of heart rate was seen after administration of medetomidine.
 Pain threshold to electric stimulation of the tooth pulp and cutaneous heat pain threshold were uninfluenced by medetomidine.
 An index of cutaneous thermal sensitivity to innocuous stimuli, the width of the thermoneutral zone, also was uninfluenced by medetomidine.
 Medetomidine produced a significant attenuation of the affective-motivational component (unpleasantness) of tourniquet-induced ischemic pain, whereas the sensory-discriminative component (pain magnitude estimate) of the ischemic pain was not attenuated.
 The results suggest that systemic medetomidine alone at subanesthetic but sedative and hypotensive doses does not significantly influence the intensity and thresholds of experimental pain, whereas the affective-motivational component of pain can be attenuated.
",9
1433,"Pupil-sparing oculomotor nerve palsy due to midbrain infarction.
 Vasculopathic oculomotor nerve palsies with pupillary sparing are thought to be due to ischemic damage to the nerve in the subarachnoid space or the cavernous sinus.
 We present two cases of patients with isolated pupil-sparing oculomotor nerve palsies due to midbrain infarcts.
 Focal ischemic midbrain lesions should be considered in cases of pupil-sparing oculomotor nerve palsies.
",9
1434,"Initial therapy of patients with Wilson's disease with tetrathiomolybdate.
 Patients with Wilson's disease who present with acute neurological symptoms often become clinically worse when initially treated with penicillamine.
 Other available anticopper drug therapies do not appear to offer a solution to this treatment problem.
 We are developing and evaluating a new drug, ammonium tetrathiomolybdate for this purpose.
 Theoretically, tetrathiomolybdate has optimal properties, including an immediate blockade of copper absorption and the property of forming complexes with copper in the blood, rendering the copper nontoxic.
 In this article, we present results from six patients treated with tetrathiomolybdate for up to 8 weeks as initial therapy.
 None of the five patients who had presented with acute neurological symptoms worsened.
 Also presented are methods of assay, preliminary stability studies, and methods of evaluating therapeutic end points with respect to copper metabolism.
",9
1435,"Cognitive and behavioural impairment among elderly people in institutions providing different levels of care.
 OBJECTIVE: To compare the prevalence and degree of cognitive and behavioural impairment in elderly patients in institutions providing different levels of care.
 DESIGN: Prevalence study.
 SETTING: A nursing home, a home for the aged and psychogeriatric wards in a provincial psychiatric hospital.
 PATIENTS: Only subjects 65 years of age or older were eligible for inclusion.
 A random sample was selected comprising 25% of the residents in the nursing home and the home for the aged; of the 119 asked to participate 95 agreed (44 in the nursing home and 51 in the home for the aged).
 All 50 on the psychogeriatric wards agreed to participate.
 MAIN OUTCOME MEASURES: The Mini-Mental State Examination (MMSE) and the Kingston Dementia Rating Scale (KDRS).
 RESULTS: An MMSE score of less than 24 (cognitive impairment) was given to 37 (84%) of the residents in the nursing home, 43 (84%) of those in the home for the aged and 48 (96%) of the patients in the psychiatric hospital; the corresponding numbers for a KDRS score of more than 0 (cognitive impairment) were 41 (93%), 48 (94%) and 50 (100%).
 The seven patients receiving the highest level of care at the home for the aged (special care) had more behavioural problems than those in the psychiatric hospital did (p less than 0.001).
 CONCLUSIONS: Cognitive and behavioural impairment was widespread in the three institutions regardless of the level of care.
 When planning services and allocating resources government funding agencies should consider the degree and prevalence of such impairment among elderly people in institutions.
",9
1436,"Evolution of energy expenditure and nitrogen excretion in severe head-injured patients.
 OBJECTIVE: The aim of the study was to estimate the influence of therapeutic changes on the level of energy expenditure (EE) and N excretion in a homogeneous group of patients usually considered hypermetabolic.
 DESIGN: EE and N excretion of head-injured patients were measured simultaneously at phases 1 and 2 (patients treated 4 +/- 3 and 18 +/- 8 days after injury, respectively).
 SETTING: Acute care hospital.
 PATIENTS: Eight severe head-injured patients, mean weight 63.1 +/- 6.1 (SD) kg, mean age 21 +/- 3.8 (SD) yr.
 INTERVENTIONS: At phase 1, all patients were sedated with fentanyl (6.7 +/- 1.9 micrograms/kg.hr) plus flunitrazepam (9.1 +/- 4.8 micrograms/kg.hr) and were mechanically ventilated.
 All patients received continuous total parenteral nutrition.
 The nonprotein caloric intake averaged 1092 +/- 200 kcal/day, including 77% glucose and 23% fat (Intralipid 20%).
 The total N intake averaged 7 +/- 5 g/day, consisting of crystalline amino acids.
 At phase 2, no patient received any sedative and all were breathing spontaneously via tracheostomy.
 All patients received parenteral and/or enteral nutrition.
 The nonprotein caloric intake averaged 1929 +/- 200 kcal/day consisting of 65% carbohydrates and 35% fat.
 The total N intake averaged 13 +/- 2 g/day.
 MEASUREMENTS AND MAIN RESULTS: The EE was significantly higher at phase 2 than at phase 1 (2121 vs.
 1737 kcal), but the interindividual variability was low at both phases.
 N excretion was high at the two periods of the study and not correlated to the level of EE.
 The RQ was 0.75 at both periods, indicating predominant fat oxidation.
 CONCLUSIONS: We could not demonstrate any parallelism in the evolution of EE and protein catabolism in head-injured patients.
 The therapeutics (mechanical ventilation, sedation, and nutrition) have a major effect on EE but little on N excretion.
",9
1437,"Noninvasive cerebral optical spectroscopy for monitoring cerebral oxygen delivery and hemodynamics.
 OBJECTIVE: To present an algorithm for noninvasive measurement of cerebral oxygen saturation (cerebral oximetry) and cerebral hemodynamics with near infrared spectroscopy.
 DESIGN: In vitro correlation of oximetry measurements with reference measurements; illustrative cases of hemodynamic and oximetric recordings.
 SETTING: Tertiary care neuroscience ICU.
 PATIENTS: Brain-injured patients with a prolonged, decreased level of consciousness chosen as illustrative examples.
 INTERVENTIONS: Two-channel multiple wavelength diffuse infrared transmission spectroscopy was interfaced with the scalp using adhesive.
 Transmission data were collected with gross superficial-to-deep spatial resolution.
 Saturation calculation based on the deep signal was observed longitudinally in the patient.
 With the same technology, arterial input and cerebral response functions, generated by iv tracer bolus, were deconvoluted to measure mean cerebral transit time.
 MEASUREMENTS AND MAIN RESULTS: A positive linear regression fit between diffuse transmission oximetry and measured blood oxygen saturation over the range 23% to 99% (r2 = .98, p less than .001) was noted.
 CONCLUSIONS: The approach used overcomes previously identified difficulties with cerebral oximetry, and demonstrates excellent in vitro correlation.
 The technique can be performed clinically without difficulty.
 A simultaneous measure of mean cortical transit time is possible.
",9
1438,"Individual differences in children's response to pain: role of temperament and parental characteristics.
 Sixty-five families were enlisted in a study exploring factors associated with distress behavior in 5-year-old children receiving diphtheria-tetanus-pertussis immunizations.
 At a home visit 1 month before the immunization, the following measures were obtained: (1) the Behavioral Style Questionnaire, a measure of temperament: (2) parental self-reports of medically related attributes (eg.
 ""good patient""); (3) parental attitudes toward pain in children and responsiveness to their child's pain; and (4) parental prediction of distress at upcoming immunization.
 The child's distress behavior during the immunization was evaluated using a modification of the Procedure Rating Scale-Revised and, after the procedure, the child's assessment of his or her pain was elicited using the Oucher.
 Children's mean Procedure Rating Scale-Revised score was 2.57 of a possible 11.
 Thirty-one (48%) had low (less than or equal to 1) and 7 (11%) had high distress scores (greater than or equal to 2 SD above the mean).
 Factors positively correlated with distressed behavior included more ""difficult child"" cluster characteristics, the individual temperamental dimension of adaptability, but few parental attitudes and attributes.
 Parent's predictions of distress were the strongest correlates.
 These findings document the variation that children demonstrate in response to pain and offer some insight into associated innate and environmental factors.
 These results imply that treatment strategies derived from parental knowledge and tailored to individual characteristics of the child may be most effective in alleviating pain-related distress in medical settings.
",9
1439,"Methsuximide for intractable childhood seizures.
 Methsuximide was added to the therapeutic regimens of 25 children with intractable epilepsy.
 In 15 patients the drug was well tolerated and resulted in a 50% or greater reduction in seizure frequency.
 No serious or irreversible adverse effects were seen.
 Methsuximide is frequently overlooked and may be an effective adjunctive antiepileptic for children with intractable seizures.
",9
1440,"Sucrose as an analgesic for newborn infants.
 The effectiveness of sucrose as an analgesic agent for newborn infants was assessed during two standard painful hospital procedures: blood collection via heel lance and circumcision.
 Infants who drank 2 mL of a 12% sucrose solution prior to blood collection cried 50% less during the blood collection procedure than did control infants who had received 2 mL of sterile water.
 Crying of infants who ingested sucrose returned to baseline levels within 30 to 60 seconds after blood collection whereas control infants required 2.5 to 3.0 minutes to return to baseline.
 Like findings were obtained for infants who received sucrose on a pacifier prior to and during circumcision.
 Specifically, control infants who underwent a standard circumcision procedure without intervention cried 67% of the time.
 A water-moistened pacifier reduced crying to 49% (P less than .01).
 Crying was reduced further to 31% (P less than .05) by providing infants with a sucrose-flavored pacifier to suck.
 These findings, which parallel results obtained in studies of pain in infant rats, provide a potent yet simple, benign intervention to help alleviate stress and pain routinely experienced by human infants.
",9
1441,"Cerebral venography with MR.
 The authors describe a two-dimensional time-of-flight magnetic resonance (MR) angiography technique to create projection venograms of the head.
 The technique was applied to 27 healthy volunteers and 39 patients.
 The superior sagittal and straight sinuses, the internal cerebral veins, and the Galen vein were visualized in all the volunteers.
 Other veins were seen in a high percentage of subjects.
 Systematic comparison of digital subtraction angiography (DSA) after intraarterial contrast medium injection and MR venography in patients showed good correlation between the two techniques.
 MR venography proved helpful in identifying thrombosis or patency of cerebral veins and sinuses and showed collateral venous drainage and venous drainage from arteriovenous malformations.
 There was good correlation between conventional contrast angiography and MR venography.
 In conclusion, MR venography is considered reliable for showing the cerebral venous system and provides information additional to that of conventional spin-echo imaging.
",9
1442,"Marked cerebrospinal fluid void: indicator of successful shunt in patients with suspected normal-pressure hydrocephalus.
 The authors blindly reviewed the charts of 20 patients with normal-pressure hydrocephalus (a disease of unknown cause characterized radiologically as chronic communicating hydrocephalus and clinically by gait apraxia, dementia, and incontinence) who had undergone creation of a ventriculoperitoneal shunt.
 The initial clinical response to surgery was graded excellent, good, fair, or poor; 5-year follow-up was available in 55% of cases.
 The magnetic resonance (MR) images obtained in these patients were also blindly reviewed for the magnitude of cerebrospinal fluid (CSF) flow void (graded on the basis of extent rather than degree of signal loss) in the cerebral aqueduct.
 A significant (P less than .003) correlation existed between good or excellent response to surgery and an increased CSF flow void.
 The presence of associated deep white matter infarction on MR images did not correlate with a poor response to surgery.
 On the basis of these findings, it is suggested that patients who fulfill the clinical criteria of NPH and have an increased CSF flow void undergo creation of a shunt.
",9
1443,"Functional outcome measures in stroke rehabilitation.
 I examine statistical considerations in the analysis of functional outcome following stroke and discuss the mathematical relation between improvement in function and discharge functional score.
 I demonstrate mathematically that the predictor variables of improvement and discharge functional score are the same and that the regression coefficients for improvement and discharge functional score will be equal, except for the admission functional score, for which a mathematically defined relation exists.
 I argue that the relation between admission functional score and discharge functional score must be positive and strong and that the relation between admission functional score and improvement must be negative for the stroke population.
 I believe that an ignorance of statistical concepts, especially confounding, and of the differences between raw correlations, partial correlations, and predictors have led to much confusion in functional outcome research.
",9
1444,"Platelet volume, aggregation, and adenosine triphosphate release in cerebral thrombosis.
 We compared whole blood platelet aggregation, adenosine triphosphate release, platelet count, platelet crit (percentage volume of platelets), and mean platelet volume during the acute, subacute, and chronic periods of cerebral thrombosis in 22 patients with value in 29 controls.
 During the acute and subacute periods, platelet aggregation, platelet count, platelet crit, and mean platelet volume were significantly less in the patients than in the controls (p less than 0.05-0.01) while the adenosine triphosphate release rate per volume of platelets was significantly greater (p less than 0.05).
 During the acute period, infarct size showed a significant positive correlation with platelet aggregation (r = 0.59, p less than 0.01) and adenosine triphosphate release rate (r = 0.70, p less than 0.001) but a negative correlation with platelet count (r = -0.44, p less than 0.05).
 Our results suggest that platelet aggregation is reduced during the acute period due to the consumption of platelets during thrombogenesis but that the remaining individual platelets are hyperactive.
 Platelet consumption during the acute period increases with infarct size.
 During the chronic period, platelet crit and mean platelet volume were significantly less in the patients than in the controls (p less than 0.01) while the adenosine triphosphate release rate was significantly greater (p less than 0.01), suggesting sustained platelet consumption and chronically enhanced secretion of individual platelets.
",9
1445,"A novel treatment for ischemic intracranial hypertension in cats.
 There is no accepted efficacious treatment for ischemic cerebral edema.
 We show in a cat model of focal cerebral ischemia that infarct volume can be reduced (p less than 0.05) by ventriculocisternal perfusion with an oxygenated fluorochemical emulsion (bis-perfluorobutylethylene).
 An accompanying effect of such ventriculocisternal perfusion is a reduction in intracranial pressure.
 At 18 hours following the start of the perfusion, there was a significant (p less than 0.05) difference in intracranial pressure between nonperfused controls (mean 11.4 [range 2.3-23.0] torr, n = 6) and cats perfused with an oxygenated nutrient solution not containing fluorochemical (mean 11.3 [range 3.0-29.0] torr, n = 8) or animals perfused with the oxygenated fluorochemical emulsion (mean 2.21 [range 0-3.5] torr, n = 7).
 Perfusion with this oxygenated fluorochemical emulsion warrants further study as a treatment for elevated intracranial pressure.
",9
1446,"Persistence and remission of depressive symptoms in late life.
 OBJECTIVE: The relation of poor health to the onset of depression symptoms in late life is well recognized, but little attention has been given to characteristics that might predict persistence or remission of depressive symptoms.
 In previous analyses the authors found that increasing disability and declining health preceded the emergence of depressive symptoms in older community residents and accounted for 70% of the variance explained by discriminant analyses.
 The aim of the present analysis was to examine the relevance of changes in health and disability to the persistence of depressive symptoms.
 METHOD: A representative sample of 1,855 adults aged 65 or older were assessed with the Center for Epidemiologic Studies Depression Scale at baseline.
 Twenty-four months later, 1,577 individuals were available for a second assessment of depressive symptoms.
 The characteristics of the 97 community residents whose depressive symptoms persisted over 24 months were compared to those of the 114 whose symptoms remitted.
 RESULTS: Changes in health, differences in age, sleep disturbance, and added formal support services accounted for more than 30% of the variance between the persistently depressed and remission groups.
 Advanced age and worsening health were associated with persistent symptoms, improved health with remission.
 CONCLUSIONS: Previous studies have indicated that untoward changes in health and disability play a major role in the onset of depressive symptoms.
 These findings show a substantial contribution to chronicity as well.
",9
1447,"Cerebral palsy: why we must plan for survival.
 The survival of children in the South East Thames region, born between 1970 and 1979 and diagnosed as having some form of cerebral palsy was investigated.
 Of the 732 children studied, 651 (90%) are still alive, and hence cerebral palsy must be regarded as a condition with which people live rather than a condition of which they die.
 Survival varies considerably among the different diagnostic groups: those suffering from spasic quadriplegia, dyskinetic and 'mixed' cerebral palsy are most severely affected.
 Our evidence suggests that, though immobility and severe mental subnormality are the strongest predictors of mortality in children with cerebral palsy, the majority of even the most severely affected patients survive to adulthood.
 It is therefore appropriate to plan for their survival by funding and evaluating programmes to maximise health, independence, and quality of life.
",9
1448,"Glossopharyngeal neuralgia associated with cardiac syncope: long term treatment with permanent pacing and carbamazepine.
 Glossopharyngeal neuralgia associated with cardiac syncope developed in a 53 year old man.
 Symptoms were controlled with temporary and permanent transvenous pacing and carbamazepine.
",9
1449,"99mTc HM-PAO SPECT in pediatric migraine.
 99mTC HM-PAO SPECT brain imaging was performed during the headache-free period in 19 young migraineurs, affected by common migraine (CM, 10 cases), classic migraine (CLM, 6 cases) and hemiplegic migraine (HM, 3 cases).
 SPECT findings were negative in all 10 patients with CM, in 3 cases of CLM and in 2 cases of HM.
 Positive findings in the remaining 4 patients (3 cases of CLM and 1 of HM) showed a decreased tracer distribution in the temporo-occipital regions (2 cases) and parietal regions (2 cases): the two with decreased temporo-occipital perfusion reported prodromal symptoms exclusively contralateral to the areas of hypoperfusion.
 An impaired regional cerebral vascular autoregulation may exist even during headache-free intervals in patients suffering from classic and hemiplegic migraine.
",9
1450,"Cerebral vein thrombosis shown by MRI.
 A 46 year old man with a short history of left facial pain and numbness, and subsequently headaches, had a normal physical examination and a normal CT scan of head.
 Lumbar puncture yielded normal CSF under increased pressure.
 MRI showed thrombosis of the superior sagittal sinus, subsequently confirmed by angiography.
 MRI is a sensitive test for detecting intracranial venous thrombosis, and may be the investigation of choice when this disorder is suspected.
",9
1451,"The cluster diathesis.
 We present further evidence for a sympathetic defect of vasomotor control of the anterior cerebral artery (ACA) on the side of the headache during cluster periods.
 In 119 cluster headache patients, utilizing transcranial Doppler, we measured CO2 reactivity of the major intracranial vessels, in and out of cluster.
 Reactivity was significantly lower during the cluster period, but only in the ACA on the side of the headache.
 Nineteen patients followed sequentially for a full cycle (ie/both in and out of a cluster period) showed the same changes.
 In 3 out of 6 patients in an active cluster period, we describe a lesion on Gallium single-photon emission computerized tomography (SPECT) in the region of the cavernous sinus which fades as the patient moves out of cluster.
 It is felt that this lesion may represent the cavernous sinus plexus lesion postulated as the central lesion in cluster.
 Changes in the sympathetic outflow at this point could explain the changes we have described in ACA CO2 reactivity during cluster.
",9
1452,"Relaxation training in school classes does not reduce headache complaints.
 The effect of teacher-presented Progressive Relaxation Training (PRT) on headaches, fear of failure and school problems was studied in school students.
 During ten physical education lessons, students received either PRT (n = 110) or placebo training (n = 92).
 The effect of the training was investigated in students who indicated the presence of headaches in a pre-training diary.
 No significant differences were found between both training groups regarding headache frequency, duration and intensity and the psychological variables.
 On the basis of these and previous findings, it is recommended to present PRT to fairly small groups of self-selected subjects instead of complete classes.
",9
1453,"Pharmacokinetics of tiaprofenic acid after oral administration in fasting patients during and between migraine attacks.
 This study examined the pharmacokinetics of 300 mg of tiaprofenic acid, a NSAID belonging to the 2-arylpropionic class, as a single oral dose, in 10 migraine patients during and out of migraine attacks.
 Plasma concentration of tiaprofenic acid was determined by HPLC analysis.
 Drug absorption appeared to be the same during and out of migraine attacks (absorption half life: during attack, 0.249 +/- 0.122 hr; out of attack, 0.249 +/- 0.105 hr; maximum plasma concentration: during attack, 37.8 +/- 9.8 ug/ml; out of attack, 40.1 +/- 13.2 ug/ml).
 The other pharmacokinetic parameters evaluated were not affected by headache attacks as well.
 We conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks.
 Also, our data suggest that tiaprofenic acid might be useful in the treatment of migraine.
",9
1454,"Paratope- and framework-related cross-reactive idiotopes on anti-acetylcholine receptor antibodies.
 Cross-reactive idiotopes are a possible target for therapeutical interventions in autoimmune diseases.
 To investigate their role in the pathogenesis of experimental autoimmune myasthenia gravis (EAMG) we analyzed the Id of rat anti-AChR mAb 6, 35, 61, 65 and a control myeloma protein IR27.
 Anti-Id 6, 35, 61, 65 bound in a direct binding assay with various affinity to all rat anti-AChR mAb that were tested.
 Anti-Id IR27 recognized none of the anti-AChR mAb.
 The specificity of these crossreactions was confirmed by inhibition studies with anti-AChR mAb and two control rat myeloma proteins (IR27 and IR241).
 In addition, the Id expression on mAb D6, a mouse anti-human AChR mAb was recognized by anti-Id 6, 35, and 65.
 Anti-Id, except anti-Id IR27, bound to affinity purified IgG from the sera of rats with EAMG, but not to preimmune Lewis IgG.
 These results suggest extensive sharing of idiotopes among anti-AChR mAb, which are also present in EAMG serum.
 Anti-AChR mAb against the main immunogenic region (6, 35, 65) from different rat strains, shared at least one paratope-related cross-reactive idiotopes.
 In the view of the fact that anti-main immunogenic region antibodies might form a predominant fraction of the polyclonal response against AChR, it is conceivable that an anti-Id recognizing these antibodies could have therapeutical applications as for example a selective immune absorbent or in immunotoxin therapy.
",9
1455,"Skin and epidural recording of spinal somatosensory evoked potentials following median nerve stimulation: correlation between the absence of spinal N13 and impaired pain sense.
 A clinical lesion study and intraoperative epidural recordings were made to test the origin and clinical significance of the spinal N13 and P13 of somatosensory evoked potentials (SEP) that follow median nerve stimulation.
 Intraoperatively, the respective peak latencies of spinal P13 and N13 coincided with those of the N1 component of the dorsal cord potential and its phase reversed positivity.
 On both the ventral and dorsal sides of the cervical epidural space, maximal amplitude was at the C5 vertebral level to which nerve input from the C6 dermatome is the main contributor.
 The modality of sensory impairment in the hand dermatome was examined in selected patients with cervical lesions, who showed such normal conventional SEP components as Erb N9, far-field P9, P11, P14, N18 and cortical N20, with or without loss of spinal N13.
 Statistically, the loss of spinal N13 was associated with decrease of pain sensation in the C6 dermatome.
 This was interpreted as being due to damage to the central grey matter of the cord, including the dorsal horn.
 Our results suggest the spinal N13 and P13 originate from the same source in the C6 spinal cord segment and that they are good indicators for the detection of centromedullary cervical cord damage.
",9
1456,"The development of infratentorial atrophy in patients with idiopathic cerebellar ataxia of late onset: a CT study.
 The development of infratentorial atrophy in six patients suffering from idiopathic cerebellar ataxia of late onset was studied by a retrospective evaluation of consecutive computed tomography (CT) scans.
 Four patients had evidence of olivopontocerebellar atrophy (OPCA) both on clinical testing and magnetic resonance imaging (MRI).
 In these four patients, atrophy of the cerebellum and brain stem became visible at the same time and progressed in a roughly parallel manner, whereas in the remaining two the brain stem was left intact.
 In all patients with OPCA, definite brain-stem atrophy was visible earlier than the appearance of non-cerebellar clinical symptoms.
 The present data suggest that CT investigations at regular intervals may be of prognostic value in cerebellar ataxias.
",9
1457,"Impairment of vertical motion detection and downgaze palsy due to rostral midbrain infarction.
 We present two cases with acute onset of vertical gaze palsy, mainly consisting of impaired downgaze and apraxia of downward head movements, together with neuropsychological deficits (hypersomnia, impaired attention and disorders of memory and affective control).
 CT and MRI revealed bilateral post-ischaemic lesions in the dorsomedial thalamus and the mesodiencephalic junction, dorsomedial to the red nucleus, thus being restricted to the territory of the posterior thalamosubthalamic paramedian artery, which includes the region of the rostral interstitial nucleus of the medial longitudinal fascicle as the main premotor nucleus for the generation of vertical saccades.
 In our patients, oculographic examination with electro-oculography and magnetic search coil recording showed severe impairment of downward more than upward saccades and only minor deficits of vertical pursuit and the vestibulo-ocular reflex.
 Visual functions were normal, with one exception: a psychophysical test of motion perception revealed a significant deficit in the detection of vertical movements.
 This could be due to a central adaptive mechanism which, in order to minimize oscillopsia, might elevate thresholds for vertical motion perception in cases of vertical gaze palsy.
 As an alternative explanation, lesions within the midbrain tegmentum could have damaged subcortical visual pathways involved in motion perception.
",9
1458,"Cerebral palsy and rhizotomy. A 3-year follow-up evaluation with gait analysis.
 A recent increase in the popularity of selective rhizotomy for reduction of spasticity in cerebral palsy has led to a demand for more objective studies of outcome and long-term follow-up results.
 The authors present the results of gait analysis on 14 children with spastic cerebral palsy, who underwent selective posterior rhizotomy in 1985.
 Sagittal plane gait patterns were studied before surgery and at 1 and 3 years after surgery using a digital camera system.
 The parameters measured included the range of motion at the knee and thigh, stride length, speed of walking, and cadence.
 The range of motion at the knee was significantly increased at 1 year after surgery and further improved to a nearly normal range at 3 years after surgery.
 In contrast, postoperative measurements of thigh range exceeded normal values at 1 year, but decreased toward normal range at 3 years.
 While improvements in range of motion continued between Years 1 and 3, the children developed a more extended thigh and knee position, which indicated a more upright walking posture.
 Stride length and speed of walking also improved, while cadence remained essentially unchanged.
 This 3-year follow-up study, the first to examine rhizotomy using an objective approach, has provided some encouraging results regarding early functional outcome.
",9
1459,"Spontaneous decompression of syringomyelia: magnetic resonance imaging findings. Case report.
 The case of a 30-year-old woman with Chiari I malformation and a cervicothoracic syrinx is presented.
 The patient was followed clinically over a 2 1/2-year period.
 Spontaneous and complete resolution of the syrinx, as documented by serial magnetic resonance studies, was accompanied by only a minimal change in objective symptomatology.
",9
1460,"Carbon monoxide-induced delayed amnesia, delayed neuronal death and change in acetylcholine concentration in mice.
 We investigated the interrelationship of delayed amnesia, delayed neuronal death and changes in acetylcholine concentration induced by carbon monoxide (CO)-exposure in mice.
 In the test for retention of the passive avoidance task, amnesia was observed 5 and 7 days after CO-exposure when the mice were exposed to CO 1 day after training; in the case when the mice were exposed to CO 5 and 7 days before training, amnesia was also observed in a retention test given 1 day after training.
 The number of pyramidal cells in the hippocampal CA1 subfield was lower than that of the control 3, 5 and 7 days after CO-exposure.
 But the neurodegeneration in the parietal cortex, area 1, was not observed until 7 days after CO-exposure.
 The findings indicated that the amnesia and the neuronal death were produced after a delay when the mice were exposed to CO.
 In addition, the delayed amnesia was closely related to the delayed neuronal death in the hippocampal CA1 subfield.
 Moreover, [3H]glutamate and [3H]glycine binding sites did not change after CO-exposure but, 7 days after CO-exposure, the concentration of acetylcholine and the binding of [3H]quinuclidinyl benzilate in the frontal cortex and the striatum were found to have significantly changed, but those in the hippocampus did not show significant change.
 Therefore, we suggest that delayed amnesia induced by CO-exposure may result from delayed neuronal death in the hippocampal CA1 subfield and dysfunction in the acetylcholinergic neurons, in the frontal cortex, the striatum and/or the hippocampus.
",9
1461,"A self-administered hand symptom diagram for the diagnosis and epidemiologic study of carpal tunnel syndrome.
 Noninvasive tests for carpal tunnel syndrome (CTS) are of limited diagnostic value.
 A self-administered hand symptom diagram has been developed for use in the diagnosis and epidemiologic study of CTS.
 Diagrams are rated classic CTS, probable, possible or unlikely.
 Diagram ratings were compared with nerve conduction diagnoses in 110 patients with upper extremity complaints.
 A hand diagram rating of classic or probable CTS had sensitivity of 0.64, specificity of 0.73 and positive predictive value of 0.58.
 The negative predictive value of an unlikely diagram was 0.91.
 We conclude that the diagram is a useful diagnostic tool and may be valuable for occupational and population screening.
",9
1462,"Motor neuron disease (amyotrophic lateral sclerosis).
 Amyotrophic lateral sclerosis is an insidiously developing, adult-onset, progressive anterior horn cell degeneration with associated degeneration of descending motor pathways.
 It has been recognized as an important clinical syndrome since the middle of the 19th century.
 Despite increasing clinical and research interest in this condition, its cause remains obscure, even in the broadest terms.
 Epidemiologic characteristics of the disease have been interpreted as evidence of both genetic and environmental causes.
 A major change in the view of this disease is the widely developing perception that it is a disease of elderly persons more than of middle-aged adults as was previously taught.
 Etiologic hypotheses encompass a broad range of postulated pathophysiologic mechanisms, and we review these in detail.
 The clinical limits of the disease can now be better defined by using modern diagnostic techniques.
 Although interest in supportive symptomatic therapy is growing, no intervention has yet been shown to modify the biologically determined motor system degeneration.
",9
1463,"Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and treatment.
 In this report, we discuss the definition, characteristics, pathophysiology, and treatment of tic disorders with a major emphasis on Tourette syndrome.
 Although the diagnosis of a tic disorder depends on the presence of motor and/or phonic tic(s), patients with these problems also have a variety of co-morbid features including obsessive-compulsive symptoms, attention-deficit hyperactivity disorder, behavioral difficulties, and learning disabilities.
 Conservative estimates for Tourette syndrome suggest a prevalence rate of 0.1-1.0 per 1000.
 This syndrome is inherited in a sex-influenced autosomal dominant pattern with either chronic multiple tic disorder or obsessive-compulsive disorder as alternative phenotypes of the putative gene.
 Current evidence continues to support a pathophysiologic mechanism involving synaptic neurotransmission, with the dopaminergic system as a primary candidate.
 Therapeutically, it is essential to clarify whether a patient's problems are related to tics or associated behavioral difficulties.
 Pharmacotherapy for motor and phonic tics is strictly symptomatic and should be reserved for those with functionally disabling symptoms.
 A comprehensive individualized treatment program is often required in the care of individuals with tic disorders.
",9
1464,"Effect of hydrocephalus on prostaglandins and thromboxane B2 in ventricular cerebrospinal fluid.
 The concentrations of prostaglandin F2 alpha, prostaglandin E2, 6-ketoprostaglandin F1 alpha (prostacyclin metabolite), and thromboxane B2 were assayed in ventricular cerebrospinal fluid obtained from 28 patients with hydrocephalus (17 obstructive, 11 communicating).
 Seven patients received dexamethasone or hydrocortisone on the day of sampling.
 No patient received nonsteroidal anti-inflammatory compounds for 48 hours before sampling.
 The median values did not differ significantly between the two types of hydrocephalus or from the concentrations in lumbar cerebrospinal fluid obtained from patients without intracranial pathology during lumbar myelography for possible lumbar disc disease.
 Hence, there is no evidence that eicosanoids accumulate in the ventricles in hydrocephalus, and it is unlikely that they have a significant role in its symptomatology.
",9
1465,"Reflex sympathetic dystrophy syndrome: consensus report of an ad hoc committee of the American Association for Hand Surgery on the definition of reflex sympathetic dystrophy syndrome.
 This report proposes that reflex sympathetic dystrophy be defined as a pain syndrome in which the pain is accompanied by loss of function and evidence of autonomic dysfunction.
 In the clinical setting, this diagnosis is usually associated with other anatomic and psychological diagnoses and may be associated with a variety of systemic illnesses and medicolegal factors.
 All components should be assessed before a treatment plan is established.
 Priorities should go to emergency care, acute injuries, and systemic illness, psychiatric problems, and chronic anatomic problems, in that order.
 Early, accurate diagnosis improves prognosis.
",9
1466,"Congenital demyelinating motor and sensory neuropathy with focally folded myelin sheaths.
 Six patients (5 index cases and 1 sib) with a congenital motor and sensory neuropathy are described.
 The clinical, genetic and electrophysiological features resembled Dejerine-Sottas disease or hereditary motor and sensory neuropathy (HMSN) type III.
 Sural nerve biopsy of 5 patients revealed segmental demyelination and remyelination with hypertrophic changes, although onion bulbs were not as ubiquitous as in classical HMSN type III.
 A striking discriminating feature from HMSN type III was an abundance of focal myelin thickenings (tomacula) present in nearly all teased fibres.
 Possible pathogenic implications are discussed.
 These cases corroborate the heterogeneity of congenital motor and sensory neuropathies.
",9
1467,"Experiential phenomena of temporal lobe epilepsy. Facts and hypotheses.
 Experiential phenomena that occur in temporal lobe seizures and can be reproduced by electrical stimulation of temporal lobe structures typically encompass perceptual, mnemonic and affective features, either in combination or in isolation, which commonly relate to the patient's individual past experience.
 These phenomena raise interesting questions concerning brain mechanisms involved in human psychophysiology.
 The anatomical substrates for the evocation of these phenomena are widely distributed within the temporal lobe and include temporal isocortex and limbic structures (amygdala, hippocampus and parahippocampal gyrus).
 Arguments are presented which indicate that experiential phenomena are positive expressions of temporal lobe and limbic function and do not result from its ictal paralysis.
 Recent concepts of parallel distributed processing (Rumelhart and McClelland, 1986) and the importance of parallel distributed cortical networks for higher cognitive functions (Goldman-Rakic, 1988a, b) provide a theoretical framework on which a hypothesis explaining experiential phenomena can be based.
 In conformity with these concepts the hypothesis assumes that temporal lobe epileptic discharge or electrical stimulation of temporal lobe structures can induce the elaboration of patterns of excitation and inhibition in widely distributed neuronal networks, some of which are capable of forming a specific matrix representing the substrate of a given experience.
 Neuronal networks engaged in parallel distributed processing (1) have the capacity to recreate the totality of a given experience when only a fragment of the network is activated, and (2) they tolerate a great deal of degradation by random inactivation of its components or by interference through random noise without serious loss of information content.
 These features are compatible with the assumption that localized epileptic neuronal discharge or electrical stimulation involving some temporal lobe structures could create a matrix representing features of individual experience of the kind activated in the course of temporal lobe seizures.
 Such an experience could, up to a certain limit, resist the degrading influence of mounting noise which inevitably must attend seizure discharge.
",9
1468,"The role of diencephalic pathology in human memory disorder. Evidence from a penetrating paranasal brain injury.
 A patient (B.J.) is reported who developed severe memory impairment following a penetrating brain injury caused by a snooker cue which entered through his left nostril into the basal regions of the brain.
 Initially, his memory disorder had the clinical features of a dense amnesic syndrome, with both anterograde and retrograde amnesia, but B.J.
 subsequently showed significant recovery of memory function.
 Formal memory testing was carried out 21 months after injury.
 This demonstrated marked verbal memory impairment, as severe as that seen in patients with the amnesic syndrome.
 On nonverbal memory tests, his impairment was relatively mild and patchy.
 His retrograde amnesia had regressed mainly to affect a 6 month period before the injury.
 On other cognitive tasks, he performed at an average or above average level, and there was no neuropsychological evidence of frontal lobe dysfunction.
 Neuroradiological investigations at various stages after his injury failed to demonstrate a lesion in any of the thalamic nuclei.
 Magnetic resonance imaging showed a lesion in the hypothalamus in the region of the mamillary bodies.
 Our study demonstrates that marked, relatively focal, memory disorder after diencephalic injury can occur without direct pathology to the body of the thalamus.
 It also indicates that structures in or adjacent to the hypothalamus, such as the mamillary bodies, may play a more important role in human memory functioning than has hitherto been considered.
",9
1469,"Single unit analysis of the human ventral thalamic nuclear group. Activity correlated with movement.
 During neurosurgical operations for the relief of movement disorders, single thalamic neurons (n = 107) were identified with activity which was related to verbally cued active movements (movement-related cells).
 The activity of each neuron was examined during different contralateral movements in order to determine the movement which was associated with the most consistent and pronounced change in firing rate (the optimal response).
 The optimal response was determined by analysis of histograms of neuronal activity which were constructed by using the onset of EMG activity to synchronize successive repetitions of the active movement.
 Movement-related cells exhibited optimal responses associated with such movements as making a fist, extension or flexion of the wrist, flexing or extending the elbow, pointing with the entire upper extremity, extending the tongue and lifting the leg.
 Most movement-related cells recorded in a single parasagittal plane in an individual patient had optimal responses related to movements involving the same part of the body.
 Movement-related cells were classified into those that were activated in response to somatosensory stimulation (combined cells, n = 20) and those which were not (voluntary cells, n = 87).
 Combined cells were activated in advance of EMG activity during active movement and so could be distinguished from cells responding only to sensory stimulation (sensory cells).
 Movement-related cells (combined and voluntary cell types) were located anterior to sensory cells and tended to show a mediolateral somatotopic organization parallel to that of sensory cells with cutaneous receptive fields.
 Combined cells responded to somatosensory stimulation of the same part of the body as that involved in the active movement related to the optimal response of the cell.
 Combined cells responding to passive movements of a joint always had their optimal response during active movement about the same joint.
 The activity of combined cells during parkinsonian tremor may clarify the role of sensory feedback in tremor.
",9
1470,"Spongiform encephalopathy transmitted experimentally from Creutzfeldt-Jakob and familial Gerstmann-Straussler-Scheinker diseases.
 A comparison was made of the effects of experimental intracerebral inoculation into marmosets of brain homogenates from a case of Creutzfeldt-Jakob disease (CJD) and from a member of the Wo.
 family with cerebral amyloid and spongiform encephalopathy--the Gerstmann-Straussler-Scheinker (GSS) syndrome.
 All the inoculated marmosets developed spongiform encephalopathy (SE) after incubation times of 20-23 months in the CJD group and 25-32 months in the GSS group.
 Subsequent passage from 1 affected animal in each group resulted in SE developing after 17 months incubation.
 In every animal inoculated with CJD or GSS material and in the 2 passage experiments the most severely affected region of the brain was the thalamus which in all cases was almost totally occupied by vacuoles.
 Other grey matter masses were less severely and less consistently affected.
 Vacuolation was observed in the cerebellar granule cell layer as well as in the molecular layer and the brain stem was finely vacuolated in all cases.
 There were only minor and inconsistent differences between the disease transmitted from CJD compared with GSS and some differences between the original transmissions and the SE caused by passaged inocula.
 Severe astrocytic gliosis accompanied the spongiform changes but no amyloid was identified in any of the marmosets with experimentally transmitted disease.
 The pathogenesis of the spongiform change in the thalamus was studied in a series of marmosets by light and electron microscopy 3-22 months after the intracerebral inoculation of CJD or GSS homogenates and was compared with controls.
 Dilated irregularly-shaped cisternae and the large complex vacuoles typical of SE, present in abundance after 18 and 22 months incubation, were considered most probably to be derived from cisternae of neuronal smooth endoplasmic reticulum.
",9
1471,"Hemodynamic effects of nasal CPAP examined by Doppler echocardiography.
 The effects of incremental application of nasal continuous positive airway pressure (0 to 15 cm H2O) on heart rate, pulmonary artery pressure, and cardiac index were studied noninvasively by Doppler echocardiography.
 By two-way analysis of variance within two groups (19 normal volunteers and six sleep apnea patients), no significant effects on heart rate, pulmonary artery pressure, ventricular size, or cardiac index could be found with increasing positive intrathoracic pressures and consequent lung hyperinflation.
 In subjects with normal cardiac function, nasal CPAP is safe from a hemodynamic viewpoint.
 This simple, repeatable and noninvasive technique may be used to assess the clinical safety and efficacy of prescribed nasal CPAP on cardiac hemodynamics in individual patients.
",9
1472,"Respiratory muscle strength and control of ventilation in patients with neuromuscular disease.
 To assess the relationship between respiratory mechanics and muscle strength and control of ventilation in patients with neuromuscular disease (NMD), we compared PImax and PEmax at RV, FRC and TLC, total respiratory elastance (Ers) with VT, TI, TT, VE, VT/TI, TI/TT, P.01, and P.01/(VT/TI) effective impedance in 21 patients with NMD and 21 healthy control (C) subjects, in seated position breathing room air.
 Ers in NMD patients was 79 percent higher than in the C subjects.
 While TI, TT, and VT in NMD were approximately half the corresponding C values, P.01 was 66 percent greater than in the C subjects (both p less than 0.001).
 NMD PImax and PEmax ranged from 37 to 52 percent of corresponding C values, respectively.
 Despite significant respiratory muscle weakness, only 7 of 16 patients demonstrated a PaCo2 greater than 45 mm Hg.
 Ventilatory output in NMD was modulated by respiratory mechanics as indicated by the increased P.01.
 In spite of muscle weakness, central drive in patients with NMD is not decreased, and in fact, is often increased.
 VE is not an accurate measure of central drive because of abnormal intrinsic respiratory mechanics and the effects of conscious responses or reflexes.
",9
1473,"Effect of cardiac output reduction on rate of desaturation in obstructive apnea.
 The nadir of SaO2 during an obstructive apnea is dependent upon the apnea's duration and the rate of fall of saturation (dSaO2/dt).
 We postulated that a low Q, such as in patients with congestive heart failure with sleep apnea, or a reduction in Q, as seen in some humans during obstructive sleep apnea, might steepen dSaO2/dt.
 The mechanism postulated was lowering of SvO2 with increased pulmonary capillary blood oxygen uptake and faster depletion of alveolar oxygen.
 This study examines dSaO2/dt following the onset of apnea in eight spontaneously breathing adult baboons.
 Nonrepetitive obstructive apneas (30, 45, and 60 seconds) were created by clamping an indwelling cuffed endotracheal tube at the end of expiration.
 Following baseline measurements, the animals were given a bolus of a rapid-acting beta-adrenergic blocker followed by continuous infusion to reduce cardiac output and to limit the cardiovascular response to obstructive asphyxia.
 Fiberoptic catheters were used for continuous monitoring of SaO2, SvO2, and cardiac output.
 Esophageal pressure and relative thoracic gas volume (Respitrace) were monitored to insure equivalence of lung volume at the onset of apnea.
 Beta-adrenergic blockade reduced resting Q by a mean of 25 percent.
 The blocked vs unblocked dSaO2/dt was 0.73 vs 0.72 percent/s, 0.76 vs 0.73 percent/s, and 0.70 vs 0.71 percent/s for 30-second, 45-second, and 60-second apneas, respectively.
 Thus, mean dSaO2/dt for all durations of apneas was unaffected by beta-adrenergic blockade.
 We concluded that dSaO2/dt is not influenced by limited Q preceding or induced by obstructive asphyxia.
",9
1474,"Hyperprolactinemia increases and hypoprolactinemia decreases tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nuclei, but not the substantia nigra or zona incerta.
 The effects of experimentally produced hypoprolactinemia and hyperprolactinemia on tyrosine hydroxylase (TH) mRNA signal levels were examined in dopaminergic neurons ovariectomized rats.
 TH mRNA signal levels and relative TH quantity in the arcuate nuclei, zona incerta, and substantia nigra were evaluated by in situ hybridization and immunocytochemistry, respectively.
 The catalytic activity of TH in the stalk-median eminence (SME) was determined from the in vitro rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine.
 Chronic administration of bromocriptine (BROMO), a dopamine (DA) agonist, for 3 days reduced circulating rat PRL (rPRL) levels compared to those in the vehicle-treated controls.
 BROMO treatment decreased TH mRNA signal levels in the arcuate nuclei, the intensity of TH immunostaining in the arcuate-median eminence area, and the rate of DOPA accumulation in the SME.
 Concomitant administration of ovine PRL (oPRL) reversed the effects of BROMO on TH, resulting in markedly increased TH mRNA signal levels, intensity of TH immunostaining, and rate of DOPA accumulation.
 Treatment with oPRL by itself for 3 days increased TH mRNA signal levels in the arcuate nuclei and TH activity in the SME, compared to vehicle.
 Chronic treatment with haloperidol, a DA antagonist, increased circulating levels of endogenous rPRL and increased TH activity in the SME to values similar to those after oPRL treatment.
 However, in contrast to oPRL, mRNA levels in the arcuate nuclei of haloperidol-treated rats were similar to levels in vehicle-treated animals.
 To evaluate whether the effect of PRL on TH was species specific, oPRL or rPRL was continuously infused into the jugular vein using an osmotic minipump.
 TH mRNA levels in the arcuate nuclei were elevated above control levels by either oPRL or rPRL administration.
 TH mRNA levels in the DA perikarya located in the zona incerta and substantia nigra were not altered by treatment with a DA agonist, a DA antagonist, or PRL.
 These results indicate that hypoprolactinemia or hyperprolactinemia can selectively reduce or augment, respectively, TH mRNA levels in the tuberoinfundibular dopaminergic neurons.
 The alterations in TH mRNA content probably contribute to the decrease or increase in TH activity associated with hypoprolactinemia or hyperprolactinemia, respectively.
",9
1475,"Humor, aggression, and aging.
 Humor response to aggressive cartoons was investigated by using ratings of pain and funniness of cartoons by 154 young and elderly men and women.
 No significant age differences were found; however, sex differences were found.
 For both young and elderly females, an inverted-U described the relationship between pain and funniness ratings.
 For young and elderly males, there was no relationship between pain and funniness.
 This is a preliminary step in exploring age differences in humor but may be relevant for those working with elderly persons.
",9
1476,"Approach to diagnosis of meningitis. Cerebrospinal fluid evaluation.
 CSF evaluation is the single most important aspect of the laboratory diagnosis of meningitis.
 Analysis of the CSF abnormalities produced by bacterial, mycobacterial, and fungal infections may greatly facilitate diagnosis and direct initial therapy.
 Basic studies of CSF that should be performed in all patients with meningitis include measurement of pressure, cell count and white cell differential; determination of glucose and protein levels; Gram's stain; and culture.
 In bacterial meningitis, Limulus lysate assay and tests to identify bacterial antigens may allow rapid diagnosis.
 Where there is strong suspicion of tuberculous or fungal meningitis, CSF should also be submitted for acid-fast stain, India ink preparation, and cryptococcal antigen; unless contraindicated by increased intracranial pressure, large volumes (up to 40-50 mL) should be obtained for culture.
 If a history of residence in the Southwest is elicited, complement-fixing antibodies to Coccidioides immitis should also be ordered.
 Newer tests based on immunologic methods or gene amplification techniques hold great promise for diagnosis of infections caused by organisms that are difficult to culture or present in small numbers.
 Despite the great value of lumbar puncture in the diagnosis of meningitis, injudicious use of the procedure may result in death from brain herniation.
 Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension.
 Institution of antibiotic therapy for suspected meningitis should not be delayed while neuroradiologic studies are obtained to exclude abscess or while measures are instituted to reduce intracranial pressure.
",9
1477,"Fluctuations of interictal brain imaging in repeated 123I-IMP SPECT scans in an epileptic patient.
 Single photon emission computed tomography (SPECT) brain scans with N-isopropyl-(iodine 123) p-iodoamphetamine (123I-IMP) were performed three times in interictal periods in a 35-year-old man with intractable frontal lobe epilepsy and normal X-ray CT findings.
 The first scan showed decreased 123I-IMP uptake in the right frontal lobe.
 This abnormal image was regarded as the primary focus of his epilepsy on the basis of its regional agreement with focal epileptic discharges on EEGs.
 In the second scan, he showed normal imaging, while the third scan showed the same abnormal image as before, in the right frontal lobe.
 The frequency of his clinical seizures was almost unchanged during the intervals between scans and further EEGs recorded soon after each scan showed almost no changes in the basic activities and frequency of the epileptic discharges.
 Such fluctuations in SPECT brain imaging suggest that the severity of functional inactivation underlying the focal hypoperfusion image as an epileptic focus may fluctuate considerably in the interictal state with no relation to the clinical features of epilepsy.
",9
1478,"Aberrant regeneration in a case of syringobulbia: selective co-activation of abducens and facial nerves during saccades.
 A patient suffering from syringobulbia and syringomyelia exhibited a phasic contraction of the ipsilateral facial muscles, mainly the levator labii, whenever he looked to the left or right.
 Facial muscle twitches occurred exclusively with saccades.
 The selective co-activation of abducens and facial nerves is interpreted as the result of bilateral misrouting of regenerating neurons from the parapontine reticular formation to the facial nerve in the tegmentum pontis.
",9
1479,"Familial eating epilepsy.
 Eating-related seizures affecting 20 individuals among 59 siblings belonging to nine families are presented.
 The type of epilepsy was partial in all the affected individuals, and the seizures complex in 15 and simple in 5, secondarily generalized in the majority.
 The onset of epilepsy, in most cases, was in the second decade of life.
 A remarkable degree of intra-family consistency was observed with regard to age at onset, symptomatology of seizures and timing of eating seizures.
 The study demonstrates sibling clustering in a partial epilepsy, implicating for the first time genetic susceptibility in the aetiology of eating epilepsy.
",9
1480,"Transient ischaemic attacks and small-vessel disease. Dutch TIA Study Group 
 Histories and computed tomograms of 606 patients with transient cerebral ischaemia were studied.
 All symptoms and signs had completely resolved within 24 hours, and any episodes suggestive of posterior fossa ischaemia were excluded.
 Computed tomography, done after the clinical features had resolved, showed 79 relevant infarcts: 46 were small, deep, lacunar infarcts (58%, 95% confidence interval [CI] 47-69%), and 33 were larger cortical infarcts.
 The histories and the type of infarct in these 79 patients were compared to see whether lacunar infarcts were preceded by a history of unilateral motor or sensory symptoms without features usually attributed to the cerebral cortex.
 The positive predictive value of such lacunar symptoms was 0.74, with a negative predictive value of 0.61.
 11 patients had a cortical infarct despite a history of lacunar TIAs, but only one occurred in the left hemisphere and speech was not affected.
 Of 527 patients with transient ischaemic attacks without a relevant infarct visible on computed tomography, 335 (64%) had a history suggestive of lacunar ischaemia, whereas in several other studies 20-25% of patients with ischaemic stroke have evidence of lacunar infarcts.
 Lacunar TIAs may therefore have a better prognosis than cortical TIAs or may often precede cortical infarcts; alternatively, many cortical infarcts may occur without warning.
",9
1481,"The role of conditioning and verbal expectancy in the placebo response.
 Both conditioning and expectancy models have been offered in recent years as explanations for the placebo response.
 Following our earlier work on conditioning placebo responses in human subjects the current study examined the relative contribution made by conditioning and verbal expectancy.
 Group 1 received a Combined Expectancy and Conditioning Manipulation; group 2 received Expectancy Alone; group 3, Conditioning Alone; and group 4 was the control group.
 Subjects' responses were compared with and without a placebo cream, using iontophoretic pain stimulation.
 The results suggest that conditioning was more powerful than verbal expectancy in creating a placebo response.
",9
1482,"Profiles of opioid analgesia in humans after intravenous bolus administration: alfentanil, fentanyl and morphine compared on experimental pain.
 This report examines the relationship of plasma drug concentration to analgesic effect following bolus doses of alfentanil, fentanyl and morphine and assesses individual differences in analgesic response among volunteers.
 We predicted that the 3 opioids would yield disparate analgesic profiles because their physicochemical and pharmacokinetic characteristics differ.
 Ten healthy volunteers received intravenous bolus doses of either alfentanil, fentanyl, morphine or normal saline on different days.
 We stimulated their teeth electrically and measured brain evoked potential (EP) and pain report (PR) repeatedly over 2 h to assess analgesic effect.
 Concurrently, we drew 18 blood samples to assess opioid plasma concentrations during the test period.
 The relationship between opioid plasma concentration and analgesic effect was well defined for alfentanil but ambiguous for morphine.
 Fentanyl exhibited a marked hysteresis.
 We observed noteworthy individual differences in analgesic response with all 3 drugs but these differences were greatest for morphine and least for alfentanil.
 Inter- and intrasubject variability in analgesic response across drugs is related to the physicochemical properties of the drugs tested.
",9
1483,"Heart rate changes as an autonomic component of the pain response.
 Autonomic variables have been recommended as measures of the affective-motivational component of the pain response in objective algesimetry.
 In the present study components of heart rate responses to painful heat stimuli and their relation to stimulus and sensation variables were analyzed.
 Twelve healthy subjects served.
 Sixty phasic stimuli of varying temperatures above and below pain threshold were delivered through a Marstock thermode in 1 session.
 Heart rate, respiration, and subjective stimulus ratings were recorded simultaneously.
 Phasic heat stimulation above and below pain threshold induced a tonic increase of the heart rate lasting up to more than 20 sec.
 High intensity stimulation generated steeper rises and greater mean increase than low intensity stimulation.
 In general, heart rate responses were more closely related to subjective sensation than to stimulus intensity.
 However, differential temporal analysis demonstrates that, until about 3 sec after stimulation, the autonomic response is determined solely by stimulus temperature, whereas, after approximately 6 sec, it is related only to subjective judgement.
 Accordingly, the heart rate responses reflect both a brief nocifensive reflex induced by the sensory component and, subsequently, a longer-lasting response which seems to be related to affective and/or cognitive evaluation.
 This separation of different stages of pain-processing by an autonomic indicator may be useful in clinical algesimetry.
",9
1484,"Effects of the calcium antagonist nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats.
 We studied the efficacy of preischemic and postischemic systemic treatment with a new calcium antagonist nilvadipine in a permanent focal cerebral ischemia model of spontaneously hypertensive rats.
 Rats that underwent microsurgical middle cerebral artery occlusion were blindly assigned to a single intraperitoneal injection of nilvadipine (0.32 mg/kg) or the same amount of polyethylene glycol either 15 minutes before, immediately after, 1 hour after, or 3 hours after occlusion of the left middle cerebral artery.
 Neurologic conditions of rats were closely examined, and rats were killed 24 hours later.
 Removed brains were sliced coronally, stained with triphenyltetrazolium chloride, and the size of infarct was determined.
 Although no neurologic improvements were observed in the treated rats, the area of infarcts was significantly reduced in the groups treated before, immediately after, and 1 hour after occlusion of the middle cerebral artery.
 Treatment started 3 hours after occlusion was ineffective.
",9
1485,"A single case of Huntington's disease simultaneously occurring with obstructive hydrocephalus.
 A case of simultaneously occurring Huntington's disease and obstructive hydrocephalus is presented.
 Huntington's and other neurodegenerative diseases have been described with normal-pressure hydrocephalus; however, no such description with obstructive hydrocephalus has been reported.
 The obstructive hydrocephalus displays a familial tendency in its presentation.
",9
1486,"Why are autism and the fragile-X syndrome associated? Conceptual and methodological issues.
 Investigations of the association between autism and the fragile-X syndrome have yielded conflicting results with some studies indicating a strong correlation and others indicating no relation between the disorders.
 In this paper, we review the relevant research on this controversy and discuss the conceptual and methodological problems involved in such an inquiry.
 We conclude that autism and fragile X are associated and that this relation will prove fruitful in understanding the role of the X chromosome in a variety of behavior disorders and in unraveling various theoretical accounts on the etiology of autism.
",9
1487,"Progress in the search for genetic linkage with Tourette syndrome: an exclusion map covering more than 50% of the autosomal genome.
 Gilles de la Tourette syndrome is a neuropsychiatric disorder with an autosomal dominant mode of inheritance and reduced penetrance at a single genetic locus.
 Several research groups have genetic linkage studies underway to detect the chromosomal location of the gene that predisposes for this disorder.
 Strong and clear evidence of linkage has not yet been produced for Tourette syndrome.
 This paper presents an overview of the methods and progress of the groups centered at Yale University and Erasmus University in excluding linkage from a large portion of the genome.
 Our labs have screened 228 genetic marker loci for linkage with a gene for this disorder in a series of affected families in the United States, Canada, The Netherlands, and Norway.
 More than 50% (and perhaps as much as 66%) of the autosomal genome has now been excluded on the assumption that genetic heterogeneity is not an important factor in the Tourette syndrome pedigrees pooled for this summary.
",9
1488,"Molecular genetic basis of maple syrup urine disease in a family with two defective alleles for branched chain acyltransferase and localization of the gene to human chromosome 1.
 Maple syrup urine disease in humans results from inherited defects in branched chain alpha-ketoacid dehydrogenase, a mitochondrial multienzyme complex.
 A variety of genetic changes may produce this phenotype by affecting the function of any of the three complex-specific subunits.
 The varied clinical expression observed in patients may be partially explained by the defects in the involved subunit.
 Here we report localization of the gene for the branched chain acyltransferase component of the complex to human chromosome 1 and describe a proband who is a compound heterozygote at this locus.
 One allele, inherited from the father, produces transcripts with 124 nucleotides deleted from the coding region.
 The deletion is not found in the branched chain acyltransferase gene, implying that the deleted transcripts arise by an error in transcript processing.
 Cells from the patient's mother contain 50% of the normal amount of mRNA for the subunit, and the proband has inherited this nonexpressing allele from her.
 As a result, the proband produces no acyltransferase protein and therefore has greatly impaired complex activity.
 A phenotypically normal sibling is shown to be genetically similar to the mother having inherited the mother's nonexpressing allele and the father's normal allele.
",9
1489,"Tay-Sachs disease in Moroccan Jews: deletion of a phenylalanine in the alpha-subunit of beta-hexosaminidase.
 Tay-Sachs disease is an inherited lysosomal storage disorder caused by defects in the beta-hexosaminidase alpha-subunit gene.
 The carrier frequency for Tay-Sachs disease is significantly elevated in both the Ashkenazi Jewish and Moroccan Jewish populations but not in other Jewish groups.
 We have found that the mutations underlying Tay-Sachs disease in Ashkenazi and Moroccan Jews are different.
 Analysis of a Moroccan Jewish Tay-Sachs patient had revealed an in-frame deletion (delta F) of one of the two adjacent phenylalanine codons that are present at positions 304 and 305 in the alpha-subunit sequence.
 The mutation impairs the subunit assembly of beta-hexosaminidase A, resulting in an absence of enzyme activity.
 The Moroccan patient was found also to carry, in the other alpha-subunit allele, a different, and as yet unidentified, mutation which causes a deficit of mRNA.
 Analysis of obligate carriers from six unrelated Moroccan Jewish families showed that three harbor the delta F mutation, raising the possibility that this defect may be a prevalent mutation in this ethnic group.
",9
1490,"Propofol infusion for control of status epilepticus.
 Two patients with status epilepticus who were resistant to conventional treatment but responded to propofol infusions are reported.
 An electroencephalogram confirmed the seizures and their successful treatment.
",9
1491,"32-gauge spinal catheters through 26-gauge needles 
 Small diameter intrathecal catheters potentially combine the certainty of intrathecal injection and the advantage of repeatability, without the risk of a high incidence of headache after dural puncture.
 We report problems placing such catheters.
",9
1492,"Paraesthesia with lumbar epidural catheters. A comparison of air and saline in a loss-of-resistance technique.
 The epidural space was located in 32 obstetric patients using loss of resistance to air, while in a further 35 saline was used.
 The incidence of paraesthesia was 56% in the air group and 57% in the saline group.
 There was no significant difference between the groups in terms of other complications or in the quality of analgesia provided.
",9
1493,"Telephone use to elicit voice or speech in brain injured subjects.
 The initiation of speech is often delayed in the early stages of recovery from a serious brain injury.
 We have found a high percentage of patients with both speech and swallowing problems.
 This makes bedside assessment of swallowing safety difficult because one cannot listen for the sound of aspirated material on the vocal cords when a patient is at high risk for silent aspiration and is often unable to cooperate with a videofluoroscopic study.
 The use of the telephone has been described several times for aphasia treatment, but not to elicit speech or assess swallowing safety early after brain injury.
 This study, therefore, recruited subjects who had brain injuries and (1) were referred early for swallowing and other evaluations, (2) were out of coma and able to follow some commands, and (3) did not initiate voice or speak when asked to.
 Subjects were asked three questions under two different conditions: face to face and after ringing the telephone from another room.
 The results were recorded on videotape and analyzed by another investigator for quantifiable differences.
 Six of the seven subjects responded better with the telephone stimulus than without.
 This technique may elicit voice or speech early after brain injury in some patients and may be useful in bedside assessment of swallowing safety.
 It may also serve as an example of appropriate stimulation of brain injured subjects coming out of coma.
",9
1494,"The disabled driver: an unmet challenge.
 A survey was undertaken to determine if driving impairment secondary to a disabling injury is addressed in state licensing laws and training programs.
 In 35 states drivers submit voluntarily to reevaluation after disabling injuries, but no provision is made for reporting such individuals.
 Only 15 states authorize physicians to report impaired drivers, and only seven require such reporting.
 Based on a survey of licensing bureaus in the capital or a major city of every state, clerks (who are likely to be the source of information to injured persons) are generally not aware of reporting requirements and supervisors are only slightly better informed.
 Of the 100 rehabilitation centers surveyed, only 36 provided on-site training for disabled drivers.
 Voluntary submission for reevaluation after head injury does not often occur.
 Despite being asked to do so, none of the 35 head injured patients, followed up to two years post-onset, sought reevaluation, although 21 had resumed regular driving.
 Two of the 21 were involved in subsequent traffic accidents.
 Common guidelines need to be established across states to ensure reevaluation of individuals with disabling conditions, delivery of accurate information concerning licensing, and availability of training programs.
",9
1495,"Costs of operating a supported work program for traumatically brain-injured individuals.
 This paper presents a preliminary analysis of costs associated with a return-to-work program emphasizing a supported employment approach for persons who had sustained severe traumatic brain injuries.
 This analysis spans almost three years.
 Results indicated that a mean of 237.8 hours of staff intervention time was required to achieve job stabilization, at a cost of +6896.
 Ongoing follow-along and support services averaged 1.64 hours per week at a cost of +47.56.
 Over 68% of total staff time and costs were expended in job-site training and advocacy efforts.
 Application of these findings to state-level and agency-level policies should be weighed against individual characteristics and needs of clients, program design, and outcomes which clients achieve as a result of services.
",9
1496,"Reversible nerve conduction block in patients with polyneuropathy after ultrasound thermotherapy at therapeutic dosage.
 This study investigated the effect of ultrasound on nerve conduction in patients with polyneuropathy.
 Eight able-bodied controls (Group C) and 16 patients with clinical and physiologic evidence of polyneuropathy were tested.
 Eight patients (Group NP) had no aching pain symptoms; eight patients (Group P) had severe aching pain, burning sensation, unpleasant tingling, and/or hyperesthesia in the lower extremities.
 For two minutes, therapeutic ultrasound in doses of 0.5, 1.0, and 1.5W/cm2 were applied over the anterior surface of the leg along the pathway of the deep peroneal nerve.
 Peroneal nerve conduction studies were performed before, during, and after ultrasound treatment.
 The compound muscle action potential (CMAP) was recorded from the extensor digitorum brevis muscle.
 Nerve conduction studies on all eight patients in Group P revealed a significant decrease (41.4% and 44% reduced for doses of 1.0W/cm2 and 1.5W/cm2, respectively; p less than .05) in amplitude of CMAP (from baseline to the first negative peak), and an increase (6.4% and 6.7% increased for doses of 1.0W/cm2 and 1.5W/cm2, respectively; p less than .05) in proximal latency one minute after ultrasound application with a dose of 1.0 or 1.5W/cm2, but not with a dose of 0.5W/cm2 (p greater than 0.1).
 Changes returned to pretreatment values within five minutes of cessation of ultrasound therapy.
 In Groups C and NP, there were no significant changes in amplitudes of CMAP or proximal latency before, during, or after ultrasound therapy at a dose of 0.5, 1.0, or 1.5W/cm2.
 It was concluded that ultrasonic therapy with therapeutic dosage may cause a reversible conduction block on patients with painful polyneuropathy.
",9
1497,"Goal attainment scaling and outcome measurement in postacute brain injury rehabilitation.
 Relationships among two-month and final goal attainment scaling (GAS) scores, preadmission and final Portland Adaptability Inventory (PAI) scores, and work outcome for 16 graduates of a comprehensive, postacute brain injury rehabilitation program were examined.
 Final GAS scores were higher for program graduates who obtained the most desirable work outcomes, and preadmission and final PAI scores were lower for the successful program graduates.
 Final GAS scores were significantly correlated with other outcome measures.
 Preadmission PAI scores predicted work outcome, and two-month GAS scores predicted final GAS scores.
 Initial PAI scores distinguished between program successes and failures, but not between program successes and dropouts.
 A brief look at one case illustrates the modified application of GAS in postacute brain injury rehabilitation.
 Results of this study and case analyses support GAS as a quantifiable, individualized measure that is useful for (1) monitoring patient progress, (2) structuring team conferences, (3) ongoing rehabilitation planning and decision-making, (4) concise, relevant communication to family, referral sources, and funding sources, and (5) overall program evaluation when used in the context of other objective outcome measures.
 Although our results support the clinical utility of GAS, further study is recommended to assess the psychometric characteristics of GAS in this application.
",9
1498,"Factors predicting satisfactory home care after stroke.
 This study prospectively investigated factors predicting optimal poststroke home care.
 One hundred and thirty-five first occurrence stroke patients and their primary support persons were evaluated during the initial hospitalization after stroke and again one year poststroke.
 Discriminant function analysis was used to identify two groups from the baseline data: home care situations which were rated optimal and those which were not.
 Group membership was predicted and validated with 72.6% accuracy.
 Patients at risk for less than optimal home care had caregivers who were (1) more likely to be depressed, (2) less likely to be married to the patient, (3) below average in knowledge about stroke care, and (4) reporting more family dysfunction.
 Our findings suggest that caregiver-related problems can have a collective effect on rehabilitation outcome and that treatment should reduce caregiver depression, minimize family dysfunction, and increase the family's knowledge about stroke care.
",9
1499,"Visual illusions in a patient with lateral medullary syndrome.
 The disturbance of visual perception associated with nystagmus is a rare phenomenon.
 This is a case of a 61-year-old woman who developed progressive right hemisensory deficit, left facial sensory deficit, vertigo, staggering to the left, left ptosis, vertical diplopia, and ataxia of the left upper extremity.
 She had rotatory nystagmus in primary position, which increased in amplitude with left gaze.
 The above signs and symptoms were consistent with lateral medullary syndrome.
 During her rehabilitation, the patient complained of visual disturbances typical of oscillopsia.
 These disturbances, or illusions, are compensatory mechanisms for nystagmus and its resultant retinal error.
 The purpose of this case presentation was to study the pathophysiology underlying oscillopsia in patients with nystagmus and to stimulate awareness of such visual disturbances in stroke patients.
",9
1500,"Higher incidence of carpal tunnel syndrome in oophorectomized women.
 To determine whether the hormonal changes of the menopause are related to the onset of carpal tunnel syndrome (CTS), 53 healthy women, younger than 44 years, and subjected to bilateral oophorectomy between 1 and 4 years before the study, were evaluated.
 Seventy healthy menstruating women matched for age were used as controls.
 In those complaining of symptoms and presenting signs suggestive of CTS, sensory and motor nerve conduction studies were done.
 In the oophorectomized group, 17 of 53 (32%) had clinical CTS, while only seven of 70 of the control group (10%) did so (relative risk for the oophorectomized group = 4.25; 95% confidence intervals 1.47 and 12.61).
 The nerve conduction studies were abnormal in 14 of 16 oophorectomized women (87.5%), and in only one of seven of the control group (14.2%; P less than 0.002).
 Symptoms tended to be milder in the controls.
 Symptoms developed in the first year after oophorectomy in 14 of the 17 women with CTS.
 This suggests that women develop CTS after oophorectomy more frequently than controls.
",9
1501,"Advances in the treatment of complex cerebrovascular disorders by interventional neurovascular techniques.
 Treatment of complex cerebrovascular disorders, including intracranial aneurysms, carotid cavernous sinus fistulas, vertebral fistulas, arteriovenous malformations, atherosclerosis of brachiocephalic vessels, and arterial vasospasm, is being performed in selected cases by interventional neurovascular techniques.
 Recent advances in microballoon technology, permanent solidifying polymers, newer embolic agents, high-resolution digital subtraction angiography with road-mapping technique, and steerable micro-guide wires and catheters have greatly improved access in the distal intracranial circulation and markedly reduced the morbidity associated with these procedures.
 Interventional neuroradiology is emerging as an important adjunct to neurosurgery for selected cerebrovascular disorders.
",9
1502,"Antiepileptic drugs, cognitive function, and behavior in children: evidence from recent studies.
 The effects of antiepileptic drugs (AEDs) on cognitive function and behavior in children are reviewed on the basis of published studies.
 Individual AEDs have been shown to differ--the deleterious effects of phenytoin generally contrasting with the relatively minimal effects of valproate and carbamazepine.
 Some of the differences between results may be attributed to the psychological tests used and to age differences.
 However, there appears to be a dissociation between AEDs that affect higher cognitive function, e.g., phenytoin, and those mainly affecting motor function, e.g., carbamazepine, which appears to increase speed of performance, AEDs should be prescribed with care in children with epilepsy, taking account of their differing effects on cognitive function and behavior.
",9
1503,"Computerized neuropsychological assessment of cognitive functioning in children with epilepsy.
 The value of a range of computer-aided tests in the neuropsychological assessment was investigated in 94-177 children with epilepsy, aged 8-18 years, compared with 68-161 controls in the same age group.
 Children from the age of 8 years could cope with rather complex tests in a wide range of functions: reaction time measurements, motor speed, information processing, and memory.
 The speed of performance tended to increase with age in both groups, with differences in information processing becoming apparent from the age of 12 years.
 The precise control of stimulus and response required to define the mainly minor differences between the epilepsy and control groups can only be fulfilled by computerized testing, which should undergo further refinement including voice and language recognition, followed by artificial intelligence.
",9
1504,"Electroencephalographic parameters in assessing the cognitive function of children with epilepsy.
 Many biological and psychological possibilities have to be considered when attempting to explain cognitive dysfunction in the individual child with epilepsy.
 Electroencephalographic (EEG) information, which may be particularly relevant in some children, has mainly been studied in relation to the possible direct effects of seizure discharges on learning and behavior.
 Such discharges can be divided into transient, brief or prolonged.
 Prolonged seizure discharges includes nonconvulsive status epilepticus during wakefulness and status epilepticus during slow-wave sleep.
 In addition to the influence of seizure discharges, preliminary findings suggest that some children with epilepsy might have a subtle disorder of arousal mechanisms in sleep, possibly associated with impaired daytime performance.
",9
1505,"Discontinuation of antiepileptic drugs in children who have outgrown epilepsy: effects on cognitive function.
 Cognitive function is frequently impaired in children with epilepsy, compared with age-matched controls.
 It can be hard to evaluate the significance of various contributory factors.
 The effects of antiepileptic drugs may be studied in children who have outgrown their epilepsy but are still being treated.
 A multicenter study to assess various aspects of cognitive function in children with different forms of epilepsy, both during and after treatment with antiepileptic drugs, is currently under way.
 Definitive results are not yet available; interim analysis of the findings suggests that short-term memory is decreased in all subgroups of children being treated for epilepsy, compared to controls.
",9
1506,"MRI, CT, SPECT, PET: their use in diagnosing dementia.
 The differential diagnosis of the dementia syndrome may pose a difficult clinical problem, since the most common dementia, Alzheimer's disease (AD), is marked by normal laboratory tests.
 Neuroimaging has played an important role in evaluating the demented patient, and its uses are growing.
 Computed tomography (CT) is useful for excluding reversible and treatable causes of dementia, such as subdural hematoma and tumor.
 More recently, magnetic resonance imaging (MRI) has improved our ability to diagnose vascular disease and may show the presence of cerebral infarcts and white matter disease not visible on CT.
 Single photon emission computed tomography (SPECT) and positron emission tomography (PET), techniques that visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence supportive of the diagnosis of AD.
",9
1507,"Intravenous administration of phosphorylated acid alpha-glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice.
 The lysosomal storage disorder glycogenosis type II is caused by acid alpha-glucosidase deficiency.
 In this study we have investigated the possible applicability of mannose 6-phosphate receptor-mediated enzyme replacement therapy to correct the enzyme deficiency in the most affected tissues.
 Bovine testes acid alpha-glucosidase containing phosphorylated mannose residues was intravenously administered to mice and found to be taken up by heart (70% increase of activity) and skeletal muscle (43% increase); the major target organs.
 The uptake of nonphosphorylated human placenta acid alpha-glucosidase by heart and skeletal muscle appeared to be significantly less efficient, whereas uptake of dephosphorylated bovine testes enzyme was not detectable.
 The phosphorylated bovine testes acid alpha-glucosidase remained present in mouse skeletal muscle up to 9-15 d after administration, with a half-life of 2-4 d.
 Besides being measured in skeletal muscle and heart, uptake of phosphorylated bovine testes and nonphosphorylated human placenta acid alpha-glucosidase was measured in several other organs, but not in brain.
 The increase of acid alpha-glucosidase activity was highest in liver and spleen.
 We concluded that application of mannose 6-phosphate receptor-mediated enzyme replacement therapy may offer new perspectives for treatment of glycogenesis type II.
",9
1508,"The timed ""Up & Go"": a test of basic functional mobility for frail elderly persons.
 This study evaluated a modified, timed version of the ""Get-Up and Go"" Test (Mathias et al, 1986) in 60 patients referred to a Geriatric Day Hospital (mean age 79.5 years).
 The patient is observed and timed while he rises from an arm chair, walks 3 meters, turns, walks back, and sits down again.
 The results indicate that the time score is (1) reliable (inter-rater and intra-rater); (2) correlates well with log-transformed scores on the Berg Balance Scale (r = -0.81), gait speed (r = -0.61) and Barthel Index of ADL (r = -0.78); and (3) appears to predict the patient's ability to go outside alone safely.
 These data suggest that the timed ""Up & Go"" test is a reliable and valid test for quantifying functional mobility that may also be useful in following clinical change over time.
 The test is quick, requires no special equipment or training, and is easily included as part of the routine medical examination.
",9
1509,"Mini-Mental State exam scores vary with education in blacks and whites.
 Previous studies have suggested that education and race may affect performance on standardized mental status tests.
 In order to more clearly define these relationships, a prospective longitudinal study was devised to answer two questions: (1) whether race or level of education affects scores on the Mini-Mental State (MMS) exam in non-demented people and (2) what numerical cutpoints maximize the sensitivity and specificity of utilizing the MMS to help diagnose dementia in blacks of varying educational attainment.
 A total of 100 white and 258 black individuals, recruited from two city hospital primary care geriatric clinics, were evaluated and subsequently followed longitudinally over a 2 1/2 year period in order to assess accurately the presence or absence of dementia.
 In the non-demented, total MMS scores and performance on each item of the MMS were analyzed, revealing that people with an 8th grade or less education consistently had significantly (P less than .01) worse results than the better educated (9th grade or better) on borough, attention items, recall of table and dog, copying, sentence writing, phrase repeating, and total score.
 Furthermore, a total of 25% of the lower education group had an MMS score in the 18-23 range, traditionally thought to suggest dementia.
 There were no consistently significant differences between blacks and whites of equal education.
 In the better educated groups, using a score of 23 or less to define dementia maximizes the sensitivity and specificity of using the MMS in this diagnosis at 93% and 100%, respectively.
 In the lower education group, using 17 or less to define dementia maximizes sensitivity and specificity at 81% and 100%, respectively.
",9
1510,"Physician practices in the diagnosis of dementing disorders.
 Because there are both treatable and untreatable causes of dementia, the physician's ability to conduct (or refer a patient for) a differential diagnosis could have a profound effect on health outcomes for patients and on health care costs.
 This study was undertaken to assess physician practices with regard to the diagnosis of dementing disorders.
 Data from 53 physicians (a response rate of 48%) in several specialties were obtained from a self-administered mail questionnaire.
 Results indicate that the majority of physicians provided history taking, physical examination, and neurological examination.
 Physicians were more likely to refer patients for psychiatric and neuropsychological examinations than to provide these services themselves.
 The results also point to deficiencies in two key areas: the use of formal, published diagnostic criteria, and the use of mental status and cognitive function tests.
 Over 75% of physicians surveyed did not use either DSM-III or NINCDS-ADRDA diagnostic criteria, and 42% of physicians did not provide any mental status tests themselves.
 The need for continuing education to close knowledge gaps is emphasized.
",9
1511,"Localization of technetium-99m-glucarate in zones of acute cerebral injury.
 The potential structural similarity of technetium-99m-labeled glucaric acid (99mTc-glucarate) to that of fructose suggests that this agent may enter cells by a sugar transport system.
 Studies with LLC-PK1 cells demonstrated inhibition of 99mTc-glucarate uptake by fructose, confirming this potential relationship.
 Since anaerobic metabolism can use either glucose or fructose, we hypothesized that 99mTc-glucarate may concentrate in areas of acute ischemic injury.
 To test this hypothesis, 63 adult rats with middle cerebral artery (MCA) occlusion followed by reperfusion were injected with 99mTc-glucarate and in vivo and ex vivo images were acquired.
 Seven animals were also studied with 18FDG and high resolution PET imaging.
 The radionuclide images were compared to the results of triphenyl tetrazolium chloride (TTC) staining and conventional histopathology.
 Thirty-five rats had significant accumulation of 99mTc-glucarate and no TTC staining (indicating infarction) in the involved hemisphere.
 Of the remaining 28 rats with TTC staining (suggesting viability) of the involved hemisphere, 16 (57%) had 99mTc-glucarate accumulation.
 In the seven rats that were studied with both 99mTc-glucarate and 18FDG, 99mTc-glucarate accumulated at the center of the occluded MCA territory while 18FDG activity was decreased in this region.
 These results suggest that 99mTc-glucarate is a sensitive marker of acute severe cerebral injury, but its mechanism of localization is probably different from that of 18FDG.
",9
1512,"Meralgia paresthetica after coronary bypass surgery.
 Meralgia paresthetica is a neurologic disorder characterized by localized paresthesia and numbness on the anterolateral aspect of the thigh and involving the lateral femoral cutaneous nerve.
 It involves no motor deficits.
 Meralgia paresthetica, which may result from a variety of causes, has been observed as a rare complication in heart operations.
 Its cause when associated with such operations is uncertain but may be prolonged relaxed positioning on the operating table and recovery room stretcher.
 Another possible cause of meralgia paresthetica after heart operations is the ""frog-leg"" position of the legs during vein harvesting.
 Patients with this condition should be advised of its untreatable, but benign and self-limiting, nature.
",9
1513,"Neurofibromatosis type 2: report of a family and review of current evaluation and treatment.
 Significant advances during the past decade have greatly improved our understanding of neurofibromatosis type 2, a genetic disease which results in bilateral acoustic neuromas.
 The emergence of gadolinium-enhanced magnetic resonance imaging has allowed early detection of minute intracanalicular eighth-nerve tumors, less than 1 cm in diameter.
 Recombinant DNA studies have clarified the genetics that underlie neurofibromatosis type 2 and separate it from a variety of related conditions, such as von Recklinghausen's neurofibromatosis.
 Early diagnosis and surgical removal of these tumors may offer the only hope of preserving hearing and facial nerve function.
 A report of the evaluation and treatment of a family with multiple affected individuals will exemplify these conclusions.
",9
1514,"Reversible myeloneuropathy of nitrous oxide abuse: serial electrophysiological studies.
 Detailed electrophysiological studies were performed in 4 patients with myeloneuropathy induced by abuse of nitrous oxide for 1 to 4 years.
 All presented with paresthesias, weakness, and Lhermitte's phenomena, and exhibited signs of sensorimotor polyneuropathy, ataxia, and arreflexia.
 Two had subnormal serum vitamin B12 levels.
 Baseline electrophysiologic testing revealed reduced motor unit potentials, prolonged F wave latencies, absent H reflexes, denervation potentials, and delays in motor and sensory conduction.
 Three had peripheral and nuchal delay after median nerve stimulation.
 All were reevaluated after 3 to 12 months' abstinence and treatment with vitamin B12, and all showed substantial clinical improvement.
 Parallel improvement in electrophysiologic findings occurred, but residual minor conduction delays, loss of H reflexes, electromyographic evidence of denervation, or abnormalities of posterior tibial SEP were noted.
 These findings confirm the reversibility of myeloneuropathy of nitrous oxide abuse and describe the profile of electrophysiologic recovery in subjects who abstain from further neurotoxic exposure.
",9
1515,"Nerve-muscle involvement in a large family with mitochondrial cytopathy: electrophysiological studies.
 Thirteen patients with mitochondrial cytopathy were investigated.
 They represent different generations, ages, stages, and severities of the disease.
 All were assumed to have the same metabolic defect.
 The disease is a multisystem disorder with a metabolic defect located at complex 1 in the respiratory chain.
 Clinically, the disorder gives symptoms such as hearing loss, retinal pigmental degeneration, ataxia, cardiomyopathy, muscular fatiguability and neuropathy.
 The patients were investigated with nerve conduction studies, concentric needle EMG, SFEMG, and macro EMG examinations.
 Neurophysiologic studies revealed signs of myopathy in both the younger members and in those with slight muscular symptoms.
 In the more advanced stages, neuropathic changes of the axonal type were seen as well.
 Macro EMG was interpreted as indicating muscle fiber membrane abnormalities in the early stages.
 Single fiber EMG studies indicate that this metabolic defect does not disturb neuromuscular transmission.
",9
1516,"Diagnostic and prognostic value of electrophysiologic tests in meralgia paresthetica.
 Electrophysiologic diagnosis of unilateral meralgia paresthetica is usually assessed by side-to-side comparison of SNAP amplitudes, SNCVs, and SEP latencies following stimulation of lateral femoral cutaneous nerves.
 To determine the relevance for diagnosis of these tests and side-to-side comparison, the results were compared in patients with unilateral meralgia paresthetica and normal subjects.
 The long-term outcome was also considered, in order to determine whether electrophysiologic findings contribute to the prognosis.
 In our study, SNAP amplitude comparison was found to be more useful for diagnosis than SNCV and SEP latency comparisons.
 However the value of the SNAP amplitude on the affected side, just as the results of the other tests, was not found to be predictive of the outcome.
 Also the results of the tests depend on the methods used and on the nerve's route.
",9
1517,"Effects of short spaceflights on mechanical characteristics of rat muscles.
 The aim of this study was to investigate the contractile protein characteristics after 5-day (Cosmos 1514) and 7-day (Cosmos 1667) spaceflights.
 The experiments were performed on skinned fibers from the soleus, gastrocnemius lateralis, and plantaris muscles isolated from Wistar rats.
 A reduction in fiber diameter might explain the decrease in the maximal tension in the soleus, whereas this tension was unaltered in the gastrocnemius and the plantaris.
 Moreover the calcium sensitivity of the myofilament appeared modified in the soleus and in the gastrocnemius: The tension/pCa relationships were shifted toward higher calcium concentrations, indicating a decrease in the apparent calcium binding constant of the troponin C.
 The tension/pCa relationship appeared unaltered in the plantaris after spaceflight.
 Finally, the studies of the time to reach a steady tension indicated an increase in the rate of force development in the soleus and, on the contrary, a slowing down in the plantaris.
 No change in the gastrocnemius was found.
 The results were analyzed with references to the different muscle functions in disuse atrophy.
",9
1518,"Patient perception of tics and other movement disorders.
 To determine the subjective perception patients have of abnormal movements, 170 patients with various hyperkinesias were interviewed with questions directed at the ""voluntary"" or intentional versus ""involuntary"" aspects of their symptoms.
 One hundred and two of 110 patients with non-tic disorders thought that the abnormal movements were entirely involuntary.
 Forty-one of 60 tic disorder patients stated that all their motor and phonic tics were intentionally produced.
 Fifteen others had both voluntary and involuntary components, usually with the former predominating.
 A ""voluntary"" response could be used to predict the correct diagnostic category (tic versus non-tic) in 8 of 9 patients for whom the referral category was incorrect.
 These results suggest that a large proportion of the motor and phonic symptoms experienced by tic patients are irresistibly but purposefully executed, more akin to compulsions than to the other ""involuntary"" hyperkinesias with which they are commonly discussed.
",9
1519,"Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study.
 To identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls.
 Ninety percent of the IIH patients were women; the mean age was 33.
 Obesity and recent weight gain were much more common among patients than controls.
 Symptoms most commonly reported by IIH patients were headache (94%), transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%).
 Daily occurrence of these symptoms was much more common among patients than controls.
 Controls also reported these and other IIH symptoms, but at lower frequencies.
 Several conditions previously associated with IIH were no more common in patients than controls including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives.
 We conclude that previous studies of IIH, mostly uncontrolled and retrospective, have underestimated the frequency of symptoms in IIH patients and reported chance and spurious associations with common medical conditions and medications.
 The profile of a young obese woman with headaches and either TVO or ICN should alert the clinician to the diagnosis of IIH, especially when the symptoms occur daily.
",9
1520,"Infarction in the anterior rostral cerebellum (the territory of the lateral branch of the superior cerebellar artery).
 We report 9 patients with an isolated infarct of the anterior part of the rostral cerebellum, ie, the territory of the lateral branch of the superior cerebellar artery.
 Clinicoanatomic correlations are based on CT, MRI, or both in 8 patients and on pathologic data in the ninth.
 The main clinical features were ipsilateral dysmetria and axial lateropulsion, dysarthria, and unsteadiness.
 In 1 patient, the clinical presentation mimicked a lacunar stroke (dysarthria and clumsy hand syndrome).
 There were no edematous cerebellar infarcts with signs of brainstem compression, and all patients spontaneously improved without significant sequellae.
 Angiography in 2 patients and pathologic examination of arteries in 1 patient disclosed no occlusion in the vertebrobasilar system.
 Six patients had a cardiac source of emboli.
 In conclusion, infarcts of the anterior part of the rostral cerebellum can be regarded as a benign condition in which there is, frequently, a cardiac source of emboli.
",9
1521,"Comparison of functional and structural brain disturbances in Wilson's disease.
 We assessed the functional and structural brain disturbances in Wilson's disease (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI).
 All the 25 neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or brain atrophy.
 Our findings indicate that EPs and MRI are sensitive techniques for the evaluation of brain involvement in WD.
",9
1522,"Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy.
 We examined variations in interictal spiking during sleep and wakefulness to assess differences in reliability for localizing epileptic foci.
 Forty patients were studied prospectively.
 Spikes were assessed for rates, field, and appearance of new foci.
 Final localization was determined by surgery, electrocorticography, and seizure onset.
 Comparison of interictal EEG foci with final localization was made.
 In 39 patients, slow-wave sleep activated spiking compared with wakefulness.
 Most patients showed maximal spiking in sleep stages 3 or 4.
 Restriction of field in rapid eye movement (REM) sleep and wakefulness, and extension of field in slow-wave sleep occurred.
 New foci appeared in non-rapid eye movement sleep in 53% of patients.
 Similar but not identical spiking rates, foci, and field distributions were seen in wakefulness and REM sleep.
 All REM foci were unilateral.
 Our findings suggest that localization of the primary epileptogenic area is more reliable in REM sleep than in wakefulness, and in wakefulness more than in slow-wave sleep.
",9
1523,"Phenytoin toxicity due to interaction with clobazam.
 The benzodiazepine antiepileptic drug clobazam can be added to existing AED treatment, usually without clinical toxicity.
 We report 3 patients in whom the addition of clobazam led within several weeks to clinically obvious phenytoin (PHT) intoxication in patients who had been taking maximum tolerable PHT doses.
 Symptoms and high PHT levels resolved with lowering the PHT dose.
 Clobazam and norclobazam levels were not elevated.
 This interaction is probably related to interference with hepatic degradation of PHT.
 Clinicians should be aware of possible PHT intoxication in patients starting clobazam.
",9
1524,"Prediction of free phenytoin levels based on [total phenytoin]/[albumin] ratios. Potential errors with hypoalbuminemia.
 Therapeutic monitoring of the pharmacologically active (free drug) fraction of protein-bound medications (e.g., phenytoin) represents a major diagnostic challenge in clinical and laboratory medicine.
 While free drug levels may be beneficial in many clinical situations, current methods for predicting free phenytoin concentrations are unreliable and not recommended for general use.
 The authors have demonstrated a linear relationship (r2 = 0.98) between serum levels of total and bound phenytoin in 56 patients with seizure disorders.
 No significant correlations were observed when total phenytoin and albumin levels were compared independently to measured concentrations of free phenytoin or percent free phenytoin.
 A good correlation (r2 = 0.89) existed between free phenytoin levels and [total phenytoin]/[albumin] ratios in patients with normal or elevated albumin levels, but significantly weaker correlations were found in patients with hypoalbuminemia.
 Thus, [total phenytoin]/[albumin] ratios may have clinical value in predicting free phenytoin levels in uncomplicated patients without hypoalbuminemia.
",9
1525,"A critical appraisal of mitogen-induced lymphocyte proliferation in depressed patients.
 OBJECTIVE: The authors' goal was to evaluate the utility of mitogen-induced lymphocyte proliferation assays in clinical research in psychoimmunology.
 METHOD: They examined 23 depressed patients and 23 matched comparison subjects with this assay.
 There were no significant differences between these groups.
 They then combined the results of this study with the results of their previous study of 20 depressed patients and 20 comparison subjects to examine possible determinants of lymphocyte proliferation in depression.
 RESULTS: Depressed patients with lower proliferative responses than their matched comparison subjects had lower depression subscale, anergia subscale, and total scores on the Brief Psychiatric Rating Scale than did patients with higher proliferative responses than their matched comparison subjects.
 This finding was unexpected and unexplained.
 Depressed patients with lower proliferative responses than their matched comparison subjects also had fewer obsessions and compulsions and less psychomotor agitation according to the Schedule for Affective Disorders and Schizophrenia interview than did patients with higher proliferative responses than their matched comparison subjects.
 Stepwise discriminant analysis and cluster analysis contributed little further understanding of the determinants of in vitro lymphocyte proliferation of cells from depressed patients.
 CONCLUSIONS: Longitudinal studies using multiple serial determinations of mitogen-induced lymphocyte proliferation are the minimal design needed to make this assay useful in further evaluating any immune system changes in depression.
",9
1526,"Depressive symptoms following stroke.
 OBJECTIVE: The primary purpose of this study was to assess the relation of lesion location to mood and vegetative disturbance following stroke.
 METHOD: Fifty-two inpatients and outpatients who had had single, unilateral strokes were included.
 Patients with past CNS or psychiatric disorders were excluded.
 A modified Visual Analogue Dysphoria Scale was used to allow the inclusion of all but the most impaired aphasic patients.
 Sleep and eating disturbances were measured by using both self-report and nursing assessments.
 Location of lesions was determined by CT scan and classified according to three dimensions: right-left, dorsal-ventral, and frontal-nonfrontal.
 RESULTS: On measures of dysphoric mood and sleep disturbance, results indicated significant three-way interactions among the three lesion dimensions.
 No differences were found with regard to eating disturbance.
 Greater dysphoria and sleep disturbance were found in subjects with left parietal/occipital, left inferior frontal, right superior frontal, and right temporal lesions than in subjects with lesions in other locations.
 Depressive symptoms were not associated with functional impairment as measured by activities of daily living, motor strength, or severity of aphasia.
 CONCLUSIONS: These results support the hypothesis that lesion location is a valid and significant factor in the mixture of influences which may result in a dysphoric mood state following stroke.
 The relation between the site of the lesion and subsequent depressive symptoms, however, may be more complex than has been reported previously.
",9
1527,"The nature and course of olfactory deficits in Alzheimer's disease.
 OBJECTIVE: The aim of this study was to determine the specific nature and course of olfactory deficits in Alzheimer's disease.
 Previous studies had noted impaired odor identification, but there was no unanimity about the presence of odor detection deficits.
 METHOD: Odor identification was tested in 55 patients with Alzheimer's disease and 57 elderly control subjects by using the University of Pennsylvania Smell Identification Test.
 Odor detection was assessed in 46 subjects with Alzheimer's disease and 40 control subjects by using a forced-choice threshold test with geraniol as the odorant.
 RESULTS: Significant deficits in olfactory identification were present in subjects who were in the earliest stages of cognitive impairment, and these deficits increased as Alzheimer's disease progressed.
 There was some overlap in individual smell identification test scores between cognitively impaired patients and normal elderly subjects.
 On the other hand, odor detection deficits did not appear until Alzheimer's disease was relatively advanced.
 Smell identification test scores were correlated with Mini-Mental State scores, but geraniol detection was not.
 CONCLUSIONS: Odor identification is impaired early in Alzheimer's disease and may be more influenced by cognitive status than is acuity of odor detection, which is not altered until later in the disorder.
 The pattern of hyposmia in Alzheimer's disease suggests that the disorder may not ""begin in the nose,"" as has been theorized previously.
 Further refinement of olfactory testing may be useful in the diagnostic evaluation of early dementia.
",9
1528,"Nonfearful panic disorder in neurology patients validated by lactate challenge.
 OBJECTIVE: Nonfearful panic disorder meets the DSM-III-R criteria for panic disorder but is not associated with subjective fear and anxiety.
 The authors determined its prevalence in a group of neurology patients and assessed its diagnostic validity as a panic disorder subtype by evaluating the response of the patients with nonfearful panic disorder to sodium lactate and antipanic pharmacotherapy.
 METHOD: The subjects were all neurology patients referred over 1 year to a university hospital's psychiatric consultation service because of negative medical workups for their symptoms (N = 48).
 Patients who met the DSM-III-R criteria for panic disorder but did not report subjective anxiety or fear during panic episodes were diagnosed as having nonfearful panic disorder.
 Afterward, each of those patients received a sodium lactate infusion and, 5 hours later, a sodium chloride infusion.
 They were then treated with antipanic medication and followed for at least 6 months.
 RESULTS: Of the 48 neurology patients referred for psychiatric evaluation, 11 (23%) met the criteria for panic disorder, and all 11 met the criteria for nonfearful panic disorder.
 All 11 responded positively to lactate but not to placebo, and they each experienced an at least 75% reduction in symptoms during the 6-month follow-up period.
 Detailed case reports of three of these patients are presented.
 CONCLUSIONS: These findings support the construct and predictive diagnostic validity of nonfearful panic disorder as a subtype of panic disorder and suggest that a lack of attention to this group leads to both the underestimation of the prevalence of panic disorder and to the withholding of potentially successful treatments for this group.
",9
1529,"Organ procurement in patients with fatal head injuries. The fate of the potential donor.
 A 46-month, retrospective review of all victims of fatal head injury at a level 1 trauma center was undertaken to estimate donor organ availability, determine causes of procurement failure, and analyze the functional results of organs transplanted from this group of donors.
 Causes of procurement failure in 126 patients who died principally from their head injuries included failure of initial resuscitation (14%), ineligibility (28%), failure of physiologic support (14%), and denial of consent (20%).
 Of 73 eligible donors, 29 (41%) were able to donate one or more vascular organs (heart, liver, kidney).
 In only one instance was an eligible donor not appropriately identified as such.
 Failure of physiologic support to prevent early death (25%), and denial of consent (34%) were found to be the two major, potentially remediable causes of procurement failure in this series.
 Based on this data, an estimated 29 patients/million population/year will survive initially and meet all eligibility requirements for organ donation.
 Data on 47 kidneys transplanted from the donor group demonstrated a 77% overall graft survival rate at a follow-up period averaging 23 months.
 Prolonged donor hypotension, but not the use of high-dose vasopressors, adversely affected allograft survival.
 The current limitations of organ procurement in victims of fatal head injury stem from a limited ability to maintain cardiopulmonary function long enough for the procurement process to be completed and a high overall rate (46%) of denial of consent for organ harvest by next of kin.
",9
1530,"P300 brain activity in seizure patients preceding temporal lobectomy.
 Event-related potentials were recorded over occipital and parietal scalp from 20 patients suffering from intractable partial complex seizures prior to undergoing a temporal lobectomy.
 Subjects were presented with language and nonlanguage visual stimuli using a divided-field, ""odd-ball"" paradigm.
 Although behavioral performance (button-press accuracy, reaction time, and running counts) was comparable across all groups (although accuracy was worse for those in the left temporal group), patients showed tremendous variability in both the amplitude and latency of the P300 response.
 Particularly notable was the observation that more slow wave activity was present among the patients than among the control subjects, and those scheduled for a left temporal resection evinced more amplitude reduction than those scheduled for a right temporal resection.
 In addition, a number of patients appeared not to show a P300 response at all.
 These results are discussed in the context of the utility of using noninvasive event-related potential measures to examine both memory impairment and the integrity of the neural structures that mediate memory functioning in certain patient populations.
",9
1531,"Age at onset of Alzheimer's disease. Relation to language dysfunction.
 A later age at onset of Alzheimer's disease (AD) was found to be related to diminished language performance in 86 patients with probable AD.
 A hierarchical linear model was constructed to assess effects of age at onset and disease duration on the performance of patients with AD on four language tasks (naming, reading, auditory comprehension, and writing to dictation) after controlling for disease severity.
 Results of univariate analysis, in which the dependent variable was the averaged language task performances, revealed a significant effect for age at onset of AD, but not for disease duration.
 To assess the possibility that the relationship between the age at onset of AD and language performance reflects effects of normal aging, the language tasks were given to 33 normal subjects of similar ages who scored perfectly on dementia severity measures.
 A convincing relationship was not found between test score and age.
",9
1532,"The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography.
 A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4-iodobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls.
 High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IQNB.
 In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum.
 Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex.
 Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects.
 A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls.
 This study demonstrates the practicability of acetylcholine receptor imaging with 123IQNB and single photon emission computed tomography.
 The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.
",9
1533,"Widespread functional effects of discrete thalamic infarction.
 In order to investigate functional effects of various thalamic structures on metabolism in remote, morphologically intact cerebral regions, we used positron emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose to study regional cerebral metabolic rates of glucose (rCMRGlu) in 11 patients with chronic unilateral or bilateral infarcts strictly confined to the thalamus.
 Patients were grouped according to computed tomographic scans showing anterior (three), medial (four), or posterior (four) lesions.
 Compared with a matched group of 11 healthy subjects (hemispheric CMRGlu 35.2 +/- 3.49 mumol/100 g per minute), glucose metabolism was significantly lower in the hemisphere ipsilateral to the infarction (31.2 +/- 2.97 mumol/100 g per minute).
 Patients with bilateral infarcts had lower hemispheric CMRGlu (29.9 +/- 2.74 mumol/100 g per minute) than those with unilateral lesions (32.2 +/- 2.97 mumol/100 g per minute).
 Depending on infarct location within the thalamus, there was differential depression of rCMRGlu, with the largest effects on frontal and occipital areas in medial infarctions.
 Except for ipsilateral thalamic deactivation, metabolic patterns with anterior thalamic infarcts were close to normal, while posterior infarcts mostly depressed rCMRGlu in the visual and in the inferior limbic cortex.
 Cerebellar metabolic rates were within normal limits in most cases.
 These patterns of regional cerebral deactivation may be related to categories of thalamic projections--intrathalamic, to limbic system and basal ganglia, diffuse to most cortical areas, and specific to defined neocortical areas.
 Even small brain lesions may have widespread functional sequelae, potentially demonstrable by positron emission tomography.
",9
1534,"The effect of sleep on the dyskinetic movements of Parkinson's disease, Gilles de la Tourette syndrome, Huntington's disease, and torsion dystonia.
 The effect of sleep on the involuntary movements or dyskinesias in Parkinson's disease, Huntington's disease, primary and secondary torsion dystonia, and Gilles de la Tourette syndrome was studied in a total of 52 patients and 10 normal subjects using video electroencephalographic telemetry.
 Movements typical of the wake pattern were seen occasionally during unequivocal sleep in all but two completed studies, and in each condition reappeared under similar circumstances.
 The movements were most likely to occur after awakenings or lightenings of sleep, or in stage one sleep.
 The movements were very rare during the deeper phases of sleep.
 Those movements that occurred during sleep without awakenings were usually preceded by arousal phenomena and, rarely, by sleep spindles or slow waves.
 The control group showed normal ""semipurposeful"" movements under the same conditions during sleep.
 The rare appearance of the different dyskinesias and normal movements under similar circumstances during sleep could be a result of common effects on the generator systems or changes in the excitability of the final common motor pathway.
",9
1535,"Posttraumatic torticollis.
 We report six cases of torticollis precipitated by neck trauma.
 The dystonia began 1 to 4 days after the trauma and differed clinically from idiopathic torticollis by marked limitation of range of motion, lack of improvement after sleep (""honeymoon period""), and absence of geste antagonistique.
 Worsening with action was not present; nor was there improvement with support as seen with idiopathic torticollis.
 Onset of pain immediately after the trauma and marked spasms of the paracervical muscles were other predominant features.
 Anticholinergic therapy was without benefit; however, some improvement occurred with botulinum toxin injection.
 It is concluded that torticollis can be caused by peripheral trauma and that it has unique clinical characteristics.
",9
1536,"An early description of slowly progressive aphasia.
 Slowly progressive aphasia without generalized dementia has become an important issue of present-day neuropsychological research.
 Historically, credit for the first description is usually given to Pick.
 Another German-speaking author who has published a vivid description of a pertinent cases is Pick's contemporary, Max Rosenfeld.
 This author has also observed a patient with slowly progressive spatial disorientation and visual recognition deficit, and he has discussed these patients in a remarkably modern way in the context of partial atrophy of the brain.
",9
1537,"Frontal impairment and hypoperfusion in neuroacanthocytosis.
 Cerebral blood flow tomography, by xenon 133 inhalation or HMPAO (99mTc-d, l-hexamethyl-propylene amine oxime) technetium Tc 99m injection, revealed a severe hypoperfusion in both frontal lobes of a 40-year-old woman with confirmed neuroacanthocytosis.
 This finding occurred in conjunction with neuropsychological deficits consistent with selective frontal lobe dysfunction.
 This observation is the first documentation of this type of dementia in neuroacanthocytosis.
",9
1538,"Comparison of motor response to apomorphine and levodopa in Parkinson's disease.
 The magnitude and pattern of motor responses to single doses of subcutaneous apomorphine and oral levodopa were compared in 14 patients with Parkinson's disease.
 Although apomorphine produced much shorter motor responses than levodopa, the quality of response to the two drugs was virtually indistinguishable.
 These clinical observations support the notion that integrity of striatal post-synaptic dopamine receptors is a key determinant of responsiveness to dopaminergic treatment in Parkinson's disease.
",9
1539,"Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy.
 The effects of the addition of Vigabatrin, a new anti-epileptic drug, to the therapy of 128 patients with severe medically refractory epilepsy is reported.
 Forty two (33%) of patients experienced side effects, which were predominantly neurotropic.
 In 28 (22%), the drug was withdrawn because of these side effects.
 The commonest side effects were drowsiness and behavioural change.
 The remaining 100 patients were followed for a mean of 30 weeks (range 12-75).
 Forty one of these patients showed a marked improvement in seizure frequency (a 50% or more reduction when compared with the pre-trial period), and nine (7%) were rendered seizure free.
 Apparent tolerance to the effects of the drug were noted in five patients.
 An exacerbation of seizures may occur if the drug is withdrawn too quickly.
 Vigabatrin appears to be a promising new anti-epileptic drug.
",9
1540,"Diurnal differences in response to oral levodopa.
 Diurnal differences in duration and quality of motor response to levodopa are frequently described by patients.
 The quality and duration of motor responses were objectively assessed to morning and afternoon oral levodopa doses in five patients with Parkinsonian motor fluctuations who complained of diurnal variation in response to their normal levodopa medication.
 Results suggest that under controlled conditions which eliminated the effects of diet and overlapping levodopa effects the response to levodopa remained unchanged throughout the day, and that the duration of response could be predicted by plasma levodopa levels.
",9
1541,"The accuracy of predictions about progress of patients on a stroke unit.
 The aim of the study was to check the accuracy of predictions about the factors which affect the progress, in physical abilities and activities of daily living, of patients admitted to a stroke unit.
 A series of 60 patients admitted consecutively to a stroke unit were assessed on tests of motor, functional and cognitive abilities at admission.
 On the basis of these assessments predictions were made about the abilities of the patients at discharge.
 Patients were assessed for level of motor abilities and activities of daily living at discharge and the accuracy of the predictions checked.
 Predictions were found to be significantly correlated with outcome but the relationships were not so close as to be useful for the clinical management of individual patients.
",9
1542,"Shy-Drager syndrome. Effect of fludrocortisone and L-threo-3,4-dihydroxyphenylserine on the blood pressure and regional cerebral blood flow.
 In nine cases of Shy-Drager syndrome, the changes in blood pressure and cerebral blood flow on sitting up from a supine position were studied.
 The influence of fludrocortisone, a synthetic mineralocorticoid, and L-threo-3,4-dihydroxyphenylserine (DOPS), a precursor of norepinephrine, on these changes was examined.
 On sitting up, the regional cerebral blood flow (rCBF) measured by Xe133 inhalation showed a tendency to decrease.
 Fludrocortisone reduced the fall of the mean blood pressure significantly.
 DOPS reduced the fall of both the diastolic blood pressure and rCBF significantly.
",9
1543,"Functional outcomes following selective posterior rhizotomy in children with cerebral palsy.
 The recent increase in popularity of selective posterior rhizotomy demands objective documentation of surgical outcome.
 For this reason, the authors have analyzed the status of 25 children with spastic cerebral palsy before and after rhizotomy to determine the effects of this therapy on muscle tone, range of movement, and motor function.
 Postoperative tests showed a reduction in muscle tone compared with preoperative assessments.
 Range of motion in the lower extremities was significantly increased and improvements in functional gross motor skills were noted.
 An increase in range of motion in the knees and thighs during gait was detected in 18 ambulatory patients studied with computerized two-dimensional motion analysis.
 Preliminary findings indicate that selective posterior rhizotomy reduced spasticity, thereby increasing range of motion and contributing to improvements in active functional mobility.
",9
1544,"Spontaneous neuronal hyperactivity in the medial and intralaminar thalamic nuclei of patients with deafferentation pain.
 Electrical activity was recorded from single cells in the thalamus of 10 patients with chronic pain associated with deafferentation.
 Under local anesthesia, these patients underwent either electrode implantation or thalamotomy for treatment of their pain.
 In eight of the 10 patients, single units were identified as discharging spontaneously in high-frequency, often rhythmic, bursts.
 The discharges were of two types: short bursts comprised of two to six spikes with a burst frequency of one to four per second; and long trains of 30 to 80 spikes of similar frequency.
 Reconstruction of electrode trajectories indicated that recordings were made from the region corresponding to the lateral aspect of the mediodorsal thalamic nucleus, the central lateral nucleus, a small part of the central median nucleus, and the parafascicular nucleus.
 In the eight patients in whom spontaneous neuronal burst activity was exhibited, it was impossible to study activity evoked by natural cutaneous stimulation due to the continuous spontaneous neuronal discharges.
 Both animal and human studies have suggested that pain related to deafferentation is accompanied by spontaneous hyperactivity in the dorsal horn of the spinal cord and in the ventral posterior thalamic nuclei.
 The authors present evidence of spontaneous neuronal hyperactivity in the intralaminar thalamic nuclei of patients with pain related to deafferentation.
 The findings suggest that spontaneous neuronal discharge in patients with pain related to deafferentation is more widespread in the central nervous system than has been previously appreciated.
 The results have important implications for the surgical treatment of chronic pain.
",9
1545,"Relationship between body and brain temperature in traumatically brain-injured rodents.
 Recent work has shown that mild to moderate levels of hypothermia may profoundly reduce the histological and biochemical sequelae of cerebral ischemic injury.
 In the present study, the authors examined the effect of fluid-percussion injury on brain temperature in anesthetized rats and the effect of anesthesia on brain temperature in uninjured rats.
 The relationship between the brain, rectal, and temporalis muscle temperatures during normothermia, hypothermia, and hyperthermia was studied following a moderate magnitude of fluid-percussion brain injury (2.10 to 2.25 atmospheres) in rats.
 The results showed that mean brain temperature in 10 anesthetized injured rats, in 21 anesthetized uninjured rats, and in 10 unanesthetized uninjured rats was a mean (+/- standard error of the mean) of 36.04 degrees +/- 0.20 degrees C, 36.30 degrees +/- 0.08 degrees C, and 37.95 degrees +/- 0.09 degrees C, respectively.
 There was no significant difference in temperature under general anesthesia between injured and uninjured rats (p greater than 0.05).
 In the absence of brain injury, mean brain temperature was significantly lower in anesthetized rats than in unanesthetized rats (p less than 0.001).
 In anesthetized brain-injured rats, temporalis muscle temperature correlated well with brain temperature over a 30 degrees to 40 degrees C range, even when brain temperature was rapidly changed during induction of hypothermia or hyperthermia (r = 0.9986, p less than 0.0001).
 In contrast, rectal temperature varied inconsistently from brain temperature.
 These observations indicated that: 1) brain injury itself does not influence brain temperature in this model; 2) anesthesia alone decreases brain temperature to levels producing cerebral protection in this model; and 3) external monitoring of temporalis muscle temperature can provide a reliable indirect measure of brain temperature in the course of experimental brain injury.
 The authors believe that it is essential to monitor or control brain temperature in studies of experimental brain injury.
",9
1546,"Anticonvulsant and behavioral effects of two novel competitive N-methyl-D-aspartic acid receptor antagonists, CGP 37849 and CGP 39551, in the kindling model of epilepsy. Comparison with MK-801 and carbamazepine.
 The orally active competitive N-methyl-D-aspartate (NMDA) receptor antagonists CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid) and its ethyl ester CGP 39551 were evaluated in amygdala-kindled rats, a model for complex partial and secondarily generalized seizures.
 Anticonvulsant and behavioral effects of these novel compounds were compared with those of the noncompetitive NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e] and the antiepileptic drug carbamazepine, one of the major drugs for treatment of partial and generalized seizures in humans.
 For comparative evaluation, the compounds were injected i.p.
 at the following doses: 1 to 10 mg/kg (CGP 37849 or CGP 39551), 0.05 to 0.3 mg/kg (MK-801) and 20 to 40 mg/kg (carbamazepine), respectively.
 In contrast to carbamazepine, CGP 37849, CGP 39551 and MK-801 exerted only weak anticonvulsant effects in fully kindled rats and did not increase the focal seizure threshold.
 The weak anticonvulsant effects of the NMDA receptor antagonists in kindled rats were associated with profound untoward behavioral effects.
 The behavioral syndrome induced by the NMDA receptor antagonists in kindled rats was characterized by marked ataxia, hyperactivity and, in case of CGP 37849 and MK-801, stereotypies, such as head weaving.
 The low or absent effectiveness of the novel NMDA receptor antagonists against kindled seizures suggests that these compounds will not be clinically useful antiepileptics against partial and secondarily generalized seizures.
 Furthermore, in view of the recent clinical findings on psychotomimetic effects of MK-801 in epileptic patients, the similarities in the excitatory effects produced by CGP 39551, CGP 37849 and MK-801 in kindled rats may indicate that competitive NMDA receptor antagonists may also produce psychotomimetic effects in humans.
",9
1547,"Rediscovering tactile agnosia.
 Eighty-four patients with damage to various levels of the nervous system, ranging from the peripheral nerves to the cerebral cortex, underwent somesthetic assessment in order to determine the degree to which basic and complex perceptual and motor disorders affect tactile object recognition (TOR) and to determine whether TOR can be impaired in the absence of more basic sensorimotor imperception.
 The results suggest that (1) basic and intermediate disorders of somesthetic function impair TOR but are commensurately more severe for any given degree of TOR impairment in patients with peripheral lesions than in patients with cortical lesions; (2) neither hemiparesis nor hemianopia alone precludes normal TOR; (3) hemineglect contributes substantially to TOR impairment; (4) impairment of TOR can occur in the absence of more basic somesthetic dysfunction and constitutes tactile agnosia; (5) tactile agnosia is a subtle, nondisabling disorder that should be distinguished from the nonagnosic, severe and disabling disorder, astereognosis; and (6) tactile agnosia results from unilateral damage to parietotemporal cortices, possibly including the second somatosensory cortex, in either hemisphere.
",9
1548,"Monitoring of cortical blood flow during temporary arterial occlusion in aneurysm surgery by the thermal diffusion method.
 During aneurysm surgery, regional cortical blood flow (CoBF) was continuously monitored in 12 patients with a thermal diffusion flow probe in an attempt to assess the effects of temporary major arterial occlusion on blood flow and outcome.
 When the CoBF was above 30 ml/100 g/min, the safe period for temporary clipping applied distal to the perforators was 15 minutes.
 The occlusion time should be shortened when the CoBF is below 30 ml/100 g/min.
 Two patients suffered basal infarction, which was not detected by CoBF monitoring.
 Attention should be paid to the blood flow in the deep structures when a temporary clip is applied at a site proximal to the perforating branches.
 Direct measurement of CoBF may be of value in estimating the time that temporary occlusion of a major vessel can be tolerated.
",9
1549,"Chronic headache associated with a functioning shunt: usefulness of pressure monitoring.
 Chronic headaches in a shunt-dependent patient with small ventricles has long been treated with little or no regard to intracranial pressure.
 In this study, pressure monitoring on 12 such patients demonstrated that they fell into three distinct categories: 3 had headaches caused by intracranial hypertension, 2 had headaches from hypotension, and 7 showed no relation of symptoms to pressure.
 As therapeutic procedures for treating these three categories are entirely different and sometimes opposing, it is clear that intracranial pressure monitoring is essential to successful management of this complaint.
",9
1550,"Intracranial aneurysms: interventional neurovascular treatment with detachable balloons--results in 215 cases 
 Patients with complex or surgically difficult intracranial aneurysms are being treated with interventional neurovascular techniques.
 With neuroleptic anesthesia and a transfemoral femoral approach, a silicone micro-balloon can be flow directed through the intracranial circulation, guided directly into the aneurysm, and detached.
 The aneurysm is thus eliminated from the circulation, and the parent artery is preserved.
 For broad-based or ectatic aneurysms, test occlusion followed by permanent occlusion of the aneurysm and parent vessel can be performed.
 Since 1981, 211 patients with 215 aneurysms, including 177 cases involving the anterior and 38 cases involving the posterior circulation, have been treated with this technique.
 In 127 cases (59.1%), the parent vessel was occluded; in 88 cases (40.9%), primary occlusion of the aneurysm was achieved with preservation of the parent artery.
 Therapy-related complications included 21 deaths (9.8%) and 16 strokes (7.4%).
 Follow-up examinations were performed at 1, 3, and 12 months after treatment, and follow-up ranged from 5 months to 9 years.
 In patients in whom standard surgical therapy fails or for aneurysms in surgically inaccessible anatomic locations, interventional techniques that make use of detachable balloons may be a useful therapeutic alternative.
",9
1551,"Mapping the distribution of amobarbital sodium in the intracarotid Wada test by use of Tc-99m HMPAO with SPECT.
 The intracarotid amobarbital sodium, or Wada, test has been used to localize speech and memory function prior to surgical treatment of temporal lobe seizures.
 The authors mixed technetium-99m hexamethyl-propyleneamine oxime (HMPAO) with amobarbital sodium and injected the mixture in 25 patients with epilepsy.
 Single photon emission computed tomography (SPECT) of the brain was then performed to determine intracerebral distribution of the amobarbital sodium.
 Results of SPECT were compared with those of conventional and digital subtraction angiography (DSA).
 The distribution of Tc-99m HMPAO and, presumably, amobarbital sodium varied from patient to patient.
 SPECT revealed a statistically different distribution from that predicted with conventional angiography.
 The distribution also often differed from that of DSA, although the difference was not significant.
 SPECT revealed infrequent delivery to mesial temporal lobe structures.
 This emphasizes the need for caution in the use of the intracarotid amobarbital sodium test to predict the outcome of removal of these areas.
",9
1552,"Developmental dyslexia in women: neuropathological findings in three patients.
 Brains from male cases with dyslexia show symmetry of the planum temporale and predominantly left-sided cerebrocortical microdysgenesis.
 We now report on three women with dyslexia.
 In all brains, the planum temporale was again symmetrical.
 Also, in two of the brains, multiple foci of cerebrocortical glial scarring were present.
 In both women, many of the scars were myelinated, suggesting origination during late intrauterine or early postnatal life.
 In one, scars were mainly left perisylvian and involved portions of the vascular border zone of the temporal cortex.
 In the other, scars were more numerous and occurred in the border zone of the anterior, middle, and posterior cerebral arteries symmetrically.
 All three cases showed to a variable extent brain warts, molecular layer ectopias, and focal architectonic dysplasia identical to those seen in the male cases.
 Two women had primary brain neoplasms, an oligodendroglioma and a low-grade astrocytoma, respectively, and two women showed small angiomas.
 Reexamination of previously reported male cases disclosed one with myelinated glial scars.
 Two control brains with asymmetrical plana temporale showed myelinated glial scars as well.
 The significance of the anatomical findings is discussed, and possible etiological factors are considered with known effects of autoimmune diseases on the nervous system.
",9
1553,"Timing and topography of cerebral blood flow, aura, and headache during migraine attacks.
 Ten years of study has resulted in considerable but fragmented knowledge about regional cerebral blood flow in migraine with aura (classic migraine).
 In the present study, the number of repeatedly studied patients (n = 63) was large enough to determine statistically significant sequences of events and statistically significant spatial relations.
 The first observable event was a decrease of regional cerebral blood flow posteriorly in one cerebral hemisphere.
 Further development of this pathological process was accompanied by the aura symptoms.
 Thereafter headache occurred while regional cerebral blood flow remained decreased.
 During the headache phase, regional cerebral blood flow gradually changed from abnormally low to abnormally high without apparent change in headache.
 In some patients headache disappeared while regional cerebral blood flow remained increased.
 Although regional cerebral blood flow reduction and aura symptoms in the great majority of patients were unilateral, one-third had bilateral headache.
 Unilateral headache usually localized to the side on which regional cerebral blood flow was reduced and from which the aura symptoms originated (i.e., aura symptoms were perceived to occur contralaterally but presumably originated in the hypoperfused hemisphere).
 Our results suggest a simple model for migraine attacks: A pathological disturbance in one cerebral hemisphere causes the aura symptoms and after a time delay, it also causes the headache by stimulating local vascular nociceptors.
 Bilateral headache caused by a unilateral cerebral disturbance may be explained by recent neuroanatomical and neurophysiological findings.
",9
1554,"Ataxia and peripheral neuropathy: a benign variant of peroxisome dysgenesis.
 A 5-year-old boy with panperoxisomal dysfunction is described.
 Clinical features included hypotonia, areflexia, and ataxia.
 Cognition, vision, hearing, and hepatic function were normal.
 A panel of peroxisomal markers, including very-long-chain fatty acids, phytanic acid, pipecolic acid, and catalase compartmentalization, were abnormal.
 This is a uniquely benign syndrome of disordered peroxisome biogenesis.
",9
1555,"OKT3 encephalopathy.
 OKT3 therapy for induction immunosuppression in a patient who underwent renal transplantation produced obtundation and quadriparesis associated with computed tomographic scan evidence of brain edema.
 These findings resolved over 3 days with supportive therapy and OKT3 withdrawal.
",9
1556,"Orocaecal transit time in Duchenne muscular dystrophy.
 Smooth muscle degeneration may occur in Duchenne muscular dystrophy.
 We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls.
 No significant differences were found.
 In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.
",9
1557,"The effect of pH buffering on reducing the pain associated with subcutaneous infiltration of bupivicaine [published erratum appears in Am J Emerg Med 1991 Jul;9(4):410]
 The authors propose that pH buffering of bupivicaine with sodium bicarbonate reduces the pain associated with its local subcutaneous infiltration.
 In a double-blind, prospective study, 62 healthy adult volunteers received a 0.5 mL subcutaneous infiltration of 0.5% buffered bupivicaine into the dorsum of a randomly chosen hand.
 The pH was adjusted to 7.0 by adding 0.05 mL of sodium bicarbonate (1 mEq/L [corrected]) to 10 mL vials of commercially available bupivicaine (1:200 dilution).
 The control hand was injected with the same amount of unbuffered agent.
 Pain was scored after each infiltration using a nonsegmented visual analogue scale.
 Student's t-test for paired measurements was used to analyze intergroup pain score differences.
 Forty-three subjects (69%) reported less pain with buffered bupivicaine and only 17 (27%) noted a modest increase: two subjects (3%) reported no difference.
 The mean pain score for the buffered agent was 22 mm compared with 30 mm for the control.
 The mean difference (control-experimental) was 8 mm (t = 4.64, df = 61, P less than .001).
 The authors conclude that the addition of sodium bicarbonate to bupivicaine reduces the pain associated with its local infiltration.
",9
1558,"Research in physical medicine and rehabilitation. XII. Measurement tools with application to brain injury.
 There are basic principles and techniques of measurement that are relevant across biomedical disciplines.
 The purpose of this article is to explain some of the most important of these for medical rehabilitation, to illustrate how to use them to choose assessment instruments and to describe the nature of measurement in medical rehabilitation by examples in brain injury rehabilitation.
 Reliability is basic to any scientific measure.
 Validity, the ultimate criterion, is closely associated with the purpose of the measure.
 Content validity, criterion validity and construct validity are explained.
 Sensitivity to rehabilitative interventions and significance in patients' real lives (ecological validity) are emphasized.
 Measures of functional outcomes (disability) may show improvement after rehabilitation even when impairment measures do not.
 An extensive but selected list of measures of coma, global status, disabilities, communicative and cognitive impairments, and handicaps is presented, and their main uses are illustrated.
 Examples illustrate how to choose measures to study comprehensive program-level outcomes, to study learning-based interventions and to develop a general purpose database.
 Although there are many measures of activities of daily living and mobility, little published evidence of reliability and validity could be found even for some well-known scales.
 Ecologically valid and sensitive outcome measures are especially needed.
 Studies of the clinical utility of measures were also scarce.
 Many of these gaps can be spanned by clinical researchers with limited resources.
 Physical medicine and rehabilitation will benefit from formal studies of the reliabilities and validities of both its old and its new measurement instruments and by increased sophistication in choice of measures.
",9
1559,"Recovery time of independent function post-stroke.
 Stroke patients undergoing physical rehabilitation were monitored daily to determine the length of time needed to recover independent function.
 Of the 93 patients admitted, there were 45 who could not attain the sitting position independently, 75 who could not walk independently and 75 who could not negotiate the stairs independently.
 By discharge, 25 of 45 patients (55.6%) were able to attain sitting from supine independently, 35 of 75 patients (46.7%) achieved the ability to walk independently but only 25 of 75 patients (33.3%) learned to negotiate stairs independently.
 The time from admission to achievement of independent function and the time from onset of stroke to achievement of independent function was modeled in relation to explanatory variables: age, sex, side of lesion, comorbidity, the presence of depression and the extent of impairment in perception, cognition, auditory comprehension and verbal expression.
 Four variables were found to influence recovery time: age influenced the rate of recovery of walking and stair climbing; perceptual impairment influenced the rate of achieving independent sitting and stair climbing; and depression and comprehension influenced walking.
",9
1560,"Ventilatory function as a predictor of fatal stroke.
 OBJECTIVE--To investigate the relation between ventilatory function and subsequent mortality due to cerebrovascular disease.
 DESIGN--Prospective longitudinal study.
 SUBJECTS--A total of 18,403 male civil servants aged 40-64 years at entry examination for the Whitehall study.
 MAIN OUTCOME MEASURE--Mortality from cerebrovascular disease (ICD8 430-438) after 18 years of follow up.
 RESULTS--In all, 262 men with sinus rhythm at entry died due to stroke during the 18 years of follow up.
 Compared with men with a forced expiratory volume in one second of greater than or equal to 3.5 litres those with a value of less than 3.0 litres were almost twice as likely to die of cerebrovascular disease (rate ratio adjusted for age and systolic blood pressure = 1.88, 95% confidence interval 1.32 to 2.69).
 This increased risk occurred within each tertile of systolic blood pressure.
 Nested case-control analyses were used to control precisely for confounding effects of age, height, and smoking (by matching) and employment grade and physiological risk factors (by modelling).
 The effect of forced expiratory volume in one second was independent of age, height, smoking habits, employment grade, blood pressure, weight, cholesterol concentration, glucose tolerance, electrocardiographic abnormalities, history of chest pain, and history of intermittent claudication.
 CONCLUSIONS--Measurements of ventilatory function may assist clinical decisions about whether to treat mild hypertension.
 Impaired ventilatory function and stroke may share common causes.
",9
1561,"Availability of transplantable organs from brain stem dead donors in intensive care units.
 OBJECTIVE--By audit from January to June 1989 to quantify, separately for hearts, kidneys, liver, lungs and corneas, the possible increases in transplantable organs from brain stem dead potential donors in intensive care units and to compare them with the increases achieved in October-November 1989, during intense, national publicity about transplantation.
 DESIGN--Prospective audit of all deaths in intensive care units in England from 1 January to 30 June 1989 and subsequent case study of the impact of publicity on offers and donations during October-November 1989.
 SETTING--15 regional and special health authorities in England.
 PATIENTS--5803 patients dying in intensive care units, of whom 497 were confirmed as brain stem dead and had no general medical contraindication to organ donation.
 MAIN OUTCOME MEASURES--Organ specific suitability for transplantation (as reported by intensive care units); consent for donation of specific suitable organs; and procurement of specific organs reported as suitable for transplantation and offered.
 RESULTS--In the 497 (8.6%) brain stem dead potential donors were estimated the organ specific suitability for heart as 63%, kidneys 95%, liver 70%, lungs 29%, and corneas 91%.
 Refusal of relatives (30%) accounted for major losses of suitable organs of all types.
 For kidneys the loss was equivalent to 44% of brain stem dead actual kidney donors.
 No discussion of organ donation was the second most important reason for missed kidney donors, the loss being equivalent to 10% of brain stem dead actual donors.
 Non-procurement or difficulties with allocating organs was the second most notable cause of missed suitable liver and lung donors; 29% (55) of the offered total of 189 liver donors and 27% (21) of 78 offered suitable lung donors in six months.
 Non-procurement of suitable, offered organs was rare for kidneys and modest, of the order of 13% and 10% respectively, for heart and corneas.
 Corneal donation from brain stem dead potential donors might be improved nearly as much (that is, a 78% increase in brain stem dead actual corneal donors) by specific measures to promote corneal donation when other organs are offered as by reducing the overall refusal rate.
 Restricted offers, non-procurement, and no discussion of donation accounted for nearly equal numbers of lost donations of hearts (each equivalent to 15% of donated hearts).
 During October-November 1989 when there was intense, positive publicity about transplantation the rates of refusal and non-discussion fell compared with during January-June (22%, 36/163 v 30%, 138/460; 7%, 33/497 v 2%, 4/167 respectively).
 Offers of suitable donors increased significantly (p less than 0.02) compared with the first six months of 1989, most notably for heart donors (80 v 60.1 expected) and kidney donors (122 v 102.1 expected) but only for kidneys was there a noticeable 17% increase in actual donors (118 actual audited donors v 100.8 expected donors; p = 0.09).
 CONCLUSIONS--Four strategies to increase the supply of transplantable organs from brain stem dead potential donors in intensive care units were identified: (a) reducing refusal of relatives (b) avoiding non-procurement of actually suitable organs (by logistical initiatives) and deterioration of initially suitable organs (by donor care initiatives); (c) converting restricted offers to unrestricted offers; and (d) ensuring discussion with families.
 Early referral to the transplant team or coordinator gives time for discussion about donor care and agreement on medical suitability for donation of specific organs.
 Solving some of the logistical problems of non-procurement may be a prerequisite for increased offers to be translated into increased donations.
 The impact of publicity therefore needs to be measured on offers of suitable donors as well as by actual donations.
",9
1562,"Dacron-woven pacemaker pouch. Influence on long-term pacemaker mobility.
 Pacemaker migration can interfere with correct pacing system function and patient comfort.
 A Dacron pouch has been developed which may prevent these problems.
 To assess the efficacy of the pouch, we measured various factors of pacemaker mobility in 100 patients after long-term follow-up.
 The patients were divided into three groups on the basis of their dictated operative reports: group 1, no pouch or anchoring stitch; group 2, pouch only; group 3, anchoring stitch to pacemaker header or pouch.
 The average age of the study population was 74.3 +/- 11 years.
 Total follow-up time was 42 +/- 28 months (group I, 53 +/- 32 months; group 2, 36 +/- 23 months; group 3, 34 +/- 25 months).
 There were no significant differences when pacemakers were measured for movement in the inferosuperior and lateromedial directions, nor was there any difference in the distance between the incision scar and the pacemaker header in any group.
 There was a significant difference between group 1 and groups 2 and 3 when the degree of tilt of the pacemaker off the chest wall was compared.
 This was 46 degrees +/- 34 degrees for group 1 and 27 degrees +/- 26 degrees and 26 degrees +/- 27 degrees for groups 2 and 3, respectively (p less than 0.02 for both).
 These data suggest that the Dacron pouch does not restrict pacemaker mobility parallel to the chest wall during long-term follow-up but does reduce the angle to which the pacemaker can be tilted relative to the chest wall.
",9
1563,"Sleepwalking precipitated by treatment of sleep apnea with nasal CPAP.
 A 33-year-old man with a long history of snoring, observed apneic episodes, and excessive daytime sleepiness, underwent all-night polysomnography, which demonstrated severe obstructive sleep apnea.
 During the nasal CPAP trial, two episodes of sleepwalking were observed during a period of delta sleep rebound.
",9
1564,"Alzheimer's disease and related disorders in state mental hospitals: data from a nationwide survey.
 Notwithstanding three decades of transferring of the elderly to nursing homes, geriatric patients continue to reside in state mental hospitals.
 Many of these patients, perhaps one-third or more, are thought to suffer from Alzheimer's disease and related disorders (ADRD).
 This study reports data from a nationwide survey of state hospitals that provides an exploratory look at the ADRD patients currently served in state hospitals.
 Admission trends, reasons for admission, and sources of referral are described.
 Civil commitment of nursing home patients with dementing illnesses and the place of the state hospital in the continuum of care for ADRD patients are discussed.
",9
1565,"Differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie- or Creutzfeldt-Jakob disease-infected brains.
 The membrane interaction and hydrophobicity of the normal (PrPC) and infectious isoform (PrPSc/CJD) of scrapie and Creutzfeldt-Jakob disease amyloid precursor proteins was studied.
 The normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal/synaptosomal membranes anchored solely by the C-terminal glycolipid.
 Glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein, susceptible to proteases.
 In contrast, the PrPSc/CJD isoform was resistant to release by glycolipid-cleaving enzymes.
 A part of PrPSc/CJD was released from the membranes after prolonged trypsin treatment, yielding a further protease-resistant product of 27-30 kDa.
 The results demonstrate the proteolytic resistance of the membrane-bound PrPSc/CJD isoform and also indicate the presence of a different, apparently disease-induced mechanism of membrane interaction in the scrapie- and CJD-infected microsomal and synaptosomal membranes.
",9
1566,"Creutzfeldt-Jakob disease from allogeneic dura: a review of risks and safety.
 Surgeons and the lay public have recently expressed concern over the safety of allogeneic dura as it relates to the transmission of Creutzfeldt-Jakob Disease.
 Indeed, two cases have resulted from use of tissue procured from a commercial agency that did not adhere to criteria accepted by the American Association of Tissue Banks or the Southeast Organ Procurement Foundation.
 This review discusses the risks and safety of allogeneic dura.
 The findings should reassure the surgeon of the safety of allogeneic dura when it is properly processed and catalogued by a bona fide, reputable tissue bank.
 To date, there have been no documented cases reported to the Center for Disease Control in which Creutzfeldt-Jakob Disease was transmitted from allogeneic dura obtained from a registered tissue bank.
",9
1567,"Clinical diagnostic considerations on cocaine abuse.
 Following a review of the research literature on the psychophysiological effects of cocaine, a study is described of a group of 120 cocaine addicts.
 Of the 120 patients, 10 (8.33%) exhibited fleeting, unformed, organic delusions and hallucinations.
 Case reports of the 10 cases are presented.
 The quality of the adverse subjective effects of cocaine is emphasized, and the differential diagnosis between Cocaine Delusional Disorder and Paranoid Schizophrenia is discussed.
 Guidelines for a more accurate differential diagnosis are provided.
",9
1568,"Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures 
 In order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures, 244 subjects were randomized to phenytoin or placebo.
 They received neurobehavioral assessments at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs.
 In the severely injured, phenytoin significantly impaired performance at 1 month.
 No significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year.
 Patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures.
 We conclude that phenytoin has negative cognitive effects.
 This, combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week, raises questions regarding its use for long-term prophylaxis.
 Our findings do not negate phenytoin's proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs.
",9
1569,"Physical and pharmacologic restraint of nursing home patients with dementia. Impact of specialized units 
 This case-control study of 31 specialized dementia units and 32 traditional units in five states investigated use of physical and pharmacologic restraints among 625 patients with the diagnosis of dementia.
 Physical restraints were observed in use on 18.1% of dementia unit patients and on 51.6% of comparison unit patients who were out of bed during the day (adjusted odds ratio, 0.283;95% confidence interval, 0.129 to 0.619).
 Pharmacologic restraints were routinely given to 45.3% of dementia unit patients and 43.4% of comparison unit patients (adjusted odds ratio, 0.950; 95% confidence interval, 0.611 to 1.477).
 We used multivariate logistic regression to identify residence in a nonspecialized nursing home unit, nonambulatory status, transfer dependency, mental status impairment, hip fracture history, and a high nursing staff-to-patient ratio, which we found to be independent predictors of physical restraint use.
 Physically abusive behavior, severe mental status impairment, and frequent family visitation were found to be significant predictors of pharmacologic restraint use, while advanced patient age, large nursing home size, and patient nonambulatory status were protective against such use.
 These results support the conclusion that physical and pharmacologic restraint constitute separate treatment modalities with different risk factors for use, and indicate that specialized dementia units are successful in reducing the use of physical but not pharmacologic restraints.
",9
1570,"Retrovirus-induced spongiform myeloencephalopathy in mice: regional distribution of infected target cells and neuronal loss occurring in the absence of viral expression in neurons.
 The Cas-Br-E murine leukemia virus (MuLV) induces a spongiform myeloencephalopathy resulting in a progressive hindlimb paralysis.
 We have used in situ hybridization with a Cas-Br-E MuLV-specific probe to study viral expression in the central nervous system.
 Infected cells were concentrated in regions where spongiform lesions and gliosis are detected (lumbosacral spinal cord, brainstem, deep cerebellar regions), suggesting a causative link between the level of virus expression and the degree of pathological changes in this disease.
 However, viral expression was not in itself sufficient to cause disease, since significant viral expression was observed in regions that did not exhibit pathological changes (cerebellar cortex, hippocampus, corpus callosum, peripheral nervous system).
 In both diseased and nondiseased regions, endothelial and glial cells were identified as the main target cells.
 Neurons in diseased regions did not show viral expression.
 The regional distribution of the spongiform changes appears to be laid down very early following infection, since expression could be detected at 10 days postinfection in regions that become diseased.
 These results indicate that nonneuronal cells have distinct properties in various regions of the central nervous system and suggest an indirect mechanism of neuronal loss consequent to viral expression in nonneuronal cells.
",9
1571,"Response to suxamethonium in a myasthenic patient during remission.
 A cumulative dose followed by an infusion was used to determine the dose response to suxamethonium in a patient with diagnosed myasthenia gravis who was in true remission (asymptomatic while receiving no therapy).
 The ED50 and ED90 values for suxamethonium were 0.08 mg/kg and 0.20 mg/kg, and an infusion rate of 3.2 mg/kg/hour was required to maintain a 90-95% depression of the single twitch response as monitored by integrated electromyography.
 These values are within the range for normal patients, and we conclude that myasthenic patients during a true remission may not demonstrate resistance to suxamethonium.
",9
1572,"Modification of pain on injection of propofol--a comparison between lignocaine and procaine.
 Pain on injection of propofol was assessed in a controlled, randomised study of 273 patients.
 They received either lignocaine 10 mg, procaine 10 mg or isotonic saline 0.5 ml, 15 seconds before the injection of propofol into a vein on the back of the hand.
 The incidence of pain on injection in the control group (51%) was comparable with other studies.
 Lignocaine and procaine both significantly reduced the pain (35% and 34% respectively, p less than 0.05) but there was no statistical difference between these two groups.
",9
1573,"Lidocaine potentiation of cocaine toxicity.
 STUDY HYPOTHESIS: The toxic effects of cocaine are enhanced in the presence of lidocaine.
 STUDY POPULATION: Male Sprague-Dawley rats weighing 200 to 300 g.
 METHODS: Animals received intraperitoneal injections of cocaine (10, 20, 35, or 50 mg/kg), lidocaine (30 or 40 mg/kg), or a combination of all doses of cocaine given simultaneously with 30 or 40 mg/kg lidocaine.
 The incidence and time to seizure and death were recorded in these groups and compared by chi 2 and analysis of variance analyses, respectively.
 RESULTS: At doses of 30 or 40 mg/kg, lidocaine does not induce seizures or death.
 The effect of simultaneous injection of both cocaine and lidocaine was to dramatically increase the incidence of both seizures and death over that of cocaine alone.
 The incidence of seizures in animals receiving 35 mg/kg cocaine alone was 10%; this increased to 50% and 80% with the addition of 30 and 40 mg/kg lidocaine, respectively (P less than or equal to .05; P less than or equal to .01).
 Death did not occur in animals receiving 35 mg/kg cocaine alone; the addition of 30 and 40 mg/kg lidocaine resulted in death in 30% and 60% of animals, respectively (P less than or equal to .01 each group).
 Similarly, in rats receiving 50 mg/kg cocaine, the incidence of death increased from 0% to 60% and 80% with 30 and 40 mg/kg lidocaine, respectively (P less than or equal to .01).
 CONCLUSION: In the rat, overall toxicity of cocaine is significantly increased with simultaneous exposure to lidocaine.
",9
1574,"Genetic cause of a juvenile form of Tay-Sachs disease in a Lebanese child.
 Abnormality in the beta-hexosaminidase alpha gene underlying the clinical phenotype of a Lebanese patient with a juvenile form of Tay-Sachs disease has been studied.
 Clinical features were progressive spasticity, ataxia, and cognitive decline.
 The protein coding sequence of several beta-hexosaminidase alpha-chain complementary DNAs isolated by polymerase chain reaction was completely normal except for a G-to-A transition at nucleotide position 1511 within exon 13, which resulted in substitution of the normal arginine 504 (CGC) with histidine (CAC).
 Although the patient was from a first-cousin marriage, she was heterozygous for this mutation.
 The abnormality in the other allele, which is carried by the father, was not identified, except that it is neither of the two mutations responsible for the infantile Jewish Tay-Sachs disease.
 Biosynthetic and immunoprecipitation studies in cultured fibroblasts showed synthesis of the alpha-chain precursor, but the mature form of the alpha-subunit was not detected.
",9
1575,"Neuroanatomy of fragile X syndrome: the posterior fossa.
 The occurrence and specificity of posterior fossa abnormalities as measured from magnetic resonance images of the brain were investigated in a group of 14 males with fragile X syndrome and comparison groups consisting of 17 males with other causes of developmental disability and 18 males with normal IQs.
 The size of the posterior cerebellar vermis was significantly decreased and the fourth ventricle significantly increased in the group of males with fragile X syndrome compared with males in both comparison groups.
 These neuroanatomical abnormalities appeared to be secondary to hypoplasia rather than atrophy.
",9
1576,"Visual dysfunction in Alzheimer's disease: relation to normal aging [published erratum appears in Ann Neurol 1991 Mar;29(3):271]
 In patients with Alzheimer's disease (AD), compared with age-matched and young healthy control subjects, visual deficits in the following functions were observed: color, stereoacuity, contrast sensitivity, and backward masking (homogeneous and pattern).
 Critical flicker fusion thresholds were normal, relative to age-matched healthy subjects.
 For color, the majority of the errors were tritanomalous (blue axis).
 Color and stereoacuity deficits were unrelated to severity of dementia, in accordance with models of vision that describe these functions as modular rather than diffuse for cortical localization.
 Although contrast sensitivity was depressed throughout the frequency range in AD, more patients were impaired at low than at high spatial frequencies, contrasting with the observed normal aging pattern of high-frequency loss.
 Healthy elderly subjects showed depressed critical flicker fusion thresholds and reduced contrast sensitivity at high frequencies, relative to the young group; differences between these groups were not found for the other vision tests.
 A subset of the AD group received detailed neuro-ophthalmological examination, and no abnormalities were found.
 This finding, taken together with normal thresholds for critical flicker fusion, suggests that the widespread visual dysfunction reported here is more likely to be related to known pathological changes in primary visual and association cortex in AD than to changes in the retina or optic nerve.
",9
1577,"Nerve growth factor prevents toxic neuropathy in mice.
 Taxol is a promising new antitumor drug with therapeutic use that is limited by a toxic sensory neuropathy.
 Taxol is also cytotoxic to dorsal root ganglion neurons in vitro, but this effect is prevented by cotreatment with the trophic protein, nerve growth factor.
 We sought to develop an animal model and then to determine whether nerve growth factor can prevent taxol neuropathy in vivo.
 Administration of taxol to mice resulted in a profound sensory neuropathy characterized by decreases in dorsal root ganglion content of the peptide neurotransmitter, substance P, elevated threshold to thermally induced pain, and diminished amplitude of the compound action potential in the caudal nerve.
 Coadministration of nerve growth factor prevented all of these signs of neurotoxicity.
 These findings suggest that administration of nerve growth factor may prevent certain toxic sensory neuropathies.
",9
1578,"Localization of 3H-dihydroergotamine-binding sites in the cat central nervous system: relevance to migraine.
 Dihydroergotamine (DHE) is the treatment of choice in aborting the acute attack of migraine.
 Although its efficacy has been known for 40 years, its mechanism of action is still disputed.
 Data regarding the site of action of dihydroergotamine may provide an insight into its mechanism of action and thus identify a locus of potentially abnormal pathophysiology in migraine.
 By using in vitro and ex vivo autoradiographic techniques, the localization of specific binding sites for 3H-dihydroergotamine in the cat brain has been examined.
 Binding was seen in the dorsal horn of the cervical spinal cord, in the medulla, associated with the nucleus of the tractus solitarius, area postrema, and descending spinal trigeminal nucleus, and in the mesencephalon and the cerebral cortex.
 The highest density of binding sites was found in the dorsal and medial raphe nuclei of the midbrain.
 Furthermore, these same brain regions were also labeled after intravenous administration of 3H-dihydroergotamine.
 It is important that the brain areas specifically labeled are key nuclei involved in cranial pain transmission, suggesting that dihydroergotamine may act at these central sites in migraine.
",9
1579,"Neurologic status of spina bifida patients and the orthopedic surgeon.
 The purpose of this paper is to review recent developments in the neurologic assessment of spina bifida patients.
 Determination of the neurosegmental level of the lesion, recognition of spasticity and progressive paralysis, the potential for deformity, and functional expectations are described.
 The status of the neurologic deficit remains the most important factor in determining the myelomeningocele patient's ultimate functional abilities.
 Accurate neurologic assessment will assist in meeting the aims of orthopedic management, which include preventing joint contracture, correcting deformity, preventing skin sores, and obtaining the best possible locomotor function.
",9
1580,"Gait analysis in the treatment of the ambulatory child with cerebral palsy.
 Surgical treatment of children with cerebral palsy has changed from staged, single joint procedures to comprehensive simultaneous bony and soft-tissue corrections.
 This regimen of treating multiple joint levels and planes of abnormality is subject to error when based solely on the clinical examination.
 A more scientific evaluation can be provided by the use of clinical gait analysis.
 Both preoperative and postoperative analyses provide the clinician with information from which neurologic patterns can be determined and surgical protocols can be judged.
",9
1581,"Impact of day care on dementia patients--costs, well-being and relatives' views.
 Forty-seven patients in psychogeriatric day centre were analysed regarding use of resources, costs and well-being.
 The level of well-being was based on interviews with staff and relatives and related to the economic outcome--a cost utility analysis.
 A 6 month period prior to day care was compared with the first 6 months in such care.
 The use of resources at home increased by 20% while the use of institutional care was reduced by 22%.
 Fifty-three percent of the patients improved in their well-being after participation in day care.
 When the cost of utility analysis was applied, the cost for a well-year was 4293 pounds.
",9
1582,"Serum creatinine: an independent predictor of survival after stroke.
 We prospectively studied the relationship between serum creatinine and survival among 492 elderly subjects admitted for stroke and monitored for a mean period of 18 months post-stroke.
 In multivariate proportional hazards models, serum creatinine remained an independent predictor of mortality (P = 0.0001) after accounting for other important predictors such as level of consciousness.
 Mini-Mental State Score, age, leucocyte count, presence of heart disease, diabetes, heart failure, atrial fibrillation and use of cardiovascular medication.
 This association between elevated serum creatinine and mortality was also found in patient subgroups with CT-proven infarction and intracerebral haematoma.
 It is concluded that serum creatinine is an independent predictor of survival after stroke.
 Further studies are required to confirm this relationship and to elucidate the underlying mechanism.
",9
1583,"Intracranial hypertension in relation to memory functioning during the first year after severe head injury.
 The relationship between intracranial hypertension and residual memory deficit after closed head injury was evaluated using the 6-month and 1-year neurobehavioral outcome data obtained by the Traumatic Coma Data Bank.
 Intracranial pressure was analyzed using the percentage of time that it exceeded 20 mm Hg and the maximum value recorded during the first 72 hours after injury.
 Memory measures included recall of word lists, prose recall, and visual memory for designs that were obtained 6 months (n = 149) and 1 year (n = 132) after injury.
 Intracranial hypertension occurred in more than half of the Traumatic Coma Data Bank cohort who met the criteria for the neurobehavioral follow-up study.
 Linear regression analysis disclosed an effect of elevated intracranial pressure on some, but not all, measures of memory at 6 months, whereas the results were negative for the 1-year follow-up examination.
 We conclude that the elevation of intracranial pressure exerts little if any effect on later memory functioning, and that any effect it does have diminishes over 1 year in survivors of severe head injury.
",9
1584,"The influence of the calcium antagonist nimodipine and induced hypertension on the behavior of the cerebral pial arteries, the blood-brain barrier, cerebral edema, and cerebral infarction in cats with one-hour occlusion of the middle cerebral artery.
 Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each: nimodipine treatment, nimodipine treatment combined with induced hypertension, or a control group.
 The behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window.
 The middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach.
 Five hours after circulation was reestablished in the middle cerebral artery, Evans blue dye was injected intravenously: 30 minutes later, the animal was killed.
 Administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment.
 Induced hypertension was produced by administration of dopamine during the occlusion.
 Damage to the blood-brain barrier (BBB) was judged by extravasation of Evans blue dye.
 Cerebral edema and infarction were evaluated from histological findings.
 They were most prominent in the control group: the extent of hemisphere affected was as follows (mean +/- standard error): extravasation, 40.5 +/- 8.8%; edema, 43.2 +/- 5.7%; infarction, 35.5 +/- 9.6%.
 On the other hand, the extravasation of Evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension (extravasation, 28.2 +/- 9.6% of the hemisphere; edema, 30.3 +/- 7.1%) than in the group treated with nimodipine alone (extravasation, 18.5 +/- 8.7% of the hemisphere; edema, 19.4 +/- 6.3%), but the infarction size was similar in both groups (16.6 +/- 4.9% of the hemisphere in the former; 17.0 +/- 6.2 in the latter).
",9
1585,"Kenneth McKenzie, Harvey Cushing, and the early neurosurgical treatment of spasmodic torticollis.
 In 1923, Dr.
 Kenneth McKenzie trained at the Peter Bent Brigham Hospital under Dr.
 Harvey Cushing.
 At that time, a patient with spasmodic torticollis came to Cushing and was treated with an innovative operation for this disorder with good results.
 This case sparked an interest in Dr.
 McKenzie, who published the case 1 year later.
 In reviewing the surgical histories from the Peter Bent Brigham Hospital, we have found the original records of this well-documented case.
 The record includes postoperative drawings of the intraoperative field by Dr.
 Cushing, a sketch by Dr.
 McKenzie illustrating the postoperative sensory examination, and pre- and postoperative photographs of the patient.
",9
1586,"Spinal man after declaration of brain death 
 Complex spinal automatism in a patient who was declared brain dead is described.
 These movements tend to appear once cerebrospinal shock has abated.
 We postulate that these manifestations are a reflection of the physiological potential of the isolated spinal cord.
 These spinal movements should be included in the revised guidelines for the determination of cerebral death.
",9
1587,"A comparison of midazolam with and without nalbuphine for intravenous sedation.
 The introduction of nalbuphine to intravenous sedation with midazolam added little to the quality of sedation for short operative procedures.
 There was a greater tendency for patients who received nalbuphine and midazolam to sleep in the afternoon after treatment compared with those who received only midazolam.
 Significantly more patients had nausea and vomiting in the midazolam/nalbuphine group than did patients in the midazolam-only group.
",9
1588,"Genetic mapping of new DNA probes at Xq27 defines a strategy for DNA studies in the fragile X syndrome.
 The fragile X syndrome is the most common cause of familial mental retardation and is characterized by a fragile site at the end of the long arm of the X chromosome.
 The unusual genetics and cytogenetics of this X-linked condition make genetic counseling difficult.
 DNA studies were of limited value in genetic counseling, because the nearest polymorphic DNA loci had recombination fractions of 12% or more with the fragile X mutation, FRAXA.
 Five polymorphic loci have recently been described in this region of the X chromosome.
 The positions of these loci in relation to FRAXA were defined in a genetic linkage study of 112 affected families.
 The five loci--DXS369, DXS297, DXS296, IDS, and DXS304--had recombination fractions of 4% or less with FRAXA.
 The closest locus, DXS296, was distal to FRAXA and had a recombination fraction of 2%.
 The polymorphisms at these loci can be detected in DNA enzymatically digested with a limited number of restriction endonucleases.
 A strategy for DNA studies which is based on three restriction endonucleases and on five probes will detect one or more of these polymorphisms in 94% of women.
 This strategy greatly increases the utility of DNA studies in providing genetic advice to families with the fragile X syndrome.
",9
1589,"Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations.
 Four subjects with thermolabile methylenetetrahydrofolate reductase (MTHFR) were discovered among 16 ""obligate"" heterozygotes for severe MTHFR deficiency and their family members.
 All four subjects had less than 25% of normal mean MTHFR specific activity in lymphocyte extracts.
 Three of them with normal serum folate and cyanocobalamin had intermediate hyperhomocysteinemia, and one with high serum folate and cyanocobalamin had no excessive accumulation of serum homocysteine.
 The biochemical features in these four subjects are distinguishable from subjects homozygous for the thermolabile MTHFR, whose specific activity is approximately 50% of the normal mean, and from heterozygotes for severe MTHFR deficiency, in whom the enzyme is thermostable and has a specific activity of about 50% of the normal mean.
 We propose that these four subjects are genetic compounds of the allele for the severe mutation and the allele for thermolabile mutation of the MTHFR gene.
 It is postulated that subjects with this genetic compound are more susceptible to the development of intermediate hyperhomocysteinemia despite normal folate and B12 levels.
 Nonetheless, hyperhomocysteinemia due to this compound heterozygosity is correctable by oral folic acid therapy.
",9
1590,"Distribution of three alpha-chain beta-hexosaminidase A mutations among Tay-Sachs carriers.
 DNA from 176 carriers of the Tay-Sachs gene was tested for the presence of the three mutations most commonly found among Ashkenazi Jews: the so-called insertion, splice junction, and adult mutations.
 Among 148 Ashkenazi Jews tested, 108 had the insertion mutation, 26 had the splice junction mutation, five had the adult mutation, and nine had none of the three.
 Among 28 non-Jewish carriers tested, most of whom were obligate carriers, four had the insertion mutation, one had the adult mutation, and the remaining 23 had none of the three.
",9
1591,"Muscle rehabilitation in impaired elderly nursing home residents.
 Based on observations of changes in muscle function associated with aging, and the exacerbation of these changes with frailty, a program of muscle strengthening has been developed to correct specific defects in muscles.
 This pilot study was undertaken on 18 functionally impaired nursing home residents (age range 60 to 90 years) with markedly deteriorated muscle function (50%) secondary to age, disuse, and multiple chronic illnesses.
 Fourteen of the subjects completed the six-week program without adverse effects.
 In 75% of the patients, there was improved muscle function, with endurance, strength, and speed increasing 35%, 15%, and 10%, respectively.
 After the program, many subjects increased their spontaneous activity and decreased their dependency.
 The improvements were still evident four months after rehabilitation.
 These results suggest that it may be possible, through a carefully supervised, short-term program of muscle rehabilitation, for nursing home residents to achieve an enhanced level of physical functioning.
",9
1592,"Wrist flexion as an adjunct to the diagnosis of carpal tunnel syndrome.
 The effects of five minutes of wrist flexion on median motor and sensory evoked potential latencies in 87 individuals were studied.
 Nineteen subjects had carpal tunnel syndrome (CTS) as diagnosed by increased median nerve latencies across the wrist, and 68 had values in the normal range and were assigned to the control group.
 A slight prolongation of up to 0.5m sec of evoked potential latencies was observed in both groups after flexion, but the differences between the two groups were not significant to establish the value of adding wrist flexion to conventional screening methods.
",9
1593,"Detecting lower motor neuron dysfunction of the pharynx and larynx with electromyography.
 This study assessed the utility of clinical electromyography (EMG) for detecting lower motor neuron (LMN) or upper motor neuron (UMN) dysfunction affecting the intrinsic muscles of the larynx and pharynx.
 Twenty-nine subjects were examined; their clinical diagnoses included perioperative nerve injury, cerebral infarction, and lateral medullary infarction.
 Resting activity, motor unit action potential (MUAP) morphology, and MUAP recruitment were evaluated in every case.
 Medical records (excluding EMG data) were analyzed for clinical evidence of LMN or UMN dysfunction in the intrinsic muscles of the larynx and pharynx.
 The diagnosis of LMN dysfunction rested on clinical data consistent with cranial nerve injury, poliomyelitis, Wallenberg syndrome, or unilateral bulbar palsy.
 Criteria for UMN dysfunction included previous cerebral (not brainstem) infarction or mass lesion or the presence of hemiparesis.
 Electromyographic abnormalities were significantly associated with LMN dysfunction (p less than .05), but they were not significantly associated with UMN dysfunction.
 Of the parameters tested, MUAP recruitment was the most sensitive (82%) and specific (92%).
",9
1594,"Neurobehavioral effects of phenytoin, carbamazepine, and valproic acid: implications for use in traumatic brain injury.
 Due to the risk of posttraumatic epilepsy, phenytoin, carbamazepine, and valproic acid are often prescribed for patients with traumatic brain injury (TBI).
 In this review the literature is examined for evidence of neurobehavioral impairment due to carbamazepine, phenytoin, and valproic acid.
 No comparative studies have been performed in the TBI population, making if difficult to determine if one of these medications is preferable.
 Direct inference from studies on epilepsy patients to TBI patients is hazardous due to underlying differences in the two populations.
 Reported findings for epilepsy patients are subtle and not consistent across studies.
 All three drugs appear to exert some effect on cognitive and motor functions in epileptic patients, and these impairments worsen at increasing serum levels.
 The varied length of experience with each drug makes it difficult to assign relative weight to the evidence for or against each.
 A comparative assessment of cognitive and behavioral effects of anticonvulsants should be done in the TBI population.
",9
1595,"Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases.
 Nineteen cases are described, including 12 cases from three different families and 7 nonfamilial cases, in which multisystem neurological disease was associated with acanthocytosis in peripheral blood and normal plasma lipoproteins.
 Mild acanthocytosis can easily be overlooked, and scanning electron microscopy may be helpful.
 Some neurologically asymptomatic relatives with significant acanthocytosis were identified during family screening, including some who were clinically affected.
 The mean age of onset was 32 (range 8-62) yrs and the clinical course was usually progressive but there was marked phenotypic variation.
 Cognitive impairment, psychiatric features and organic personality change occurred in over half the cases, and more than one-third had seizures.
 Orofaciolingual involuntary movements and pseudobulbar disturbance commonly caused dysphagia and dysarthria that was sometimes severe, but biting of the lips or tongue was rarely seen.
 Chorea was seen in almost all symptomatic cases but dystonia, tics, involuntary vocalizations and akinetic-rigid features also occurred.
 Two cases had no movement disorder at all.
 Computerized tomography often demonstrated cerebral atrophy.
 Caudate atrophy was seen less commonly, and nonspecific focal and symmetric signal abnormalities from the caudate or lentiform nuclei were seen by magnetic resonance imaging in 3 out of 4 cases.
 Depression or absence of tendon reflexes was noted in 13 cases and neurophysiological abnormalities often indicated an axonal neuropathy.
 Sural nerve biopsies from 3 cases showed evidence of a chronic axonal neuropathy with prominent regenerative activity, predominantly affecting the large diameter myelinated fibres.
 Serum creatine kinase activity was increased in 11 cases but without clinical evidence of a myopathy.
 Postmortem neuropathological examination in 1 case revealed extensive neuronal loss and gliosis affecting the corpus striatum, pallidum, and the substantia nigra, especially the pars reticulata.
 The cerebral cortex appeared spared and the spinal cord showed no evidence of anterior horn cell loss.
 Two examples of the McLeod phenotype, an X-linked abnormality of expression of Kell blood group antigens, were identified in a single family and included 1 female.
 The genetics of neuroacanthocytosis are unclear and probably heterogeneous, but the available pedigree data and the association with the McLeod phenotype suggest that there may be a locus for this disorder on the short arm of the X chromosome.
",9
1596,"Idiopathic intracranial hypertension. A prospective study of 50 patients.
 Management of patients with idiopathic intracranial hypertension (IIH) should be based on the presence and progression of visual loss.
 To characterize the clinical course of IIH more completely, we monitored the clinical status, especially visual function, in 50 consecutive newly-diagnosed patients over a period of 2 to 39 months (average follow-up 12.4 months).
 The mean age at onset of symptoms was 31 (range 11-58) yrs; 46 (92%) were women and 47 (94%) were obese (mean weight 90 kg).
 Common symptoms were headache (92%), transient visual obscurations (72%) and intracranial noises (60%); 13 of the patients (26%) initially had complaints of sustained visual loss.
 There was visual loss as determined by Goldmann perimetry in 96% and by automated perimetry in 92%.
 Contrast sensitivity testing was abnormal in 50% and Snellen acuity in 22%.
 Two patients (4%) became blind in both eyes.
 The Goldmann visual field grade improved in 60% of patients but visual function deteriorated in 5 (10%).
 Deterioration of visual field grade was significantly associated only with weight gain during the year before diagnosis.
 Visual loss in patients with IIH is common and is often reversible.
 Patients should be evaluated by perimetry using an appropriate strategy and contrast sensitivity testing, along with careful examination of the optic discs.
",9
1597,"Dual task performance and processing resources in normal subjects and patients with Parkinson's disease.
 In recent years, there has been a growing consensus among investigators that the presence or absence of external cues guiding behaviour and attention is an important factor in determining whether or not deficits are found in patients with Parkinson's disease (PD).
 In an earlier study, the authors suggested that the pattern of impaired and intact performance could be explained in terms of differential resource demands of the tasks, combined with depleted levels of central processing resources in PD patients.
 Two experiments are reported, both employing dual-task paradigms.
 The first assessed, in normal subjects, the relative processing demands of a cued and an uncued version of the Stroop task.
 The results supported the proposal that the noncued task made greater demands on the subject's limited processing resources.
 Further, performing a resource demanding secondary task concurrently with the Stroop test produced, in normal subjects, the same pattern of impaired performance as that reported previously in PD patients.
 In the second experiment the same dual-task paradigm was employed with a group of PD patients and normal aged-matched controls.
 Only the patients showed an increase in reaction time on the Stroop task when performing a resource demanding secondary task.
 The patients also showed an interfering effect with concurrent foot tapping but not with an articulatory suppression task.
 The results were taken to support the hypothesis that PD patients have depleted central processing resources.
 In considering the present data, alternative explanations for the results are considered, in particular the possibility that they represent a deficit in switching processing resources between two tasks as the combined demands outweigh available resources.
",9
1598,"Short-term memory and sentence comprehension. An investigation of a patient with crossed aphasia.
 The relationship between short-term memory impairment and sentence comprehension is explored in a right-handed patient with a focal temporoparietal lesion of the right hemisphere.
 The general clinical profile, as well as characteristics of the patient's immediate memory for word lists, suggests the occurrence of a 'mirror image' crossed aphasia.
 Detailed analysis of the patient's ability to repeat and to comprehend sentences, however, indicates some important differences between this case and previously reported patients with short-term memory impairment.
 It is suggested that these differences, which may be related to an unusual pattern of neuroanatomical organization of cognitive functions, involve symptom dissociations with implications for models of normal language/memory interactions.
",9
1599,"Task-dependent variations in parkinsonian motor impairments.
 Studies of visually-guided arm movements in patients with Parkinson's disease (PD) have suggested a relationship between slowness of movement and a reduction in the ratio of movement amplitude and peak velocity.
 Recent studies indicate, however, that PD impairments may be different for well-learned, natural movements performed without visual guidance, or movements associated with sequential motor behaviours such as speech.
 To address this issue, PD subjects and age/sex-matched controls were compared on the performance of three tasks, all of which required lowering the jaw: (1) single, rapid, visually-guided movements; (2) equivalent movements associated with a single speech syllable (inherently without visual guidance), and (3) well-learned speech movements produced in a natural sequence.
 PD subjects manifested similar deficits for visually-guided jaw lowering as those previously reported for arm movements, namely reduced velocity/amplitude ratios and increased movement durations.
 By contrast, analogous jaw movements during the sequential speech tasks were unimpaired on these measures.
 These results suggest that PD motor impairments are influenced by a variety of factors, including the degree to which tasks are familiar and natural, and the availability of visual information.
",9
1600,"Effects of anticonvulsant treatment and low levels of folate and thiamine on amine metabolites in cerebrospinal fluid.
 A total of 157 epileptic patients were studied with respect to (1) biogenic amine precursors and metabolites in the CSF, (2) levels of folate and thiamine in the blood and CSF, (3) length of treatment with phenytoin (PHT), (4) PHT intoxication, (5) CNS atrophy.
 Alterations in CSF amine metabolite levels were related primarily to PHT intoxication, and low CSF folate and thiamine levels, but not to length of treatment or CNS atrophy.
 PHT intoxication increased CSF 5-hydroxyindoleacetic acid (5HIAA).
 Low folate levels were associated with decreased CSF 5HIAA and homovanillic acid, while low thiamine levels were associated with decreased CSF 5HIAA and 3-methyoxy-4-hydroxyphenylethylene glycol.
 It remains to be seen to what extent these alterations in biogenic amine metabolism, mediated by low CNS vitamin levels, also lead to deficits in cerebral function.
",9
1601,"Human olfactory discrimination after unilateral frontal or temporal lobectomy.
 Olfactory discrimination and detection was studied in 106 patients with unilateral cerebral excision in the right or left temporal lobe, right or left frontal lobe, left parietal lobe, or right frontal and temporal lobes, and in 20 normal control subjects.
 Detection thresholds for n-butyl alcohol, measured separately in each nostril, did not differ across subject groups or across nostrils, thus excluding any primary sensory loss.
 The discrimination task involved monorhinal presentation of repairs of unfamiliar odorants, which the subjects judged as same or different in quality.
 The results showed a significant deficit in discrimination confined to the nostril ipsilateral to the lesion in patients with temporal lobe removals.
 Patients with frontal lobe excisions were also impaired and, for patients with right frontal lesions including the orbital cortex, the impairment was found in both nostrils.
 Patients with left parietal lesions did not demonstrate any significant deficits.
 Normal subjects showed consistently better performance in the right than in the left nostril.
 The results are interpreted as reflecting the importance of the orbitofrontal cortex in olfactory discrimination.
 Temporal lobe lesions may disrupt the input to the orbitofrontal cortex, thereby producing poorer performance.
 The nostril difference in the normal subjects, together with the birhinal impairment in patients with right orbitofrontal damage, suggest a relative advantage of the right orbital region in olfactory processing.
",9
1602,"Sequencing in Parkinson's disease. Abnormalities in programming and controlling movement.
 Central programming deficits in Parkinson's disease (PD) were studied in two reaction time (RT) experiments.
 In Experiment 1, PD patients and controls performed sequences of hand postures that varied in length, the number of different postures (repetitive vs heterogeneous), and the delay interval before movement.
 Before movement, the PD group planned repetitive movements like controls whereas for heterogeneous sequences RT increased less with sequence length for the PD group, implying less preprogramming.
 The interresponse time (IRT) data from repetitive sequences showed that the PD group had difficulty controlling movement such that IRTs were faster when sequences were longer, thus allowing more time to schedule the termination of the sequence during the course of movement.
 For heterogeneous sequences, the PD group made more errors and were slower than controls when changing hand postures, suggesting a deficit in switching between different responses.
 While RT decreased with a longer delay similarly for both groups, IRT1 continued to improve only for the PD group but similarly for both types of sequences, suggesting a deficit specific to programming the first response.
 In Experiment 2, subjects made decisions about the number of different hand postures contained within a sequence.
 PD patients' decision times improved more with a longer delay only for heterogeneous sequences, suggesting a problem in identifying the number of different hand postures.
 The results have implications for levels of motor dysfunction in PD which emphasize the influence of sequence length and complexity.
",9
1603,"Pain control in the ambulatory elderly.
 Pain control in the elderly, no matter what the etiology or setting, can be a major clinical challenge.
 Aging causes unique physiologic changes, eg, a decreased perception of pain and an enhanced sensitivity to opioid analgesics.
 Principles regarding evaluation of patients with pain are reviewed, including the use of an objective instrument for pain assessment from the viewpoint of both physician and patient.
 Good pain control can be achieved with the nonopioids, such as acetaminophen and the nonsteroidal anti-inflammatory drugs, the opioid analgesics, and, in some cases, adjuvant agents.
 Discussed also are the concerns for patient addiction and the WHO Cancer Pain Relief program.
",9
1604,"Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro.
 Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits were revealed in endoneurium, perineurium, and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies.
 The alpha 2 subunit was expressed only on Schwann cells both in fetal and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells.
 The alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve.
 The tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have the potential to express also the alpha 3 subunit in vivo.
 Cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent Schwann cells at cell-cell contacts.
 Our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by, for example, axons, humoral factors, or the extracellular matrix of the peripheral nerve.
 This plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve.
",9
1605,"Differential diagnosis of mut and cbl methylmalonic aciduria by DNA-mediated gene transfer in primary fibroblasts.
 Methylmalonic aciduria can be caused by mutations in the gene encoding the methylmalonyl coenzyme A mutase apoenzyme (mut) or genes required for the provision of cofactor B12 (cbl).
 The mut and cbl forms are classically differentiated by somatic cell complementation.
 We describe a novel method for differential diagnosis of mut and cbl methylmalonic aciduria using DNA-mediated gene transfer of a methylmalonyl CoA mutase cDNA clone.
 Gene transfer of a functional methylmalonyl CoA mutase cDNA clone into mut fibroblasts reconstitutes holoenzyme activity measured by metabolism of [14C]-propionate in culture.
 Identical gene transfers into cbl fibroblasts have no effect.
 This method is used for the differential diagnosis of mut and cbl genotypes in cells from patients with a clinical diagnosis of methylmalonic aciduria and is shown to be a facile, sensitive, and specific method for genetic diagnosis.
 This work establishes the principle of using DNA-mediated gene transfer to identify the genotype of diseases which can result from mutations at several different genetic loci.
 This type of differential genotypic diagnosis will be particularly important for establishing the applicability of somatic gene therapy in individual patients.
",9
1606,"Modifying the translabyrinthine approach to preserve hearing during acoustic tumour surgery.
 Removing an acoustic schwannoma using the translabyrinthine approach has previously been considered incompatible with hearing preservation.
 By modifying the approach and preventing the loss of endolymph, we have successfully removed an intracanalicular acoustic schwannoma, which originated from the inferior vestibular nerve, and preserved hearing in the operated ear.
 This report represents the preliminary findings using this particular technique in the management of an intracanalicular acoustic tumour.
",9
1607,"Clinical features and associations of 560 cases of motor neuron disease.
 In 560 cases of motor neuron disease, studied retrospectively from their case notes in three teaching centres, the age at onset ranged from 13 to 87 years (mean 56 years), and the mean duration of illness until death was 2.6 years.
 In the subgroup of the disease presenting with progressive bulbar palsy presenting after age 59 years, there was a previously unrecognised excess of females sufficient to equalize the sex ratio of incidence of the disease in this age group.
 No potentially causative clinical associations emerged; no relation was noted between occupational exposure to leather products, trauma or surgical procedures and the disease.
 There was a trend for patients with motor neuron disease to give a history of abstention from alcohol.
",9
1608,"Progressive degeneration of the right temporal lobe studied with positron emission tomography.
 A 79 year old man with a twelve year progressive history of prosopagnosia and recent naming difficulty, in whom other intellectual skills were preserved, is described.
 Positron emission tomography (PET) revealed an area of right temporal lobe hypometabolism, with an additional area of less severe hypometabolism at the left temporal pole.
 This may represent an example of progressive focal cortical degeneration similar to that associated with primary progressive dysphasia, but affecting the right temporal lobe.
",9
1609,"Cyclosporin-associated akinetic mutism and extrapyramidal syndrome after liver transplantation.
 Three patients developed akinetic mutism on the third day after the introduction of intravenous cyclosporin A, given for immunosuppression after liver transplantation.
 One patient in addition developed a florid orofacial dyskinesia, which resolved completely, as did the akinetic mutism, after withdrawal of cyclosporin.
 In these patients the time course of the akinetic mutism and extrapyramidal syndrome, which developed in the absence of any other identifiable cause, suggests cyclosporin A was the precipitating factor.
 Subsequently, two of the patients showed signs of pseudobulbar palsy with abnormalities in the pons on MRI scanning, suggesting central pontine myelinolysis (CPM).
 None of the patients had experienced significant fluctuations in serum sodium or other risk factors for central pontine myelinolysis and the exact relationship to the earlier cyclosporin related mutism was not clear.
",9
1610,"Grading white matter lesions on CT and MRI: a simple scale.
 We developed and tested a simple three-point scale for grading white matter lesions in anterior and posterior regions of the brain.
 Twenty four CT scans and 24 MRI scans were separately judged by 11 and five observers, respectively, on the presence and severity of white matter lesions.
 The observers were radiologists and neurologists.
 For CT scans, these periventricular changes were graded according to their extent as absent, or partly involving the white matter, or extending up to the subcortical region.
 The MRI lesions were graded as no lesion or only a single one, multiple focal lesions, and multiple confluent lesions.
 The pairwise agreements of all possible combinations of observers for each scan were corrected for chance (kappa statistics; maximal agreement 1.0).
 The weighted kappa value, for anterior and posterior regions combined, was 0.63 for CT scans, and 0.78 for MRI scans.
 This three-point scale for two separate regions seems suitable as a basis for cross-sectional or longitudinal studies of large series of patients.
",9
1611,"The community hospital-based stroke programs in North Carolina, Oregon and New York--V. Stroke diagnosis: factors influencing the diagnostic evaluation of patients following acute stroke.
 Among the 4129 patients of the Community Hospital-based Stroke Program, 30% had an unspecified stroke diagnosis.
 Since specific diagnosis and, perhaps, eventual treatment, derives in part from diagnostic testing, we examined the effect of clinical condition, geographic and demographic factors on the incidence of certain diagnostic tests after acute stroke.
 In this multivariable analysis, race, sex, history of hypertension and history of diabetes did not influence the chance of having any test, but older age strongly reduced the chances of receiving extensive evaluation.
 When CT scanning was available, the utilization of a CT as well as other diagnostic studies including cerebral angiography, radionuclide brain scan, EEG and EKG was increased.
 The odds of receiving a CT scan increased if the patient was married, and decreased with a history of previous stroke.
 A history of previous TIA increased the chance of having a cerebral angiogram while a history of cardiac disease decreased the chance.
 There were striking regional geographic differences in the use of CT, radionuclide brain scanning and cerebral angiography which may, in part, reflect differences between the availability of these technologies in urban and rural hospitals.
 These results indicate that evaluation of stroke patients remains heterogenous.
",9
1612,"Intrathecal baclofen for spasticity in cerebral palsy 
 Seventeen patients with congenital spastic cerebral palsy and six patients with other forms of spasticity were injected intrathecally with doses of placebo or baclofen, 25 micrograms, 50 micrograms, or 100 micrograms, in a randomized, double-blind manner.
 Muscle tone in the upper and lower extremities was assessed by Ashworth scores both before the injections and every 2 hours afterward for 8 hours.
 Function of the upper extremities was evaluated before the injections and 4 hours afterward.
 Muscle tone in the lower extremities was significantly decreased within 2 hours after baclofen injection and remained lower than baseline 8 hours afterward.
 Upper extremity tone and function were not significantly affected by these single doses.
 Confusion and drowsiness occurred in two of the youngest children in the study after the 50-micrograms dose, but cleared within 2 hours.
 Our findings indicate that intrathecal baclofen reduces spasticity in children with cerebral palsy, as it does in adults with spasticity of spinal origin.
",9
1613,"No confirmation of visual evoked potential diagnostic test for migraine.
 We have attempted to replicate the results of studies on a diagnostic test reported to have 90% sensitivity and 89-96% specificity for migraine.
 The technique is based on peak-to-peak measurements of fast background electroencephalographic activity during a visual evoked potential (VEP) study.
 VEP latencies and amplitudes did not differ significantly, and showed substantial overlap, between a group of eight migraine patients and ten age-matched healthy controls.
 We could not recognise previously described fast activity or measure it objectively by peak-to-peak measurements.
 We cannot confirm that measurement of fast wave activity in the VEP background is useful in diagnosis of migraine.
",9
1614,"Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis.
 The fragile-X syndrome is the most frequent inherited form of mental retardation, with an incidence of 1 in 1,500 males.
 It is characterized by the presence of a fragile site at Xq27.3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis.
 Its mode of inheritance is unusual for an X-linked trait, with incomplete penetrance in both males and females.
 Some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms, but penetrance is high in sons and daughters of these carrier women.
 Genetic and physical mapping of the Xq27-q28 region has confirmed that the disease locus is located at or very near the fragile site.
 Hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination or a mutation that affects reactivation of an inactive X chromosome during differentiation of female germ cells.
 To detect such rearrangements, or methylation changes that may reflect a locally inactive X chromosome, we used pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus.
 The probe Do33 (DXS465) detected abnormal patterns in fragile-X patients, but not in normal controls or in non-expressing male transmitters.
",9
1615,"Lexical organization of nouns and verbs in the brain.
 The analysis of neuropsychological disorders of lexical processing has provided important clues about the general organization of the lexical system and the internal structure of the processing components.
 Reports of patients with selective dysfunction of specific semantic categories such as abstract versus concrete words, living things versus inanimate objects, animals, fruits and vegetables, proper names and so forth, support the hypothesis that the neural organization of the semantic processing component is organized in these categories.
 There are reports of selective dysfunction of the grammatical categories noun and verb, suggesting that a dimension of lexical organization is the grammatical class of words.
 But the results reported in these studies have not provided unambiguous evidence concerning two fundamental questions about the nature and the locus of this organization within the lexical system.
 Is the noun-verb distinction represented in the semantic or in the phonological and orthographic lexicons? Is grammatical-class knowledge represented independently of lexical forms or is it represented separately and redundantly within each modality-specific lexicon? Here we report the performance of two brain-damaged subjects with modality-specific deficits restricted principally (H.W.) or virtually only (S.J.D) to verbs in oral and written production, respectively.
 The contrasting performance suggests that grammatical-class distinctions are redundantly represented in the phonological and orthographic output lexical components.
",9
1616,"The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions.
 In recent years, the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome, such as its pathophysiology, has evolved into the belief that certain types of pain, e.g., neuropathic pains, may be unresponsive to these drugs.
 This concept has important implications for both clinical practice and basic understanding of opioid mechanisms.
 We critically evaluate opioid responsiveness, particularly as it relates to neuropathic pain, and propose a clinically relevant definition and a paradigm for its investigation.
 The paradigm is illustrated by analgesic responses to opioid infusion in 28 patients with neuropathic pains and by a detailed presentation of the pharmacokinetic and pharmacodynamic relationships in one of these patients, whose central pain responded promptly to an infusion of hydromorphone.
 From this analysis, we hypothesize that (1) opioid responsiveness in man can be defined by the degree of analgesia achieved during dose escalation to either intolerable side effects or the occurrence of 'complete' or 'adequate' analgesia; (2) opioid responsiveness is a continuum, rather than a quantal phenomenon; (3) opioid responsiveness is determined by a diverse group of patient characteristics and pain-related factors, as well as drug-selective effects; and (4) a neuropathic mechanism may reduce opioid responsiveness, but does not result in an inherent resistance to these drugs.
 Given the complexity of factors contributing to opioid responsiveness and the observation that outcome cannot be reliably predicted, opioids should not be withheld on the assumption that pain mechanism, or any other factor, precludes a favorable response.
 Both the clinical use of opioids and paradigms to investigate opioid responsiveness should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects.
",9
1617,"Pain 'memories' in phantom limbs: review and clinical observations.
 This paper reviews reports of phantom limb sensations which resemble somatosensory events experienced in the limb before amputation.
 It also presents descriptions of this phenomenon in 68 amputees who took part in a series of clinical studies.
 These somatosensory memories are predominantly replicas of distressing pre-amputation lesions and pains which were experienced at or near the time of amputation, and are described as having the same qualities of sensation as the pre-amputation pain.
 The patients who experience these pains emphasize that they are suffering real pain which they can describe in vivid detail, and insist that the experience is not merely a cognitive recollection of an earlier pain.
 Reports of somatosensory memories are less common when there has been a discontinuity, or a pain-free interval, between the experience of pain and amputation.
 Among the somatosensory memories reported are cutaneous lesions, deep tissue injuries, bone and joint pain and painful pre-amputation postures.
 The experience of somatosensory memories does not appear to be related to the duration of pre-amputation pain, time since amputation, age, gender, prosthetic use, level of amputation, number of limbs amputated, or whether the amputation followed an accident or illness.
 The results suggest that somatosensory inputs of sufficient intensity and duration can produce lasting changes in central neural structures which combine with cognitive-evaluative memories of the pre-amputation pain to give rise to the unified experience of a past pain referred to the phantom limb.
 Implications for pre- and post-operative pain control are discussed.
",9
1618,"Diphtheria-tetanus-pertussis vaccine and serious neurologic illness: an updated review of the epidemiologic evidence.
 A widespread impression that DTP vaccine does cause brain damage has been based first on historical precedent--smallpox and rabies vaccines were recognized as sometimes causing devastating neurologic illness; analogy to pertussis--the disease can cause encephalopathy; and more recently on anecdotal evidence, particularly case series.
 A noncausal relationship--coincidence--could explain the temporal relation between DTP vaccine and neurologic illness, inasmuch as DTP vaccine is given at the age of emergence of idiopathic neurologic disease.
 The relationship between DTP vaccine and neurologic illness lacks specificity.
 Case series have had an impact on both physicians' and the lay public's impression of the safety of pertussis vaccine greatly out of proportion to their scientific importance.
 Case series can be useful for generating hypotheses but cannot provide evidence that pertussis vaccine is causally related to acute neurologic illness or brain damage.
 Observational studies using cohort and ecologic designs did not find an association between DTP vaccine and serious neurologic illness, but they were not powerful enough to detect an association as rare as that observed by the NCES investigators.
 The case-control design offers the best chance of providing causal evidence regarding DTP vaccine and serious neurologic illness.
 The NCES is the only published case-control study of this issue.
 This study found a rare association between DTP vaccine and some types of acute neurologic illness.
 Bias and chance are unlikely to account entirely for the association demonstrated by the NCES.
 However, the association has not yet been replicated by other case-control studies.
 The NCES does not demonstrate that DTP vaccine causes permanent brain damage.
",9
1619,"Can clinical judgment detect children with speech-language problems?
 Pediatricians often rely on clinical judgment derived from observation or parental concern to identify children with developmental problems.
 The less popular but recommended alternative is to repeatedly administer standardized screening tests.
 Such tests are time consuming but, unlike clinical judgment, have known detection rates.
 Preliminary research concerning clinical judgment showed that clusters of parental concerns related to their childrens' performances on screening tests.
 In the present study, previous research was refined by assessment of the meaning of parents' concerns about their childrens' speech-language development.
 In this study of 157 families seeking pediatric care, 72% of children whose speech-language screening yielded positive results had parents who were concerned about their speech-language development.
 Of children with negative screening results, 83% had parents with no concerns about their speech-language development.
 Although standardized screening tests should be used occasionally in the developmental surveillance process, the findings show that the problems of most children with developmental problems were detected through clinical judgment based on parental concern.
",9
1620,"Pain management in the orthopedic patient.
 Pain is a familiar phenomenon to all orthopedic nurses.
 As Dunwoody said, ""Few things we do for patients are more fundamental to the quality of life than relieving pain."" We as orthopedic nurses are in a position to contribute to the positive management of pain by using a comprehensive approach to pain management that involves the participation of the patient.
 We need to believe the patient's pain, try new approaches, and help our patients achieve pain relief.
",9
1621,"Help for the hurting elderly. Safe use of drugs to relieve pain.
 Pharmacologic management of pain in elderly patients is a common and difficult clinical problem.
 Because of altered drug metabolism and pharmacodynamics in the elderly, the drugs of choice are different than in younger patients and side effects occur more often.
 However, with judicious use and monitoring for toxicity, oral medications given as part of a multimodality approach can achieve adequate analgesia in most elderly patients.
",9
1622,"Movement analysis--an aid to early diagnosis of cerebral palsy.
 The purpose of this article is to review research related to the use of clinical analysis of movement as an aid to the early diagnosis of cerebral palsy.
 A historical perspective of clinical techniques used by physicians and physical therapists in the early diagnosis of cerebral palsy will be presented first, including recent research findings on clinical signs that were most predictive of this movement disorder.
 Predictive neuromotor behaviors common across several recent studies will be highlighted.
 Future trends in the use of movement analysis, including digitized kinematic analysis of term and preterm infants and fetal ultrasound techniques, will be discussed as well.
",9
1623,"Implications of a dynamical systems approach to understanding infant kicking behavior.
 Implications of the dynamical systems approach to understanding movement dysfunction in infants are discussed.
 Traditional theories of motor development attribute changes in movement to the hierarchical maturation of the central nervous system.
 The dynamical systems approach emphasizes that movement self-organizes as the result of the interaction of the participating subsystems in developmental and real time.
 In this article, I discuss, from the theoretical perspective of the dynamical systems approach, the organization of leg movements in low- and high-risk preterm and full-term infants, developmental changes in movement in low-risk preterm infants from 34 weeks' gestational age to 40 weeks' postgestational age, and differences in movement between low-risk preterm infants at 40 weeks' postgestational age and full-term infants.
 Preliminary data on high-risk preterm infants are presented.
 Based on these data, the necessity to review and reinterpret traditional concepts of motor development is explored.
 Suggestions are offered and questions posed on how the dynamical systems perspective may influence the practice of physical therapy in the evaluation, and treatment of infants at risk for movement dysfunction.
",9
1624,"Cognitive strategies during coincident timing tasks.
 Research findings suggest that experience and cognitive strategies contribute to successful performance during perceptual-motor tasks.
 This article critically reviews selected literature on the effects of information-processing skills, preferred movement time, experience, and task difficulty on performance during coincident timing tasks.
 Theoretical information and research findings are discussed, and their applications to clinical practice are considered.
 Clinical recommendations include assessment of coincident timing skills and use of functional activities that provide opportunities to explore and dynamically interact with the environment.
",9
1625,"Measurement and treatment in cerebral palsy: an argument for a new approach.
 This article describes the need for a shift in our therapeutic strategies for patients with cerebral palsy.
 Changes in functional abilities must be stressed in therapy.
 Coincident with this emphasis must be the development of functional assessments to be used when documenting intervention outcomes.
 Research on functional arm movement using kinematic analysis is described for this patient group.
",9
1626,"Dorsal rhizotomy for children with cerebral palsy: support for concepts of motor control.
 The results from selective dorsal rhizotomy research suggest that therapists need to question some common clinical assumptions about movement dysfunction.
 The rationale for performing a selective dorsal rhizotomy is based on the clinical assumptions that spasticity is the underlying cause of disordered movement and that reducing or eliminating the spasticity will improve movement.
 This article reviews the literature related to movement dysfunction, the effects of selective dorsal rhizotomy, and the evidence for disordered motor control in children with spastic cerebral palsy.
 Selective dorsal rhizotomy appears to reduce spasticity and increase joint range of motion.
 Abnormal movement patterns, however, persist after the spasticity is reduced.
 Well-coordinated movement patterns are acquired slowly and appear to be related to an intense period of physical therapy.
 I argue that these results provide evidence that the presence of spasticity alone is an insufficient explanation for abnormal movement patterns.
 I propose that physical therapists redirect their efforts from developing methods for reducing spasticity to developing adequate assessment, treatment, and measurement techniques for assessing motor control in children with cerebral palsy.
 I believe we can maximize the functional potential of children with cerebral palsy by identifying problems related to motor control and applying sound principles of motor learning to treatment.
",9
1627,"Cerebellar degeneration and Meige's syndrome.
 We have reported a case of Meige's syndrome in a middle-aged man who eventually had a cerebellar degeneration syndrome.
 The extrapyramidal symptoms preceded cerebellar signs and symptoms by 5 years.
 Most patients with idiopathic Meige's syndrome show some improvement with high-dose anticholinergic therapy.
 Our patient's lack of response to such agents and his subsequent cerebellar symptoms are reminiscent of the situation seen with parkinsonian patients who do not respond to medications, indicating a more widespread degenerative disease.
 The association of extrapyramidal symptoms with some spinocerebellar disorders, and the pathologic changes seen in the one reported autopsy case, should place the group of spinocerebellar disorders high on the differential list.
",9
1628,"Experience with surgical treatment of Takayasu's disease.
 We reviewed 28 patients with Takayasu's disease to determine the incidence of stroke and its relationship to the involvement of the thoracic aortic arch and its branches.
 We describe surgical experiences with 10 of the 28 patients who required 21 vascular surgical procedures for critical thoracic aortic arch arterial stenoses, upper and lower extremity ischemia, and renal artery stenoses.
 Four of the 28 patients initially had a stroke caused by occlusion of one or more thoracic aortic arch arteries.
 Six of the 10 patients underwent 7 bypass procedures for critical thoracic arch stenoses.
 All have remained free of stroke for 5 or more years.
 Four patients had five anastomotic stenoses or graft occlusions in late follow-up; the development of these stenoses did not relate to disease activity at the time of the operative procedure.
 All bypass grafts originating from the subclavian axillary artery developed anastomotic stenoses; no anastomotic stenoses occurred in bypass grafts originating from the ascending aorta.
 In contrast to other reports, no anastomotic false aneurysms occurred.
 Occlusions of major aortic arch arteries in Takayasu's disease cause stroke.
 Bypass of critically stenoses aortic arch arteries protects against stroke and is best performed with grafts originating from the ascending aorta.
 Anastomotic stenoses but not anastomotic aneurysms are common.
 This study suggests that aggressive surgical treatment can be performed with good results.
",9
1629,"Murine retroviral neurovirulence correlates with an enhanced ability ofvirus to infect selectively, replicate in, and activate resident microglial cells [published erratum appears in Am J Pathol 1991 May;138(5):1058]
 To determine the biologic basis of ts1 MoMuLV neurovirulence in vivo, newborn CFW/D mice were inoculated with neurovirulent ts1 MoMuLV and nonneurovirulent wt MoMuLV and the temporal response to virus infection in the central nervous system (CNS), spleen, and thymus was studied comparatively.
 Experimental procedures included single and double labeling in situ immunohistochemistry with selective morphometric analyses, and steady state immunoblotting of viral proteins.
 Cellular targets for virus infection were identical for both ts1 and wt MoMuLV and consisted sequentially of 1) splenic megakaryocytes, 2) splenic and thymic lymphocytes, 3) CNS capillary endothelial cells, and 4) CNS pericytes and microglia.
 Resident microglial cells served as the major reservor and amplifier of virus infection in the CNS of ts1 MoMuLV-infected mice; a similar but much less significant role was played by microglia in wt MoMuLV-infected mice.
 The genesis and progression of severe spongiform lesions in ts1 MoMuLV-infected mice were both temporally and spatially correlated with amplified virus infection of microglia, and hyperplasia and hypertrophy of both virus-infected and nonvirus-infected microglial cells.
 Direct virus infection of neurons was never observed.
 The development of clinical neurologic disease and spongiform lesions in ts1 MoMuLV-infected mice correlated with the accumulation of both viral gag and env gene products in the CNS; there was no selective accumulation of env precursor polyprotein Pr80env.
 When compared to wt MoMuLV-infected mice, the neurovirulence of ts1 MoMuLV-infected mice occurred by an enhanced ability to replicate in the CNS and to infect and activate more microglia, rather than by a fundamental change in cellular tropism or topography of virus infection.
",9
1630,"Secondary deposition of beta amyloid within extracellular neurofibrillary tangles in Alzheimer-type dementia.
 The hippocampal areas of 34 autopsy specimen brains from aged demented and nondemented subjects were examined using double staining of Bodian and beta protein.
 In 18 cases (75.5 +/- 7.4 years old), none of the extracellular neurofibrillary tangles (E-NFTs) were immunoreactive with beta protein.
 In 16 cases (82.9 +/- 5.4 years old), the minority of E-NFTs were immunoreactive with beta-protein antiserum.
 These beta-immunoreactive E-NFTs frequently appeared in the areas having senile plaques, while they were not observed in the area lacking beta-immunoreactive senile plaques.
 The ultrastructure of beta-immunoreactive E-NFTs revealed that they consisted of extracellular amyloid fibrils, extracellularly located bundles of paired helical filaments, astroglial processes and degenerating neurites.
 These findings suggest that the beta immunoreactivity of E-NFTs comes from secondary deposition of amyloid fibrils.
",9
1631,"The induction dose of propofol in infants 1-6 months of age and in children 10-16 years of age.
 The propofol dose needed for satisfactory induction of anesthesia was determined in 22 infants 1-6 months of age and 22 children 10-16 yr of age.
 A single bolus of propofol was given over 10 s.
 Thirty seconds after injection the lid reflex was tested and the anesthesia mask was applied.
 The patient was considered to be asleep if there were no gross movements during the next 30 s while the patient breathed O2.
 The dose required for satisfactory induction in 50% of patients (ED50) (+/- SE) was 3.0 +/- 0.2 mg/kg in infants and 2.4 +/- 0.1 mg/kg in older children (P less than 0.02).
 Pain on injection occurred in 50% of the infants and 18% of the children.
",9
1632,"Changing indications for penetrating keratoplasty in Vancouver, 1978-87.
 Indications for penetrating keratoplasty (PK) were assessed by clinicopathological review of 659 corneal buttons submitted from 1978 to 1987 to the Ophthalmic Pathology Service in Vancouver.
 Leading indications for PK were bullous keratopathy (22.2%), keratoconus (17.1%), scarring with or without chronic inflammation (13.5%), graft failure (12.1%), scarring or active keratitis secondary to virus (9.0%) and Fuchs' dystrophy (8.3%).
 The principal factors responsible for graft failure were also judged by clinicopathological correlation.
 The authors compare their findings with those in other series.
",10
1633,"The management of chalazion: a survey of Ontario ophthalmologists.
 Owing to the variability and lack of standardization of chalazion management, a survey of Ontario ophthalmologists was undertaken.
 The results highlight what ophthalmologists consider to be problems in chalazion management and suggest that a chalazion operation should be treated with the same respect given any other operation.
",10
1634,"Thromboxane A2-mimetics are potent microvascular permeability factors in the conjunctiva.
 These studies demonstrate that the thromboxane (Tx) A2 mimetics U-46619, U-44069 and carbocyclic-TxA2 elicit a microvascular permeability response in the conjunctiva.
 U-46619 and U-44069 are among the most potent microvascular permeability factors described to date for the conjunctiva; their potency is exceeded only by that reported for leukotrienes D4 and E4.
 The conjunctival microvascular permeability response to U-46619 was inhibited by the TxA2-antagonists daltroban (BM 13505) and SQ 29548.
 Prostaglandin (PG) D2 also increased conjunctival microvascular permeability, but was less potent than U-46619 and far less susceptible to pretreatment with daltroban or SQ 29548.
 PGE2, PGF2 alpha and the prostacyclin analog carbocyclin did not increase conjunctival microvascular permeability.
 It appears that the conjunctiva exhibits a unique microvascular permeability response to TxA2-mimetics: this view is experimentally supported by the absence of a cutaneous microvascular permeability response to U-46619, U-44069 and carbocyclic-TxA2.
",10
1635,"Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase 
 Mice homozygous for the rd mutation display hereditary retinal degeneration and the classic rd lines serve as a model for human retinitis pigmentosa.
 In affected animals the retinal rod photoreceptor cells begin degenerating at about postnatal day 8, and by four weeks no photoreceptors are left.
 Degeneration is preceded by accumulation of cyclic GMP in the retina and is correlated with deficient activity of the rod photoreceptor cGMP-phosphodiesterase.
 We have recently isolated a candidate complementary DNA for the rd gene from a mouse retinal library and completed the characterization of cDNAs encoding all subunits of bovine photoreceptor phosphodiesterase.
 The candidate cDNA shows strong homology with a cDNA encoding the bovine phosphodiesterase beta subunit.
 Here we present evidence that the candidate cDNA is the murine homologue of bovine phosphodiesterase beta cDNA.
 We conclude that the mouse rd locus encodes the rod photoreceptor cGMP-phosphodiesterase beta subunit.
",10
1636,"Phacofragmentation of a hard lens nucleus in the posterior segment.
 Foreign body forceps were used to stabilize a hard lens nucleus during phacofragmentation in the posterior segment.
 This technique allows removal of the hard lens nucleus with minimal manipulation and without the need for a larger incision.
",10
1637,"The Glaucoma Laser Trial (GLT). 2. Results of argon laser trabeculoplasty versus topical medicines. The Glaucoma Laser Trial Research Group 
 The Glaucoma Laser Trial, a multicenter, randomized clinical trial involving 271 patients, was designed to assess the efficacy and safety of argon laser trabeculoplasty (ALT) as an alternative treatment with topical medication for controlling intraocular pressure (IOP) in patients with newly diagnosed, previously, untreated primary open-angle glaucoma (POAG).
 Each patient had one eye randomly assigned to ALT (the laser first [LF] eye) and the other eye assigned to timolol maleate 0.5% (the medication first [MF] eye).
 Medication was initiated or changed for either eye according to the same stepped regimen if the IOP was not controlled.
 Throughout the 2-year follow-up, LF eyes had lower mean IOPs than MF eyes (1-2 mmHg), and fewer LF eyes than MF eyes required simultaneous prescription of two or more medications to control IOP (P less than 0.001).
 After 2 years of follow-up, 44% of LF eyes were controlled by ALT, 70% were controlled by ALT or ALT and timolol, and 89% were controlled within the stepped medication regimen.
 After 2 years, 30% of MF eyes remained controlled by timolol, and 66% were controlled within the stepped regimen.
 There were no major differences between the two treatment approaches with respect to changes in visual acuity or visual field over the 2 years of follow-up.
",10
1638,"Nystagmus in Down's syndrome.
 The incidence and characteristics of nystagmus in Down's syndrome are unclear.
 In 188 consecutive patients, 56 had nystagmus.
 Most had no clinically recognizable ocular pathology to account for the nystagmus.
 Twenty-nine had fine rapid horizontal nystagmus, 14 had a dissociated nystagmus which appeared pendular, whereas 9 had a form of latent or manifest latent nystagmus.
 Of the total patients with nystagmus, 41 had esotropia.
 Our findings suggest that fine rapid horizontal nystagmus, sometimes dissociated, occurs frequently in patients with Down's syndrome.
",10
1639,"Intraocular lens implantation after penetrating keratoplasty. Improved unaided visual acuity, astigmatism, and safety in patients with combined corneal disease and cataract.
 Twenty-two eyes with combined corneal disease and cataract were followed prospectively after nonsimultaneous intraocular lens (IOL) placement after penetrating keratoplasty; the majority had a penetrating keratoplasty and planned extracapsular cataract extraction (ECCE) followed later by the placement of an IOL.
 The mean follow-up after IOL placement was 25 months (range, 3-55 months).
 No graft failures occurred after secondary surgery.
 All graft sutures were removed in 86% (19/22) of eyes before IOL surgery.
 Ninety-five percent (21/22) of the eyes achieved refractive errors within 2 diopters (D) of the desired result.
 Corneal astigmatism decreased from 4.88 to 2.92 D after secondary surgery and wound revision.
 Unaided visual acuity was 20/40 or better in 68% (15/22) and 20/100 or better in 91% (20/22) of the eyes.
 The advantages of excellent unaided visual acuity, reduced astigmatism, and lack of anisometropia and graft failure outweigh the disadvantage of some delay in final visual rehabilitation (11 months) and increased secondary capsulotomy rate (85%) in this series with two separate surgeries compared with previously reported triple procedure results.
",10
1640,"Results of blepharoptosis surgery with early postoperative adjustment.
 The authors reviewed 157 cases (207 eyes) of blepharoptosis corrected by external levator resection.
 Twenty-eight patients (29 eyelids) had unsatisfactory results.
 The authors adjusted 13 eyelids within 1 week of surgery.
 Eleven eyelids were reoperated 6 or more weeks after surgery.
 The mean delay between the initial and final surgery in the early group was 2.0 weeks; and, for the late group, 33.5 weeks.
 For those having reoperations, there was no difference in the number of procedures required to achieve satisfactory outcomes.
 Four patients (5 eyelids) with unsatisfactory results were offered, but declined, late repair.
 Early or late reoperation is effective in correcting unsatisfactory results after external levator resection.
 The benefits of early surgery are a reduction in time to final result, the ease with which it is performed, potential cost savings, and the opportunity one has to correct unsatisfactory results.
",10
1641,"Visual prognosis correlated with the presence of internal-limiting membrane in histopathologic specimens obtained from epiretinal membrane surgery.
 Forty-one patients with a unilateral, macular epiretinal membrane (ERM) underwent pars plana vitrectomy and membrane peeling to improve the visual acuity.
 The authors retrospectively reviewed the histopathology of the vitrectomy specimen in each instance to determine whether the presence of internal-limiting membrane (ILM) had an adverse effect on visual acuity.
 Eleven specimens contained long segment of ILM, as determined by light microscopy.
 With a minimum of 6 months of follow-up, none of these 11 eyes achieved a visual acuity of better than 20/60.
 Of 30 eyes that did not have ILM present, 41% achieved a visual acuity of 20/60 or better.
 Overall, 29% of the eyes in the entire series achieved 20/60 or better visual acuity.
 The difference between the group with ILM versus that without ILM was statistically significant (P = 0.01).
 The presence of long segments of ILM within the histopathologic specimen after vitreous surgery for removal of a macular ERM appears to indicate a less favorable visual outcome.
",10
1642,"Semiconductor diode laser photocoagulation in retinal vascular disease.
 The authors successfully performed clinical transpupillary retinal photocoagulation in 30 eyes of 26 patients with retinal vascular disease using a gallium-aluminium-arsenide (GaAlAs) diode laser emitting at 805 nm.
 Retinal photocoagulation was performed at treatment powers of 300 to 1300 mW and exposure durations of 0.2 to 0.5 seconds with a 200-microns diameter treatment spot.
 Patients treated with both diode and argon green lasers required 4.5 +/- 1.8 times greater mean laser energy with diode compared with argon to create ophthalmoscopically similar lesions.
 Parallel experimental retinal photocoagulation in Chinchilla rabbits required 3.1 +/- 0.9 times more power to create ophthalmoscopically similar lesions with the diode laser than with the argon laser.
 Intraoperative subretinal hemorrhage occurred rarely in patients with an incidence of 4 (0.44%) of 9021 treatment spots.
 Patients complained of moderate-to-marked pain in 10 (43%) of 23 treatments initiated under topical anesthesia.
 A transpupillary diode laser may be used clinically to perform therapeutic retinal photocoagulation.
",10
1643,"The repair of rhegmatogenous retinal detachments. American Academy of Ophthalmology.
 Current techniques of rhegmatogenous retinal detachment repair allow most retinal detachments to be repaired successfully.
 The success of repair depends on a careful preoperative examination and choice of an appropriate surgical procedure.
 The surgical procedure must be tailored to the individual eye based on a detailed preoperative examination of the retina and vitreous.
 Postoperative complications are not infrequent compared to many other ophthalmic surgical procedures such as cataract extraction and strabismus repair.
 The surgeon must observe the eye carefully in the postoperative period to monitor and treat any complications as they arise.
 Improvements in surgical techniques coupled with a better understanding of the pathophysiology of rhegmatogenous retinal detachment continue to improve the anatomic and functional success of retinal detachment repair.
",10
1644,"Retinal pigment epithelial tears through the fovea with preservation of good visual acuity.
 We describe two patients with spontaneous retinal pigment epithelial tears through the fovea who have maintained at least 20/40 visual acuity for 1 year and 3 years following the rip.
 Both patients had long-standing serous detachments of the retinal pigment epithelium associated with age-related macular degeneration prior to the development of the tear.
 Each tear was at least five disc areas in size and centered on the fovea.
 Foveal fixation was documented despite the presumed absence of pigment epithelium.
 This observation suggests either that there may be remaining or redundant pigment epithelium or that pigment epithelium directly beneath the central macula is not required for maintenance of 20/40 visual acuity.
",10
1645,"Inflammatory mediators in postoperative aphakic and pseudophakic baboon eyes.
 We measured prostaglandin E2 and leukotriene B4 in the aqueous humor of baboon eyes, 1 or 8 days after phacoemulsification, with or without posterior chamber lens implantation.
 We also evaluated the effects of steroid eye drops and cyclooxygenase inhibitor eye drops on the synthesis of these mediators of inflammation.
 Eyes that had undergone phacoemulsification showed significant elevation of prostaglandin E2 at both postoperative periods compared with normal, phakic control eyes.
 The level of prostaglandin E2 was significantly (P less than .05) higher in eyes with posterior chamber lens implantation than in those without it, and was significantly (P less than .05) higher on the eighth than on the first postoperative day.
 The amount of leukotriene B4 was below the detection limit, except in the few eyes in which complications developed.
 Cyclooxygenase inhibitor eye drops significantly reduced the amount of prostaglandin E2 on both postoperative days, while steroid eye drops had no such effect.
",10
1646,"The potential for mental status changes associated with systemic absorption of anticholinergic ophthalmic medications: concerns in the elderly.
 Several cases have been reported of anticholinergic toxicity following the administration of commonly used parasympatholytic cycloplegics and mydriatics.
 Cases have been reported in children, adults, and the elderly.
 The risk of developing mental status changes secondary to anticholinergic ophthalmic medications is of particular concern in the elderly.
 Drug-induced mental status or behavior changes should not be mistaken for exacerbation of an underlying disorder or the onset of a new disease (e.g., Alzheimer's disease, dementia).
 Clinicians should be aware of these potential complications, monitor for changes in mental status, and take appropriate action.
",10
1647,"Pathophysiologic effect of interleukin-1b in the rabbit retina.
 Interleukin-1 is a potent immunomodulator and has been shown to initiate many aspects of the inflammatory response.
 To determine the effects of IL-1b in the central nervous system (CNS), the rabbit retina was used, adjacent to which factors can be injected with minimal trauma and both pathologic and physiologic effects can be monitored.
 Intravitreal injection of 300 units of IL-1b induced an alteration in the visual evoked potentials (VEP) that was associated with marked intravascular red blood cell accumulations, hemorrhage, and cellular inflammation of the epiretinal vessels.
 Analysis of these events showed slowing and occasional hyper-excitability of the compound action potential of the optic tract and of the cortical VEP that correlate with the maximum inflammatory response.
 Histologic studies show the following: no apparent response occurs within the first 1.5 hours after intraocular challenge; and between 3 and 6 hours after injection an extensive intravascular red blood cell accumulation and progressive hemorrhage is accompanied by an increase in the number of mononuclear (MN) cells and the appearance of polymorphonuclear (PMN) cells.
 Polymorphonuclear cells continue to increase with time to give a single wave of inflammation that peaks 24 hours after injection, while the number of MN cells steadily increases.
 These events are associated with changes in the permeability of the blood-brain barrier and correlate with the electrophysiologic dysfunctions.
 Forty-one hours after injection, MN inflammation, reactive gliosis, and residual PMN inflammation are evident.
 Neutralization with specific antibody inhibited the responses through 6 hours after injection.
 It is concluded that the rabbit retina provides a valuable model for the in vivo analysis of CNS inflammation.
",10
1648,"Eyelid movements before and after botulinum therapy in patients with lid spasm.
 Quantitative analysis of lid motility is presented for 4 individuals with hemifacial spasm and 1 with Meige's syndrome.
 The data were obtained, by means of a magnetic search coil technique, prior to and 1 week after injection of botulinum toxin into the orbicularis oculi muscle.
 Before treatment, the peak velocity of blink-related lid lowering and lid raising was slower than normal, yet lid saccades were normal.
 After botulinum treatment, significant decreases occurred in (1) the amplitude of blinks and lid saccades, and (2) the peak velocity of the blink down-phase.
 Botulinum treatment significantly alters blink lid-lowering kinematics, while saccadic lid-lowering kinematics are normal, providing further evidence that the orbicularis oculi muscle does not play a primary role in downward lid saccades.
",10
1649,"Scientific basis for medical therapy of cataracts by antioxidants.
 Cataract is one of the major causes of age-dependent visual impairment and blindness.
 The geographic distribution of cataract is known to be associated with the intensity and duration of sunlight--especially of the ultraviolet frequency--at particular places.
 Exposure of animals and humans to oxygen has also been known to result in cataract formation.
 Studies described in this communication indicate that the ocular lens is physiologically damaged when exposed to an environment of active species of oxygen, commonly referred to as oxyradicals.
 Several photochemical and nonphotochemical models have been described.
 The results suggest that an intraocular generation of active oxygen may constitute a significant risk factor in the overall pathogenesis of senile cataracts.
 The cataractogenic effect of oxyradicals, however, can be thwarted by nutritional and metabolic antioxidants such as ascorbate, vitamin E, and pyruvate.
 These agents, therefore, may be useful for prophylaxis or therapy against cataracts.
",10
1650,"A possible role for vitamins C and E in cataract prevention.
 Biochemical evidence suggests that oxidative stress caused by accumulation of free radicals is involved in the pathogenesis of senile cataracts.
 If so, appropriate amounts of the antioxidant vitamins C and E might be expected to prevent or retard the process.
 Such activity has been observed in several in vitro and in vivo studies of experimentally-induced cataracts.
 A recent epidemiologic study found that cataract patients tended to have lower serum levels of vitamins C, E, or carotenoids than did control subjects.
 The present investigation, which compared the self-reported consumption of supplementary vitamins by 175 cataract patients with that of 175 individually matched, cataract-free subjects, revealed that the latter group used significantly more supplementary vitamins C and E (P = 0.01 and 0.004, respectively).
 Because the results suggested a reduction in the risk of cataracts of at least 50%, a randomized, controlled trial of vitamin supplementation in cataract prevention may be warranted.
",10
1651,"Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention.
 The relationship between antioxidant nutrient status and senile cataract was examined in 77 subjects with cataracts and 35 control subjects with clear lenses.
 Subjects with low (below the 20th percentile) and moderate (20th-80th percentiles) plasma nutrient and nutrient intake levels of vitamin C, vitamin E, and carotenoids were compared with subjects with high levels (above the 80th percentile).
 The odds ratio (OR) of cortical (CX) cataract among subjects with low plasma carotenoid levels was 7.2 (P less than 0.05) and the OR of posterior subcapsular (PSC) cataract for persons with low plasma vitamin C was 11.3 (P less than 0.10).
 Low vitamin C intake was associated with an increased risk of CX (OR = 3.7, P less than 0.10) and PSC (OR = 11.0, P less than 0.05) cataract.
 Subjects who consumed fewer than 3.5 servings of fruit or vegetables per day had an increased risk of both CX (OR = 5.0, P less than 0.05) and PSC cataract (OR = 12.9, P less than 0.01).
",10
1652,"Prevalence of lattice degeneration and its relation to axial length in severe myopia.
 We studied 436 eyes of 218 patients with myopia of -6.00 diopters or more in both eyes.
 Of 218 patients, 72 (33.0%) had lattice degeneration of the retina.
 Among these 72 patients, lattice lesions were uniocular in 39 (54.2%) and binocular in 33 (45.8%).
 Of 105 males, 33 (31.4%) had lattice degeneration; of 113 females, 39 (34.5%) had lattice degeneration.
 Contrary to previously published data, we found an inverse relationship between axial length and the prevalence of lattice degeneration in severely myopic eyes.
 The greatest prevalence of lattice degeneration (63 of 154 eyes, 40.9%) was found in eyes with an axial length of 26.0 to 26.9 mm (-6.00 to -8.70 diopters), and the least prevalence of lattice degeneration (five of 71 eyes, 7.0%) was found in eyes with an axial length of 32.0 mm (-24.00 diopters) or greater.
 This may explain the observation that retinal detachment after cataract surgery has been noted more commonly among patients with moderate than severe myopia.
",10
1653,"Photic retinal injury from endoillumination during vitrectomy.
 We treated a patient who developed a paramacular area of light-induced retinal damage after endoscopic epimacular membrane removal.
 Postoperative color photographs showed complete absence of the membrane, but fluorescein angiography demonstrated a previously absent superior paramacular lesion consistent with a photic injury.
 Operative microscope illumination had been eliminated by corneal shielding, which implicated endoillumination as the source of injury.
 We recommend the following procedures to avoid this complication: careful planning of vitreous surgery for epimacular membrane removal; using filters; minimizing the length of surgery; keeping the light output low; maintaining maximal light pipe distance from the retina; eccentric orientation of the light pipe; and use of intermittent and variable site illumination techniques.
",10
1654,"Light damage in detached retina.
 We injected homologous fibroblasts over the retinal vascular wing in five rabbits to induce a tractional retinal detachment.
 Eleven days later, a focal area of detachment was exposed to 30 minutes of visible light by an intraocular fiberoptic probe.
 Histologic damage to the detached retina exposed to light was demonstrated.
 The outer retina was affected most severely.
",10
1655,"Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma.
 Fifty-five patients with primary open-angle glaucoma and early glaucomatous damage who had medical therapy and laser trabeculoplasty were followed up for four to 11 years or until progressive glaucomatous damage was documented.
 Factors associated with the stability or progression of glaucoma were evaluated.
 Eyes with mean intraocular pressure higher than 21 mm Hg during the follow-up period uniformly had progressive glaucomatous changes.
 Conversely, eyes with mean intraocular pressure less than 17 mm Hg remained stable, and approximately half of the eyes with mean intraocular pressure between 17 and 21 mm Hg had progressive glaucomatous changes.
 Patients who remained stable were slightly younger than those with progressive glaucomatous changes (P less than .05), but initial optic nerve head appearance, initial visual field findings, number of medicines used, medical history, and patient gender or race were not statistically associated with stability or progression of the glaucoma.
 These findings reinforce the importance of intraocular pressure control in primary open-angle glaucoma and the need to identify other markers that help determine the proper level of intraocular pressure for individual patients.
",10
1656,"A new method for documenting lens opacities.
 We tested an anterior segment camera and digital analyzer on 32 eyes of 22 patients to determine whether its measurement of lens opacities correlated with measurements obtained by a standardized clinical grading system.
 The lenses were graded clinically for nuclear opacity, nuclear color, cortical opacity, and posterior subcapsular opacity.
 The lenses were then photographed and analyzed with this new device, and the results were compared.
 The camera system showed good reproducibility.
 Its results correlated well with the clinical gradings for nuclear capacity (P = .001) and cortical opacity (P = .001) but less well with posterior subcapsular opacity (P = .3), although there were only seven eyes with posterior subcapsular opacities.
 This camera system could help document and follow up lens opacity with more accuracy and reproducibility than has been previously possible.
",10
1657,"Causes of failure after initial vitreoretinal surgery for severe proliferative vitreoretinopathy.
 We performed initial vitreoretinal surgery on 81 eyes with rhegmatogenous retinal detachments complicated by severe proliferative vitreoretinopathy.
 Of 81 eyes, 68 (84%) had undergone previous scleral buckling.
 We performed vitreous base dissection on all 18 eyes (22%) that had anterior proliferative vitreoretinopathy.
 With one vitreoretinal operation, 66 of 81 eyes (81%) remained totally reattached.
 The main cause of initial anatomic failure and reoperation was either new or recurrent proliferation at the vitreous base.
 With additional vitreoretinal surgery and after a mean follow-up period of 19 months, 73 of 81 retinas (90%) were totally reattached.
 The final causes of anatomic failure were anterior proliferative vitreoretinopathy and proliferation from relaxing retinotomies.
 Of the 73 successfully reattached eyes, 62 (85%) had postoperative visual acuity of 5/200 or better.
",10
1658,"Aphakic visual fields by automated perimetry.
 Accurate testing of the visual field of aphakic patients is demanding due to the optical distortion induced by high plus corrective lenses.
 This testing procedure can be improved by using an aspheric contact lens instead of a full-aperture loose trial lens.
 We found that the contact lens enhances the ability of the pattern-deviation printout of the Statpac analysis to identify glaucomatous visual field abnormalities in program 30-2 of the Humphrey Visual Field Analyzer.
",10
1659,"The predictability of infant visual-evoked response testing on future visual acuity.
 We reviewed the records of 27 infants with abnormal eye examinations and visual-evoked response (VER) testing (mean age, 10.5 months) who subsequently underwent a long-term follow-up ophthalmology examination (mean duration, 41 months).
 The infants were initially diagnosed with various ocular disorders including cortical blindness (eight), optic nerve hypoplasia (six), congenital cataract (two), and retinopathy of prematurity (one).
 Standard optotype visual-acuity determinations were available in the follow-up records of 11 children (21 eyes), and fixation behavior was obtained in the remaining 16 children (32 eyes).
 Results revealed that pattern-reversal VER P1 latency was predictive (87%) of whether visual acuity was equal to (or better than) or worse than 20/100 and whether a patient would have good fixation behavior (fix and follow, FF) or poor fixation (no FF) (86%) (P less than .001).
 Although flash VER P1 latency was also predictive of later visual acuity or good fixation (73%), it was not statistically significant.
 Pattern VER P1 amplitude and flash VER P1 amplitude were not predictive of later visual function.
 The predictive power of pattern VER P1 latency for later visual function probably relates to its reflection of macular function and low variability.
 An analysis of the variability of each of the four VER factors in normal infants (n = 50) indicated that pattern VER P1 latency was the least variable, and consequently most sensitive, VER factor for detecting and quantifying pathology.
 Overall, the results of this retrospective study suggest that pattern VER P1 latency may have important predictive power for later visual function in infants with an initially abnormal ophthalmologic examination.
",10
1660,"Clear ultraviolet blocking lenses for use by PUVA patients.
 It is well recognized that patients receiving photochemotherapy (PUVA) need to wear UV-blocking sunglasses on the day of ingestion of 8-methoxypsoralen.
 For many patients the wearing of tinted sun-glasses causes difficulties because they interfere with colour perception, reduce definition in conditions of low background light and often because they are considered 'cosmetically unacceptable'.
 In this study the UV-blocking properties of a number of lenses with little or no tint were assessed.
 The following lenses or lens coatings were found to be suitable for use by PUVA patients: Orcolite UV 400, Orma UVX, Rodenstock Lambda 400, Sola UV Gard 400 and Polaroid polarizing lenses.
",10
1661,"Graves' disease. Current concepts.
 Graves' disease is an organ-specific autoimmune disorder.
 There is no universal agreement on the mechanism of Graves' disease, but the over-activity of the thyroid is due to an antibody capable of attaching to and activating the TSH receptor of follicular cells.
 There are other extrathyroidal features that are not caused either by this antibody or by hyperthyroidism.
 The clinical diagnosis is generally straightforward and can be confirmed by in vitro measurement of thyroid hormones and TSH.
 A measurement of radioiodine uptake is also valuable.
 Treatment is not specific for the immunologic defect, but its purpose is to lower the thyroid hormone levels to normal.
 This can be achieved with antithyroid medication, radioiodine iodine-131, or thyroidectomy.
 In most clinical situations, a strong argument can be made for iodine-131 therapy, which is safe and definitive, although posttreatment hypothyroidism and the need for lifelong thyroxine are to be expected.
",10
1662,"The ophthalmopathy of Graves' disease.
 Fortunately, most patients with thyroid-related eye disease have mild ocular involvement that spontaneously involutes.
 Less than 5% of patients with hyperthyroidism will develop sufficiently severe ocular abnormalities that will require surgical intervention.
 Most patients with thyroid eye findings should be symptomatically managed.
 Some will require use of either topical drops or oral steroids to alleviate their eye problems.
 In approximately one half of those patients who present acutely with severe thyroid orbital finding, nonsurgical therapies will be sufficient to control their eye disease.
 In the other half, eventually multiple surgical procedures may be required, and as discussed previously, the timing and sequence of those procedures are crucial to achieve optimal results.
",10
1663,"Cyclocryotherapy in selected cases of congenital glaucoma.
 We investigated the efficacy of cyclocryotherapy, a procedure which destroys the ciliary epithelium, thereby decreasing the production of aqueous humor, by retrospectively studying 109 eyes with advanced primary congenital glaucoma that had undergone the procedure.
 The eyes were divided into two groups: group I comprised 75 eyes (69%) that had undergone conventional surgical procedures for congenital glaucoma prior to cyclocryotherapy; group II, 34 eyes (31%) that had not undergone any such previous procedures.
 All eyes were followed for at least 12 months after the last cyclocryotherapy.
 With ""success"" defined as ""having an IOP greater than or equal to 8 mmHg, greater than or equal to 19 mmHg with or without medication,"" the success rate in all eyes was 30%, with no significant difference between the success rates in groups I and II (P greater than .05).
 Chronic hypotony (IOP less than 8 mmHg) was found in seven eyes (6%).
 Six eyes (6%) developed cataract during the course of treatment with cyclocryotherapy.
 Cyclocryotherapy appears to be a reasonable addition to the treatment of eyes with advanced, uncontrolled, primary congenital glaucoma.
",10
1664,"Factors associated with delay in diagnosis of childhood amblyopia.
 The prevention of permanent visual impairment from amblyopia is an important goal of pediatric vision screening.
 Unfortunately, many cases of amblyopia are not diagnosed until the child is too old to benefit maximally from treatment.
 A review of patient records from the practice of a private pediatric ophthalmologist confirmed that late detection is a frequent occurrence among children with amblyopia who have had good access to health care.
 A case-control study was then used to identify factors associated with delayed diagnosis, in which children with an adverse outcome (diagnosed at or after 5 years of age) were compared with those with an optimal outcome (diagnosed before 5 years of age).
 The chart review identified 161 children with amblyopia who participated in this study; 75 had late diagnoses (case patients) and 86 served as control patients.
 Children with early diagnoses more often had the following characteristics: a positive family history of strabismus, greater degrees of strabismus (when strabismus was present), higher maternal educational level, greater parental suspicion that an eye problem existed, and an increased chance that the parents requested the eye examination that led to the diagnosis.
 The parents of children with late diagnoses expressed less concern over the seriousness of amblyopia but were more likely to report that their children had suffered adverse consequences of amblyopia.
 When diagnosed early, amblyopia was more often detected by the child's primary health care provider.
 Physicians of the children with early diagnoses more often reported compliance with both the American Academy of Pediatrics guidelines for vision screening in infancy and referral for vision problems.
",10
1665,"Differentiation of detached retina and vitreous membrane with color flow Doppler.
 The sonographic criteria for diagnosis of retinal detachment and vitreous membranes are well established, and in most cases a diagnosis can be made.
 However, in difficult cases, differentiation between the two may be difficult.
 In this study the use of high-resolution color flow Doppler was evaluated for differentiating between retinal detachments and vitreous membranes.
 Sonographic evaluation, including color flow Doppler, was performed in 25 symptomatic eyes.
 Seven eyes had areas of retinal detachment, all of which had detectable blood flow within at least a portion of the detached retina.
 Fifteen eyes had vitreous hemorrhages or membranes in which no flow was detected.
 Two diabetic patients with vitreous membranes and no retinal detachment did have flow detectable within the neovascular membranes.
 Another patient, who had a complete choroid detachment after surgery, demonstrated good flow within the area of detachment.
 It is concluded that in difficult cases high-resolution color flow Doppler can enable differentiation of an area of retinal detachment from a vitreous membrane in a patient without diabetes.
",10
1666,"Acepromazine. Effects on intraocular pressure.
 We investigated the effects of the topical application of acepromazine maleate on the intraocular pressure (IOP) in 27 adult rhesus monkeys.
 The monkeys were divided into two groups: group 1 (16 monkeys) had both eyes normal, and group 2 (11 monkeys) had experimental chronic glaucoma in one eye and a normal fellow eye.
 One drop of 1% acepromazine maleate solution was instilled in one eye of monkeys in group 1 and in the glaucomatous eye of monkeys in group 2; the other eye served as the control.
 The IOP was measured before drug administration and 1, 4, 8, 24, and 32 hours after, with detailed slit-lamp examination of the anterior segment.
 Acepromazine produced no change in IOP in eyes in group 1, but it produced a fall in pressure in all eyes with high IOP in group 2, evident 1 hour after instillation, maximal between 4 and 8 hours, and still remaining after 32 hours.
 The pupil showed no change in size, but a transient ptosis was observed in the treated eye in all monkeys.
",10
1667,"Conjunctival retraction suture for fornix adjustable strabismus surgery.
 The fornix approach to strabismus surgery is advantageous because the incision is made under the eyelid, there is no need for conjunctival sutures, it is comfortable for the patient, and there is minimal postoperative scarring.
 The major disadvantage of the fornix approach for the adjustable suture technique has been poor exposure to the muscle-suture apparatus and poor postoperative knot exposure.
 We describe herein the use of a subconjunctival retraction suture for adjustable suture surgery with the fornix approach.
 This suture retracts the conjunctiva, exposing the adjustable muscle-suture apparatus while simultaneously fixating the globe.
 A novel way of tying the noose around the pole sutures and preventing noose slippage is also presented.
 This technique provides excellent exposure, fixation of the globe, and complete coverage of the knot with conjunctiva after adjustment.
",10
1668,"Multiple-dose, dose-response relationship for the topical carbonic anhydrase inhibitor MK-927.
 The multiple-dose, dose-response curve of MK-927 was studied in a five-center, double-masked, randomized, placebo-controlled, parallel study of 2%, 1%, and 0.5% MK-927 in 76 patients with bilateral primary open angle glaucoma or ocular hypertension and intraocular pressure greater than 24 mm Hg following washout of ocular hypotensive medications.
 Patients received doses at 8 AM and 8 PM for 14 days, and parallel 12-hour intraocular pressure curves were performed prestudy and on day 14, with 4-hour curves on days 1 and 4.
 There was a significant dose-response relationship, with 0.5% MK-927 twice daily being a minimal-effect dose.
 Both 1% and 2% MK-927 were active through 12 hours postdose, and peak mean percent decrease in pressure at 2 hours postdose was 18.6% and 20.6%, respectively.
",10
1669,"Multiple-dose efficacy comparison of the two topical carbonic anhydrase inhibitors sezolamide and MK-927.
 The multiple-dose twice-daily efficacy of the topical carbonic anhydrase inhibitor MK-927, a racemic compound, was compared with that of its pharmacologically more active S-enantiomer in a four-center, double-masked, randomized, placebo-controlled, parallel study of 1.8% sezolamide hydrochloride (MK-417), 2% MK-927, and placebo, given twice daily to 48 patients with bilateral primary open angle glaucoma or ocular hypertension and morning intraocular pressure greater than 24 mm Hg in both eyes following washout of ocular hypotensive medications.
 Parallel 10-hour modified diurnal curves were performed before the study and on day 14, with 4-hour curves on days 1 and 4.
 Both compounds demonstrated significant lowering of intraocular pressure at 8 AM, 12 hours following the evening dose, and through 10 and 6 hours following the 8 AM dose for sezolamide and MK-927, respectively.
 Morning trough (evening) activity as measured by mean percent change in intraocular pressure from prestudy was -9.2% for sezolamide and -11.1% for MK-927 (-13.5% and -9.6%); peak effect occurred 2 hours after dose administration and was -19.4% and -19.2% for sezolamide and MK-927, respectively.
 From 2 hours after dose administration, sezolamide consistently demonstrated a slightly greater decrease in intraocular pressure than MK-927; however, these differences were not statistically significant.
",10
1670,"The relationship of visual acuity, refractive error, and pupil size after radial keratotomy.
 To better define the relationship between residual refractive error, uncorrected visual acuity, and pupil diameter, we compared 42 eyes that had an eight-incision radial keratotomy according to the Prospective Evaluation of Radial Keratotomy Study protocol with 42 matched control eyes.
 The parameters measured were best corrected visual acuity, uncorrected visual acuity, and the change in cycloplegic refraction with enlarging pupil diameter.
 The best corrected visual acuity was 20/16 in both the radial keratotomy and control groups, but the variability (SD) was higher in the radial keratotomy group.
 The average uncorrected visual acuity was 0.35 (35%) better in the radial keratotomy group, but the variability was 1.77 times higher.
 Change in refraction with dilation occurred in 9% of the controls and 36% of the radial keratotomy patients, indicating a significant difference (P = .002).
 The change in refraction with dilation in the eyes with radial keratotomy was almost equally split between a hyperopic change (17%) and a myopic change (18%), which was much different than in the control eyes, only 2% of which changed in a hyperopic direction and 7% in a myopic direction.
 The radial keratotomy patients with a myopic change had the best uncorrected visual acuity, indicating that positive spherical aberration yielded the best aspherical surface for uncorrected visual acuity.
",10
1671,"Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss.
 Standardized perimetry and nerve fiber layer and color fundus photography were performed annually on 1344 eyes with elevated intraocular pressures.
 In 83 eyes, glaucomatous field defects developed that met rigid criteria on manual kinetic and suprathreshold static perimetry.
 Individual nerve fiber layer photographs were read by two masked observers.
 The more sensitive of the two identified nerve fiber layer defects in 88% of readable photographs at the time field loss first occurred; 60% (6/10) of eyes already had nerve fiber layer defects 6 years before field loss.
 In contrast, the nerve fiber layer was considered abnormal in only 11% (3/27) of normal eyes and 26% (84/327) of hypertensive eyes.
 The location of nerve fiber layer and field defects closely corresponded, but nerve fiber layer loss was generally more widespread.
 Examiner experience and severity of optic nerve damage influenced results.
 Mild focal defects were more readily recognized than more severe diffuse atrophy.
 Nerve fiber layer defects expanded with time, often by the development and coalescence of adjacent areas of damage.
",10
1672,"Radiation safety considerations for post-iodine-131 hyperthyroid therapy.
 The purpose of this study was to develop guidelines based on patient measurements as to when iodine-131- (131I) treated hyperthyroid patients may resume close personal contact.
 External exposure rates were measured on 59 patients using an ionization survey meter in the upright position.
 The initial measurement was recorded within 20 min post-dose administration at one meter.
 Exposure rates were measured 2-11 days post-dose administration at 1, 0.6, and 0.3 meters from the patient's thyroid.
 In the administered dose range of 3 to less than 12 mCi of 131I, all 40 patients measured less than or equal to 2.0 mR/hr at one meter on Day 0, and 25 patients (25/29) were less than or equal to 2.0 mR/hr at 0.6 meter on Days 2-4.
 Guidelines can be prepared based on the administered dose that are rational and in conformity with existing radiologic health standards.
",10
1673,"Treatment of exophthalmos.
 Current procedures for Graves' exophthalmos fail to achieve complete correction.
 The standard orbital decompressions were therefore modified to maximize the degree of volumetric increase behind the axis of the globe.
 In 15 orbits, the preoperative exophthalmos averaged 9.5 mm, whereas the postoperative exophthalmos was 4.1 mm.
 Postoperative CT study demonstrated that the remaining posterior orbital wall, combined with the persistently increased intraocular muscle volume, blocked retrodisplacement of the globe, despite adequate total volumetric increase.
 The increased muscle volume varied from 2 to 5 cc.
 Despite this residual exophthalmos, the modified four-wall expansion provides excellent aesthetic results with visual improvement and resolution of chemosis and exposure keratitis.
",10
1674,"Systemic drug interactions with topical glaucoma medications.
 Topically administered ophthalmic medications are capable of attaining clinically important serum concentrations, as evidenced by the variety of systemic side effects they can produce.
 These drugs are therefore also capable of interacting with other drugs administered orally and intravenously.
 This is especially important when medications are administered to an elderly population, who are often receiving multiple medications.
 The Physician's Desk Reference and the United States Pharmacopeia Drug Information directory contain numerous warnings of potential interactions between topical glaucoma medications and systemically administered drugs.
 Unfortunately, literature supporting such interactions is limited, both in quantity and quality, being anecdotal in many cases.
 This report summarizes available information regarding the nonocular interactions between topical ophthalmic glaucoma medications and other systemically administered medications.
 Clinical evidence of these interactions is lacking in many cases.
",10
1675,"Fifty years in ophthalmology.
 This renowned glaucoma expert began his residency just as gonioscopy came into existence, to be followed shortly by tonography.
 In this memoir, Dr.
 Shaffer shares anecdotes and insights gained over a half century of ophthalmology practice.
",10
1676,"When is it safe to stop patching?
 Prior reports indicate that about half of amblyopia patients successfully treated with occlusion subsequently require maintenance patching.
 This retrospective study was designed to discover what clinical characteristics might be associated with a stable outcome following primary occlusion.
 Included were 188 patients who: (1) had amblyopia related to strabismus, anisometropia or media opacity; and (2) were followed up for at least one year after successful primary occlusion.
 Patients who did not comply with treatment or who did not achieve equal vision were excluded.
 Their ages ranged from 2 to 119 months (mean 29 months).
 Eighty-eight patients (47%) who required no further occlusion were designated the clinically stable group (CSG).
 The remaining 100 (53%), who subsequently needed patching because of unequal acuities, constituted the maintenance patching group (MPG).
 CSG patients were older at the beginning (mean 33 months) and at the end (mean 40 months) of primary occlusion than were MPG patients (means 26 and 31 months).
 Primary occlusion was more likely to have been discontinued because of equal recognition acuities in CSG patients, while equal fixation behaviour or preferential looking was more likely in MPG patients.
 Distribution of diagnoses, severity of amblyopia at presentation, and length of follow-up were similar in the two groups.
 Visual outcomes at last follow-up were slightly better in the CSG (p = 0.002).
 We conclude that, in general, patching can be safely discontinued after the third birthday.
 Although follow-up after primary occlusion is important to ensure stable results in all patients, preverbal children are more likely to require maintenance patching.
",10
1677,"Peripheral contrast sensitivity in glaucoma and ocular hypertension.
 Contrast sensitivity has been measured in patients with glaucoma and ocular hypertension, the latter graded into high, medium, and low risk clinical groups.
 Measurements were made centrally and peripherally at 10 degrees, 15 degrees, 20 degrees, and 25 degrees off-axis at each of the four meridians 45 degrees, 135 degrees, 225 degrees, and 315 degrees.
 A sine wave grating of 1.9 cycles/degree, reversing at 1 Hz was used.
 It was displayed on a 100-Hz refresh rate monitor.
 Normal values were established to compare those from 41 eyes from patients with either primary open angle glaucoma (POAG) with minimal field loss detectable on a Humphrey perimeter, or raised IOP and/or disc changes but no field loss (OH).
 Those with POAG had normal central contrast sensitivity, but at 20 degrees and 25 degrees eccentricity the values were greater than 2 standard deviations above the normal mean.
 This was also the case for high risk OH, but not for low risk patients.
 All the high risk patients except one who had abnormal peripheral contrast sensitivity had possible field defects (threshold elevation at one or more points more than 5 but less than 10 dB above normal mean).
 Only one of those with normal peripheral contrast sensitivity had such 'suspect points'.
 The results are assessed in terms of screening of glaucoma suspects.
",10
1678,"Precapsular film on the aging human lens: precursor of pseudoexfoliation?
 In many older patients we observed a layer of subtle opacification on the anterior lens capsule, appearing as a ground glass film biomicroscopically.
 This precapsular film (PCF) could be uniform but often had radial grey lines in the mid zone, holes in the paracentral region, and was occasionally rolled up in strings.
 Lens capsular material obtained at cataract extraction was studied in patients with and without the film.
 By scanning electron microscopy the PCF appeared as a friable, incomplete fibrillar layer, with rolling of the edges suggesting loose attachment.
 Ultrastructurally its component fibrils were from 3-6 nm in diameter, similar to the finer fibrils in pseudoexfoliation (PSX) material.
 Life PSX material the layer stained positively for the elastic microfibril-associated protein, fibrillin, in a lens with radial striations.
 These similarities suggested that the two conditions have some relationship and that the PCF may be a precursor of PSX.
 Finding patches of the fibrillar network in some control patients implies that the PCF is common in patients of cataract age, though seldom detected clinically.
",10
1679,"Diode laser trabeculoplasty (DLT) for primary open-angle glaucoma and ocular hypertension.
 A pilot study has been carried out to examine the efficacy of diode laser trabeculoplasty in the treatment of primary open-angle glaucoma and ocular hypertension.
 The device used was portable and could be attached to a standard slit-lamp microscope.
 Powers of 0.8-1.2 W were used, with a spot size of 100 microns and a pulse of 0.20 second.
 Laser trabeculoplasty carried out on 20 eyes for glaucoma resulted in a mean ocular hypotensive effect of 10.2 mmHG at two weeks after treatment and of 9.55 mmHg at 6 months.
 It is concluded that diode laser trabeculoplasty is an effective mode of treatment for eyes with open-angle glaucoma or with ocular hypertension.
",10
1680,"A century of cerebral achromatopsia.
 This review is an enquiry into why the early clinical evidence for a colour centre in the cerebral cortex of man was so successfully dismissed for the best part of a century.
 The imperfection of this evidence cannot be the reason, for the same evidence that was rejected earlier is accepted today.
 Instead, it was because the prevalent concepts of vision as a function, and of the role of the cerebral cortex in it, dominated facts and prevented acceptance of evidence showing a specialization for colour in the visual cortex.
 It was only after those concepts were overthrown by the demonstration of functional specialization in the visual cortex of the primate that the evidence for a colour centre in the human brain became acceptable.
 Today, our new knowledge of the colour areas and pathways in the primate brain allows us to give a more complete account of the pathophysiology of cerebral achromatopsia in man.
",10
1681,"Ocular muscle proprioception and visual localization of targets in man.
 Passive deviation of one eye through 18 degrees, 30 degrees and 42 degrees, achieved by force applied to a sucked-on contact lens, caused the direction of visual targets seen by the other eye to be misjudged in the direction of the passive movement by an amount roughly one-sixth of the angle of passive deviation.
 The result was the same when the perceived direction was indicated by hand, as when the instant at which a moving target seemed straight ahead was signalled.
 This result is interpreted by considering that muscular efferents were identical in normal and eye-deviated subjects.
 The main difference between the two target localization conditions results from the proprioceptor output of the deviated eye.
 Our data demonstrate that the assessment of the direction of a target seen by an eye that is free to move depends in part on information received by the brain from proprioceptors in the orbit (in our case the contralateral orbit).
 It would be surprising if the ipsilateral orbit did not contribute as much or more.
 We therefore consider that this constitutes clear evidence against the pure outflow theory of visual direction judgement (Helmholz, 1867), additional to that provided by the all-or-nothing situation of complete versus incomplete oculomotor paralysis.
 Two models have previously been proposed to describe the function of the visual localization mechanism.
 Both assume that the necessary information is derived from the coding of the position of the eye in the orbit, either through a copy of the muscular activation or through eye muscle proprioception.
 We propose an alternative model in which both afferent and efferent signals from all actively contracted or stretched muscles provide the necessary information to the CNS.
 The data gathered so far from normal subjects made strabismic with a suction lens, and from a fair proportion of strabismic patients, support our model describing the mechanism of localization of a single punctate target in darkness.
",10
1682,"Audit of an ophthalmology waiting list.
 The hospital case notes of 209 (98%) of the 213 patients placed on an adult ophthalmic surgical waiting list between mid 1984 and mid 1985 were reviewed.
 Information on referral sources, previous eye surgery, outpatient visits, and treatment up to the end of 1987 was recorded.
 The vital status of patients up to the end of 1988 was also ascertained.
 Waiting list patients (123 women, 86 men) were elderly (73% over 65 years) and most (70%) were listed for cataract surgery.
 By the end of 1987 (30-42 months after waiting list entry) 64% of all patients (and 56% of cataract patients) had received surgery under the care of the health authority.
 The remainder had either died (12%), received surgery elsewhere (7%), were still on the waiting list (7%), no longer wanted or were unfit for surgery (6%), or had left the district (4%).
 By the end of 1988 (42-54 months after waiting list entry) 28% of the original waiting list population had died.
",10
1683,"Mast cell numbers and staining characteristics in the normal and allergic human conjunctiva.
 In this study we report the numbers and metachromatic dye-staining characteristics of mast cells (MCs) in the conjunctiva of normal subjects and patients with seasonal allergic conjunctivitis caused by pollenosis.
 In addition, we have used a monoclonal antibody to the MC-specific enzyme, tryptase, to enumerate tryptase-positive cells immunohistochemically.
 Tarsal conjunctival MCs were found to be present in increased numbers in the allergic compared to the nonallergic subjects.
 Most of the MCs exhibited staining that was formaldehyde resistant, compatible with their identification as connective tissue MCs or basophils.
 The high positive staining for tryptase confirmed that the metachromatic cells stained with toluidine blue were MCs and not basophils, both in normal and allergic subjects.
",10
1684,"Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse.
 Retinal degeneration slow (rds) is a retinal disorder of an inbred strain of mice in which the outer segment of the photoreceptor cell fails to develop.
 A candidate gene has recently been described for the rds defect [Travis, G.
 H., Brennan, M.
 B., Danielson, P.
 E., Kozak, C.
 & Sutcliffe, J.
 G.
 (1989) Nature (London) 338, 70-73].
 Neither the identity of the normal gene product nor its intracellular localization had been determined.
 We report here that the amino acid sequence of the bovine photoreceptor-cell protein peripherin, which was previously localized to the rim region of the photoreceptor disk membrane, is 92.5% identical to the sequence of the mouse protein encoded by the normal rds gene.
 The differences between the two sequences can be attributed to species variation.
 Monoclonal antibodies were used with Western blot analysis to localize the wild-type mouse peripherin/rds protein to isolated mouse rod outer segments and to show that it, like bovine peripherin, exists as two subunits linked by one or more disulfide bonds.
 The relative amounts of peripherin/rds protein and rhodopsin in retinal extracts of normal and rds mutant mice were also compared.
 Identification of peripherin as the protein encoded by the normal rds gene and its localization to membranes of rod outer segments will serve as a basis for studies directed toward defining the role of this protein in the morphogenesis and maintenance of the outer segment and toward understanding the mechanism by which the rds mutation causes retinal degeneration.
",10
1685,"A comparison of penetrating keratoplasty to epikeratoplasty in the surgical management of keratoconus.
 Of 40 patients intolerant to contact lenses, 47 eyes with keratoconus were surgically corrected with either epikeratoplasty (N = 31) or penetrating keratoplasty (N = 16).
 The percentage of eyes in both groups that had visual acuity of 20/40 or better with contact lenses at one year were equal (14 of 15 eyes [93.3%] in the penetrating keratoplasty group; 27 of 29 eyes [93.1%] in the epikeratoplasty group); however, the penetrating keratoplasty procedure resulted in a higher percentage of eyes that had visual acuity of 20/20 than the epikeratoplasty group (11 of 15 eyes [73%] compared with seven of 29 eyes [24.1%], respectively).
 Both procedures resulted in significant corneal flattening, with the penetrating keratoplasty group producing an average of 3 diopters more keratometric reduction than the epikeratoplasty group one year postoperatively.
 Although no irreversible graft failures occurred, five of 16 eyes (31%) in the penetrating keratoplasty group had graft reactions.
 No serious complications were noted in the eyes of the epikeratoplasty group.
 Both procedures were effective in the surgical management of keratoconus.
",10
1686,"Quantitative analysis of lens changes after vitrectomy by fluorophotometry.
 We measured the amount of autofluorescence in the lens to evaluate quantitatively lens changes after vitrectomy.
 Thirteen phakic patients, ranging in age from 12 to 75 years, were studied after unilateral vitrectomy, with a follow-up period of more than two years (range, 26 to 55 months).
 Autofluorescence in the lens was measured at the center along the ocular axis by fluorophotometry.
 Lens autofluorescence in the eyes that underwent vitrectomy was significantly higher than in the contralateral eyes that were not operated on (P = .0003).
 The increase of autofluorescence was correlated significantly with the age at time of vitrectomy (P = .0008).
 There was no correlation between the increase in autofluorescence and the length of postoperative follow-up or the use of air during vitrectomy.
 Based on these results, we believe that oxidation of lens proteins intraoperatively may be one of the causes of development of nuclear cataract after vitrectomy.
",10
1687,"Reproducibility of topographic measurements of the normal and glaucomatous optic nerve head with the laser tomographic scanner.
 We acquired five independent topographic images of the optic nerve head of eight normal eyes and eight eyes with primary open-angle glaucoma with a laser tomographic scanner.
 Each image had a field of view of 15 x 15 degrees with a resolution of 256 x 256 pixels.
 The pixel size was approximately 15 x 15 microns.
 The value of a pixel of a topographic image represented the height at this position.
 The mean height and the standard deviation over the five topographic images were calculated for each of the 65,536 pixel positions.
 The standard deviation of a single height measurement in normal eyes was 38.7 microns (range, 23.4 to 62.2 microns) for areas in the peripapillary retina and 42.6 microns (range, 24.4 to 53.7 microns) for measurements within the optic nerve head area.
 In glaucomatous eyes, the standard deviation was 41.2 microns (range, 23.2 to 59.6 microns) in the peripapillary retina and 49.4 microns (range, 28.1 to 72.8 microns) within the optic nerve head.
 There was no significant difference between the standard deviation of a single height measurement in normal and glaucomatous eyes (P = .34 within the optic nerve head area; P = .57 on peripapillary retina).
 No correlation was found between standard deviation of the measurements and pupil size or age of the subject.
",10
1688,"Falls in elderly patients with glaucoma.
 We analyzed the determinants of serious falls among 489 ambulatory elders aged 65 years and older who received a comprehensive examination at a glaucoma consultation service.
 For the previous year, at least one fall requiring medical attention or restricted activity was reported by 9.6% (95% confidence interval [CI], 7.0% to 12.2%) of participants.
 Using logistic regression to adjust for potential confounding variables, the greatest single risk factor for falls was the use of nonmiotic topical eye medications (odds ratio [OR], 5.4; 95% Cl, 1.8 to 16.4).
 Additional risk factors for falls were female sex (OR, 2.3; 95% Cl, 1.1 to 4.7) and use of cardiac medications (OR, 2.5; 95% Cl, 1.1 to 5.6).
 Three other characteristics were also associated with the risk of falls: use of miotic eye medications (OR, 3.2; 95% Cl, 1.0 to 10.1); visual field impairment of 40% or greater (OR, 3.0; 95% Cl, 0.94 to 9.8); and use of sedatives (OR, 2.4; 95% Cl, 0.89 to 6.7).
 These findings suggest that ocular and systemic medications are the major predictors of falls even in this elderly population seeking ophthalmologic care for glaucoma.
 Medications appear to pose a greater risk for falls than even major visual impairment.
",10
1689,"Loculated fluid. A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Macular Photocoagulation Study Reading Center.
 The Foveal Photocoagulation Study, a component of the Macular Photocoagulation Study, is designed to evaluate whether laser treatment can reduce the risk of severe visual loss in eyes with well-defined choroidal neovascular membranes associated with macular degeneration that extend through the foveal center.
 On one third of the 554 baseline angiograms of study patients enrolled in and whose eyes were graded in the study as of January 31, 1990, the Reading Center staff has noted an unusual pattern of hyperfluorescence in the late-transit frames that has not been described previously.
 This pattern, which we call ""loculated fluid,"" consists of a well-demarcated area of hyperfluorescence that appears to represent pooling of fluorescein in a compartmentalized space anterior to the choroidal neovascular leakage.
 Although the loculated fluid may conform to a pattern of typical cystoid macular edema, it can also pool within an area deep to the sensory retina in a shape that does not bear any resemblance to cystoid macular edema.
 This pattern is important to recognize because it (1) should not be confused with the angiographic pattern or extent of choroidal neovascularization and (2) should be differentiated from a serous detachment or tear of the retinal pigment epithelium.
",10
1690,"Low-dose aspirin and risks of cataract in a randomized trial of US physicians.
 Observational studies have raised the question of a possible benefit of aspirin on the development of cataract.
 The Physicians' Health Study, a randomized double-masked placebo-controlled trial among 22,071 male physicians, aged 40 to 84 years, provided the opportunity to collect information about whether low-dose aspirin therapy (325 mg on alternate days) affects the development or extraction of cataract.
 There were 173 age-related cataracts among those physicians assigned to aspirin therapy and 180 among those given placebo (relative risk, 0.95; 95% confidence interval, 0.74 to 1.22).
 Cataract extractions were less frequent in the aspirin than in the placebo group, but this difference was not statistically significant (relative risk, 0.80; 95% confidence interval, 0.56 to 1.15).
 Among younger men (aged 40 to 59 years), the relative risks were 0.62 (95% confidence interval, 0.40 to 0.94) for cataract development and 0.67 (95% confidence interval, 0.38 to 1.31) for cataract extraction.
 These randomized trial data tend to exclude any large benefit of aspirin.
 While the overall findings concerning cataract development seem to be null, the data on extraction of age-related cataract, while not statistically significant, cannot exclude a possible small to moderate benefit of alternate-day aspirin therapy on the extraction of age-related cataract.
",10
1691,"Exposure to phenothiazine drugs and risk of cataract.
 Clinical reports have indicated an increased risk of ocular opacities in users of phenothiazine drugs, and some recent epidemiologic studies have found an association between cataract and a history of tranquilizer use.
 To examine the effects of major tranquilizers (phenothiazines and haloperidol) on the risk of cataract extraction, while controlling for suspected risk factors such as diabetes and steroid use, a matched cohort study was performed using information from a large health maintenance organization in Seattle, Wash.
 The use of either antipsychotic or other phenothiazine drugs increased the risk of cataract extraction by roughly 3.5 times in individuals who were both current users and were exposed some time in the 2 to 5 years prior to their extraction.
 Risk was also increased in individuals with prior use of antidiabetic agents, systemic steroids, and benzodiazepines.
 Contrary to some prior reports, there was no elevated risk associated with use of antihypertensives, and there was no protective effect for aspirin, acetaminophen, or ibuprofen.
",10
1692,"Effects of antiflammins on endotoxin-induced uveitis in rats.
 Antiflammins are phospholipase A2-inhibitory, anti-inflammatory, synthetic oligopeptides derived from the region of the highest amino-acid sequence similarity between uteroglobin and lipocortin I.
 Endotoxin-induced uveitis is a model for anterior uveitis of the eye, which has been suggested to be induced through phospholipase A2 activation.
 In a preliminary report we demonstrated that topical administration of antiflammins could inhibit endotoxin-induced uveitis in rats.
 In this study, the anti-inflammatory effects of antiflammins were compared with those of corticosteroids on endotoxin-induced uveitis as measured by phospholipase A2 enzyme activity, inflammatory cell counts in the aqueous humor, and histopathologic features.
 Antiflammins are as effective as corticosteroids in their ability to suppress endotoxin-induced uveitis.
",10
1693,"Autogenous fascial grafts for exposed retinal buckles.
 Three patients with exposed scleral buckling elements received autogenous fascial grafts as an alternative to buckle removal.
 All three patients had successful coverage of their scleral buckles.
 There were no redetachments or infections.
 One patient had a postoperative ptosis that required repair.
 Autogenous fascial grafts are useful procedures in patients with exposed retinal buckles who have a significant risk of retinal redetachment with buckle removal.
",10
1694,"A longitudinal study of children with a family history of strabismus: factors determining the incidence of strabismus.
 A longitudinal study of ocular refraction, position, and fixation was performed in children with a family history of strabismus.
 The children were examined at regular intervals between 3 months and 4 years of age, and the results are discussed in terms of changes in refraction between different ages and correlations between refraction and development of strabismus and amblyopia.
 Six of 34 children (17.6%) developed constant or intermittent esotropia.
 The strabismus was first noted between 18 and 30 months of age except in one case.
 All esotropic children were 4 dioptres hypermetropic or more at 6 months, and their hypermetropia remained almost unchanged through the years.
 Seven additional children were 4 dioptres or more hypermetropic at 6 months but did not develop a squint.
 In contrast to the squinting children the hypermetropia in these children changed towards emmetropia.
 This emmetropisation was most pronounced during the first 2 years of age.
 The implications of these results for an early diagnosis of strabismus amblyopia are discussed.
",10
1695,"The association of Fuchs's corneal endothelial dystrophy with axial hypermetropia, shallow anterior chamber, and angle closure glaucoma.
 A series of 24 patients with Fuchs's dystrophy are presented in whom detailed clinical measurement showed an association with axial hypermetropia and shallow anterior chamber.
 In 14 of these patients one cornea had developed oedema, of which 11 had required penetrating keratoplasty.
 Comparison of these eyes with the fellow eyes without corneal oedema revealed that the anomalies in measurement were not due to the process of decompensation.
 These 14 patients were then compared with the remaining 10 patients without corneal oedema in either eye, and a similar profile of anomalous measurements was observed.
 The whole group of 24 patients were then compared with three separate control groups, and in each case a significant trend towards hypermetropia, short axial length, and shallow anterior chamber was noted.
 The mean spherical equivalent refractive error in the patients with Fuchs's dystrophy was +2.48 D compared with -0.31 D for controls; corresponding means for axial length were 22.1 mm compared with 23.4 mm; and for anterior chamber depth were 2.2 mm compared with 2.7 mm.
 Each of these differences was statistically significant, but there was no significant difference for the keratometry measurements between patients and controls.
 Five of 24 (21%) of the patients had problems related to shallow anterior chambers of whom 3 (12%) had manifest angle closure glaucoma requiring surgical peripheral iridectomy.
 The aetiology of Fuchs's dystrophy and of ametropia is discussed and possible modes of association outlined.
 This previously unrecognised association gives a rational basis for the widely accepted practice of combining penetrating keratoplasty with lens extraction and has several other practical implications which are important in the differential diagnosis and treatment of Fuchs's dystrophy and angle closure glaucoma.
",10
1696,"Effect of a beta-blocker on altered body position: induced ocular hypertension.
 The intraocular pressures (IOP) were measured in both eyes of 25 healthy volunteers in various body positions.
 One eye was pretreated with levobunolol 0.5% or placebo applied in a masked, randomised fashion, while the other served as control.
 IOP changes in response to levobunolol and to changes in position were significant (p less than 0.0001).
 However, pressure rises relative to position were not significantly different in eyes treated with drug vs placebo.
 Levobunolol did not alter relative changes in IOP from changes in body position.
 However, the overall lowering effect may offer some protection to patients with glaucoma.
",10
1697,"A functional vagotomy induced by unilateral forced right nostril breathing decreases intraocular pressure in open and closed angle glaucoma.
 There is evidence of the central regulation of intraocular pressure, and it has been suggested that vagal tone might be increased in glaucoma simplex.
 The nasal cycle, the simultaneous congestion-decongestion response in the nasal cavities, reflects the dynamic lateralisation of the autonomic nervous system.
 Since this lateralisation presents with sympathetic activity induced by left brain hemisphere stimulation and parasympathetic activity induced by right hemisphere stimulation, it was subsequently demonstrated that forced unilateral nostril breathing induces selective contralateral hemispheric stimulation as measured by relative increases in the electroencephalographic amplitude in the contralateral hemisphere as well as alternating lateralisation of plasma catecholamines.
 Using this functional vagotomy, we report that left hemispheric stimulation by 20 minutes of forced unilateral right nostril breathing led to a significant bilateral decrease of 4.6 mmHg (25%) in intraocular pressure in 46 patients with open and closed angle glaucoma.
 However, it significantly increased the IOP in three patients with neovascular, one with juvenile onset, and one with closed angle glaucoma.
",10
1698,"Injector for highly viscous silicone oil.
 A syringe device for the injection and evacuation of highly viscous silicone oil was developed.
 The problem of removing the air interfering with these manoeuvres was solved by providing special outlets in the plunger and handle of a conventional glass syringe.
 A slightly modified commercial motor perfusor was chosen to power this device, which has proved to be good and fail-safe in more than 100 cases.
",10
1699,"Anisometropic and strabismic amblyopia in the age group 2 years and above: a prospective study of the results of treatment.
 Forty-four children aged 2-9 years with strabismic and anisometropic amblyopia were prospectively followed up during amblyopia treatment.
 The efficacy of optimised treatment in terms of number of cured children, time to achieve cure, and rate of initial improvement of visual acuity was evaluated in relation to age at start of treatment, type and initial degree of amblyopia, and adherence to treatment regimen.
 Compliance with treatment was the most critical factor predicting a successful outcome.
 Among the compliant children 35 out of 36 were cured (visual acuity difference between amblyopic and non-amblyopic eyes not more than one line) within five months regardless of age, treatment regimen, and type or initial degree of amblyopia as compared with none in the group with low compliance.
 Most of these compliant children were cured within three months, with shorter treatment times on average for the younger children.
 The initial improvement of visual acuity was also faster at 2 years than at 4 years of age.
 Anisometropes with moderate amblyopia at the start of treatment were over-represented in the group with low compliance.
 We conclude that early diagnosis of strabismus in combination with general population screening at the age of 4 to detect amblyopia caused by anisometropia or microstrabismus seems to be efficacious for the cure of most cases.
 The major factor in treatment failure was found to be inadequate adherence to the treatment regimen.
",10
1700,"Postural studies in pulsatile ocular blood flow: I. Ocular hypertension and normotension.
 Measurements of pulsatile ocular blood flow (POBF) have been recorded in a group of healthy, ocular normotensive volunteers and ocular hypertensive patients recruited from outpatients.
 Use of a pneumotonometric probe linked to a Langham ocular blood flow system enabled readings of intraocular pressure and its variation with heart rate (ocular pulse) to be taken in erect and supine positions.
 Pulsatile ocular blood flow was calculated from these values by means of the pressure-volume relationship previously described for living human eyes.
 Assumption of the supine posture was accompanied by a significant rise in intraocular pressure; in normal eyes (mean, with SEM) (3.1 (0.4) mmHg, p less than 0.0001) and to a greater extent in ocular hypertensive eyes (4.7 (0.6) mmHg, p less than 0.0001).
 The POBF did not differ significantly between normotensive and ocular hypertensive groups in either the erect or supine postures.
 In both groups, however, assumption of the supine posture was accompanied by a significant fall in POBF (normals: -121 (21) microliters/min, p less than 0.0001; ocular hypertensives: -75 (16) microliters/min, p less than 0.0002).
 These reductions in POBF represent decrements of 27.5 (3.0)% and 17.1 (3.8)% respectively.
 Pulsatile ocular blood flow is reduced in the supine posture, and this may result in tissue hypoxia in subjects at risk of developing glaucoma.
 A companion paper describes the measurement of POBF in a group of patients with chronic open angle glaucoma treated with topical timolol 0.25%.
",10
1701,"Prognostic significance of the pattern visual evoked potential in ocular hypertension.
 This paper reports a prospective study on 49 ocular hypertensive patients to evaluate the prognostic significance of transient abnormalities in the pattern visual evoked potential (VEP) in the development of glaucoma.
 Seven of 24 patients with VEP abnormalities at diagnosis of ocular hypertension developed glaucomatous field defects in the follow-up period as compared with none of 25 patients with normal VEPs at diagnosis.
 We conclude that appropriately designed pattern VEP testing is a valuable complement to careful (preferably computerised, static) perimetry.
 In addition, our findings support the contention that, in glaucomatous disease of the optic nerve, rudimentary pattern processing mechanisms--that is 'Y'-type units of the magnocellular pathways--may be affected earlier than luminance processing mechanisms.
",10
1702,"Cocaine-induced iritis.
 The case of a 31-year-old man who presented to the emergency department with iritis from intranasal cocaine use is described.
 This was the second episode of iritis in this patient after casual cocaine use.
 The differential diagnosis of iritis and a proposed pathophysiologic mechanism are discussed.
",10
1703,"Eye infections.
 This article provides an overview of the diagnosis and treatment of eye infections.
 The seriousness of eye infections can range from benign and self-limiting to lethal.
 The primary care physician must determine the seriousness of each particular infection and then, based on that determination, must treat or refer the patient.
",10
1704,"Hereditary hemorrhagic macular dystrophy.
 We treated two brothers who had a hemorrhagic macular lesion in one eye; a similar problem affected the fellow eye of both patients within eight months.
 Generalized fine granularity of the retinal pigment epithelium and peripheral iris transillumination defects were observed in both siblings.
 A study of the family suggested that the disorder was dominantly inherited and probably was Sorsby's pseudoinflammatory macular dystrophy.
 The macular lesions in one brother were treated by argon green laser photocoagulation and in the other brother by krypton red laser photocoagulation.
 Although the brother treated by krypton red laser photocoagulation attained better final visual function, additional differences in treatment methods also may have contributed to the final outcome.
",10
1705,"A simple transposition procedure for complicated strabismus.
 We combined a recession or resection of recti muscles with a vertical or horizontal transposition to correct a complicated paralytic ocular deviation in eight patients.
 The transposed muscles were reattached to the globe parallel to the spiral of Tillaux and adjacent to the paralyzed muscle.
 Postoperatively, seven patients demonstrated fusion in the primary position or required a slight head turn to fuse.
 There were no surgical complications, and no patient developed symptomatic cyclotropia, diplopia, or anterior segment ischemia.
",10
1706,"A comparison of total and partial tenonectomy with trabeculectomy.
 We compared the results of two methods of tenonectomy at the time of trabeculectomy.
 Of 49 eyes, 23 were randomly assigned to a partial tenonectomy and 26 to a total tenonectomy.
 There was no statistically significant difference in the success rate between the two surgical groups using an upper limit of intraocular pressure of either 18 or 21 mm Hg as the criterion for success.
 There was no difference in the need for postoperative medications or further surgical intervention between the two groups.
 Although certain advantages exist with each technique, these findings suggest that equivalent results can be anticipated with either a total or partial tenonectomy.
",10
1707,"Therapeutic ultrasound for the treatment of glaucoma [published erratum appears in Am J Ophthalmol 1991 Jul 15;112(1):105]
 A multicenter clinical trial of therapeutic ultrasound for the treatment of glaucoma included 20 centers in the United States in which 1,117 treatments were performed on 880 eyes.
 The study was limited to patients with refractory glaucoma who had not benefited from conventional medical and surgical techniques.
 Approximately 782 of 1,117 treatments (70%) showed an initial decrease in intraocular pressure from a pretreatment mean of 38.1 mm Hg to 22 mm Hg or less.
 By Kaplan-Meier survival analysis, the single treatment success rate (intraocular pressure between 6 and 22 mm Hg) was 48.7% at six months posttreatment.
 When retreatment was used subsequent to failure, the one-year multitreatment success rate was 79.3%.
 The most common complications were an immediate posttreatment intraocular pressure increase lasting a few hours and mild iritis.
 Other complications included scleral thinning in 28 of 1,117 treatments (2.5%) and phthisis bulbi in 12 of 1,117 treatments (1.1%).
",10
1708,"Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy.
 Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents.
 A simple new technique has been developed for the insertion of these stents.
 Using the flexible cystoscope, the procedure is performed on an out-patient basis under local anaesthesia.
 Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients.
",11
1709,"Use of the double pigtail stent in stone retrieval following unsuccessful ureteroscopy.
 Insertion of a double pigtail stent is known to cause ureteric dilatation.
 We analysed the effect of an indwelling double pigtail stent on the success rate of calculus extraction by second ureteroscopy when the initial ureteroscopy fails.
 Over a 12-month period, a first ureteroscopy failed in 42 patients; 30 were then treated by ureteroscopy combined with a ureteric stent and 12 were treated without a ureteric stent.
 The group with an indwelling stent had a successful second ureteroscopy or spontaneously passed the calculus in 24 cases (84%) compared with 5 unstented cases (45%).
 Ureterolithotomy was necessary in 2 patients with a stent and 3 with no stent.
 It was concluded that following failed ureteroscopic manipulation of calculi, insertion of a double pigtail stent was associated with a higher subsequent success rate for removal of stone by ureteroscopy and a consequent lower rate of ureterolithotomy.
",11
1710,"Immunofluorescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis.
 Interstitial cystitis comprises a complex of diseases typified by symptoms of pelvic pain.
 Functional complaints do not aid the clinician in determining loss of anatomical capacity.
 Histochemical staining with PAS-colloidal iron/Van Geison's counterstain offers improved diagnostic ability for the pathologist and correlates well with immunofluorescent findings.
 Four distinct diseases can be identified through immunofluorescent staining, indicating that each is the result of different responses of the urothelium and endothelium to injury.
 Loss of bladder capacity associated with these diseases can be expected with age, but immunofluorescent staining for IgM within the capillaries of the interstitium is a more sensitive predictor.
",11
1711,"Do women with idiopathic sensory urgency have early interstitial cystitis?
 Interstitial cystitis is rarely considered as a cause of urinary symptoms in referrals to gynaecology clinics.
 Recent concepts in the diagnosis of this condition mean that it is emerging as a much more common entity, with both early and late forms of the disease being described.
 Mast cell density in the detrusor muscle has been reported to be useful as a disease marker to substantiate the diagnosis of interstitial cystitis where no classical diagnostic features exist.
 We assessed mast cell counts in bladder biopsies from 27 women with idiopathic sensory urgency and 10 control patients about to undergo a colposuspension procedure for pure genuine stress incontinence; 30% of the study group had a clear increase in the detrusor muscle mast cell population (detrusor mastocytosis).
 No control patient showed such an increase.
 Early interstitial cystitis should be considered as a possible cause of lower urinary tract symptoms in patients with apparently idiopathic sensory urgency.
",11
1712,"Symptoms versus flow rates versus urodynamics in the selection of patients for prostatectomy.
 Many prostatectomies are performed on the basis of symptoms alone; 39% of patients referred by their family doctors and 23% of patients who were on waiting lists for prostatectomy of other hospitals, but who had not undergone any urodynamic investigations, were found to be unobstructed on urodynamic criteria.
 A screening peak urinary flow rate of 12 ml/s or less was associated with urodynamic evidence of obstruction in 95% of cases; 35% of patients with symptoms of outflow obstruction and a flow rate greater than 12 ml/s were also found to be obstructed.
 One year post-operatively, 84% of patients who were selected for surgery on combined symptomatic and urodynamic criteria were pleased symptomatically with their result.
 The failure of detrusor instability to resolve following prostatectomy was associated with symptomatic failure of treatment.
 Residual obstruction was demonstrated in 5 patients who had undergone prostatectomy and were asymptomatic at this time.
 This study illustrates that objective measures are necessary in the assessment of patients prior to prostatectomy in order to select only patients who are obstructed.
 The importance of a screening flow rate is emphasised.
 All patients who underwent surgery had cystometric evidence of obstruction but the symptomatic results of surgery were no better than the results in patients who had been assessed according to non-urodynamic selection criteria.
 We have thus failed to identify a need for routine cystometry in the pre-operative assessment of these patients.
 Cystometry does, however, have a role in assessing patients with pre-operative flow rates greater than 12 ml/s and in those who remain symptomatic following prostatectomy.
",11
1713,"Pathologic delineation of the papillonodular type of cystic partially differentiated nephroblastoma. A review of 11 cases.
 Eleven cases of a previously unrecognized papillonodular variant of cystic partially differentiated nephroblastoma (CPDN) are described.
 This type of CPDN has all the features of the conventional type of CPDN; however, in addition, there are grossly demonstrable papillonodular projections extending from the septa into the cyst lumina.
 The septa do not show any expansile tumor masses.
 Like most cases of the conventional type, this new type of CPDN was usually diagnosed in infants.
 Nephrectomy (total in 10 and partial in 1) was done in these cases.
 Additional chemotherapy with or without radiation therapy was given in seven cases.
 No recurrence was noted during the period extending from 21 months to 8 years in the eight cases in which follow-up data are available.
 Nephrectomy with regular follow-up visits for possible recurrence may be the management of choice.
 Pathologists should be aware of this variant of CPDN so that overtreatment can be avoided.
 The revised criteria for CPDN can be summarized as follows: (1) The discrete entirely cystic tumor contains luminal papillonodules in some cases.
 (2) Septa and the papillonodules, when present, are the only solid portion of the tumor and contain blastemal cells admixed with their normal and aberrant derivatives.
 (3) The tumor without and with papillonodules is classified as a conventional and papillonodular type of CPDN, respectively.
",11
1714,"Acute effects of captopril and ibuprofen on proteinuria in patients with nephrosis.
 Captopril decreases protein excretion in patients with nephrosis.
 To evaluate whether captopril has an acute antiproteinuric effect and to evaluate the role of changes in renal hemodynamics or glomerular permselectivity on this effect, renal clearance studies were performed in patients without diabetes but with nephrosis.
 Protein excretion and renal hemodynamics were measured at baseline and after the administration of captopril.
 To measure the contribution of renal prostaglandins, patients were restudied on a separate day, after the combined administration of captopril and the prostaglandin synthetase inhibitor ibuprofen.
 Both treatments significantly reduced mean protein excretion, but the change was greater with combined therapy than with captopril alone (40.6% vs 20.0%).
 Mean glomerular filtration rate (GFR) decreased by 4.8% (not significant) and 16.5% (p less than 0.001), and filtration fraction (FF) decreased by 13.6% (p less than 0.001) and 14.9% (p less than 0.001) after captopril alone and combined therapy, respectively.
 No significant correlation was found between changes in proteinuria and changes in GFR or FF after treatment with captopril alone.
 In contrast, the decrease in proteinuria correlated with the change in GFR after combined drug administration (r = 0.68, p = 0.06).
 The ratio of immunoglobulin G to albumin clearance, an index of glomerular permselectivity, was unaffected by captopril but decreased significantly (by 43%) after combined drug administration.
 The results suggest that the acute antiproteinuric effect of captopril is not due to changes in FF, GFR, or glomerular perselectivity.
 The addition of ibuprofen enhances the antiproteinuric effect of captopril by decreasing the GFR as well as by enhancing the permselectivity of the glomerular capillary membrane.
",11
1715,"Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study.
 Cytotoxic chemotherapy has not provided survival benefit in metastatic prostate cancer, although it has been used most frequently in patients with far-advanced, refractory disease.
 To evaluate the effects of chemotherapy given earlier in the course of the disease, the Southwest Oncology Group (SWOG) performed a randomized trial between September 1982 and October 1986 comparing endocrine therapy (diethylstilbestrol [DES] or orchiectomy) alone followed by cyclophosphamide-Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy at progression versus initial combined chemo-endocrine therapy.
 One hundred forty-three patients were registered, and only six were declared ineligible.
 Patients on the combined chemo-endocrine therapy arm had a slightly higher response rate (63%) compared with endocrine therapy alone (48%).
 A log-linear model of tumor response and treatment arm adjusted for the stratification factors favored the combination arm (P = .059).
 Only three of 27 patients on the endocrine therapy alone arm had an objective partial response when crossed over to chemotherapy, while two others had stable disease.
 Despite the difference in initial response rate, time to treatment failure and survival were identical in the two treatment arms.
 Seventy-seven percent of patients on the initial endocrine therapy alone arm have died (median survival, 25.6 months) compared with 78% on the chemo-endocrine therapy arm (median survival, 22.0 months).
 No significant effect of treatment on survival was observed even after adjustment for the stratification variables in a Cox regression model.
 Exploratory survival analyses with patients on both arms combined did show a marginally significant time to treatment failure and survival advantage for patients treated with DES rather than orchiectomy as initial endocrine therapy.
 Eighty-six percent of patients treated by orchiectomy have died compared with only 65% of those treated with DES.
 These data do not support the addition of cytotoxic chemotherapy to initial endocrine therapy in patients with metastatic prostate cancer.
",11
1716,"Cardiovascular effects of microinjection of angiotensin II in the brainstem of renal hypertensive rats.
 The cardiovascular effects of microinjection of angiotensin II (AII) into the area postrema (AP), nucleus of the solitary tract (NTS) and rostroventrolateral medulla were studied in urethane anesthetized sham-normotensive (NT) and two-kidney, one-clip renal hypertensive rats.
 Microinjection of AII (2-2000 ng) in the AP of renal hypertensive rats elicited a dose-dependent decrease in blood pressure, heart rate and renal sympathetic nerve activity.
 Similar effects were observed in the NTS.
 In the NT rats, low doses of AII (2 and 20 ng), either in the AP or NTS, were also depressor.
 High doses of AII (200-2000 ng) were needed to observe a modest pressor effect in the NT animals.
 A decrease in heart rate and renal sympathetic activity was observed with the pressor effect.
 The AII-antagonist, [Sar1,Val5,Ala8]-AII, into the NTS or AP increased blood pressure and heart rate and inhibited the cardiovascular effects of low doses of AII in both group of rats.
 In contrast, [Sar1,Val5,Ala8]AII did not affect the pressor action of high doses of AII in the NT group.
 While the microinjection of AII into the rostroventrolateral medulla did not produce any significant cardiovascular effect in the renal hypertensive group, it resulted in a modest pressor effect in the NT rats.
 These results indicate that acute activation of AII receptors in the AP or NTS does not contribute to the pressor effect of AII in renal hypertensive rats.
",11
1717,"Problems in the clinical diagnosis of stress incontinence.
 A significant number of women suffer from urinary incontinence, which often requires surgical intervention.
 Prior to proceeding with surgery, it is essential that all women undergo a thorough preoperative assessment to detect nonsurgical causes of their urinary leakage.
 This paper reviews the reliability of the initial history and basic clinical tests in the evaluation of women with lower urinary tract abnormalities.
",11
1718,"Nonsurgical treatment of detrusor overactivity in postmenopausal women.
 Detrusor overactivity with subsequent urge incontinence becomes increasingly more prevalent as women age.
 Because of that, most women treated for detrusor instability and hyperreflexia are postmenopausal and are not always good candidates for the same treatments given to their younger counterparts.
 Nonsurgical treatments of detrusor overactivity are available to postmenopausal women.
",11
1719,"Histology of the connection between the vagina and levator ani muscles. Implications for urinary tract function.
 The proximal urethra is a mobile structure, and voluntary control of its position is an integral part of the initiation of urination and continence.
 This paper describes the histology of the vagina's attachment to the medial portion of the levator ani muscles, which, because of the intimate attachment of the vagina and urethra, is responsible, in part, for control of the urethral position.
 A histologic examination of 1,500 serial microscopic slides from eight women, dissection of four bodies and study of whole pelvis cross-sections from two cadavers were performed.
 Smooth muscle, collagen and elastin fibers of the vaginal wall and paraurethral tissues directly interdigitate with the muscle fibers of the most medial portion of the levator ani, in the region of the proximal urethra.
 This strong connection lies at a level just below the entry of the urethra into the bladder and extends downward to the level of the perineal membrane (urogenital diaphragm) in an area corresponding to the mobile portion of the urethra.
 The inseparable nature of the vagina and urethra in this region makes it possible for the connection of the levator ani to the vagina to control the proximal urethral position.
 These observations suggest a specific role of the medial levator ani muscle in controlling vesical neck position and open the question of the specific part played by this arrangement in voiding and continence relative to other factors known to influence lower urinary tract function.
",11
1720,"Urethral mobility and its relationship to stress incontinence in women.
 Multiple physiologic factors, only one of which is urethral support, make up the female continence mechanism.
 Abnormal urethral support leads to deficient transmission of abdominal pressure to the urethra, which results in genuine stress incontinence in some women.
 Many techniques are available for measuring urethral mobility.
 The determination of urethral mobility is not useful in the diagnosis of urinary incontinence.
 However, it provides some information about which surgical procedure is most appropriate for the correction of genuine stress incontinence.
",11
1721,"Rise in prostatic cancer incidence associated with increased use of transurethral resection 
 We examined the association between prostatic cancer incidence rates and the rates of transurethral prostatectomy to explore reasons for the nationally reported dramatic increases in incidence rates of prostatic cancer from 1973 through 1986.
 There was a strong correlation between both incidence of all stages of prostatic cancer combined and of localized disease and the increasing use of transurethral resection, a common surgical procedure usually performed to relieve urinary obstruction due to benign enlargement of the prostate.
 Our analyses suggest that increased detection of existing tumors via transurethral resection was the primary reason for the observed increase in incidence rates of prostatic cancer.
 However, analyses of mortality trends, particularly among nonwhites, and laboratory studies of the histologic nature of clinically asymptomatic tumors suggest that part of the increase may reflect changes in the real risk of prostatic cancer.
",11
1722,"Unexplained excess risk of bladder cancer in men.
 In nearly all populations studied, the risk of bladder cancer is two to four times as great in men as in women.
 We estimated what the gender-specific incidence rates would be in the absence of exposure to known carcinogenic factors.
 The data used were obtained from interviews with 2,806 white individuals with bladder cancer and 5,258 white controls in the National Bladder Cancer Study and from incidence data for 1978 from the National Cancer Institute Surveillance, Epidemiology, and End Results Program.
 The total age-adjusted incidence of bladder cancer was 27.5 cases per 100,000 person-years for men and 7.0 for women, yielding a ratio of 3.9.
 Even in the absence of exposure to cigarettes, occupational hazards, or urinary tract infection, the gender-related risk persisted; the incidence of bladder cancer was 11.0 in men and 4.1 in women, yielding a ratio of 2.7.
 Possible explanations for the excessive risk in men include environmental and dietary exposures not yet identified and innate sexual characteristics such as anatomic differences, urination habits, or hormonal factors.
",11
1723,"Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility 
 A multicentre study (ten centres) in seven countries was done to assess the contraceptive efficacy of hormonally-induced azoospermia in 271 healthy fertile men.
 Each subject received 200 mg testosterone enanthate weekly by intramuscular injection.
 157 men (cumulative rate at 6 months 65%) became azoospermic in three consecutive semen samples.
 These men entered a 12-month efficacy phase during which continuing testosterone injections were the only form of contraception.
 There was 1 pregnancy during 1486 months of the efficacy phase (0.8 conceptions [95% confidence interval 0.02-4.5] per 100 person-years).
 Discontinuations from the study were mainly because azoospermia was not achieved within 6 months and because of dislike of the injection schedule.
 The mean time to become azoospermic was 120 days (SD 40); reappearance of spermatozoa was detected in 11 men and in no case led to discontinuation from the study or to pregnancy.
 After the testosterone injections had been stopped, the estimated median time from azoospermia to recovery (sperm concentration of at least 20 million/ml) was 3.7 months (3.6-3.9) and to the subject's mean baseline sperm concentration was 6.7 months (6.2-8.7).
 Hormonal regimens that induce azoospermia can provide highly effective, sustained, and reversible male contraception with minimum side-effects.
",11
1724,"The epidemiology and clinical aspects of the hemolytic uremic syndrome in Minnesota 
 BACKGROUND.
 The frequency of the hemolytic uremic syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, is increasing.
 Although Escherichia coli serotype 0157:H7 has been implicated as a causative agent, more information is needed about the basic epidemiology and clinical aspects of this syndrome.
 METHODS.
 We conducted a retrospective population-based study of hemolytic uremic syndrome in Minnesota residents less than 18 years of age from 1979 through 1988 to assess trends in disease occurrence, describe the clinical illness, and identify predictors of disease severity and outcome.
 We also conducted a case-control study of patients with onsets of illness from 1986 through 1988 to examine risk factors.
 RESULTS.
 One hundred seventeen patients were identified.
 The mean annual incidence increased from 0.5 case per 100,000 child-years among children less than 18 in 1979 (6 cases) to 2.0 cases per 100,000 in 1988 (26 cases) (P = 0.000004).
 E.
 coli 0157:H7 was isolated from 13 of 28 patients (46 percent) who had stool specimens submitted for testing.
 For those who presented with typical hemolytic uremic syndrome, an elevated polymorphonuclear-leukocyte count on hospital admission, a shorter duration of prodrome, and the presence of bloody diarrhea were predictive of severe disease.
 In the case-control study, the patients were more likely to attend large daycare centers (more than 50 children) than were the controls (odds ratio, 10.2; P = 0.03), suggesting that day-care attendance may be a risk factor.
 On the basis of the population-attributable risk, however, this factor could account for no more than 16 percent of the cases.
 CONCLUSIONS.
 This study provides evidence for an increase in the incidence of hemolytic uremic syndrome, which is probably related to an increased incidence of E.
 coli 0157:H7 infections.
 Hemolytic uremic syndrome has become an important pediatric and public health problem.
",11
1725,"Successful renal transplantation accelerates development in young uremic children.
 To examine the impact of renal transplantation on subsequent development of children with chronic renal failure, 37 children undergoing primary renal transplantation at or before 30 months of age whose allograft functioned for at least 1 year were prospectively studied.
 Psychometric tests were performed an average of 4 months before transplantation; reevaluation was done an average of 14 months after surgery.
 Comparison of individual pretransplantation and posttransplantation mental development scores in 33 patients, assessed by either Bayley Mental Development Index or Stanford-Binet Intelligence Quotient, revealed an average increase of 12.6 (P less than .001).
 After transplantation, there was a significant improvement in mental performance in 12 of 18 patients (P less than .02) from the range of mild delay (Mental Development Index or Stanford-Binet IQ score = 50 to 69) to the range of normal mental development (greater than or equal to 70).
 The Bayley Psychomotor Development Index scores were frequently lower than Mental Development Index scores and also increased an average of 14.4 (P less than .01) after transplantation in all 12 patients with paired data.
 Significant individual improvement in occipital-frontal circumference standard deviation score (P less than .001) was noted in 24 children after transplantation.
 It is concluded that successful renal transplantation in young children with chronic renal failure is often associated with significant improvements in cognitive and psychomotor function, as well as improved cephalic growth.
",11
1726,"Prostate cancer: comparison of digital rectal examination and transrectal ultrasound for screening.
 A prostate cancer screening study of 315 asymptomatic men comparing digital rectal examination and transrectal ultrasound identified 23 cancers, for a detection rate of 7.3%.
 Of the cancers 17 (5.4%) were diagnosed by digital rectal examination.
 Contrary to the experience of others, this was a higher rate than achieved by transrectal ultrasound (14 cases or 4.4%).
 Systematic multiple needle biopsies of both lobes with ultrasound guidance were routinely performed.
 As a result of this technique 7 of 23 cancers (30%) were fortuitously diagnosed.
 In addition, only unilateral disease was suspected in 4 of 7 patients with bilateral disease on biopsy.
 Digital rectal examination and transrectal ultrasound identified the same number of patients with small (less than 1.5 cm.) cancers, contrary to other reports that found transrectal ultrasound to be superior.
 Digital rectal examination is considered an effective screening examination, equivalent to transrectal ultrasound and preferable because of lower cost.
 An algorithm for screening is outlined with digital rectal examination and prostate specific antigen determinations.
",11
1727,"Trace elements and urinary stone formation: new aspects of the pathological mechanism of urinary stone formation.
 The urinary stone, serum and 24-hour urine concentrations of 14 trace elements were determined in urinary stone patients by inductively coupled plasma atomic-emission spectroscopy.
 The data obtained for 25 active stone patients and 32 whose last stone episode had occurred at least 12 months previously were compared with those of 25 healthy individuals.
 Urinary nickel, manganese and lithium excretion, and serum nickel, manganese and cadmium concentrations were statistically significantly lower for active stone patients compared to those with previous stone episodes and healthy individuals.
 No difference in the concentrations of trace elements could be found, however, for patients with previous stone episodes and healthy individuals.
 Nickel, manganese, lithium and cadmium could be of significance in the pathological mechanism of stone formation, not from mineralogical or crystallographic viewpoints but for the smooth flow of enzymatic reactions in biological systems.
",11
1728,"Nonpalpable cancer of the prostate: assessment with transrectal US.
 Palpable cancer of the prostate is widely believed to be clinically significant.
 The authors compared the clinical significance of palpable prostate cancer with nonpalpable prostate cancer discovered with transrectal ultrasound (US).
 A strong association between lesion volume measured with preoperative transrectal US and volumetric measurements in 60 radical prostatectomy specimens permitted the use of tumor size measured with transrectal US as a reasonable estimation of gross tumor volume.
 In a subsequent clinical series, 147 biopsy-proved cancers were grouped according to size measured at US, the findings at digital rectal examination (DRE), and the Gleason score.
 For the 147 patients with known prostate cancer, a statistically significant difference between Gleason scores of palpable and nonpalpable cancers could not be demonstrated when the size of the tumor and its location within the prostate were held constant.
 Assuming that the Gleason score is a reliable indication of malignant potential and clinical significance, the authors conclude that nonpalpable prostatic cancer detected with transrectal US alone may be just as clinically significant as prostatic cancer discovered with DRE.
",11
1729,"Knowledge of hemodialysis and CAPD patients about their prescribed medicines.
 A questionnaire was designed to determine and compare the extent of knowledge of 40 continuous ambulatory peritoneal dialysis (CAPD) and 40 hemodialysis (HD) patients about their medicines.
 It was administered orally to outpatients attending a clinic by an investigator unknown to the patients.
 Data were collected pertaining to the following target drugs: calcium supplements, phosphate binders, vitamins B and C and folic acid.
 HD and CAPD groups were closely matched for age and sex.
 Sixty percent of CAPD and 49% of HD patients were taking four or more medications.
 The dose of folic acid was accurately recalled by 91% and 71% of CAPD and HD patients.
 Indications for calcium supplements and phosphate binders were known by only 8% and 30% of CAPD patients compared to 72% and 73% of HD patients.
 More HD patients knew the indications for all target drugs (p less than 0.01).
 More CAPD than HD patients knew the expected duration of therapy (p less than 0.01).
 There was a trend between decreased knowledge of whether the medication was working with increasing age of CAPD patients.
 Most drug information was supplied by physicians, but many CAPD patients (21%) obtained information from lay sources.
 When given the opportunity to ask questions about their medicines, only 56% CAPD and 46% HD patients did so.
 The knowledge of CAPD and HD patients studied was grossly deficient in terms of indications, effectiveness, duration and action to be taken if doses were missed.
",11
1730,"Post-traumatic priapism treated with metaraminol bitartrate: case report.
 A 30-year-old male with post-traumatic priapism for 7 days was treated successfully by metaraminol bitartrate injection into the corpus cavernosum.
 This result suggests that an alpha-adrenagic agent injection into the corpus cavernosum should be considered in post-traumatic priapism at first.
",11
1731,"Angiotensin II and the maintenance of GFR and renal blood flow during renal artery narrowing.
 The time course of the renal blood flow and GFR responses to narrowing of the renal artery in conscious dogs is reviewed.
 The initial response to this threat to renal perfusion is renal vasodilatation, but within minutes a secondary vasoconstriction mediated by angiotensin II begins to develop.
 Angiotensin II-mediated contraction of mesangial cells is also demonstrable, but this does not apparently reduce the filtration surface area of the glomerular capillaries.
 The intrarenal effects of angiotensin II restore GFR back to normal within one to two weeks, by which time circulating plasma angiotensin II levels are no longer elevated.
 In contrast to its effects on GFR, angiotensin II has minimal effects on renal blood flow after stenosis.
 This may be because, (i) blood flow is mainly determined by the hydraulic resistance of the stenosis; (ii) renal vasoconstriction has relatively little effect on flow due to the particular hemodynamic properties of the stenoses, and (iii) a major site of action of angiotensin II may be within the glomerulus.
 Thus angiotensin II has a homeostatic role in the maintenance of GFR during renal artery narrowing and one component of this role may involve mesangial contraction.
",11
1732,"Angiotensin converting enzyme inhibitors and progression of chronic renal failure.
 Renal failure, once established by loss of a critical amount of functional renal mass, tends to be progressive.
 A large body of experimental evidence supports the hypothesis that glomerular capillary hypertension is important in the pathogenesis of progressive chronic renal failure of diverse types, including subtotal renal ablation and diabetic nephropathy.
 Converting enzyme inhibitors are effective in slowing or arresting the progression of glomerular injury in these experimental models, in association with normalization of both systemic and intrarenal pressures.
 Clinical studies of diabetic nephropathy and chronic renal failure of other etiologies support the concept that these same renal hemodynamic factors are important in human renal disease and that treatment with converting enzyme inhibitors may prove to be a useful therapeutic intervention.
 Whether the converting enzyme inhibitors have specific advantages over other antihypertensive agents due to beneficial renal hemodynamic effects, as suggested by experimental studies, is a question that awaits further investigation.
 Furthermore, the pathogenesis of hypertensive glomerular injury is complex and involves the participation of diverse biologic systems.
 We predict that a wide variety of therapeutic maneuvers, with disparate mechanisms of action, may be effective in arresting or preventing glomerular injury.
",11
1733,"Molecular biology of the renal renin-angiotensin system.
 This paper describes an interrelated series of studies designed to examine molecular and cellular aspects of renin expression and release within the kidney.
 Using immunocytochemical techniques, Northern blot analysis, in situ hybridization, measurement of renin activity, and the reverse hemolytic plaque assay, it has been possible to demonstrate that the intrarenal distribution of renin, renin gene expressing cells and the number of renin secretory cells vary during diverse physiologic and pathologic conditions.
 Overall, these studies demonstrate that the renal preglomerular vasculature has the plasticity and capacity to elicit a recruitment of renin containing and/or renin gene expressing cells.
",11
1734,"Distribution of endogenous albumin in the glomerular wall of proteinuric patients.
 Glomerular proteinuria seems to be related, in part, to loss or impairment of the normal barrier function of the glomerular capillary wall.
 To investigate the functional properties of this barrier, endogenous albumin was revealed in the glomerular wall of proteinuric patients and compared with a nonproteinuric control by immunoelectron microscopy using the protein A-gold method.
 In the control biopsy, peaks of albumin accumulation were noted in the subendothelial area and in the inner portion of the lamina densa, with gradual tapering of the distribution toward the epithelial side of the basement membrane.
 The urinary space and epithelial cells were weakly labeled.
 In tissues from proteinuric patients, albumin was distributed throughout the entire width of the glomerular basement membrane, although the pattern of accumulation varied between patients.
 The urinary space showed significant labeling associated with some flocculent material.
 Mesangial areas were heavily labeled in tissues from both control and proteinuric patients.
 In the latter, lysozomes in glomerular and tubular epithelial cells also accumulated albumin, which is evidence of reabsorption.
 These results reveal the existence, in normal conditions, of a barrier located in the subendothelial area of the glomerular basement membrane, the loss of which, as in the idiopathic nephrotic syndrome, leads to diffuse distribution of albumin in the glomerular capillary wall.
",11
1735,"Guanidino compounds that are increased in cerebrospinal fluid and brain of uremic patients inhibit GABA and glycine responses on mouse neurons in cell culture.
 Four guanidino compounds that have been found to be markedly increased in cerebrospinal fluid and brain tissue of uremic patients, namely, guanidine, methylguanidine, creatinine, and guanidinosuccinic acid, were applied to mouse spinal cord neurons in primary dissociated cell culture to evaluate their effects on postsynaptic responses to gamma-aminobutyric acid (GABA) and glycine.
 Intracellular microelectrode recording techniques were used.
 Guanidine, methylguanidine, creatine, and guanidinosuccinic acid reversibly and in a dose-dependent manner inhibited both GABA and glycine responses.
 Guanidinosuccinic acid was the most potent inhibitor of the amino acid responses, followed in decreasing potency by methylguanidine, guanidine, and creatinine.
 Guanidinosuccinic acid inhibited responses to GABA and glycine, at concentrations similar to those found in cerebrospinal fluid and brain tissue of patients with terminal renal insufficiency.
 The other guanidino compounds tested exerted their effects only at concentrations higher than those found in uremic biological fluids and tissues.
 The inhibitory effect of guanidine and methylguanidine on responses to GABA was additive.
 The effect of the guanidino compounds on GABA responses was not antagonized by coapplication of the benzodiazepine-receptor antagonist CGS 9896.
 The results suggest that guanidine, methylguanidine, creatinine, and guanidinosuccinic acid inhibited responses to the inhibitory neurotransmitters GABA and glycine by blocking the chloride channel.
 The observed action of the studied guanidino compounds might contribute to the pathogenesis of the complex neurological symptomatology encountered in uremia.
",11
1736,"Alterations in renal medullary hemodynamics and the pressure-natriuretic response in genetic hypertension.
 The concept that the kidney plays a major role in the long-term control of arterial pressure is based on the pressure-natriuretic response.
 According to this hypothesis, hypertension can only develop when the relationship between sodium excretion and arterial pressure is altered.
 Transplantation studies have indicated that some form of renal dysfunction underlies the development of genetic forms of hypertension in the spontaneously hypertensive rat (SHR) and in the Dahl salt-sensitive (S) rat.
 Nonetheless, the factors responsible for ""resetting the kidney in hypertension"" remain unknown.
 We have reported that the pressure-natriuretic relationships of SHR and Dahl S rats of the Brookhaven and Rapp strains are shifted toward higher pressures prior to the development of the disease.
 Papillary blood flow is also reduced in very young ""prehypertensive"" SHR.
 Recent studies on the mechanism of pressure-diuresis indicate that it is mediated by inhibition of sodium reabsorption in the proximal tubule and/or thin descending limb of Henle of deep nephrons.
 It is also associated with changes in renal interstitial pressure and the pressure and flow in the vasa recta circulation.
 These observations suggest that an elevation in renal medullary vascular resistance may be responsible for shifting the pressure-natriuresis relationship toward higher pressures in hypertension.
",11
1737,"Incidence of advanced chronic renal failure and the need for end stage renal replacement treatment 
 OBJECTIVE--To determine the age related incidence of advanced chronic renal failure in two areas of England.
 DESIGN--Prospective study of patients newly identified as having advanced chronic renal failure within a two year period; subsequent monitoring of patients' clinical course for a further 26 months.
 SETTING--Devon and Blackburn.
 SUBJECTS--Those patients in a population of 708,997 who developed advanced chronic renal failure (serum creatinine concentration greater than 500 mumol/l) for the first time during a two year period.
 MAIN OUTCOME MEASURES AND RESULTS--210 Patients (148 per million population per year) developed advanced chronic renal failure, 117 (51%) of whom were over 70.
 The age related incidence rose from 58 per million per year in those aged 20-49 to 588 per million per year in those aged 80 or over.
 Only 54% (113) of patients were referred to a nephrologist; 120 patients (57%) needed dialysis or died within three months of presenting without receiving dialysis, and 187 (89%) died or needed dialysis within three years.
 After those unsuitable for further treatment had been excluded, 78 patients per million population per year aged under 80 needed to start long term renal replacement treatment.
 CONCLUSIONS--Many patients suitable for renal replacement treatment are still not referred for nephrological opinion and are denied treatment.
 If the treatment rate in the United Kingdom rose from the 1988 rate of 55.1 per million per year to 78 per million per year then the number of patients receiving treatment would rise to about 800 per million.
 This is double the present number and has considerable but predictable resource implications for the NHS.
",11
1738,"Prevalence of advanced renal failure in Northern Ireland 
 OBJECTIVE--To determine the prevalence of advanced chronic renal failure in Northern Ireland as part of an assessment by the Renal Association of the level of service provision for treatment of such patients.
 DESIGN--Prospective notification of patients reaching a defined level of advanced chronic renal failure (serum creatinine concentration greater than or equal to 500 mumol/l or blood urea concentration greater than or equal to 25 mmol/l) within one year and follow up for at least three, and, at most, four years after notification.
 SETTING--Northern Ireland.
 PATIENTS--122 Patients with a serum creatinine or blood urea concentration higher than the defined level newly detected from 1 March 1985 to 28 February 1986.
 MAIN OUTCOME MEASURE--Survival after notification.
 RESULTS--77 Patients of all ages/million population/year had advanced chronic renal failure compared with 67/million/year between the ages of 5 and 80 found in an earlier study of the same population.
 62% Of the patients were older than 50 years.
 Seventeen (14%) of the patients either required dialysis or died within one month of notification, 51 (42%) survived for at least three months, and 23 (19%) for one year or longer.
 Three patients, all of whom were attending a renal clinic, survived for periods of 43, 45, and 46 months respectively without renal replacement treatment.
 CONCLUSIONS--The increased number of new patients disclosed in this survey compared with the earlier survey is mainly owing to an increased number of older patients.
 Such patients often have disabilities other than renal failure, are less likely to be capable of self treatment, may develop complications more often and require more frequent hospital admissions, and may not be suitable for transplantation and consequently have considerable resource implications for the NHS.
",11
1739,"Etoposide therapy for testicular cancer.
 During the past two decades, dramatic strides have been made in the treatment of metastatic testicular cancer.
 In the early 1970s, cisplatin, vinblastine, and bleomycin (PVB) produced durable complete remissions (CR) in approximately 70% of treated patients.
 In the early 1980s, etoposide emerged as the only drug with single-agent activity in cisplatin-refractory patients.
 Based on preclinical data demonstrating synergy of cisplatin plus etoposide, the two-drug combination proved to be a useful salvage therapy, curing approximately 25% of such patients.
 Further evaluation of etoposide as part of initial therapy by the Southeastern Cancer Study Group (SECSG) compared PVB with bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with metastatic germ cell tumors.
 Not only did BEP have significantly less toxicity, it proved to be superior to PBV in patients with advanced disease.
 Varying the dose and schedule of etoposide also may provide patients with potentially useful avenues of treatment.
 High-dose etoposide plus carboplatin in drug-refractory patients has produced durable CR in a cohort of treated patients; it is currently being evaluated as part of initial salvage therapy.
 The schedule dependency of etoposide in small cell lung cancer led us to evaluate daily oral administration of etoposide in patients refractory to previous etoposide therapy; objective response rates of approximately 15% to 25% were observed.
 In summary, etoposide remains an integral part of the treatment regimen for testis cancer.
 However, the incorporation of innovative dose and schedule combinations for etoposide may further improve its therapeutic index for this disease.
",11
1740,"On the mechanism of impaired insulin secretion in chronic renal failure.
 It has been suggested that a sustained rise in resting levels of cytosolic calcium [Ca2+]i of pancreatic islets is responsible for impaired insulin secretion in chronic renal failure (CRF).
 Evidence for such an event is lacking and the mechanisms through which it may affect insulin secretion are not known.
 Studies were conducted in normal, CRF, and normocalcemic, parathyroidectomized (PTX) CRF rats to answer these questions.
 Resting levels of [Ca2+]i of islets from CRF rats were higher (P less than 0.01) than in control of CRF-PTX rats.
 [3H]2-deoxyglucose uptake and cAMP production by islets were not different in the three groups.
 Insulin content of, and glucose-induced insulin secretion by islets from CRF rats was lower (P less than 0.01) than in control and CRF-PTX rats.
 In contrast, glyceraldehyde-induced insulin release by CRF islets was normal.
 Basal ATP content, both glucose-stimulated ATP content and ATP/ADP ratio, net lactic acid output, Vmax of phosphofructokinase-1, and Ca2+ ATPase of islets from CRF rats were lower (P less than 0.02-less than 0.01) than in normal or CRF-PTX animals.
 Data show that: (a) Glucose but not glyceraldehyde-induced insulin secretion is impaired in CRF; (b) the impairment in glucose-induced insulin release in CRF is due to a defect in the metabolism of glucose; (c) this latter defect is due to reduced ATP content induced partly by high [Ca2+]i of islets; and (d) the high [Ca2+]i in islets of CRF rats is due to augmented PTH-induced calcium entry into cells and decreased calcium extrusion from the islets secondary to reduced activity of the Ca2+ ATPase.
",11
1741,"An evaluation of the efficacy and safety of doxazosin in hypertension associated with renal dysfunction. The Japanese Doxazosin Study Group.
 Doxazosin was administered once daily to 26 patients with renal hypertension or hypertension associated with renal dysfunction.
 Doxazosin produced a significant reduction in blood pressure that was stable throughout the treatment period.
 A significant change was not observed in heart rate.
 Blood pressure was ""markedly decreased"" or ""decreased"" in 80% of patients receiving doxazosin monotherapy, 78.6% of patients receiving combined therapy, and 79.2% of all the patients.
 The cumulative efficacy ratio according to final daily dose was 62.5% with 1 to 4 mg/day and 75.0% to 79.2% with 8 to 16 mg/day.
 Side effects were observed in three patients (12.0%), none of them severe, and all side effects disappeared with continued administration of doxazosin.
 Abnormal laboratory values in six items were observed in four patients.
 Serum creatinine and blood urea nitrogen values, which were regarded as renal function parameters, did not show significant changes, and no negative influence was observed with respect to doxazosin therapy.
 Overall clinical usefulness was considered ""very useful"" or ""useful"" in 80% of patients receiving doxazosin monotherapy, 78.6% of patients receiving combination therapy, and 79.2% of all patients.
 In conclusion, once-daily administration of doxazosin was considered a useful antihypertensive therapy for renal hypertension and hypertension associated with renal dysfunction.
",11
1742,"Glomerular structures and lipids in progressive renal disease.
 In the last few years, remarkable advances have been made in the understanding of lipoprotein metabolism in the pathogenesis of renal disease in animal models and in vitro cell culture.
 Central to this work is the problem of the progression of renal disease in humans.
 This review recapitulates the theory (Lancet 1982; II: 1309-1312) that the progression of disease depends in part on the damage inflicted on the glomerulus by lipoproteins.
 The glomerular environment of high or low pressure, basement membrane damage, and destruction or damage of the mesangial and epithelial cells permits the filtration of protein, the consequence of which is hyperlipidemia.
 Whatever the therapeutic measures employed, if proteinuria persists, hyperlipidemia will follow.
 This suggest that lipoprotein toxicity may contribute to the final common path of renal damage in progressive renal disease.
 ""Lipoprotein toxicity"" in arteries is called atherosclerosis, but this term ignores the complexity of the glomerulus and the possible tubular damage that might be caused by filtered lipoprotein.
 It is clear there is insufficient knowledge of the metabolism of the damaged kidney to confidently attribute the pathology of progression of disease to any single process.
",11
1743,"Similarities between glomerular sclerosis and atherosclerosis in human renal biopsy specimens: a role for lipoprotein glomerulopathy.
 Much recent work has focused on the progressive nature of renal injury, and hemodynamic alterations have been implicated in the pathogenesis of the predominant lesion, focal glomerulosclerosis.
 Despite the well-documented atherogenic toxicity of lipids in cardiovascular morbidity, little is known about lipid-associated renal injury.
 However, lipids are toxic to endothelium, and the glomerulus is a vascular bundle.
 Several authors participating in this symposium have presented evidence for an association between hyperlipidemia and glomerulosclerosis in animal models.
 This association is particularly significant given the expanded therapeutic armamentarium now available to treat hyperlipidemia.
 In fact, glomerular injury may be moderated by pharmacologic treatment of hyperlipidemia in a rat renal ablation model.
 Very little evidence exists, however, for a similar association in human renal disease.
 We have, in the course of clinical practice, made certain observations in renal biopsy specimens that may for the first time link atherogenesis and lipid deposition to human glomerular injury.
",11
1744,"Serum lipids in patients with chronic renal failure on long-term, protein-restricted diets.
 Disordered lipid metabolism is believed to play an important role in accelerating the progression of chronic renal disease toward uremia.
 We examine this hypothetic role of lipids in a large population of patients on long-term dietary protein restriction.
 In our experience, there is no conclusive evidence that lipids may accelerate the progression of functional deterioration in patients with reduced renal function.
 Hyperlipidemia seems to be only one among the many factors affecting the prognosis of primary renal disease.
 Dietary protein restriction is effective in maintaining normal or only slightly elevated serum lipid levels in patients with early renal failure.
 Moreover, patients with renal failure maintained on this diet, which provides an elevated ratio of polyunsaturated to saturated fatty acids, have a more favorable lipid composition of erythrocyte membrane (low percentage of saturated fatty acids and high percentage of polyunsaturated fatty acids) when compared with patients on an unrestricted diet.
",11
1745,"Desmopressin-induced improvement in bleeding times in chronic renal failure patients correlates with platelet serotonin uptake and ATP release.
 Hemostatic defects resulting in life-threatening hemorrhagic episodes are a common occurrence in the chronic renal failure patient.
 Hemorrhagic tendencies correlate best with laboratory tests of bleeding times.
 The identification of a specific hemostatic defect and its role in bleeding dyscrasias has yet to be elucidated.
 Our studies demonstrate that factor VIII coagulant activity and factor VIII related antigen (vWF:Ag) are normal or greatly elevated in uremic renal failure patients with greatly prolonged bleeding times.
 The multimeric state of the von Willebrand factor is also normal in these patients.
 The bleeding times were normalized in all 15 patients, 90 minutes post-infusion with desmopressin (DDAVP).
 No significant changes in factor VIII/vWF associated properties, blood cell counts, or coagulation factors were observed post-DDAVP treatment.
 However, a significant increase in platelet serotonin uptake (p less than .025) and ATP release (p less than .025) was detected after DDAVP treatment.
 These results indicate that DDAVP acts on the platelet membrane.
 This is further substantiated by the ability of DDAVP to block vasopressin-induced platelet aggregation in a dose- and time-dependent fashion.
 Perturbations in the movement and storage of serotonin and the release of adenosine 5'-triphosphate (ATP) in the platelets of uremic individuals are proposed to play a critical role in regulating bleeding times.
",11
1746,"Can the rate of progression of chronic renal failure be altered?
 The cost of renal replacement therapy for end-stage renal disease in the United States exceeds three billion dollars per year.
 Nonimmunologic mechanisms may contribute to progressive renal injury in renal failure of diverse etiologies.
 Based on the potential adverse renal effects of these processes, a number of dietary and pharmacologic interventions have been proposed as being potentially beneficial in slowing the rate of progression of chronic renal failure to end-stage renal disease.
 This article reviews current evidence in animal models and humans supporting the efficacy of each of the proposed interventions.
",11
1747,"Excretion of urinary protein induced by extracorporeal piezoelectric lithotripsy.
 An investigation was carried out into renal injury caused by extracorporeal piezoelectric lithotripsy (EPL) using an EDAP lithotriptor.
 Four urinary proteins, with a molecular weight range of 160000-14500, immunoglobulin G (IgG), N-acetyl-beta-glucosaminidase (NAG), albumin and lysozyme, were monitored in 27 patients 1 day before and 1, 7, 30, 90 and 180 days after unilateral EPL treatment.
 All patients had non-obstructive renal stones, previously untreated.
 Apart from 5 patients with stablised hypertension and 6 with persistent urinary infections due to the infected stones, all patients appeared healthy, as confirmed by clinical, haematological and biochemical investigations.
 Only albumin levels increased significantly 1 day after treatment; statistically nonsignificant increases and decreases were recorded in the levels of NAG and lysozome respectively.
 IgG was beyond the limit of detection (less than 0.5 mg%) in all patients.
 The albumin level returned to normal 7 days after treatment.
 The EPL-induced increase in albumin was recorded in 88% of patients, compared with increased levels of NAG in 46% and lysozyme in 64%, mainly in those with infected stones.
 These findings indicated a transient glomerular injury after EPL treatment.
",11
1748,"Do stone formers have lower urinary fibrinolytic activity than controls?
 A comparison of urinary fibrinolytic activity between 31 stone formers and 50 controls failed to demonstrate any significant difference and so failed to confirm an earlier independent observation.
 This may be due to methodological and design differences between the 2 studies, but does suggest reservations about the significance of lowered urinary fibrinolytic activity as a risk factor for renal stone disease.
 Dietary information from those taking part in the study suggests that a reduction of meat intake by stone formers might be associated with increased urinary fibrinolytic activity.
 This might account for the discrepancy between the 2 studies, in which case this observation could be of significance.
",11
1749,"Small cell carcinoma of the urinary tract.
 Small cell carcinomas of the urinary tract are rare, but lethal.
 We report 3 cases of primary small cell carcinoma of the kidney, urinary bladder and prostate with light microscopic, immunohistochemical and electron microscopic findings.
 One patient with small cell carcinoma of the prostate died of disseminated disease 2 years after diagnosis and another patient with small cell carcinoma of the urinary bladder was free of tumour after 6 months.
 A partial remission was induced in the third patient with distant metastases of small cell carcinoma of the kidney by using chemotherapy protocols similar to the drug regimens for small cell carcinomas of the lung; the patient survived for 5 months.
 Immunohistochemical studies revealed the absence of argyrophilic immunostaining of tumour cells in all 3 cases, positive staining for keratin in 2 and staining for neuron-specific enolase in all 3.
 In the third patient, reactivity for prostate-specific antigen was negative.
 Dense-core, membrane-bound granules were identified in the cytoplasm of 2 patients.
 The paraneoplastic syndrome was not found, indicating that in considering the occurrence of ectopic hormones, specific cytoplasmic granules of origin need not be implicated.
 Recognition of this distinct entity requires full consideration of morphological, immunohistological, ultrastructural and biological features.
 In order to define the origin of this tumour more clearly and to evaluate the effectiveness of chemotherapy, larger series of patients are needed.
",11
1750,"The effect of verapamil on the anti-tumour action of mitozantrone and doxorubicin against renal carcinoma cells in vitro.
 Ten renal carcinomas were established in culture and their sensitivity to mitozantrone +/- verapamil, as measured by (75Se) selenomethionine incorporation, was studied.
 The 5 tumours with spread beyond the kidney were those in which sensitivity to mitozantrone was enhanced by verapamil.
 With 4 of the 10 tumours and 1 further carcinoma, similar experiments were performed using doxorubicin.
 This drug was more active, its anti-tumour action being related to concentration.
 Verapamil was more effective in potentiation of doxorubicin and this action increased in proportion to the concentration of verapamil added.
",11
1751,"Caffeine: does it affect your bladder?
 Patients with symptoms of frequency and urgency often complain that their symptoms are exacerbated by tea or coffee.
 A series of 20 women with confirmed detrusor instability and 10 asymptomatic women were given 200 mg of caffeine citrate and urodynamic studies were performed.
 In the group with detrusor instability there was a statistically significant increase in detrusor pressure on bladder filling following administration of caffeine, but no difference in volume at first contraction, height of contraction or bladder capacity.
 Normal women had no abnormality on cystometry.
",11
1752,"Experience with a simplified technique for the treatment of female stress urinary incontinence.
 Over a 9-year period a simple procedure for the correction of stress urinary incontinence was performed in 86 consecutive patients, 31 of whom had failed a previous anti-incontinence procedure.
 Success was achieved in 81 cases (94%).
 Of the 5 failures, 2 were successfully treated with a repeat procedure.
 Operative time ranged from 14 to 49 min (median 27).
 The average hospital stay was 2 days.
 Because of its simplicity and reliability, this technique is recommended for the surgical correction of female stress urinary incontinence.
",11
1753,"Treatment of benign prostatic hyperplasia with phytosterols.
 In a randomised, double-blind study, the preparation Curbicin, obtained from pumpkin seeds and dwarf palm plants (Cucurbita pepo L.
 and Sabal serrulata), was compared with a placebo in the treatment of symptoms caused by prostatic hyperplasia; 53 patients took part in the study, which was carried out over a 3-month period.
 Urinary flow, micturition time, residual urine, frequency of micturition and a subjective assessment of the effect of treatment were all significantly improved in the treatment group.
 No untoward side effects were noted.
",11
1754,"Semen analysis in patients operated on for impalpable testes.
 Semen analysis was performed on 48 men who had undergone orchiopexy, 40 for unilateral impalpable testes and 8 for bilateral impalpable testes.
 Patients with unilateral impalpable testes had varying sperm analysis; 18 (86%) of the 23 patients with unilateral impalpable canalicular testes had normal sperm analysis.
 All patients with bilateral impalpable testes were azoospermic.
 The subsequent quality of the semen is dependent upon the original anatomical positions of the undescended testes.
",11
1755,"Comparison of urethral reaction to full silicone, hydrogen-coated and siliconised latex catheters.
 Indwelling urinary catheter may induce an inflammatory reaction or even stricture of the urethra.
 Catheter encrustation and urinary infection are other disadvantages associated with long-term catheterisation.
 In the present study, 77 male patients were catheterised randomly as part of their normal treatment with 1 of 3 different types of catheter: 22 siliconised latex, 28 hydrogel-coated latex and 27 full silicone catheters.
 The mean duration of catheterisation was 2.2 days.
 The urethral inflammatory reaction was assessed from cytological urethral swab specimens.
 Catheter encrustation was studied using scanning electron microscopic (SEM) analysis.
 The full silicone catheters induced the mildest degree of inflammation in the urethra, the percentage mean of inflammatory cells in smears being 20%.
 In both latex catheter groups the value was 36%.
 Neither the age of the patients nor the duration of catheterisation had any effect on the inflammatory reaction, which was more marked in patients with haemodynamic abnormalities.
 The hydrogel coating effectively prevented encrustation, while siliconised latex catheters were the least resistant to encrustation.
 The inflammatory reaction was variable in all patients.
 The use of urethral catheters should be restricted and suprapubic tubes should be used instead, particularly in patients with shock-like circulatory changes.
 By developing the biocompatibility and physical properties of urinary catheters, more compatible devices may be manufactured.
",11
1756,"Black tobacco, mate, and bladder cancer. A case-control study from Uruguay.
 A case-control study of bladder cancer involving interviews with 111 incident cases and 222 controls was carried out in Montevideo, Uruguay.
 The analysis was conducted separately for each sex.
 Point estimates of relative risk associated with smoking variables, ingestion of infusions of the herb Ilex paraguariensis (mate), and selected dietary items were obtained by stratified and logistic regression analysis.
 Among men, smokers of black tobacco showed a relative risk (RR) 2.7 higher than blond tobacco smokers and mate exposure showed a significant dose-response, after adjustment for age, residence, social class, hospital, type of tobacco, smoking intensity, smoking duration, and vegetable consumption, with a seven-fold increase in risk for heavy consumers.
 Joint exposure to type of tobacco and mate consumption showed a multiplicative effect.
 Women showed a similar increase in risk with mate consumption.
 The results suggest that the high mortality rates of bladder cancer observed in Uruguay could be explained by the combined effect of black tobacco smoking and mate ingestion.
",11
1757,"Extrarenal production of calcitriol in normal and uremic humans.
 We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25-hydryoxyvitamin D (25OHD) to anephric humans.
 Since normal alveolar macrophages are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or lipopolysaccharide, we determined whether macrophages derived from peripheral blood monocytes could be an extrarenal source of 1,25-(OH)2D3.
 Our results demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3.
 The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4 +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA.
 The activity of this enzyme was reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3 in the incubation medium.
 Normal macrophages further hydroxylated 1,25-(OH)2D3 to more polar metabolites, and this catabolic activity was significantly enhanced by physiological concentrations of 1,25-(OH)2D3.
 In chronic renal failure, peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/- 0.8 vs.
 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a decreased capacity to degrade 1,25-(OH)2D3.
 Exogenous 1,25-(OH)2D3, in physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/- 8.5%) comparable to that observed in normal cells.
 1,25-(OH)2D3 production by macrophages did not correlate with the severity of hyperparathyroidism.
 Moreover, human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L) did not stimulate the 1 alpha-hydroxylase activity of macrophages from either normal or uremic subjects.
 These results demonstrate that 1) normal peripheral macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in chronic renal failure.
",11
1758,"Progression of renal insufficiency in analgesic nephropathy: impact of continuous drug abuse.
 Twenty-three patients with analgesic nephropathy and apparent cessation of drug abuse were tested for blood acetaminophen and salicylate on the occasion of routine renal control examinations.
 In 12 patients (mean creatinine level 2.74 +/- 1.09 mg/dl) no deterioration of renal function was noted within a 1-year observation period (Group 1).
 In 11 patients a significant progression of renal insufficiency was observed (mean creatinine level rose from 3.86 +/- 1.06 to 6.40 +/- 3.18 mg/dl within the same observation period; Group 2).
 Blood tests for acetaminophen and salicylate were positive in 2 patients of Group 1 and in 9 patients of Group 2 (chi 2 = 7.326), p less than 0.01).
 Our data emphasize the importance of a continuous analgesic abuse hidden from the medical staff with regard to the progression of renal insufficiency in analgesic nephropathy.
",11
1759,"Functional status and quality of life: predictors of early mortality among patients entering treatment for end stage renal disease.
 We investigated the association between functional status and quality of life in newly-entered dialysis patients and the subsequent risk of mortality.
 We enrolled the patients from 37 dialysis facilities in two southeastern states (n = 294).
 Functional status was assessed by the Karnofsky Performance Scale (KPS) and quality of life by the Spitzer Quality of Life Index (SQLI).
 During a mean (SE) follow-up of 479.6 (109.4) days 49 patients (16.4%) of the cohort died.
 The mean KPS score (SE) for survivors was 7.31 (0.11) and for non-survivors was 5.89 (0.26), P less than 0.0001.
 The mean SQLI score (SE) for survivors was 6.74 (0.15) and non-survivors was 4.95 (0.28), P less than 0.0001.
 Strong gradients of the risk of mortality were found for both measurements.
 After controlling for other covariates including age, race, sex, primary cause of renal failure and the presence of comorbidity, both the KPS and SQLI scores were independently correlated with risk of mortality.
 We conclude that functional status and quality of life are strong independent risk factors for subsequent mortality in new dialysis patients.
 These are easily measured indicators which may serve to predict subsequent risk of mortality or adjust case-mix estimates for comparisons between dialysis populations.
",11
1760,"Effects of probucol on renal function in rats with bilateral ureteral obstruction.
 To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration.
 Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study.
 Probucol lowered serum cholesterol in both normal and BUO rats.
 Probucol did not significantly affect renal function in normal rats.
 BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol.
 Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione.
 Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol.
 A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO.
 The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy.
 The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex.
",11
1761,"Three-dimensional morphometric analysis of segmental glomerulosclerosis in the rat.
 In idiopathic nephrotic syndrome, and in experimental models of nephrosis, changes of visceral epithelial cells involve the entire glomerular population while segmental sclerotic changes are reported to affect only a certain number of glomeruli.
 Because conventional determination of the percentage of glomeruli affected by sclerotic lesions is usually based on the examination of randomly selected sections, we wondered whether glomeruli appearing normal in a given section could be affected by sclerosis in other regions of the capillary tuft (CT).
 To assess the real incidence and the spatial extension of sclerotic changes at the level of single glomerulus, we used serial-section morphological analysis to measure the volume of the glomerulus and that of sclerosis lesions.
 In glomeruli from control rats and in glomeruli from adriamycin (ADR) treated rats surface area of Bowman's capsule (BC), CT and sclerotic regions were measured using stereology techniques in all the consecutive sections containing each individual glomerulus, and corresponding volumes were then calculated.
 Mean volume of BC and CT were not significantly different between control and ADR rats (0.71 +/- 0.03 and 0.53 +/- 0.03 vs.
 0.76 +/- 0.04 and 0.53 +/- 0.02 microns 3 x 10(-6), respectively).
 The distribution of glomerular volume parameters in the ADR rats were more spread out than in control animals, indicating that some glomeruli became smaller while other became larger.
 No sclerotic changes were found in control rats, while in the three ADR rats 94, 90 and 92% of glomeruli, respectively, were affected by sclerotic lesions.
",11
1762,"Fosinopril prevents hyperfiltration and decreases proteinuria in post-transplant hypertensives.
 Hypertension and renal mass reduction induce glomerular hypertension (GH), hyperfiltration (HF) and renal injury.
 GH may contribute to allograft loss in post-transplant hypertensive patients (PT x HT).
 HF and GH may be evaluated by renal response to acute protein intake (API).
 Since ACE inhibition may prevent GH, the effects of fosinopril (Fos) were evaluated in 10 PT X HT on azathioprine and prednisone.
 Patients received 5 to 40 mg/day of Fos during 12 months.
 Baseline MAP (111.1 +/- 2.9 mm Hg) was significantly reduced by 10 to 12 mm Hg, rising to 114.7 +/- 2.7 mm Hg after Fos was administered.
 GFR (63.7 +/- 5.9 ml/min) decreased after 4 (48.1 +/- 4.6, P less than 0.05) and 12 months (50.7 +/- 4.6, P less than 0.05), rising to 59.4 +/- 5.6 after Fos was given.
 There was no GFR response to API before and after one month of Fos, however, a clear response became apparent at 4 (+ 27% P less than 0.05), and 12 months (+ 18%, P less than 0.05), disappearing after Fos discontinuation.
 Proteinuria (918.8 +/- 710.6 mg/d) decreased after 4 (72.3 +/- 21.6 mg/d, P less than 0.05) and 12 months, rising to 297.8 +/- 172.3 mg/day after therapy.
 GFR response to API in 22 controls and 17 uninephrectomized donors was 13 and 11%, respectively.
 Lack of response to API in PT x HT suggests HF and GH.
 Reduction of GFR, restoration of response to API and reduction of proteinuria, indicate that ACE inhibition with fosinopril ameliorates HF and GH.
 This effect may be beneficial in preventing hemodynamic-mediated allograft injury.
",11
1763,"L-lactate high-efficiency hemodialysis: hemodynamics, blood gas changes, potassium/phosphorus, and symptoms.
 Hemodynamic changes were measured during high-efficiency hemodialysis (HEHD) using three dialysis solutions: L-lactate (46 mM), bicarbonate (35 mM + 4 mM acetate), and acetate (39 mM).
 Cardiac output was determined by changes in thoracic electrical bioimpedance.
 Although there appeared to be subtle differences in hemodynamic response to L-lactate versus bicarbonate, the blood pressure, cardiac output, and total peripheral resistance were affected less with either of these solutions than with acetate.
 In particular, neither L-lactate nor bicarbonate HEHD were associated with a change in cardiac output, whereas with acetate HEHD a marked (22%) increase in cardiac output was seen concurrently with a moderate fall in blood pressure and TPR.
 Both acetate and L-lactate HEHD were associated with hypoxemia, whereas with bicarbonate HEHD the PO2 did not change.
 With L-lactate HEHD, correction of pH and plasma HCO3 concentrations was delayed but these values were not significantly different from those obtained with bicarbonate HEHD by one hour after dialysis.
 Potassium removal was comparable with the three dialysis solutions.
 Phosphorus removal with L-lactate tended to be slightly less than with bicarbonate, but not less than with acetate.
 Our results suggest that L-lactate (46 mM) dialysis solution may be a suitable alternative to acetate for HEHD, being associated with a hemodynamic profile that is similar to that of bicarbonate and better than that of acetate.
 Our results further suggest that the hypoxemia associated with the use of acetate dialysis solution is not intrinsic to acetate, but is due either to a low dialysis solution PCO2 level or to accelerated consumption of oxygen during substrate metabolism.
",11
1764,"Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects.
 Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure.
 We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis.
 Thirty-eight patients received up to six months of L-carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions.
 In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal, and plasma acyl levels were elevated.
 Post-dialysis plasma free and total carnitine concentrations were also subnormal.
 Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo.
 There were no significant changes observed in plasma triglycerides, HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups.
 We conclude that carnitine metabolism is altered in uremia.
 Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles.
",11
1765,"Influence of calcium acetate or calcium citrate on intestinal aluminum absorption.
 The risk of aluminum (Al) accumulation in patients with chronic renal failure has led to use of non-Al phosphate binders.
 Frequently, Al and non-Al phosphate binders are co-administered.
 Unfortunately, calcium citrate (Ca citr), when given with Al-gel, markedly enhances Al absorption.
 To determine whether calcium acetate (Ca acetate) also augments Al absorption, 10 normal volunteers were each given orally, three-day courses of the following drug combinations dosed four times daily: 1) aluminum hydroxide gel (Al[OH]3) (5 ml) alone; 2) Al[OH]3 (5 ml) plus Ca acetate (1330 mg); 3) Al[OH]3 (5 ml) plus Ca citr (950 mg).
 A nine day wash-out occurred between each course.
 Al levels were measured using flameless atomic absorption spectrophotometry.
 Daily urine Al excretion was measured during a two-day baseline before each course and during each three-day drug course.
 Plasma Al was obtained during each baseline and drug course.
 Mean 24-hour Al excretion (micrograms/g creatinine/day) at baseline versus treatment for each combination was: 1) 5.9 +/- 3.2 versus 42.0 +/- 40.7 (mean +/- SD); 2) 5.7 +/- 3.0 versus 40.3 +/- 28.6: 3) 6.3 +/- 3.4 versus 175.8 +/- 103.3.
 Al excretion was significantly greater with combination 3 than with either 1 or 2 (P less than 0.05).
 The difference between 1 and 2 was not significant.
 Plasma Al (micrograms/liter) at baseline versus treatment for each combination was: 1) 5.3 +/- 4.2 versus 8.1 +/- 2.5 (mean +/- SD); 2) 3.1 +/- 2.2 versus 7.3 +/- 2.9; 3) 3.0 +/- 2.3 versus 12.0 +/- 6.1.
",11
1766,"Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor genes.
 Two prostate carcinoma cell lines, DU-145 and PC-3, were examined for abnormalities in the retinoblastoma (Rb) and the p53 putative tumor suppressor genes.
 We found an abnormal Rb gene product in DU-145 using Western blot analysis.
 Polymerase chain reaction amplification followed by direct DNA sequencing demonstrated a base substitution mutation that generates a stop codon in exon 21.
 On Northern, Southern, and Western blot analysis, the p53 gene and its product appear to be normal in DU-145.
 PC-3, however, failed to demonstrate expression of either the p53 transcript on Northern blot analysis or the p53 protein on Western blot analysis, while the Rb gene products appeared to be normal on both Northern and Western blot analysis.
 This work extends the correlation between abnormal expression of putative tumor suppressor genes and human malignancies.
",11
1767,"Effect of ileal conduit on patients' activities following radical cystectomy.
 Over the last twenty months, 110 patients who have undergone a radical cystectomy for bladder cancer at The University of Texas M.
 D.
 Anderson Cancer Center were surveyed to assess the effect of an ileal conduit urinary diversion on postoperative activity.
 Postoperatively, 47.3 percent of the patients were very active, 34.5 percent were moderately active, and 18.2 percent were sedentary.
 Chemotherapy and the patient's gender were found to have a statistically significant effect on postoperative activity level.
 Chemotherapy resulted in a decrease of very active patients from 55.6 percent to 27.9 percent and an increase in sedentary patients from 11.2 percent to 30.2 percent (P = 0.005).
 No difference in activity levels was seen in 73.9 percent of the nonchemotherapy patients.
 Fifty-one percent of the men were very active as compared with only 19.1 percent of the women, whereas 20 percent more women than men were moderately active and 13 percent more were sedentary.
 Our experience indicates that the ileal conduit had no significant negative effect on activity if the effects of chemotherapy are controlled: 82.6 percent of the patients not receiving chemotherapy experienced either no change or an increase in their activity.
",11
1768,"Cecal tubularization: lengthening technique for creation of catheterizable conduit.
 The creation of a continent, catherizable stoma is an integral component of successful continent urinary diversion.
 A technique is described which allows lengthening of a continent appendicovesicostomy.
 This technique extends the applications for the Mitrofanoff principle of urinary tract reconstruction.
",11
1769,"Use of biofeedback in treatment of psychogenic voiding dysfunction.
 A young man with psychologic problems and a long history of social inadequacy presented with voiding dysfunction.
 Videocystometrography revealed a normal filling phase and normal initiation of voiding interrupted by considerable straining by the patient and marked sphincter electromyographic (EMG) activity.
 Temporary amelioration was achieved by infiltration of the sphincter with lignocaine hydrochloride and by biofeedback therapy.
 In such cases optimal results are expected from long-term behavioral therapy.
",11
1770,"Treatment of renal transplant stones by extracorporeal shock-wave lithotripsy in the prone position.
 Two patients with renal transplant lithiasis were successfully treated with extracorporeal shock-wave lithotripsy (ESWL) in the prone position.
 Pathogenesis and treatment of transplant lithiasis are discussed.
 Performing ESWL on renal transplant patients in the prone position has advantages over standard positioning techniques.
",11
1771,"Study of antireflux nipple valves of Kock ileal urinary reservoir. Experimental investigation in dogs.
 To better assess the construction, maintenance, and function of the Kock ileal urinary reservoir with its continent antirefluxing nipple valves, laboratory investigations in dogs were done simultaneously with clinical trials in humans in 1983.
 Fifteen dogs underwent creation of hemi-Kock ileal reservoirs (without the efferent valve and limb) that were anastomosed to their bladders as enterocystoplasties.
 The afferent antirefluxing nipple valves were intussuscepted after 7 cm of underlying mesentery had been removed.
 The nipples were further stabilized with metal and absorbable (Polysorb) staples and Marlex collars.
 The right ureters were anastomosed to the afferent limb of the reservoirs with the contralateral systems left intact as controls.
 Ten dogs were able to be followed at the vivaria for twelve to thirty-six months and then studied.
 All nipple valves remained intact, viable, and nonrefluxing without revision.
 All kidneys remained histologically normal except those in dogs with dilated ureters secondary to ureteroileal stenosis with concurrent calculi formation.
 Calculi formed on exposed metal staples and Marlex.
 The absorbable staples were found to promote appropriate healing and were never the nidus for stone formation.
 It appears that the intussuscepted nipple valve (with its mesentery removed) is reproducible and functionally reliable in preventing reflux.
 It also appears these valves can histologically preserve diverted kidneys if the upper urinary tract drainage is normal and calculi are minimized.
 The proper placement of staples and the elimination of Marlex-anchoring collars are indicated to minimize calculi.
",11
1772,"The radiographic spectrum of renal osteodystrophy.
 Chronic renal failure often results in bone changes, collectively known as renal osteodystrophy.
 These changes include osteitis fibrosa, osteosclerosis, soft tissue calcifications, osteomalacia (in adults) and rickets (in children).
 Early recognition of renal osteodystrophy allows more aggressive clinical control of serum calcium and phosphate levels.
 Intervention may spare the patient late complications such as fractures, pain and loss of skeletal function.
",11
1773,"The effect of angiotensin-converting enzyme inhibition and dietary protein restriction in the treatment of proteinuria.
 Both angiotensin-converting enzyme inhibitors and dietary protein restriction have been reported to reduce urinary protein losses in patients with chronic glomerular diseases.
 We evaluated these two therapies in 12 such patients ingesting a constant metabolic diet containing 1.6 g protein/kg body weight per day.
 After a steady-state was achieved during a 3-week baseline period, patients were randomly assigned to either enalapril, titrated to reduce mean arterial pressure by 10 mm Hg, or an isocaloric 0.8 g/kg protein diet.
 Five patients in each group completed 3 additional weeks of observation during the treatment period.
 Enalapril resulted in an average reduction in urinary protein and albumin losses of 26% and 33%, respectively, without reducing creatinine clearance.
 Albumin synthesis was unchanged and nitrogen balance increased slightly (+142.8 +/- 85.7 mmol/d [+2.0 +/- 1.2 g/d], P = 0.075).
 Dietary protein restriction had no consistent effect on proteinuria or albuminuria, whereas albumin synthesis (25.9 +/- 3.4 v 21.5 +/- 2.9 g/d/1.73 m2, P less than 0.05) and nitrogen balance (-135.6 +/- 92.8 mmol/d [-1.9 +/- 1.3 g/d], P = 0.10) decreased.
 Both therapies resulted in a modest increase in plasma potassium concentration.
 Whether the maintenance of albumin synthesis in the presence of a reduction in urinary protein losses will convey a long-term advantage to treatment of proteinuric patients with angiotensin-converting enzyme inhibitors remains to be determined.
",11
1774,"Preservation of renal reserve in chronic renal disease.
 Protein-induced increases in glomerular filtration rate (GFR), termed renal reserve, is said to be abrogated with the onset of renal disease.
 However, this notion is inconsistent with the results from animal studies which suggest that alterations in protein intake modulate the glomerular hemodynamics in experimental renal disease.
 Accordingly, 12 normal subjects and 15 patients with renal disease received a protein meal providing 1 g/kg body weight protein.
 The subjects were pretreated with either placebo or an angiotensin I converting enzyme inhibitor, enalapril.
 A significant (P less than 0.05) increase in inulin and para-aminohippurate (PAH) clearance was noted in normal subjects as well as in patients with renal disease.
 The increase in GFR over basal values in normal subjects (28 +/- 9%), patients with moderate renal failure (20 +/- 13%), and advanced renal failure (21 +/- 14%) was not different.
 Plasma renin activity was unchanged following protein meal in the placebo studies although it increased following enalapril administration.
 Enalapril pretreatment did not alter the glomerular vasodilation and hyperfiltration following protein meal.
 We conclude that protein meal induces glomerular hyperfiltration in renal disease and that this protein-induced hyperfiltration is not mediated by angiotensin II.
 Because glomerular hyperfiltration is implicated in the progression of renal disease, these data suggest that even in patients who have advanced renal failure, high-protein diets may exert a detrimental effect on the kidney.
",11
1775,"Survival in patients with end-stage renal disease.
 Based on age and medical condition at the time of treatment, 138 patients beginning dialysis for treatment of chronic renal failure between January 1, 1984 and December 31, 1988, were classified into low, average, and high risk of death.
 The survival in these three groups was shown to be significantly different after as little as 6 months.
 The classification scheme is simple, and can be performed at the bedside.
 Efforts to monitor quality assurance in the dialysis unit must account for the significant differences in expected survival that reflect the case-mix observed in a particular unit.
",11
1776,"X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry, computed tomography, and absorptiometry.
 PURPOSE AND PATIENTS AND METHODS: X-linked hypophosphatemia (XLH) is the most common inherited form of rickets, yet its influence on skeletal mass in adulthood is controversial and incompletely characterized.
 Accordingly, we measured bone mass at several skeletal sites using histomorphometric and radiographic techniques in 19 adults (four men) with XLH (age range 20 to 66 years).
 Most subjects had not received medical therapy for XLH since puberty.
 RESULTS: Eight of 14 subjects who underwent transiliac bone biopsy had an elevated cancellous bone volume (osteoid and calcified bone), and the group's mean value was supranormal (p less than 0.01).
 Mineralized bone volume, however, was above normal in only three subjects (NS).
 Another measure of trabecular bone density, vertebral mineral density by computed tomography, was elevated in three of 13 subjects, and the mean value of the group was increased (p = 0.05).
 Integral spine bone mineral density (BMD) assessed by dual photon absorptiometry (DPA) was elevated in six of 16 subjects, and the mean was also above normal (p less than 0.01).
 However, total body calcium, total body BMD (both by DPA), and forearm bone mineral content assessed by single photon absorptiometry (predominantly cortical bone) were normal in almost all subjects, as were the group means for these parameters.
 Mean regional BMD (by DPA) was below normal in the upper and lower limbs (p less than 0.001) and above normal in the spine (p less than 0.005) and ribs (p less than 0.01).
 There was no relationship between these indices of bone mass and either biochemical or clinical parameters of disease severity, although men tended to have higher z-scores for axial bone density than premenopausal women whose values, in turn, tended to be higher than those in postmenopausal women (NS).
 CONCLUSION: We conclude that axial bone mass tends to be increased in adults with XLH, sometimes dramatically so, and this is only partially attributable to hyperosteoidosis.
 Peripheral bone mass, however, tends to be diminished.
 Despite these group trends, most adults with untreated XLH have normal indices of bone mass as assessed by a variety of techniques at the commonly used measurement sites.
 These findings suggest that ""osteoporotic"" fractures are unlikely to develop as a late complication of XLH in adults.
",11
1777,"Interstitial cellular infiltration detected by fine-needle aspiration biopsy in nephritis.
 Fine-needle aspiration biopsy (FNAB) was used to detect renal mononuclear interstitial inflammation in 56 patients with various types of nephritis (20 IgA nephropathy, 8 focal necrotizing glomerulonephritis, 7 interstitial nephritis, 6 non-classifiable chronic glomerulonephritis, 5 mesangial proliferative (non-IgA) chronic glomerulonephritis, 4 focal glomerulosclerosis, 6 normal histology, who were examined for microscopic hematuria, and 7 controls).
 Regular renal biopsies for histological and immunofluorescence studies were simultaneously obtained, and available for comparative analysis (not controls).
 Differential counts of mononuclear infiltration and subtyping of T-cell infiltration into T-helper (T-h) and T-suppressor-cytotoxic (T-s-c) cells, as detected by immunoperoxidase stains from FNAB, were correlated to clinical manifestations and renal function tests.
 Generally, our results indicated increased mononuclear cell infiltration (monocytes, lymphocytes, and/or activated lymphocytes) in FNAB of patients with IgA nephropathy, interstitial nephritis or focal necrotizing glomerulonephritis (especially monocytes in IgA nephropathy and interstitial nephritis, p less than 0.05 compared with controls, lymphocytes in focal necrotizing glomerulonephritis, and non-classifiable glomerulonephritis, p less than 0.02 and 0.05, respectively).
 The number of infiltrating activated lymphocytes was significantly increased in focal necrotizing glomerulonephritis, interstitial nephritis and focal glomerulosclerosis, p less than 0.05, less than 0.01 and less than 0.01, respectively.
 FNAB was at least as sensitive as histological examination for the quantification of interstitial cellular infiltration, and it allowed for cytological differential counts.
 Patients had decreased T-h and increased T-s-c cell counts, which were accentuated in FNAB compared with peripheral blood, although there were strong positive correlations between local and peripheral counts (p less than 0.0001).
",11
1778,"Acute renal failure in critically ill patients: prognosis for recovery of kidney function after prolonged dialysis support 
 OBJECTIVE: To clarify the prognosis for eventual recovery of kidney function in patients who experience prolonged dialysis dependence after acute renal failure (ARF).
 DESIGN: Retrospective, chart review.
 SETTING: Inpatients of a large, referral-based hospital.
 PATIENTS: Twenty-six consecutive survivors of ARF who required greater than 4 wk of dialysis support.
 RESULTS: All 26 patients were critically ill and developed ARF during treatment in an ICU.
 The clinical course of these patients was characterized by multiple episodes of renal ischemia or nephrotoxin exposure during dialysis dependence.
 However, despite multiple renal insults and prolonged dialysis support (mean duration 8.4 +/- 0.7 wk), 23 (88%) of the 26 patients recovered sufficient kidney function to discontinue dialysis.
 Preexisting renal impairment was associated with a greater risk of irreversible renal failure, and, in patients able to discontinue dialysis, renal recovery was often incomplete.
 CONCLUSIONS: Despite some renal damage, most critically ill patients who survive ARF requiring prolonged dialysis support recover life-sustaining kidney function.
",11
1779,"Study of bilateral histology and meiotic analysis in men undergoing varicocele ligation.
 Fifty men underwent testicular biopsy at the time of varicocele ligation.
 The biopsies were scored and also a portion from each biopsy was subjected to meiotic analysis.
 All men were followed up (mean follow-up 19.3 months).
 There were no consistent histologic or meiotic abnormalities, and there was no evidence that the varicocele side was more defective than the contralateral side.
 Thirteen pregnancies were recorded, and these occurred only when the mean Johnsen score from one or other testis was greater than 6.0.
",11
1780,"The concentrations of transferrin, beta 2-microglobulin, and albumin in seminal plasma in relation to sperm count.
 A number of studies have shown a relationship between transferrin levels in seminal plasma and sperm count.
 In the present study, the levels of transferrin, beta 2-microglobulin and albumin were measured in 171 samples of seminal plasma (50 subjects with normal sperm count; 32 with azoospermia; 49 with oligozoospermia; 10 with polyzoospermia; and 31 vasectomized).
 All three proteins were related to sperm count.
 It is concluded that there is a general relationship between seminal plasma proteins and sperm numbers and that some products of the sperm themselves must control the entry of plasma proteins into seminal plasma.
",11
1781,"Rapid baroreceptor resetting in chronic hypertension. Implications for normalization of arterial pressure.
 The purpose of this study was to examine the ability of baroreceptors of renal hypertensive rabbits to reset rapidly during acute changes in arterial pressure.
 The carotid sinus (CS) was vascularly isolated and baroreceptor activity was recorded during slow ramp increases in CS pressure in hypertensive (one-kidney, one wrap; 127 +/- 3 mm Hg) and normotensive (one-kidney, no wrap; 85 +/- 3 mm Hg) rabbits anesthetized with chloralose.
 Control measurements were made after holding pressure for 10-15 minutes at the level of arterial pressure recorded before each experiment.
 Baroreceptor threshold pressure (Pth) was higher in hypertensives (78 +/- 4 mm Hg) compared with normotensives (55 +/- 3 mm Hg, p less than 0.05), and nerve activity was less in hypertensives over a wide range of pressure.
 CS distensibility (sonomicrometers) was not significantly different in the two groups.
 After increasing holding pressure from control by 30 and 60 mm Hg for 10-15 minutes, the extent of baroreceptor resetting (delta Pth/delta holding pressure x 100%) in normotensives was 39 +/- 6% and 33 +/- 2%, respectively, but only 14 +/- 5% and 9 +/- 3% in hypertensives (p less than 0.05).
 After decreasing holding pressure by 30 and 60 mm Hg, resetting was similar in normotensives (32 +/- 6% and 28 +/- 3%) and hypertensives (34 +/- 3% and 30 +/- 4%).
 In hypertensive rabbits, acute (10-15 minutes) exposure of baroreceptors to normotension (71 +/- 4 mm Hg) decreased Pth to 62 +/- 4 mm Hg and increased nerve activity to levels not significantly different from those of normotensive animals without altering CS distensibility.
",11
1782,"Penile duplex sonography in the diagnosis of venogenic impotence.
 This study tested the hypothesis that measurements of cavernous arterial diastolic velocity and resistance index could provide a quantitative but noninvasive measure of penile corporal venous leakage.
 Seventy-four men were studied with duplex ultrasonography after intracavernosal injection of 60 mg of papaverine.
 Fourteen men had normal erection and served as controls.
 Sixty men had a 1-year history of transient fading or incomplete erections.
 In all subjects the peak systolic velocity and end-diastolic velocity were measured, and the resistance index was calculated (peak systolic velocity--end-diastolic velocity/peak systolic velocity).
 Men with normal erections had peak systolic velocities greater than 35 cm/sec and end-diastolic velocities less than 4.5 cm/sec (group 1).
 Patients with incomplete erections (group II) could be classified into three subgroups.
 Twenty-three patients with end-diastolic velocities greater than 4.5 cm/sec and normal peak systolic velocities greater than 35 cm/sec were suspected to have corporal venous leakage (group A).
 Eighteen patients had normal end-diastolic velocities less than 4.5 cm/sec.
 Twelve of this group had peak systolic velocities less than 35 cm/sec, and six had peak systolic velocities ranging from 37 to 44 cm/sec.
 These patients were suspected of having arterial insufficiency (group B).
 Fifteen patients with end-diastolic velocities greater than 4.5 cm and peak systolic velocities less than 35 cm were suspected of having both venous leakage and arterial insufficiency (group C).
 Twenty-one patients with abnormal diastolic flow underwent infusion pharmacocavernosometry to determine the saline maintenance infusion rate necessary to maintain an intracavernosal pressure of 90 to 100 mm Hg or a full erectile response.
",11
1783,"Efficacy of bladder training in older women with urinary incontinence.
 The efficacy of bladder training was evaluated in a randomized clinical trial involving 123 noninstitutionalized women 55 years and older with urinary incontinence.
 Subjects were urodynamically categorized as those with urethral sphincteric incompetence (N = 88) and those with detrusor instability with or without concomitant sphincteric incompetence (N = 35).
 Bladder training reduced the number of incontinent episodes by 57%; the effect was similar for both urodynamic diagnostic groups.
 The quantity of fluid loss was reduced by 54%.
 This was greater for patients with detrusor instability than for those without it.
 Diurnal and nocturnal voluntary micturitions were also reduced.
 The effect on nocturnal micturition, however, was not observed in subjects with unstable detrusor function.
 It is recommended that bladder training be considered as an initial step in treatment of women with urinary incontinence.
 Provided prior comprehensive clinical evaluation is done, it can be prescribed without the need for urodynamic characterization.
",11
1784,"Simple renal cysts in children: diagnosis and follow-up with US.
 To assess the sonographic frequency of simple renal cysts in children, the authors retrospectively reviewed the results of abdominal sonographic studies of 16,102 children performed over a 5-year period between January 1, 1985, and December 31, 1989.
 Patients with abnormal renal function, dysplastic kidneys, or a family history of polycystic kidney disease were excluded from the study.
 The authors' review of the sonograms revealed 37 simple cysts in 35 patients (0.22%); the cysts were evenly distributed by age and sex and measured from 0.3 to 7.0 cm in maximum diameter.
 Sixteen cysts (43%) were in the upper pole of the right kidney.
 Follow-up sonographic studies of 23 cysts in 22 patients for up to 5 years showed no change in size in 17 cysts (74%).
 The largest cyst was drained percutaneously; all other cysts were managed conservatively.
 No patient showed deterioration of renal function.
 Therefore, the authors concluded that in a pediatric patient demonstrating normal renal function, no further intervention is necessary when a simple renal cyst is identified at sonography.
",11
1785,"Nonpalpable prostate cancer: detection with MR imaging.
 The pathologic specimens and magnetic resonance (MR) images of 53 patients with clinically palpable prostate cancer confined to one lobe were studied to evaluate the ability of MR imaging to depict clinically nonpalpable prostate cancer.
 All patients had undergone imaging with a 1.5-T imager with T1- and T2-weighted sequences in both axial and sagittal planes before undergoing radical retropubic prostatectomy.
 At pathologic examination, only the palpable tumor was present in 30 of the 53 patients (57%), and 33 unsuspected tumors were present in an area distinct from the palpable tumor in 23 of the patients (43%).
 MR imaging successfully depicted 51 palpable tumors for a sensitivity of 96% and 19 of the 33 unsuspected tumors for a sensitivity of 58%.
 The sensitivity of MR imaging in the detection of nonpalpable, posteriorly located tumors was greater than for those located anteriorly (85% vs 15%).
 MR imaging was false-positive for nonpalpable tumor in 17 of 30 patients for a specificity of 43%.
 On the basis of these data, MR imaging has greater sensitivity in the depiction of posteriorly located cancer and is limited by a high false-positive rate in the depiction of nonpalpable tumors.
",11
1786,"Determination of prostate volume with transrectal US for cancer screening. Part I. Comparison with prostate-specific antigen assays.
 To investigate whether radiologists can objectively define a high-risk group for prostate cancer, the researchers measured gland volume and compared it with results of a screening blood test, prostate-specific antigen (PSA) assay.
 A total of 768 men, aged 55-71 years, were self-referred to two prostate cancer screening programs using transrectal ultrasound (US) and digital rectal examination.
 In patients with no evidence of cancer, statistically significant increases in mean PSA values were noted with increasing gland volume ranges (P less than .05).
 PSA values in patients with cancer were more likely to exceed the volume-adjusted 95th percentile (mean + [1.65.standard deviation]) than those in patients with negative biopsy results (P less than .005).
 Patients with PSA values above the volume-adjusted 95th percentile have an estimated risk for prostate cancer up to nine times that of the general screening population.
 The researchers conclude that knowledge of transrectal US gland volume and prostate-specific antigen assay type are important objective variables for future prostate cancer screening programs.
 The volume-adjusted 95th percentiles presented may help guide cost-effective management of current early detection efforts.
",11
1787,"Primary signet-ring cell carcinoma of the urinary bladder.
 Primary signet-ring cell carcinoma is an uncommon malignancy arising in the urinary bladder.
 The authors report 12 cases collected at their institution.
 Median age for the ten men and two women was 58 years; the most frequent presentation was hematuria.
 In two of nine cases no mucosal lesion was cystoscopically visible.
 Eleven tumors were of nonurachal origin and one of urachal.
 At diagnosis, one tumor was stage B, two stage C, seven stage D, and two stages unknown.
 Nine of 12 patients were dead of disease (range, 1-16 months; median, 9 months), 1 alive with metastatic disease, 1 alive and well, and 1 dead of an unrelated cause.
 From a literature review, the authors accepted 35 cases that met their criteria and combined them with their 12 cases for statistical analysis.
 Prognosis was worse with a pure diffuse versus a mixed tumor (P = 0.004) and for nonurachal versus urachal origin (P = 0.005).
 The difference in five-year survival rates between stages B and D disease (P less than 0.05) was also statistically significant.
",11
1788,"Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit.
 The purpose of this study was to assay for the presence of collagen synthesis stimulatory activity in the kidney during immune-induced renal injury that results in severe fibrosis in both glomerular and interstitial compartments.
 A model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on day 0 by the injection of anti-GBM antibody and renal cortex tissues were then sampled at various time points.
 Only conditioned media prepared from diseased renal cortical samples showed collagen synthesis stimulatory activity when tested on rabbit mesangial cells.
 The activity had an estimated molecular weight range of 16 to 25 kd and was neutralized by antibody to transforming growth factor-beta (TGF-beta).
 A standard assay for TGF-beta using a mink lung epithelial cell line confirmed the increase in TGF-beta activity in conditioned media of diseased cortex from day 7 and day 14 animals, which was not significantly activated by previous acidification.
 This suggests that most of the TGF-beta present in renal conditioned media was in the active form.
 The increase in renal cortical secretion of active TGF-beta was accompanied by increases in renal cortical TGF-beta mRNA content on days 4 and 7 after induction, with subsequent return to control levels.
 A similar increase in TGF-beta activity was present in nonacidified conditioned media of purified glomeruli from diseased days 7 and 14 animals, which was also accompanied by significant increases in TGF-beta mRNA.
 However with acidification no significant differences were noted between control and diseased samples, suggesting the presence of substantial latent TGF-beta activity in control glomerular conditioned media.
 These same control-conditioned media contained inhibitor activity for added exogenous TGF-beta.
 These results support the conclusion that the association between increased TGF-beta secretion and increased renal cortical collagen synthesis in this model is consistent with a role for this cytokine in directing fibrogenesis in the kidney.
",11
1789,"Less frequent lithium administration and lower urine volume.
 OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day.
 METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules.
 Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality.
 RESULTS: Multiple daily doses of lithium were associated with higher urine volumes.
 The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance.
 CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose.
 Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.
",11
1790,"Dipstick analysis of urinary protein. A comparison of Chemstrip-9 and Multistix-10SG.
 The Boehringer-Mannheim Chemstrip-9 and Ames Multistix-10SG urine dipstick assays for the detection of proteinuria were evaluated.
 Chemstrip-9 was more precise than Multistix-10SG (13 inconsistencies vs 32 among duplicate pairs).
 Precision was poorest with the group of inexperienced technologists using Multistix-10SG (Chemstrip-9 yielded two inconsistencies vs 15 for Multistix-10SG) with the use of urine supplemented with protein standard.
 In the evaluation of both protein-supplemented and consecutively acquired patient specimens, Multistix-10SG and Chemstrip-9 performed in a statistically similar fashion regarding sensitivity and predictive value of a negative test result: supplemented sample sensitivity, patient sample sensitivity, and a predictive value of a negative test result of 90.3%, 46.8%, and 68.6%, respectively, for Multistix-10SG compared with 80.6%, 31.5%, and 63.5%, respectively, for Chemstrip-9.
 We conclude that neither test is sufficiently sensitive for the detection of low levels of proteinuria (1+ range) to function as a screening test for renal disease.
",11
1791,"Effect of polycations on the function of the isolated perfused rat kidney.
 1.
 In minimal change nephrotic syndrome the occurrence of heavy proteinuria can be explained on the basis of a reduction in charge selectivity of the glomerular filtration barrier, and it has been proposed that this might be caused by the neutralization of anionic groups by a circulating polycationic factor.
 2.
 The effects of two polycations, protamine and poly-L-lysine, on the function of the isolated perfused rat kidney have been examined.
 3.
 Poly-L-lysine polymers of relatively high molecular weight (8800 and 17,800) induced heavy proteinuria, while simultaneously causing a marked increase in renal vascular resistance and a fall in filtration rate.
 Protamine (approximate molecular weight 7000) at relatively high concentration induced modest proteinuria in the absence of effects on vascular resistance or filtration rate.
 4.
 A poly-L-lysine polymer of lower molecular weight (3800) did not induce proteinuria.
 Protamine at a concentration of 40 micrograms/ml and below did not affect protein excretion either.
 Both provoked substantial natriuresis.
 This appeared to be largely due to an effect on the tubular handling of sodium since the filtration rate remained steady while fractional sodium excretion rose markedly.
 5.
 The natriuretic effect of protamine was blocked by heparin, but not by indomethacin or verapamil, suggesting that the mechanism of natriuresis did not depend upon either prostaglandin production or entry of calcium through verapamil-sensitive channels.
",11
1792,"Sex or survival: trade-offs between quality and quantity of life.
 Patients with localized prostate cancer may be treated with either surgery (radical prostatectomy) or radiotherapy.
 Although controversial, many physicians believe that surgery offers a higher survival rate.
 However, the surgical treatment may also produce a higher rate of sexual impotency.
 Our study assessed how men value survival and sexual potency when asked to trade off one for the other.
 Using the treatment-choice technique, we interviewed 50 men aged 45 to 70 years without known prostate cancer.
 At hypothetical rates of survival (90% at 5 years for surgery) and impotency (90% for surgery and 40% for radiotherapy) representing published estimates, 32% of respondents were unwilling to trade off any survival, but 68% were willing to trade off a 10% or greater advantage in 5-year survival (by choosing radiotherapy) to maintain sexual potency.
 The median 5-year survival traded off was 10% (range, 0% to 80%).
 Willingness to trade off survival for sexual potency was significantly related to level of education, but not to age, interest in sex, frequency of sexual intercourse, or ability to achieve erection.
 We conclude that some men may choose treatment with lower long-term survival to increase their chance of remaining sexually potent.
 Because these men may be difficult to identify in clinical practice, physicians should thoroughly discuss both surgery and radiotherapy options with patients who have localized prostate cancer.
",11
1793,"Post-transplant renal artery stenosis: a possible immunological phenomenon.
 A retrospective review of 110 consecutive kidney transplants performed during 4 years revealed the development of renal artery stenosis in 9 patients (8.18%).
 A comparison of this group with a control group similar in patient age and interval elapsed since transplantation revealed no significant differences in donor and recipient ages, degree of HLA compatibility or serum creatinine levels.
 However, there was a significant difference in the number of acute rejection episodes.
 In our series only male patients were affected.
 A sizable proportion of the patients (50%) had no detectable murmur over the graft area despite high blood pressure and increased creatinine levels.
 The absence of surgical injury during extraction and implantation of the grafts, together with the anatomical site of the stenosis and correlation with the degree of immunological intolerance suggest an immunological factor as the underlying cause in post-transplant renal artery stenosis.
",11
1794,"Acute changes in renal function following extracorporeal shock wave lithotripsy in patients with a solitary functioning kidney.
 Twelve consecutive patients with a solitary functioning kidney were treated for renal stone by extracorporeal shock wave lithotripsy (ESWL*) with the modified Dornier HM3 lithotriptor and studied for 3 days after treatment.
 Urinary excretion of electrolytes, N-acetyl-beta-glucosaminidase (NAG), alkaline phosphatase, kallikrein, glycosaminoglycans, albumin and beta 2-microglobulin, and clearances of creatinine, inulin and para-aminohippuric acid were determined, as were serum levels of creatinine, urea, beta 2-microglobulin and aldosterone, and plasma renin activity.
 Urinary flow rate, free water clearance, and urinary excretion of NAG, kallikrein and beta 2-microglobulin were significantly increased 0 to 24 hours after ESWL.
 The urinary excretions of alkaline phosphatase, albumin and glycosaminoglycans were unchanged.
 Glomerular filtration rate was significantly decreased and effective renal plasma flow was unchanged.
 Filtration fraction was stable.
 Serum lactic dehydrogenase increased significantly after ESWL and remained high through the period of observation.
 Serum levels of creatinine, beta 2-microglobulin and aldosterone were unaltered.
 A decrease in plasma renin activity immediately after treatment is explained by the water immersion and the extracellular volume expansion during treatment.
",11
1795,"Ureteral calculi: natural history and treatment in an era of advanced technology.
 Patients with ureteral stones may be managed expectantly, or treated with a variety of invasive and noninvasive techniques depending on stone composition, size and location, expectations of the patient and experience of the surgeon.
 Of 378 patients with documented ureteral calculi 60% passed the stones spontaneously.
 Passage rates from the proximal, middle and distal ureter were 22, 46 and 71%, respectively.
 Basketing under fluoroscopic control of distal stones was successful in 79% of the attempts and for those in whom this approach failed ureteroscopy was performed, with a success rate of 90%.
 When ureteroscopy was used as the initial treatment of distal stones removal was achieved in 81% of the patients.
 These statistics serve as a reminder that traditional therapy of ureteral stones has not lost its role in contemporary practice.
",11
1796,"Management of upper tract calculi in patients with tubularized urinary diversions.
 In a retrospective review of patients with urinary diversion who presented to our stone center during a 3.5-year period 9 underwent 20 procedures for suspected stone episodes.
 Eventual outcome was excellent in all but 1 patient.
 In particular, all attempts at retrograde trans-stomal manipulation were successful.
 We present our cases, and note the technical considerations and management principles.
 Frequently, these patients are best served by a combination of percutaneous antegrade, trans-stomal retrograde and/or extracorporeal shock wave lithotripsy.
",11
1797,"Vacuum tumescence devices: the role of papaverine in the selection of patients.
 We conducted a prospective study to determine the positive predictive value of papaverine testing to select patients in whom a vacuum constriction device would be a successful alternative to operative management of impotence.
 A total of 30 men presenting to an impotence clinic was evaluated with a series of papaverine dosages up to 60 mg.
 These patients then received a physician-administered trial of a vacuum constriction device, followed by 3 months of home use and a repeat objective evaluation.
 Initial responses to the device were poor, with 46% of the patients (14) achieving a rigid erection.
 However, after 3 months of home use 83% of the patients (25) achieved a rigid erection.
 The positive predictive value of a good response to the papaverine trial was 94%.
",11
1798,"Intracavernous self-injection of vasoactive drugs in the treatment of impotence: 8-year experience with 615 cases.
 Of 615 patients with impotence of varying etiologies who were followed from 12 to 96 months after the institution of intracavernous self-injection therapy with vasoactive drugs (papaverine alone, papaverine and alpha-blockers, and Ceritine, a new multilevel acting drug) 87% (533 patients) returned for followup visits or were regularly contacted.
 Of these patients sexual activity was restored in 91%.
 The dropout rate was 11.25%.
 The 114 episodes of prolonged erections among 51 patients (4.57%) represented less than 3 per 1,000 of the 34,875 recorded injections.
 All patients were treated without complications.
 The percentage of patients suffering from nodules or permanent deformations was 2.8%.
 There were no cases of intracavernous fibrosis.
 The percentage of satisfied patients (satisfaction index 7 or greater) was 84.8%.
 Improvement in spontaneous erections during sexual intercourse was obtained in 65% of the cases: 15% no longer needed self-injections and 50% only used them occasionally while 35% remained entirely dependent.
",11
1799,"Interstitial temperature measurements during transurethral microwave hyperthermia.
 Microwave hyperthermia is presently being investigated as a treatment for alleviating the symptoms of urinary outlet obstruction associated with benign prostatic hyperplasia.
 Two clinical techniques using intracavitary microwave applicators are being evaluated for safety and efficacy at various institutions.
 The transrectal technique uses a directional microwave radiator that is inserted into the rectum adjacent to the prostate.
 The transurethral approach uses a symmetrically radiating applicator located within the prostatic urethra.
 Transrectal prostatic heating techniques require surface cooling to prevent hazardous temperatures in the intervening rectal mucosa.
 Since transurethral applicators radiate from within the prostatic urethra, heating is confined to the obstructive tissue immediately surrounding the applicator.
 Concern has been expressed regarding the possibility of thermal injury to the prostate and adjacent rectum during transurethral hyperthermia treatment.
 In this report we present interstitial temperature measurements of prostatic and rectal temperatures in 5 patients.
 Temperature was observed to decrease at a rate of about 6C/cm.
 outward from the applicator.
 No clinically significant temperature increase was observed beyond 1 cm, outside the prostatic capsule or in the rectal mucosa.
",11
1800,"Treatment of benign prostatic hypertrophy by a long-acting gonadotropin-releasing hormone analogue: 1-year experience.
 Benign prostatic hypertrophy, a common ailment among elderly men, usually is treated by surgery.
 Since androgens enhance prostatic hypertrophy, their withdrawal seems a logical way to treat this condition.
 Recently gonadotropin-releasing hormone analogues, known to produce ""chemical castration,"" have been tried in cases of benign prostatic hypertrophy.
 We report our experience with 20 men treated by a monthly injection of gonadotropin-releasing hormone for prolonged periods.
 In 17 men treated for 6 months the prostatic volume decreased to an average of 63% of the initial volume; however, this did not correlate with clinical objective improvement.
 Only 6 men attained normal flow rates.
 Residual urine volume remained unaltered.
 Ten patients experienced subjective amelioration, while only 7 (40%) reported objective and subjective improvement.
 Maximal decrease in prostatic volumes was reached at 9 months of treatment and further treatment did not cause additional shrinkage.
 At 3 months after discontinuation of treatment prostatic volumes returned to 95 +/- 10.5% of pre-treatment values.
 A similar decrease in flow rates also was noted.
 Symptoms remained improved for longer periods.
 We conclude that this mode of treatment offers little to the majority of men with benign prostatic hypertrophy.
 Proper patient selection, based perhaps on serum prostate specific antigen, might augment positive results.
 This therapy should be restricted to patients considered high risk for any surgical and anesthetic intervention, and then it will have to be continued indefinitely.
",11
1801,"Bioavailability of potassium and magnesium, and citraturic response from potassium-magnesium citrate.
 The bioavailability of potassium and magnesium, and the citraturic response were determined for the new compound, potassium-magnesium citrate, in 14 normal volunteers.
 Results were compared to those of potassium citrate and magnesium citrate.
 Each subject participated in 4 phases of study: potassium-magnesium citrate, potassium citrate, magnesium citrate and potassium chloride.
 After stabilization on a metabolic diet, each subject ingested a single load of a test medication followed by timed urine collections for the next 24 hours.
 Test loads included potassium-magnesium citrate (49 mEq.
 potassium, 24.5 mEq.
 magnesium and 73.5 mEq.
 citrate), potassium citrate (50 mEq.), potassium chloride (50 mEq.) and magnesium citrate (25 mEq.) Urinary potassium, magnesium and citrate were measured for each collection period.
 Potassium-magnesium citrate provided an equivalent potassium bioavailability as potassium citrate and potassium chloride, and a comparable magnesium bioavailability as magnesium citrate.
 However, it gave the highest citraturic response, since the cumulative increment in urinary citrate post-load was 129 mg.
 daily for potassium-magnesium citrate, 105 mg.
 daily for potassium citrate and 35 mg.
 daily for magnesium citrate.
 Thus, potassium-magnesium citrate gave an optimum citraturic response in addition to providing absorbable potassium and magnesium.
",11
1802,"Laser treatment of obstruction from incrusted ureteral catheter.
 Incrustations may develop on ureteral catheters and cause obstruction.
 We report a case in which obstruction was relieved by laser lithotripsy inside the lumen of the catheter.
 This completely noninvasive technique may prove to be useful in selected cases.
",11
1803,"Endopyelotomy for secondary ureteropelvic junction obstruction in children.
 Percutaneous endopyelotomy has been shown to be successful in treating ureteropelvic junction obstruction in adults.
 Little data have been published regarding this procedure in children.
 We describe 4 patients 6.5 weeks to 5.5 years old who underwent percutaneous endopyelotomy to treat ureteropelvic junction obstruction following failed open dismembered pyeloplasty.
 Preoperative obstruction was demonstrated by a nephrostogram, diuretic renogram and/or ultrasonography.
 Percutaneous endopyelotomy was successful in relieving the obstruction in all 4 patients, although 2 required secondary endoscopic procedures.
 One patient had persistent obstruction 40 days after endopyelotomy at the ureteropelvic junction and, subsequently, required percutaneous resection of a persistent flap of obstructing tissue.
 In another patient a ureterovesical stricture was noted at the time of stent removal, which was treated by endoscopic incision.
 All patients have been followed from 1.5 to 3 years postoperatively.
 Followup diuretic renograms, ultrasound and/or excretory urography demonstrated a patent ureteropelvic junction in all patients and all have remained asymptomatic.
 Endopyelotomy appears to be safe and effective in treating secondary ureteropelvic junction obstruction in children.
",11
1804,"Cavernous nerve grafts restore erectile function in denervated rats 
 Although potency can be preserved in most men following radical prostatectomy, in some patients one or both cavernous nerves must be sacrificed in order to excise all tumor.
 For these patients we have considered nerve reconstruction at the time of surgery using an interposition nerve graft.
 This possibility has been tested in a rat model.
 Animals were divided into three groups.
 In the sham control group, a pelvic exploration was conducted without division of the cavernous nerves.
 In the nerve ablation group, a five mm.
 segment of cavernous nerve was excised.
 In the graft group, five mm.
 of cavernous nerve was excised bilaterally and replaced with an interposition graft of genito-femoral nerve.
 At one month intervals postoperatively animals from each group underwent mating tests to determine potency; the ratio of vaginal intromission to unsuccessful mounts (I/M ratio) was determined.
 Following the mating tests the animals were re-explored and attempts were made to stimulate erections electrically via the pelvic nerve.
 Results at two months show the I/M ratio of the rats with grafts (0.05) and the nerve ablations (0.14) are low compared with the sham operated animals (1.0).
 By month four the graft group (0.89) has approached the sham group (0.91) while the ablation group (0.18) remains unchanged (p less than .05).
 Electrical stimulation at month two produced no erections in the nerve ablated or the grafted rats and 100% erections in the sham-operated animals.
 At month four, 50% of the rats with grafts, 10% of the nerve ablated animals, and 100% of the intact animals produced erections upon electrical stimulation (p less than .05).
 These results suggest that cavernous nerve grafting in rats can be successful in restoring potency after surgical injury.
 Application of these techniques to man may be indicated.
",11
1805,"Obstruction and recanalization of the ureter during embryonic development.
 Major controversies still exist regarding the terminology, the etiology and the pathogenesis of congenital obstructive diseases of the ureter.
 To try to provide some additional information to this controversial subject, a comparative study of ureteral development in rat and human embryos, using light and electron microscopy, has been performed.
 During fetal development we observed and demonstrated the existence of obstructive phenomena, both at the level of the ureterovesical junction (Chwalla's membrane) and along the ureter.
 At the end of the embryonic period, the ureter undergoes a physiologic recanalization process.
",11
1806,"Color Doppler ultrasound compared to a radionuclide scanning of spermatic cord torsion in a canine model.
 High resolution color doppler ultrasound can simultaneously display blood flow superimposed on detailed gray scale anatomic images.
 Using a single-blind study design, nine adult male dogs underwent intravaginal spermatic cord torsion and subsequent evaluation with technetium 99M-pertechnetate radionuclide, and color doppler ultrasound imaging techniques.
 Torsions of 90 to 720 degrees were created surgically, followed by examination with each modality at one hour (four animals), and four hours (five animals) following the procedure.
 Testicular torsion was diagnosed if perfusion was absent or markedly diminished on color doppler imaging or radionuclide scan.
 In all cases of 360 degrees or greater, torsion was diagnosed by either modality at both one and four hour time delays.
 If observers did not diagnose torsion, they were asked to assess the relative testicular perfusion.
 Color doppler ultrasound and radionuclide scanning were without error in correctly detecting a relative decrease in perfusion in each of these instances.
 Furthermore, color doppler imaging with spectral analysis was able to detect an enhancement of the diastolic component of the arterial signal at 180 degrees of torsion.
 This spectral pattern coupled with a relative decrease in blood flow allowed presumptive diagnosis at one hour of partial torsion that was subsequently apparent as absent perfusion only after 4 hours on radionuclide and repeat color doppler ultrasound.
 Color doppler ultrasound proved to be superior to radionuclide scanning in detecting diminished perfusion in this experiment.
 The detailed information provided by spectral and anatomic display with color doppler ultrasound recommends it for the evaluation of acute scrotal pathology of uncertain etiology.
",11
1807,"Bladder training in older women with urinary incontinence: relationship between outcome and changes in urodynamic observations.
 The purpose of this study was to clarify the mechanism by which bladder training affects urinary incontinence.
 Urodynamic data and specific urodynamic diagnoses of 108 women with urinary incontinence were compared before and 6 months after treatment with bladder training.
 Before treatment, 76 women had sphincteric incompetence, 11 had detrusor instability, and 16 had both.
 After treatment, 33 women no longer fulfilled the urodynamic diagnostic criteria for either sphincter or detrusor dysfunction.
 Controlling for severity before treatment, the number of incontinent episodes post-treatment was not associated with change in urodynamic diagnosis.
 Only the first sensation to void, voided volume, compliance, functional urethral length, and flow time showed any significant changes between pre- and post-treatment evaluations; however, none were correlated with change in the number of incontinent episodes.
 Bladder training does not appear to affect lower tract urodynamic variables or specific urodynamic diagnosis, and it is likely that its mechanism of action reflects adaptive behavioral changes.
 Physiologic changes not detected with techniques and/or criteria used in this study may still occur.
",11
1808,"Adipose tissue fatty acid composition and its relations to diet and plasma lipid concentrations in hemodialysis patients.
 Adipose tissue fatty acid composition, serum lipid profile, and dietary intake of 37 patients on maintenance hemodialysis were studied.
 In August 1982, 1984, and 1986, analyses were carried out in 15 normotriglyceridemic (NTG) and 22 hypertriglyceridemic (HTG; type IV hyperlipidemia) patients.
 No correlations were found between dietary intake of polyunsaturated fatty acids (PUFAs), ratio of polyunsaturated to saturated fatty acids (P-S ratio), and carbohydrate content on the one hand and serum lipid concentrations on the other in the two groups.
 Adipose tissue linolenic acid correlated negatively with serum cholesterol in both groups.
 Strong correlations were found between dietary intake of PUFAs and adipose tissue linoleic acid content, between PUFAs and the double-bond index, between P-S ratio and adipose tissue linoleic acid content, and between P-S ratio and the double-bond index.
 No significant differences in dietary intake or adipose tissue fatty acid composition were observed between NTG and HTG patients.
 Thus, no evidence was found for exogenous dietary influences on serum lipid concentrations.
 The adipose tissue linoleic acid content did reflect the dietary intake of PUFAs.
",11
1809,"The bed-wetting child. Current management of a frustrating problem.
 Bed-wetting is a frustrating problem experienced by a significant number of children.
 It is the role of the physician to exclude serious underlying problems and, at the same time, educate the family concerning treatment options that may be best suited to their child.
 Once parents and child have a better understanding of the problem and realize that the outlook for nighttime bladder control is excellent, it is easier to start long-term care.
",11
1810,"Human papillomavirus in prostatic cancer: no evidence found by in situ DNA hybridization.
 Human papillomavirus has been associated with benign squamous tumors, intraepithelial neoplasia, and invasive squamous cancer.
 The role of human papillomavirus as the most likely precursor of cervical dysplasia is well studied.
 We know of no available information as to the possible role of human papillomavirus in prostatic hyperplasia and cancer.
 We studied formalin-fixed paraffin-embedded tissues of 20 cases of glandular hyperplasia and 20 cases of prostatic cancer by in situ DNA hybridization for human papillomavirus using commercially available biotinylated DNA probes detected by an avidin-biotin peroxidase technique.
 We found no evidence of DNA hybridization to human papillomavirus-6, -11, -16, -18, -31, -33, or -35 in prostate tissue.
 Our results show no association between prostatic cancer or hyperplasia and the human papillomavirus genomes that were studied.
",11
1811,"Fibrin formation on vessel walls in hyperplastic and malignant prostate tissue.
 To explore mechanisms of coagulation activation in adenocarcinoma of the prostate, the occurrence and distribution of components of coagulation and fibrinolysis pathways in situ were studied by means of immunohistochemical techniques applied to frozen sections of fresh malignant and benign hyperplastic prostatic tissue obtained at transurethral resection.
 Fibrinogen was distributed throughout the perivascular and tumor connective tissue in both malignant and benign disease but was not present in adjacent areas of normal prostate.
 Antibodies specific for fibrin and D-dimer crosslink sites stained vascular endothelium focally in both malignant and benign tissues.
 Both neoplastic cells and benign hyperplastic glandular epithelial cells stained weakly and in a patchy distribution for tissue factor and focally for low-molecular-weight urokinase-type plasminogen activator.
 Focal staining of vascular endothelium was also observed for tissue plasminogen activator and plasmin-antiplasmin complex neoantigen.
 By contrast, no tissue staining was observed for factor VII, factor X, factor XIII ""a"" subunit, high-molecular-weight urokinase-type plasminogen activator, plasminogen activator inhibitors 1 to 3, protein C, and protein S.
 Thus, the similarity in findings between benign hyperplastic and neoplastic prostate tissue, the lack of either an intact tumor cell-associated coagulation pathway or fibrin formation, and the presence of fibrin on vascular endothelium are consistent with the concept that coagulation activation in prostatic cancer may not be due to a direct effect of the tumor cells on the clotting mechanism.
 Rather, such activation may be induced by a soluble tumor product that activates procoagulant activity on certain host (for example, vascular endothelial) cells.
 These findings, together with the lack of effect of warfarin anticoagulation on the clinical course of patients with prostatic cancer, contrast with findings in certain other tumor types and suggest that coagulation activation may not contribute to progression of adenocarcinoma of the prostate.
",11
1812,"Antibiotics: potential hazards to male fertility.
 Individual agents within each of the major classes of antibiotics have been shown to have significant adverse effects on spermatogenesis or spermatozoal function in mammals.
 For humans, infertility or significant alterations in semen parameters have been well documented for the nitrofurans and for patients on sulfasalazine.
 Other commonly used antibiotics, such as minocycline, have been shown to be toxic to sperm at any concentration.
 Until further information is available, clinicians must keep in mind that treatment with antibiotics may adversely affect the fertility potential of men.
 It is possible that some classes of antibiotic agents, such as the penicillins or the quinolones, may have minimal effects on male fertility and maintain the clinical efficacy for patients requiring long-term antibiotic suppressive therapy.
 Further investigation is needed into the relative toxicity of antibiotics and the mechanisms by which antibiotics affect spermatogenesis and spermatozoal function.
 A background of the current state of knowledge regarding the adverse effects of antibiotics on male fertility is presented in this review.
",11
1813,"Parathyroid function in normocalcemic renal transplant recipients: evaluation by calcium infusion.
 The extent to which secondary hyperparathyroidism may involute remains poorly defined.
 Renal transplantation offers a clinical situation in which metabolic stimuli for hyperparathyroidism are removed.
 To examine whether hyperparathyroidism resolves after transplantation, we evaluated 11 renal transplant recipients who had been normocalcemic 6 or more months after transplantation using a sensitive 2-site immunoradiometric assay for intact serum PTH.
 Nine of the 11 had PTH concentrations within the normal range.
 Of these 9, 6 were found to have abnormal parathyroid function when challenged with an iv calcium infusion.
 The other 2 patients demonstrated significantly elevated basal PTH concentrations and elevated ionized calcium despite normal total serum calcium and albumin concentrations.
 In both, the PTH response to infused calcium was markedly abnormal, confirming hyperparathyroidism.
 The estimated renal threshold phosphate concentration was low in 4 of 9 patients with normal basal PTH concentrations and in both with elevated basal PTH.
 Bone mineral density, measured at the radius by single photon absorptiometry and at the spine by dual energy x-ray absorptiometry, was normal in 8 of the 9 transplant recipients who had normal basal PTH concentrations.
",11
1814,"Macrophages from nephrotic rats regulate apolipoprotein E biosynthesis and cholesterol content independently.
 The effects of the nephrotic syndrome in rats on the cholesterol content and the biosynthesis of apolipoprotein E (apoE) by resident peritoneal macrophages have been investigated.
 Since the nephrotic syndrome has been associated with an increased risk of coronary atherosclerosis, we hypothesized that macrophages from nephrotic rats would accumulate cholesterol and undergo transformation into foam cells, with a concomitant increase in apoE biosynthesis.
 The nephrotic syndrome was induced in rats with puromycin aminonucleoside.
 Peritoneal macrophages exposed in vivo for 7-21 d to ascites fluid derived from plasma containing sixfold elevations of lipoproteins did not accumulate unesterified or esterified cholesterol.
 Nevertheless, immunoprecipitation assays after incubation of the isolated cells with [35S]methionine, or immunoblot analysis of the incubation medium demonstrated a 2.6-fold increase in apoE secretion compared with normal macrophages.
 This increase was accompanied by 5- to 10-fold increases in cellular apoE messenger RNA as determined by quantitative solution hybridization assay.
 Peritoneal macrophages cultured from nephrotic rats during the period of hypercholesterolemia also showed distinct and highly reproducible morphologic changes.
 The dissociation between apoE biosynthesis and macrophage cholesterol content provides new insight into the response of peritoneal macrophages in vivo to endogenous hyperlipemia.
",11
1815,"A randomized comparison of the nephrotoxicity of iopamidol and diatrizoate in high risk patients undergoing cardiac angiography.
 Three hundred seven high risk patients with renal impairment (serum creatinine greater than or equal to 1.5 mg/dl) were randomized in a double-blind manner to either iopamidol (a nonionic, low osmolar radiocontrast agent) or diatrizoate (a conventional radiocontrast agent) at cardiac angiography with subsequent follow-up study of renal function.
 Baseline clinical and angiographic variables were similar in the iopamidol (n = 155) and diatrizoate (n = 152) groups.
 Change in renal function after angiography was less pronounced with iopamidol compared with diatrizoate as measured by mean ( +/- SD) increase in 24 h serum creatinine (0.11 +/- 0.2 versus 0.22 +/- 0.26 mg/dl, p less than 0.001), mean maximal increase in serum creatinine (0.2 +/- 0.44 versus 0.38 +/- 0.73 mg/dl, p less than 0.0001) and percent of patients with a maximal increase in serum creatinine greater than 0.5 mg/dl (8% versus 19%, p less than 0.01).
 Such differences could not be documented in diabetic patients using insulin.
 There was no significant difference between agents in the number of patients developing clinically severe acute renal dysfunction.
 It is concluded that iopamidol is less nephrotoxic than diatrizoate in high risk patients at cardiac angiography.
 However, the difference in nephrotoxicity is small, of no major clinical significance in the majority of high risk patients and could not be documented in insulin-using diabetic patients.
 Iopamidol may be the preferred agent in certain patients with advanced renal impairment, but further study is warranted.
",11
1816,"Simple standing incremental cystometry as a screening method for detrusor instability.
 One hundred consecutive neurologically normal women complaining of urinary incontinence underwent standing incremental retrograde medium-fill water cystometrograms on two different days followed by sitting and standing continuous retrograde medium-fill water urethrocystometry on a third visit between November 1987 and February 1989.
 Studies were done to assess the reproducibility, sensitivity, specificity, and predictive values of a simple cystometer.
 Standing incremental, retrograde cystometry was found to be relatively inexpensive, simple, reproducible, and sensitive.
 The two cystometrograms yielded similar results in 84% of the patients.
 The sensitivities were found to be 84.3 and 90.2% for the first and second cystometrograms, respectively.
 Using both cystometrograms together, we were able to detect detrusor instability with a sensitivity of 92.3% and to predict its absence with a negative predictive value of 86.7%.
 Detrusor instability was found in 64% of these patients.
 Based on these results, it was concluded that when multichannel urodynamics are not available in a high-prevalence population, standing retrograde incremental water cystometry done on two occasions may offer the physician an accurate alternative for the diagnosis of detrusor instability.
",11
1817,"Use of cyproterone acetate in prostate cancer.
 Cyproterone acetate is a progestational antiandrogen with potent antigonadotropic activity that results in rapid suppression of serum testosterone.
 Used as a single agent, cyproterone acetate yields a total androgen blockade.
 It may be combined with low-dose diethylstilbestrol, orchiectomy, or LHRH agonists to improve, in theory, the results of such therapy.
 In clinical testing, cyproterone acetate has proved equivalent to diethylstilbestrol with markedly less toxicity.
 It is useful in conjunction with LHRH agonists, either transiently to block the flare phenomenon, or continuously to block peripheral androgen receptors; the necessity for this latter action has not yet been proved.
 Cyproterone acetate may afford transient objective improvement in patients not responding to other forms of hormone deprivation.
 Experience in this role is limited.
 The drug may be used to suppress the hot flushes associated with orchiectomy or LHRH agonist therapy.
 Cyproterone acetate induces local tumor regression; owing to its reversible effects, it is useful as neoadjuvant or adjuvant androgen withdrawal therapy in patients with lower-stage disease undergoing radical surgery or radiotherapy.
 Adverse effects are mostly those related to hormone withdrawal, namely, impotence, infertility, and lassitude.
 Gynecomastia and breast tenderness occur in less than 18% and cardiovascular complications in approximately 10% of treated men.
",11
1818,"Use of suramin in treatment of prostatic carcinoma refractory to conventional hormonal manipulation.
 Suramin and related compounds, in view of their growth factor and enzyme binding properties, represent in many respects a novel approach to the treatment of cancer.
 Although in this preliminary analysis of suramin use in the treatment of metastatic prostate cancer, the objective response rate does not appear impressive, much work still needs to be done to optimize suramin's administration to patients and to elucidate its various postulated mechanisms of action.
 The development of related compounds with more specific enzyme and growth factor antagonist properties is under way.
",11
1819,"Advanced prostatic carcinoma. Early versus late endocrine therapy.
 Since the landmark observations of Huggins and Hodges in 1941, androgen deprivation has been the mainstay of treatment for advanced-stage prostate cancer.
 Although early, poorly controlled studies suggested enhanced survival with hormonal therapy, this view fell into disfavor as a result of the observations of the first and second VACURG studies.
 Recently, there has been a proliferation of experimental and clinical data supporting early androgen deprivation, including a reanalysis of the VACURG data, which suggests a survival advantage for younger patients with stage D disease and high-grade tumors who undergo androgen-ablative therapy at the time of diagnosis.
 The risk-benefit analysis presented in this review is strongly supportive of early hormonal therapy.
 Finally, long-term survival of patients with metastatic prostate cancer will require the development of novel treatment strategies effective against androgen-resistant tumor cells and their use in concert with early androgen deprivation.
",11
1820,"Future developments of nonhormonal systemic therapy for prostatic carcinoma.
 Prostate cancer is the most common type of cancer in men.
 Despite increased public awareness and new screening methods, a significant proportion of men continue to present with metastatic disease.
 Most men will respond initially to hormonal intervention; however, given time, the majority will have recurrences of hormonally unresponsive tumor on which present therapies have little impact.
 Research continues to identify new cellular and molecular aspects of prostate cancer with implications as possible sites of therapeutic intervention.
",11
1821,"Total androgen ablation: Canadian experience.
 A multicenter randomized, double-blind trial comparing total androgen blockade obtained by the use of castration with a pure anti-androgen (nilutamide) with simple castration was begun.
 One hundred and five patients received the combined treatment and 103 the orchiectomy plus placebo.
 Several features were used to evaluate the efficacy.
 Bone pain responded better to combined treatment at 6 months (P = 0.042).
 The number of favorable responses, as evaluated by the NPCP criteria, was 61% with simple castration and 78% with the combined treatment (P = 0.013).
 There was no statistically significant difference between the two groups in time to progression (logrank test P = 0.462) or survival (logrank test P = 0.137) despite an increase in median survival of 5.4 months.
 All other measures showed no difference between the two treatments.
 With total androgen blockade, 50% of the patients had disease progression at 1 year, and 45% were dead at 2 years.
 A review of the results of similar reported studies suggests no improvement or very modest improvement with total androgen blockade over testicular androgen ablation alone.
",11
1822,"Megestrol acetate plus low-dose estrogen in the management of advanced prostatic carcinoma.
 Megestrol acetate plus low-dose estrogen may be an effective, low-cost alternative to pharmacologic or surgical castration plus flutamide in the management of patients with advanced prostate cancer.
 The potential benefit of combined androgen ablation achieved by any means in comparison with conventional hormonal therapy appears to be limited.
",11
1823,"Role of 5 alpha-reductase inhibitors in the treatment of advanced prostatic carcinoma.
 Everything we know about the biology of the prostate supports the concept that DHT is the obligate androgen responsible for normal and hyperplastic growth.
 Whether this selectivity is maintained during malignant transformation is unknown.
 The consistent emergence of androgen-insensitive disease highlights the spectrum of biologic evolution this cancer is capable of.
 If the tumor is dependent only on DHT for neoplastic growth, the unique characteristics of a 5 alpha-reductase inhibitor offer several potential actions that warrant a systematic evaluation.
",11
1824,"Use of the nonsteroidal anti-androgen Casodex in advanced prostatic carcinoma.
 Pure anti-androgens have advantages over steroidal anti-androgens of the cyproterone acetate type in the treatment of patients with advanced prostate cancer because they do not have steroidal side effects or such a marked inhibitory effect on libido.
 In addition, the long half-life of a pure anti-androgen such as Casodex results in maintenance of high serum anti-androgen concentrations, which allays concern over the clinical significance of any small rise in serum testosterone concentrations.
 The anti-androgen of choice for the treatment of androgen-responsive diseases has yet to be defined.
 However, this choice should be based on extensive clinical evaluations of a drug as monotherapy.
 As always, the clinical efficacy and tolerability of the drug will be important factors in determining the anti-androgen of choice; however, favorable pharmacokinetics should be emphasized in the treatment of a disease in which high and sustained concentrations of antagonist must be present to prevent androgenic stimulation.
 Casodex, a pure anti-androgen with a relatively long half-life, produces objective and subjective responses similar to those of surgical or pharmacologic castration and is well tolerated.
 Its profile makes it a strong candidate for consideration as the future anti-androgen of choice in the treatment of advanced prostate cancer.
",11
1825,"Use of standard contraceptive diaphragm in management of stress urinary incontinence.
 The management of stress urinary incontinence (SUI) consists of either surgical intervention and/or pharmacologic manipulation.
 Twelve patients with SUI were evaluated for management by the use of a fitted standard contraceptive diaphragm.
 Complete resolution of SUI was achieved in 11 of 12 patients (91%).
 Two of the 12 patients achieved continence but withdrew from the study because of associated discomfort from the diaphragm, therefore, complete resolution of SUI was achieved in 9 of 12 patients (75%).
",11
1826,"Multilocular cysts of kidney. A study of 29 patients and review of literature.
 Multilocular renal cyst is a distinct renal tumor whose gross external appearance and absence of normal renal tissue within the septa of loculi distinguish it clearly from other renal cystic lesions.
 Interlocular septa may contain either (1) fibrous tissue alone or (2) embryonic tissue separating adjacent loculi.
 Of 29 patients with multilocular renal cysts, 24 underwent a renal-sparing procedure, and only 5 had radical nephrectomy.
 None of the histologic specimens showed evidence of immature renal tissue or neoplasia.
 Patients were followed from three months to eight years (mean, 39 months), and no evidence of local recurrence or metastatic disease was found.
 Because it is difficult to distinguish multilocular renal cyst from cystic Wilms tumor and multicystic clear cell carcinoma on the basis of imaging studies alone, surgical intervention is the only effective method to differentiate multilocular renal cyst from a malignant lesion of the kidney.
",11
1827,"Mobile epididymis. A new clinicopathologic entity in genesis of male infertility and its treatment by epididymopexy.
 Mobile epididymis plays an important role in the genesis of male infertility.
 It constituted 9 percent of a consecutive series of idiopathic infertility.
 Of 200 patients examined (100 fertile and 100 infertile), mobile epididymis was detected in 9 infertile patients.
 The clinical picture is characteristic.
 Epididymis is widely separated from testicle and moves freely from side to side.
 Its body and tail are ill formed and the epididymovasal angle is obtuse.
 Azoospermia was persistent in 3 patients and intermittent in 6 patients.
 Testicular biopsy showed tubular dilatation.
 Epididymopexy was performed in the 9 patients to fix the epididymis to testicle: 3 patients showed improvement in semen quality with two resultant pregnancies.
 Failures were due to advanced testicular damage.
 Infertility in mobile epididymis appears to result from obstruction of efferent ductules, testicular ischemia, and/or interference with sperm maturation, transport, or delivery.
",11
1828,"Simple urodynamic evaluation of incontinent elderly female nursing home patients. A descriptive analysis.
 We present a descriptive analysis of the functional, mental, and urodynamic status of a population of incontinent elderly female nursing home patients.
 One hundred fifty-five intermediate care female patients with a mean age of 85.5 years were identified as being incontinent of urine at least once daily.
 After urologic evaluation, each patient was classified into one of four categories: incontinence with normal cystometrogram 68 (44%), detrusor instability (DI) 52 (34%), stress incontinence (SI) 27 (17%), or overflow incontinence (OI) 7 (4%).
 Thirteen weeks later, patients were again studied using simple water cystometry.
 At follow-up evaluation, 45 patients (33%) had urodynamic findings which differed from the initial evaluation.
 Of these women, 10 with DI, 12 with SI, and 2 with OI were found to have normal cystometric parameters at the time of follow-up study, while 19 (14%) who initially had normal cystometric findings had evidence of DI (11) or SI (3).
 Strong correlation between urinary incontinence in patients with normal cystometric findings and moderate to severe cognitive impairment was present.
 Simple urodynamic evaluation did identify patients with SI and OI who might benefit from specific therapy.
 Urodynamic evaluation of incontinent elderly female nursing home patients is indicated and may provide direction for planning treatment strategies.
",11
1829,"Pharmacokinetics and metabolism of nilutamide.
 Data are available on the pharmacokinetics and metabolism of nilutamide in the rat, dog, and human (normal volunteers and patients with advanced prostatic carcinoma).
 Studies using 14Carbon-nilutamide, radioimmunoassay, and high-performance liquid chromatography (HPLC) are reviewed.
 In the rat, bioavailability by the oral route was complete.
 The majority of the plasma radioactivity was unchanged nilutamide up to six hours, t1/2 was seven hours, and clearance was 150 mL/hour/kg body weight.
 Metabolism studies identified 6 urinary metabolites.
 The major metabolites result from reduction of the nitro group initially to an hydroxylamine (17%) and then to a primary amino (26%) group.
 In normal volunteers the compound was rapidly absorbed, displayed linear kinetics over a dose range of 100-300 mg, and declined slowly in plasma with a terminal phase t1/2 of forty-three to forty-nine hours.
 In studies in 12 patients with advanced (Stage D) prostatic carcinoma, single-dose kinetics after 14C-nilutamide and kinetics with repetitive twice-daily dosing of two to seven weeks were measured.
 Terminal phase plasma t1/2 of unchanged nilutamide was 56 +/- 19 hours and of total radioactivity 87 +/- 27 hours (mean +/- SD).
 Area under the curve of plasma radioactivity was 23 to 38 percent unchanged nilutamide.
 Urinary excretion of radioactivity was slow and incomplete because the collection time was not long enough in regard to t1/2 (mean after 5 days, 62 +/- 10%) and consisted almost entirely of metabolites.
 Steady-state plasma levels of nilutamide were reached in about two weeks.
 It can be concluded that in humans, unlike other species, plasma decay of nilutamide is very slow.
 Elimination is almost exclusively by metabolism.
 Single-daily dosing is appropriate.
 Hepatic impairment could be expected to prolong plasma decay; renal impairment is likely to have little effect.
",11
1830,"Castration plus nilutamide vs castration plus placebo in advanced prostate cancer. A review.
 Combination of antiandrogen treatment with surgical or medical castration should improve the efficacy of endocrine treatment of prostatic cancer by blocking the effects of adrenal androgens.
 A nonsteroidal antiandrogen, nilutamide, has shown promising results in preliminary open studies.
 In a short-term (29 days) comparison of nilutamide plus buserelin and buserelin plus placebo, nilutamide (300 mg/day), significantly reduced bone pain, and fewer patients experienced worsening pain than in the control group.
 The initial buserelin-induced increase in prostatic acid phosphatase was prevented by nilutamide, but there was a similar increase in testosterone and gonadotropin concentrations to that seen in the control group.
 Thus, nilutamide can prevent the tumor flare-up associated with the start of luteinizing hormone-releasing hormone (LH-RH) treatment, even though the endocrine responses are not affected.
 In three multicenter, randomized, double-blind placebo-controlled trials of castration and nilutamide involving 248 patients, the combination of nilutamide and castration decreased bone pain, improved performance status, and increased the number of patients with objective regression, compared with patients who were castrated but did not receive nilutamide.
 Nilutamide was generally well tolerated, though visual disorders, gastrointestinal disorders, and alcohol intolerance were reported in patients receiving nilutamide.
 The results suggest that nilutamide improves the efficacy of castration in patients with prostatic cancer.
 Current studies are investigating the effects of this treatment on survival and the risk-benefit ratio.
",11
1831,"Pharmacology of antiandrogens and value of combining androgen suppression with antiandrogen therapy.
 Antiandrogens are compounds able to block the effect of androgens directly on their target cells by inhibiting their binding to the androgen receptor (AR).
 Two chemical classes of antiandrogens are presently on the market or in clinical trials: steroids (cyproterone, megestrol acetates), and nonsteroids (flutamide, nilutamide).
 Steroid antiandrogens interact not only with AR but also with progestin and glucocorticoid receptors and thus give rise to progestin and glucocorticoid effects.
 By contrast, nonsteroid antiandrogens interact only with AR and are thus devoid of other hormonal or antihormonal activities.
 Nilutamide does not need to be transformed into an active metabolite, unlike flutamide, and interacts with dog, rat, and human prostate AR in vitro.
 Its kinetics lead to a prolonged interaction with AR in vivo after administration to rats.
 In prostate cancer treatment, it is necessary to combine an antiandrogen to surgical or chemical (estrogens, LH-RH agonists) castration to obtain a complete suppression of androgens.
 The antiandrogen will block specifically, at the target site, the trophic effect of adrenal androgens left intact by castration, and the secretion of which can only be suppressed by treatments (adrenalectomy, aminoglutethimide, ketoconazole) that also suppress corticoid synthesis.
 We have shown that nilutamide counteracts the trophic effect, on the prostate of castrated rats, of adrenal androgens administered continuously (minipumps) at circulating levels similar to those recorded in castrated men.
 Nilutamide will also impede the flare-up effect of the testosterone increase induced by LH-RH agonists at the beginning of treatment.
 We have shown in the rat treated with buserelin that the increase in prostate weight observed during the initial days of treatment by the LH-RH agonist can be inhibited by a combined treatment with nilutamide.
 This combined treatment ""nilutamide plus castration"" has been tested in an experimental androgen-dependent cancer model, the Shionogi tumor.
 The administration of nilutamide to mice, castrated twenty-four hours before the inoculation of tumor cells, delayed the appearance of tumors and reduced their number.
 Finally, the absence of androgen effect and the antiandrogen activity of the product were also demonstrated in human tumor cells in culture (T-47 D cells) transfected with the MMTV androgen-dependent promoter coupled with the CAT reporter gene.
",11
1832,"Antisperm antibody detection using concurrent cytofluorometry and indirect immunofluorescence microscopy.
 Anti-sperm antibodies from serum and seminal plasma were detected by concurrent flow cytometry and epifluorescence microscopy using fluorescein-conjugated antihuman immunoglobulins.
 Experimental conditions were designed, taking advantage of several monoclonal antisperm antibodies, to test aspects of the assay before clinical application.
 Perturbation of membrane integrity altered both the localization of binding and the number of sperm cells positive for bound antibodies.
 In specimens from selected infertility patients, 21.6% of the females and 40.8% of the males had significant levels of antisperm antibodies.
 Differences in the incidence of isoimmunity between female partners of antibody-positive or antibody-negative males and differences in the localization of antigens targeted by serum versus seminal plasma antibodies in men support the idea that, in some cases, immunity to sperm cells may be the result of altered sperm antigens.
",11
1833,"The effects of reprocessing cuprophane and polysulfone dialyzers on beta 2-microglobulin removal from hemodialysis patients [published erratum appears in Am J Kidney Dis 1991 Jul;18(1):144]
 To further define the relationship between dialyzer reuse and the removal of beta 2-microglobulin (beta 2M) during dialysis, 26 patients who received hemodialysis were studied.
 Thirteen patients were dialyzed with conventional cuprophane dialyzers, and thirteen patients were dialyzed with high-flux polysulfone dialyzers.
 Patients in each group were dialyzed with only new dialyzers during the primary-use phase of the study, and reprocessed dialyzers during the reuse phase.
 Dialyzers were used six times during the reuse phase.
 Serum beta 2M levels were measured both predialysis and postdialysis, and adjusted for fluid loss.
 Dialysis with conventional cuprophane new dialyzers during the primary-use phase of the study resulted in a 3.3% increase in serum beta 2M levels, and a 2.4% increase in serum beta 2M levels during the reuse phase.
 The difference in the change of the concentration of beta 2M between primary-use and reuse phases was not statistically significant.
 Dialysis with high-flux polysulfone new dialyzers during the primary-use phase was associated with a decrease of 59.5% in the mean postdialysis concentration of serum beta 2M compared with the predialysis level.
 A corresponding decrease of 62.6% in serum beta 2M levels was observed after dialysis with high-flux polysulfone reprocessed dialyzers during the reuse phase.
 These data show no evidence of an adverse effect on the clearance of beta 2M during dialysis from the reuse of dialyzers up to six times.
 The results confirm previous studies that have reported that high-flux dialysis with polysulfone dialyzers removes substantial amounts of beta 2M, and dialysis with conventional cuprophane dialyzers does not.
",11
1834,"Concomitant iron and aluminum mass transfer following deferoxamine infusion during hemofiltration.
 Variable tissue overloading can alter the removal rate of iron and aluminum from uremics.
 Owing to its higher affinity to deferoxamine (DFO) and higher plasma concentrations, Fe could impair Al removal in cases of simultaneous body burden.
 Fe and Al plasma kinetics and mass transfer were therefore studied in 12 uremic patients with different Fe and Al status: six with normal ferritin levels (less than 400 micrograms/L [ng/mL]), and Al 1.4 to 4.7 mumol/L (40 to 131 micrograms/L) (group A); six with increased ferritin (greater than 2,000 micrograms/L), and Al 1.7 to 17 mumol/L (47 to 476 micrograms/L) (group B).
 DFO (40 and 80 mg/kg in a random sequence) was administered once a week during the first hour of the first hemofiltration (HF).
 The results show that in both groups and with both DFO doses, maximum Fe and Al mass transfer was achieved in the first and second HF, respectively.
 The 80-mg/kg dose of DFO significantly raised Al mass transfer in both groups, whereas Fe mass transfer was only slightly affected.
 Even though plasma Fe levels were almost always higher than Al, Al mass transfer eventually exceeded that of Fe, in both Fe-normal and Fe-overload patients.
 The bias towards Al in mass transfer was enhanced in both groups in the second HF, and at the higher DFO doses.
 Thus, DFO once a week reduced Fe loss to less than 30 mumol/wk in patients with normal ferritin levels.
 In both Fe and Al overloaded patients, Al can be removed, and Al mass transfer may often exceed Fe mass transfer, depending on the degree of tissue burden, the time from DFO infusion, and the DFO dose.
",11
1835,"Calcitriol metabolism in patients with chronic renal failure.
 We studied calcitriol metabolism in white patients with chronic renal failure and in age- and sex-matched normal subjects.
 The plasma levels of calcitriol (21.9 +/- 1.6 pg/mL, n = 7, v control, 37.4 +/- 2.9 pg/mL, P less than 0.001), metabolic clearance rate (MCR) of calcitriol (0.45 +/- .01 mL/min/kg v control, 0.58 +/- .02 mL/min/kg, P less than 0.001), and production rate (PR) of calcitriol (14.2 +/- 1.0 ng/kg/d v control, 31.8 +/- 3.2 ng/kg/d, P less than 0.001) were significantly lower in patients with moderate renal failure (average creatinine clearance, 0.59 +/- 0.01 mL/s [35.1 +/- 6.1 mL/min]) when compared with the respective values of normal control subjects.
 The MCR of calcitriol was determined again in patients with renal failure after they received calcitriol, 1 microgram/d, for 1 week.
 The MCR remained unchanged (0.46 +/- .04 mL/min/kg, n = 7) and plasma levels of calcitriol were increased to 34.6 +/- 2.77 pg/mL.
 The mechanism by which the MCR of calcitriol decreases in renal failure is partly due to the presence of inhibitory factors of degradation enzymes in uremic plasma.
 When the ultrafiltrates of uremic plasma obtained from hemodialysis patients were infused to normal Sprague-Dawley rats, the MCRs of calcitriol (0.20 +/- .01 mL/min/kg, n = 6) were markedly suppressed in comparison to those of rats infused with the ultrafiltrates of normal plasma (0.37 +/- .01 mL/min/kg, n = 6, P less than 0.001).
 The uremic plasma also contained factors that inhibit the synthesis of calcitriol.
 We conclude that metabolic degradation of calcitriol is decreased in patients with renal failure, and uremic plasma contains inhibitory factors that suppress the synthesis and degradation of calcitriol.
",11
1836,"Community-acquired acute renal failure.
 Acute renal failure usually occurs during hospitalization, but may also be present on admission to the hospital.
 To define the causes and outcomes of community-acquired acute renal failure, we undertook a prospective study of patients admitted to the hospital with acute elevations in serum creatinine concentrations.
 Over a 17-month period, all admission serum creatinine determinations were screened for patients with values greater than 177 mumol/L (2 mg/dL).
 These values were compared with baseline creatinines to select patients with an acute elevation in serum creatinine occurring outside the hospital.
 One hundred patients were entered into the study, with an overall incidence of 1% of hospital admissions.
 Seventy percent of the patients had prerenal azotemia, 11% had intrinsic acute renal failure, 17% had obstruction, and 2% could not be classified.
 Mean peak serum creatinine (318 +/- 18 mumol/L [3.6 +/- 0.2 mg/dL]) and mortality (7%) was lowest in the group with prerenal azotemia.
 In this group, volume contraction due to vomiting, decreased fluid intake, diarrhea, fever, glucosuria, or diuretics was the most common underlying cause.
 The group with intrinsic acute renal failure had the most severe renal failure and the highest mortality (55%).
 Although ischemic acute tubular necrosis is the most common cause of hospital-acquired intrinsic acute renal failure, this etiology was seen in only one patient.
 Drug-induced nephrotoxicity and infection-related causes were the most common underlying etiologies of intrinsic acute renal failure.
 Obstructive renal failure had a mortality of 24% and was most commonly due to benign prostatic hypertrophy.
",11
1837,"Serial glomerular and tubular dynamics in thyroidectomized rats with remnant kidneys.
 Serial measurements were performed in Munich-Wistar rats with five-sixths nephrectomy that had undergone prior selective thyroidectomy (Tx group) or thyroidectomy with thyroxine replacement (TxT4 group) to determine the effects of Tx on glomerular and tubular dynamics in relation to Tx attenuation of renal failure progression.
 At 1 week, inulin clearance rates (Cin) in TxT4 and Tx rats were 0.367 +/- 0.171 and 0.120 +/- 0.036 mL/min, respectively, different at P less than 0.01.
 Corresponding single-nephron filtration rate (SNGFR), glomerular plasma flow (QA), glomerular transcapillary hydraulic pressure (delta P), and proximal tubular reabsorption (Jv) were all reduced in Tx compared with TxT4 rats (P less than 0.01).
 Protein excretion (UPROT) was 151 +/- 40 in TxT4 rats, and 9 +/- 5 mg/d in Tx animals.
 Glomerular mesangial matrix expansion and focal tubulointerstitial changes were more frequent in TxT4 than Tx rats.
 By 4 weeks, Cin, SNGFR, QA, glomerular ultrafiltration coefficient (Kf) and Jv were similar in Tx and TxT4.
 Only glomerular capillary pressure (PGC) remained lower in Tx rats (35 +/- 3 v 50 +/- 3 mm Hg in TxT4, P less than 0.001).
 UPROT was 161 +/- 24 in TxT4 and 17 +/- 12 mg/d in Tx rats.
 While 7% +/- 4% of glomeruli showed focal sclerosis in TxT4 rats, there was none in the Tx group.
 Maximal glomerular planar area increased between 1 and 4 weeks in the TxT4 group, but not in the Tx group.
 However, this measurement was not significantly different between TxT4 and Tx glomeruli at 1 or 4 weeks.
 Minimal focal tubulointerstitial changes were found in TxT4, but there were not progressive from those observed at 1 week.
 The reduced PGC at 1 week was the result of a disproportionately greater increase in afferent (RA) than efferent arteriolar resistance (RE) in Tx rats (P less than 0.025); however, at 4 weeks, both RA and RE had decreased to values identical to those in TxT4 animals and the lower PGC in Tx rats was the result of a reduced mean arterial pressure.
 In conclusion, a reduced PGC was the sole functional correlate of decreased proteinuria and glomerulosclerosis afforded by Tx in this partial nephrectomy model.
 Suppression of either nephrectomy-related hypertrophy or tubulointerstitial injury by Tx could not be excluded as at least partially protective factors.
",11
1838,"Platelet-complement interactions in mesangial proliferative nephritis in the rat.
 Complement has been reported to mediate mesangiolysis and glomerular hypercellularity in the rat in a model of glomerulonephritis (GN) induced with anti-Thy 1 antibody.
 To investigate the mechanism for the complement-mediated hypercellularity, the authors first determined if the effect of complement depletion was to inhibit cell proliferation or whether the effect was primarily to inhibit leukocyte infiltration.
 Rats depleted of complement with cobra venom factor (CVF) had 1) significantly less mesangiolysis than controls at day 5 (0.6 +/- 0.1 versus 3.4 +/- 0.4, scale 0-4+, P less than 0.001); 2) less cell proliferation, as assessed by immunostaining for the proliferating cell nuclear antigen (PCNA)/cyclin, a cell-cycle-dependent antigen (0.5 +/- 0.1 versus 2.4 +/- 0.7 cells/glomerular cross-section, P less than 0.01); and 3) less leukocyte infiltration as assessed by immunohistochemical labeling (0.6 +/- 0.1 versus 1.9 +/- 0.3 cells/glomerular cross-section, P less than 0.01).
 Because it was reported recently that platelets also mediate glomerular cell proliferation in this model, this study examined whether the mechanism for complement-mediated cell proliferation involved an effect on glomerular platelet localization.
 The glomerular uptake of 111In-labeled platelets was quantitated in normal and CVF-treated rats at 1, 4, 12, and 24 hours after induction of GN.
 Rats with anti-Thy 1 GN had substantial glomerular accumulation of platelets at all times studied, peaking at 4 hours (608 +/- 171 platelets per glomerulus).
 Complement depletion profoundly reduced glomerular platelet localization in anti-Thy 1 GN (mean less than 35 platelets per glomerulus at all times studied, P less than 0.05).
 Thus these studies demonstrate an important role for complement in mediating platelet localization in anti-Thy 1 GN, an effect that may account for the complement-dependent, neutrophil-independent glomerular hypercellularity in this model.
",11
1839,"Glomerular basement membrane expansion in passive Heymann nephritis. Absence of increased synthesis of type IV collagen, laminin, or fibronectin.
 The distribution and synthetic rate of glomerular basement membrane components was examined in the Passive Heymann Nephritis model of experimental membranous nephropathy.
 The extensive tissue injury that developed included subepithelial electron-dense deposits, podocyte foot process effacement, and expansion of the glomerular basement membrane.
 Levels of mRNA for type IV collagen, laminin, and fibronectin from isolated glomeruli was quantitated by slot-blot analysis and showed no change in experimental animals as compared to controls at either 1 week, 3 weeks, or 3 months after disease induction.
 Immunoelectron microscopy with gold-labeled anti-laminin IgG revealed no difference in the number of particles bound to the glomerular basement membrane of experimental animals and controls.
 Immunofluorescence with both type IV collagen antisera and anti-laminin antibody showed no difference in the intensity or pattern of staining.
 Despite extensive glomerular damage and glomerular basement membrane thickening, no evidence was found for either an increase in the synthetic rate of type IV collagen, laminin, or fibronectin or for an accumulation of basement membrane laminin within the damaged glomeruli.
 Alternate processes, such as diminished density of matrix components or accumulation of other unmeasured matrix constituents, presumably account for the expansion of the glomerular basement membrane seen in experimental membranous nephropathy.
",11
1840,"Management of staghorn stones using a combination of lithotripsy, percutaneous nephrolithotomy and Solution R irrigation.
 The treatment of staghorn and partial staghorn calculi remains complex despite modern methods of stone removal.
 We describe the results following treatment of 112 stones.
 Three methods were used: percutaneous nephrolithotomy, extracorporeal shockwave lithotripsy and Solution R irrigation, either alone or in combination; 57 stones (55.8%) were completely cleared, with Solution R irrigation helping to achieve complete clearance in 6 of these.
 A further 24 stones were not completely cleared (small asymptomatic fragments less than 3 mm remained).
 A satisfactory outcome (stone-free or asymptomatic fragments less than 3 mm) was achieved in 81 stones (79%).
",11
1841,"The impact of extracorporeal piezoelectric lithotripsy on the management of ureteric calculi: an audit.
 The presentation and management of 153 patients with ureteric calculi requiring active treatment over a 12-month period were reviewed; 74% of patients had primary ureteric calculi and 26% had ureteric calculi composed of fragments resulting from extracorporeal piezoelectric shockwave lithotripsy (EPL) to renal calculi; 32 patients (21%) had more than 1 calculus or a steinstrasse.
 The primary procedures included were in situ EPL (n = 54), push-bang (44), retrograde ureteroscopy (40), Dormia basket extraction (6), push-pull (1), antegrade ureteroscopy (1) and combinations of these (7).
 The success of the primary procedure could not be predicted from stone size, site or duration in the ureter, but upper tract dilatation was significantly less (p less than 0.01) in the successful group.
 The overall success rate for complete stone extraction was 97%, but 54 patients (35%) required more than 1 procedure to achieve this.
 In situ EPL and push-bang, as either primary or secondary procedures, were successful in treating 79 patients (52%); 2 patients required ureterolithotomy (1.3%).
 The overall complication rate was 18%.
 Since EPL is only successful in treating approximately half of ureteric calculi, a range of other treatments should be available to maintain a low rate of open surgery.
",11
1842,"Do extracorporeal shock waves affect urinary excretion of glycosaminoglycans?
 Urinary excretion of glycosaminoglycans (GAGs) was studied in 9 anaesthetised dogs and 10 patients with single kidneys.
 The animals were studied for 4 to 5 hours after administration of shock waves to 1 kidney, the contralateral organ serving as control.
 Urinary excretion of GAGs was measured on both sides.
 The patients were studied 0 to 24 and 32 to 56 h after extracorporeal shock wave lithotripsy (ESWL).
 In the animals an increased mean urinary excretion of GAGs was observed on both sides; this was more marked in the treated kidney.
 The increase reflects tissue injury in the exposed kidney induced by the extracorporeal shock waves.
 No increase in mean urinary excretion of GAGs was observed in the patients.
",11
1843,"Night studies for primary diurnal and nocturnal enuresis and preliminary results of the ""clam"" ileocystoplasty.
 Modified conventional urodynamic apparatus was used to provide overnight monitoring of bladder and rectal pressure.
 A group of 26 patients with primary diurnal and nocturnal enuresis underwent both daytime rapid fill cystometry and overnight natural fill cystometry.
 The overnight study was effective in detecting detrusor instability in 10 patients deemed normal on rapid fill cystometry; 6 of these have now undergone clam ileocystoplasty and 5 are dry; 3 are awaiting this procedure.
 The clam remains very effective in the management of patients with resistant nocturnal and diurnal enuresis if careful selection is adopted.
 Overnight cystometry has proved to be an invaluable adjunct to the investigation of patients with primary diurnal and nocturnal enuresis previously felt to be urodynamically normal.
",11
1844,"Is voided urine suitable for flow cytometric DNA analysis?
 Samples of bladder washings are frequently used to provide cellular material for flow cytometric DNA analysis.
 Since voided urine is a potential source of similar material, the aim of this study was to determine whether voided urine yields satisfactory specimens.
 We compared the qualitative results of flow cytometric DNA analysis of the cells in 53 specimens of voided urine and 109 samples of bladder washings; 45% (24/53) of urine specimens gave satisfactory DNA histograms compared with 93% (101/109) of bladder washings.
 This difference was apparent regardless of whether the bladder contained a tumour.
 It was concluded that bladder washings provide superior material for flow cytometric DNA analysis and that flow cytometric DNA analysis of freshly voided urine may have deficiencies which preclude its use in routine clinical practice.
",11
1845,"Radical radiation treatment of invasive and locally advanced bladder carcinoma in elderly patients.
 A total of 146 patients with invasive or locally advanced carcinoma of the bladder (T2-T4) underwent radiation treatment.
 A significantly higher complete response rate was observed with doses equal to or above 55 Gy and with doses corresponding to cumulative radiation effect (CRE) values of 1700 radiation effect units (reu) or more.
 In multivariate analysis, decreasing time from the first diagnosis of bladder carcinoma to radiation treatment and 1 or more transurethral resections was associated with a significant increase in survival; increases in T category and sedimentation rate were negative prognostic factors.
 Although both radiation dose and CRE levels had a significant effect on survival in univariate analysis, an increase in CRE levels alone was associated with a significant increase in survival in multivariate analysis.
 However, the most important predictor of survival was whether the patient showed a complete local response or not.
 This study emphasises the importance of treating patients with an adequate radiation dose over a short period of time in order to achieve the maximum radiobiological effect and thereby increase the possibility of cure.
",11
1846,"Activation of complement, kallikrein-kinin, fibrinolysis and coagulation systems by urinary catheters. Effect of time and temperature in biocompatibility studies.
 Urethral strictures induced by the use of latex catheters and combined silicone/latex catheters following open-heart surgery have been reported.
 These strictures differ from the post-catheterisation type in affecting a greater length of urethra.
 Recently it was shown that complement was activated by catheters which cause inflammation, in contrast to clinically silent catheters.
 The present study was designed to investigate a possible association between catheter-induced inflammation and activation of another mediator of inflammation, the contact system.
 We also investigated various in vitro conditions to optimise biocompatibility studies.
 Our data indicate that both the complement and the kallikrein-kinin system are activated by potentially harmful silicone/latex catheters and may be involved in the pathophysiology of catheter-induced urethral strictures.
 In vitro biocompatibility tests may be performed at both 20 and 37 degrees C.
 Glass test tubes may be used for in vitro complement but not for kallikrein-kinin investigations.
",11
1847,"Haemospermia: a prospective study.
 A prospective study of 74 men with haemospermia is presented.
 Most (76%) had experienced 1 or 2 episodes only and 9 (12%) were over 40 years old.
 Simple investigations led to a diagnosis in all 9 of these men and of those under 40, no pathology could be detected in 48%.
 A diagnosis was made in 32 of the remaining 34 men by simple investigations.
 In patients over 40 years of age with haemospermia, a potentially treatable cause will normally be found by routine investigation which should include cystoscopy.
 In younger men, non-invasive investigation alone should identify any pathology.
 Invasive investigations should be reserved for those patients in whom the problem is prolonged, excessive or in association with other symptoms.
",11
1848,"Intravascular retention and renal handling of purified natural and intramolecularly cross-linked hemoglobins.
 Plasma half time of unmodified hemoglobin (UHb) and two intramolecularly cross-linked hemoglobins (alpha alpha XL and beta beta XL) was measured in anesthetized rats after an intravenous bolus of 20 mg.100 gm.-1 To rule out the possibility that differences among plasma half times might be caused by differences in acute effects on renal excretory function, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with plasma half time.
 Experiments were also done to determine whether higher doses (60 to 100 mg-1.100 gm-1) of these compounds had a delayed effect (48 hours) on GFR or ERPF.
 Massive urinary excretion of UHb occurred; however, only 1% of the alpha alpha XL and none of the beta beta XL was excreted.
 Plasma half time of alpha alpha XL and beta beta XL averaged 3.3 hours, or four times longer than UHb.
 In no case did a decrease in GFR or ERPF occur.
 Instead, a transient increase in GFR, ERPF, urine flow, and systemic blood pressure was seen.
 Similar increases occurred after albumin administration, suggesting expansion of vascular volume as the initiating factor.
 Renal functions at 48 hours after 60 to 100 mg.100 gm-1 of UHb, alpha alpha XL or beta beta XL were not different from control (albumin).
 Intratubular hemoglobin casts or intravascular precipitates were not evident in acute or 48-hour studies.
 At 48 hours Perls' staining material was found in one alpha alpha XL specimen at 3 hours after administration.
 Perls' staining material was present in renal tubule cells in all but the albumin-treated kidneys.
",11
1849,"Factor XIII and its substrates, fibronectin, fibrinogen, and alpha 2-antiplasmin, in plasma and urine of patients with nephrosis.
 Plasma and urine concentrations of factor XIII and its circulating substrates (fibronectin, fibrinogen, and alpha 2-antiplasmin) were measured in a group of 36 patients with nephrotic syndrome.
 The results were compared with those obtained in a group of 32 normal volunteers (control group) and 12 patients with end-stage renal disease (ESRD).
 A mild but significant reduction in plasma level and an abnormal urinary excretion of alpha 2-antiplasmin was found in the nephrotic group.
 Plasma concentrations of factor XIII, fibronectin, and fibrinogen were significantly elevated in patients with nephrosis.
 In contrast, patients with ESRD showed no significant difference in the plasma concentrations of either factor XIII, fibronectin, or alpha 2-antiplasmin and only a modest elevation of fibrinogen when compared with normal controls.
 No significant correlation was found between serum creatinine concentration and plasma levels of factor XIII and its circulating substrates in the nephrotic group.
 No measurable quantities of factor XIII and only small quantities of fibronectin were found in the urine of patients with nephrosis.
 Elevation of plasma factor XIII, fibronectin, and fibrinogen concentrations in the nephrotic group is considered to be the result of a combination of increased synthesis and possibly contracted intravascular distribution of these macromolecular proteins in the face of their negligible urinary losses.
 The presence of the observed abnormalities in the nephrotic group and their absence in the non-nephrotic ESRD group tends to exclude renal failure as a cause of these abnormalities.
 Although the clinical significance of these abnormalities is uncertain, they can potentially contribute to the thrombophilic diathesis and platelet hyperaggregability in nephrotic syndrome.
",11
1850,"Fluorouracil and recombinant human interferon alfa-2a in the treatment of metastatic chemotherapy-refractory urothelial tumors.
 Thirty patients with advanced metastatic and chemotherapy-refractory urothelial tumors received a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a.
 Thirty-six sites of metastases were present in the 30 study patients, and the median Eastern Cooperative Oncology Group performance status was 3 (range, 1 to 4).
 All patients had failed to respond to primary combined methotrexate/cisplatin-based chemotherapy.
 Nine (30%; confidence interval, 15% to 47%) of the patients achieved a partial response.
 The mean duration of response was more than 5.2 months (median, 6 months; range, 3 to 8 months).
 Two patients who achieved a partial response of 5 and 7 months' duration, respectively, had control of residual disease (one with radiation and one with surgical excision) and have remained disease-free for an additional period of more than 7 and 13 months, respectively.
 These data suggest that the combination of 5-FU and recombinant human interferon alfa-2a is synergistic, with clinical significance for the treatment of urothelial tumors.
 The response rate for this combination of drugs is higher than that anticipated for either of these agents used alone.
 Additional confirmatory trials are needed to evaluate the significance of these findings.
",11
1851,"Donating a kidney to a family member. How primary care physicians can help prepare potential donors.
 When a relative needs a kidney to survive, family members often impulsively offer to donate one without stopping to consider the physical, emotional, and financial ramifications, which can be considerable.
 The family's primary care physician can be very helpful in guiding and educating potential donors and, by arranging for screening to be done in the community, can ease the financial strain.
 The authors discuss the things a potential kidney donor should consider.
",11
1852,"Comparative study of cephradine and amoxicillin-clavulanate in the treatment of recurrent urinary tract infections.
 Eighty-eight female patients with a history of recurrent urinary tract infections were treated according to a randomization scheme with either 1 g of cephradine every 12 h (47 patients) or 375 mg of amoxicillin-clavulanate every 8 h (41 patients) for 7 days.
 The treatments were equally effective (cure rates of 89% for cephradine and 88% for amoxicillin-clavulanate) and showed similar relapse rates (cephradine, 14%; amoxicillin-clavulanate, 11%).
 Adverse effects were similar in both groups (cephradine, 23%; amoxicillin-clavulanate, 22%).
",11
1853,"Self-administered intraurethral chlorpromazine: an unusual cause of priapism.
 Priapism is a prolonged, painful penile erection unaccompanied by sexual desire and not alleviated by ejaculation.
 The etiologies of priapism are numerous and diverse.
 Priapism can be a serious adverse effect of psychotropic medications.
 The case of a 36-year-old man who demonstrated priapism, 48 hours after inserting a crushed chlorpromazine tablet into the urethral meatus of his penis, is reported.
 Priapism induced by this route of drug administration has not been previously described.
 The pathophysiology and treatment of priapism are reviewed.
",11
1854,"The impact of breakthrough clinical trials on survival in population based tumor registries.
 Three statistical models are developed to study the impact that two breakthrough clinical trials (MOPP for Hodgkin's disease and PVB for disseminated testicular cancer) had on survival in the Connecticut tumor registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry program.
 A segmented regression model is used in conjunction with the Cox semi-parametric proportional hazards model, as well as the parametric Weibull and exponential cure models.
 These models allow us to determine approximately when survival first began to improve dramatically, indicating that improved treatments had become available, and how long it took for survival to level off again indicating that the full population survival impact had been realized.
 In addition, the degree to which the parametric models fit allows us to determine if the survival improvements occur within a parametric family.
 Results of the modelling indicate that dissemination took approximately 11 years in Hodgkin's disease while only 3 years in disseminated testicular cancer.
 In both disease sites survival first broke with prior trends between the time that the breakthrough trial started and its publication, indicating that earlier moderately successful 'precursor' trials with combination chemotherapy may have initiated the improved population survival trends.
 Reasons for the difference in dissemination time in the two cancer sites are examined in order to understand what factors may be responsible for the speed of dissemination and effective utilization of new therapies.
",11
1855,"Routine screening for cancer of the prostate.
 The value of screening for prostate cancer remains unclear.
 Although digital rectal examination, transrectal ultrasonography, and determination of serum prostate-specific antigen levels may lead to early detection of a malignancy, these procedures have never been shown to reduce disease-specific mortality from prostate cancer.
 Unfortunately, several potential errors found in uncontrolled trials may suggest benefit from screening where none exists.
 Only a large, randomized, controlled clinical study demonstrating decreased mortality from prostate cancer can prove that screening is beneficial.
 Until such a study is performed, patients should be informed of both the potential benefits and the risks of screening and treatment.
",11
1856,"Transient oliguria with renal tubular dysfunction after a 90 km running race.
 In the course of a 19-d study of renal function in five ultramarathon runners, before, during and after a 90 km race, one runner developed transient oliguria with renal tubular dysfunction and anuria during and immediately after the race.
 Other features of the renal failure were an 84-fold increase in urine beta 2-microglobulin excretion (from 0.19 to 16.0 micrograms.min-1) and a much smaller increase in urine total protein excretion (from 0.07 to 0.18 mg.min-1) during the post-race period.
 Post-race creatinine clearance remained below pre-race levels throughout the study, varying between 42.8 and 72.9 ml.min-1, in contrast to the post-race 49% increase in the remaining runners (from 138.1 +/- 12.9 to 205.5 +/- 59.9 ml.min-1).
 Osmolal clearance also remained low (0.31 to 0.98 ml.min-1) compared with the pre-race values (1.46 +/- 0.02 ml.min-1), as did the urine flow rates (0.11 to 0.18 ml.min-1) compared with the pre-race values (0.34 +/- 0.02 ml.min-1).
 This renal dysfunction persisted despite the patient receiving 2 l of intravenous fluids immediately after the race and probably resulted from fluid restriction during the race.
 There was full recovery of renal function 1 yr later when the subject again ran the Comrades Marathon.
",11
1857,"Photosensitized destruction of human bladder carcinoma cells treated with chlorin e6-conjugated microspheres.
 A photosensitizer conjugate, chlorin e6 (Ce6) covalently bound to 1-micron-diameter polystyrene microspheres, has been investigated in the photodynamic destruction of MGH-U1 human bladder carcinoma cells in vitro.
 The microspheres were taken up avidly by the carcinoma cells; confocal laser scanning fluorescence microscopy showed them to be localized in the cytoplasm, apparently within lysosomes, visualized by labeling with acridine orange.
 In contrast, fluorescence of unconjugated Ce6 was present within most cellular membranes.
 Use of Ce6-microsphere conjugates led to a 20-fold-higher mean intracellular concentration, compared with unconjugated Ce6.
 Cells incubated in the presence of Ce6-microsphere conjugates (0.43 microM equivalent) and subsequently irradiated at 659 nm with a dye laser pumped by an argon-ion laser showed dose-dependent phototoxicity, leading to total inhibition of colony formation at a radiant exposure of 5J/cm2; in contrast, cells incubated with either unconjugated Ce6 (0.43 microM) or unconjugated microspheres before laser irradiation were unaffected.
 Cells pretreated with Ce6-microsphere conjugates and irradiated in the presence of 90% 2H2O showed significantly increased phototoxicity, an effect consistent with an important role for excited-state singlet oxygen in the mechanism of injury.
 In solution, however, photosensitized generation of singlet oxygen with Ce6-microsphere conjugates was 9 times less efficient than with unconjugated Ce6.
 The markedly greater phototoxicity of Ce6-microsphere conjugates compared to unconjugated Ce6 was therefore a consequence of the high intracellular Ce6 concentration attained by phagocytosis of the conjugates and their particular sites of intracellular localization.
 Thus, these conjugates are an efficient system for the delivery of photosensitizing drugs to carcinoma cells.
",11
1858,"Immunotactoid glomerulopathy.
 During the past 10 years, immunotactoid glomerulopathy has become recognized with increasing frequency.
 The lesion is characterized histologically by highly organized ultrastructural deposits that appear to be composed of immunoglobulin and complement and are negative for amyloid by Congo red stain.
 Clinically and/or serologically, patients have no evidence of cryoglobulinemia, amyloidosis, systemic lupus erythematosus, or a paraproteinemia, disorders associated with glomerular deposits, which also have a highly organized tactoidal or fibrillar characteristic.
 Immunotactoid glomerulopathy does not appear to be a multisystemic disease process and thus may represent a primary glomerulopathy.
 Patients with immunotactoid glomerulopathy present with proteinuria (nephrotic range in more than 60%) and over half of the patients have hypertension, hematuria, and renal insufficiency.
 Progression to end stage renal disease has occurred in more than 40% of patients reported to date.
 The experience in treating this disorder using prednisone and/or immunosuppression is limited and has not been impressive.
 Four patients have successfully undergone renal transplantation, but proteinuria recurred in two and was associated with the recurrence of immunotactoid glomerulopathy in the renal allograft.
 Although we have gained insight into the clinical course and histopathology of this disorder over the past few years, we still know little about its pathogenesis, an area for further research.
",11
1859,"Prolonged survival with a remnant kidney.
 Surgical ablation of five-sixths renal mass in Munich-Wistar rats fed a high protein diet leads to focal sclerosis in the remnant kidney and progressive renal failure.
 Experimental data suggest that this injury results from intraglomerular hypertension and/or chronic glomerular hyperfiltration.
 Data in humans largely are limited to patients with unilateral renal agenesis or uninephrectomy, either for unilateral renal disease or for kidney transplant donation.
 Isolated case reports have documented focal sclerosis and progressive renal failure in two patients with a remnant kidney.
 To obtain data in humans with a remnant kidney, we surveyed more than 800 urologists and nephrologists in the United States and abroad.
 Criteria for inclusion in the study were (1) surgical resection (in one or more operations) resulting in the presence of a remnant kidney; and (2) an adequate period of follow-up, defined as 5 years or greater.
 A total of 13 patients were identified (from 13 different centers).
 Twelve patients had renal cancer and one had tuberculosis.
 Six patients were observed for 10 or more years postoperatively and all have stable serum creatinine levels of less than 270 mumol/L (3.0 mg/dL); two of these six patients are now more than 25 and 30 years postoperation.
 The other seven patients, observed for 5 to 7 years, have serum creatinine levels less than 270 mumol/L (3 mg/dL), while one has an increasing serum creatinine level.
 The two longest surviving patients both have undergone successful pregnancy with no overall change in serum creatinine.
 These observations demonstrate that it is possible for humans to survive more than 30 years with a stable serum creatinine, despite the presence of only a remnant kidney.
",11
1860,"Evaluation of hemodialysis patients treated with erythropoietin.
 We evaluated 20 hemodialysis patients who had been treated with erythropoietin (Epo).
 All patients had hemoglobin levels below 8.5 g/dL.
 They were randomized to receive either Epo (100 U/kg) or placebo three times per week for 12 weeks.
 All patients on Epo had a significant (P less than 0.001) elevation of hematocrit levels (19.7% v 35.7%).
 They also had a significant (P less than 0.05) increase in midweek predialysis blood urea nitrogen (BUN) levels, 27.8 versus 29.6 mmol/L (78 v 83 mg/dL), and serum phosphorus, 1.8 versus 2.1 mm/L (5.7 v 6.6 mg/dL).
 Protein catabolic rate also increased significantly (P less than 0.05).
 No changes were seen in the levels of serum creatinine and potassium, but episodes of hyperkalemia were more frequent in patients on Epo.
 No changes were seen in patients on placebo.
 When hematocrit increased, the clearance of blood-water for urea decreased 9%, and the clearance of creatinine, potassium, and phosphorus decreased 15%.
 Patients on Epo increased both their appetite and protein intake.
 More frequent episodes of hyperkalemia and elevated phosphorus level resulted from a combination of increased intake and decreased dialyzer clearance.
 We may need blood-water clearance to calculate Kt/V.
",11
1861,"Management of acute pyelonephritis in an emergency department observation unit.
 STUDY OBJECTIVES: To determine whether moderately to severely ill patients with acute pyelonephritis can be treated successfully on an outpatient basis, and whether any aspect of history, physical examination, or initial laboratory data predicts failure of outpatient therapy and the need for hospitalization.
 DESIGN: Retrospective chart review of all patients with a diagnosis of acute pyelonephritis seen during a three-year period.
 SETTING: Emergency department observation unit of an urban teaching hospital serving residents of the city and county of Denver.
 TYPE OF PARTICIPANTS: Women between the ages of 15 and 50 with symptoms, physical examination, and initial laboratory data consistent with a diagnosis of pyelonephritis.
 INTERVENTIONS: Patients received IV antibiotics, rehydration, analgesics, and antiemetics in an observation unit for up to 12 hours, when they were either admitted to the hospital or discharged home on oral antibiotics.
 MEASUREMENTS AND MAIN RESULTS: Sixty-three of 87 patients (72%) with acute pyelonephritis were managed successfully as outpatients, nine (22%) were hospitalized directly from the observation unit because they were considered to be too ill to go home, and five (6%) returned with persistent symptoms after ED therapy and were hospitalized.
 No clinical or laboratory variable predicted success or failure of ED observation unit therapy at the time of initial presentation.
 CONCLUSION: In selected patients, the observation unit may be used to initiate therapy for acute pyelonephritis.
 Those with an adequate clinical response to initial treatment may be discharged on oral antibiotic therapy with appropriate follow-up.
",11
1862,"Treatment of pyelonephritis in an observation unit.
 STUDY OBJECTIVE: To determine the feasibility of managing patients with acute pyelonephritis as outpatients after initial treatment with IV antibiotics in an emergency department observation unit.
 DESIGN: Prospective and uncontrolled.
 SETTING: ED observation unit.
 TYPE OF PARTICIPANTS: Nonpregnant female patients 14 years old or older without immunocompromise or serious underlying disease and no evidence of septic shock.
 INTERVENTIONS: All patients received two IV doses of trimethoprim/sulfamethoxazole at a 12-hour dosing interval and promethazine and acetaminophen as needed for nausea and fever, respectively.
 Baseline laboratory data, urinalysis, and urine and blood cultures were obtained.
 MEASUREMENTS AND MAIN RESULTS: Patients were observed for signs of septic shock, nausea, vomiting, and the ability to tolerate an oral intake.
 At the end of the observation period, 43 of 44 patients were discharged on oral trimethoprim/sulfamethoxazole.
 One additional patient who was doing well clinically was recalled and admitted because of a positive blood culture.
 CONCLUSION: Patients with acute pyelonephritis, despite significant fever or nausea and vomiting, can be treated effectively as outpatients after a brief period of observation and IV antibiotics.
",11
1863,"Kinetic modeling of intracellular pH and comparison with 31P NMR experimental values in dialysed uremic patients.
 Changes in intra-erythrocytic pH values over time, during and after bicarbonate hemodialysis, were studied with 31P Nuclear Magnetic Resonance.
 Simultaneously, pH values of whole blood were obtained by a gazometric method.
 A two-compartment model appeared to be the simplest kinetic model to explain the shifts in proton concentrations in extra- and intra-cellular media.
 Non-linear regression was used to determine exchange constant values.
 There was a very good correlation between the experimental and calculated proton concentrations.
 This model can describe all patients but individual experimental constants must be determined.
 Under these conditions a single blood pH determination before dialysis will permit determination of the initial intra-erythrocytic pH and monitoring of intra-erythrocytic pH during hemodialysis.
",11
1864,"A new cause of female pseudohermaphroditism: placental aromatase deficiency.
 A description is presented of the first documented case of placental aromatase deficiency.
 The deficiency caused maternal virilization during pregnancy and pseudohermaphroditism of the female fetus.
 A 24-yr-old primigravida showed progressive virilization during the third trimester.
 Urinary excretion of estrogen was less than 14 mumol/day between 35-38 weeks of pregnancy, although nonstress tests showed reactive patterns and serum levels of human placental lactogen were above 460 nmol/L.
 Maternal serum levels of estrogens were low, and those of androgens were high in the third trimester.
 A dehydroepiandrosterone sulfate loading test induced a marked increase in maternal serum levels of androgens, whereas no such increase was observed in estrogens.
 The woman delivered vaginally a live full-term infant who exhibited female pseudohermaphroditism.
 Cord serum levels of estrogens were extremely low, while those of androgens were high.
 The aromatase activity of the placenta, determined by the conversion of [7-3H]androstenedione to 17 beta-[7-3H]estradiol and [7-3H]estrone, were less than 0.03 fmol/microgram protein.min (control, 9.6 +/- 2.2 fmol/microgram protein.min).
 The sulfatase activity of the placenta was 0.63 pmol/microgram protein.min compared to 0.46 +/- 0.16 pmol/microgram protein.min in controls.
 The rate of aromatization by normal control placentas was the same as that obtained during coincubation of samples of normal placentas and that of the patient.
 Thus, the presence of aromatase inhibitor in the patient's placenta was excluded.
",11
1865,"The N-terminal sequence of the major erythropoietic factor of an anephric patient is identical to insulin-like growth factor I.
 The erythropoietic factors present in an anephric patient with nearly normal hematocrit were isolated from plasma by reversed-phase and gel permeation HPLC.
 The most active fraction was purified and the analysis of its N-terminal sequence was identical to the published sequence of the human insulin-like growth factor I (IGF I).
 Recombinant human IGF I had identical elution positions as the isolated erythropoietic factor on reversed-phase HPLC and the same molecular weight on gel permeation HPLC.
 Furthermore, hrIGF I stimulated erythroid colony formation in human bone marrow cultures as was previously shown for the isolated human erythropoietic factor.
 These results suggest that IGF I may replace erythropoietin as a stimulator of erythropoiesis in some patients with anemia and renal failure.
",11
1866,"Measurement of urinary lipopolysaccharide antibodies by ELISA as a screen for urinary tract infection.
 Five hundred and twenty two clinical urine specimens submitted for routine microbiological examination were tested in parallel by conventional microscopy and culture and for lipopolysaccharide antibodies by an enzyme linked immunoabsorbent assay (ELISA) to assess the ELISA as a screen for urinary tract infection.
 When the ELISA alone was compared with routine methods the specificity sensitivity, and predictive value of positive and negative tests was 73.2%, 75.7%, 51.1% and 38.5%.
 For ELISA with microscopy the same variables were 71.1%, 82.2%, and 92.4% and 94.7%, respectively.
 The ELISA absorbency increased with increasing bacterial numbers, but results varied widely.
 Only 65.4% of urines which contained greater than or equal to 10(5) bacteria/ml were positive by ELISA; 36.8% of urines with less than 10(3) bacteria/ml were positive by ELISA; 100% of greater than or equal to 10(5) bacteria/ml cultures of Pseudomonas sp (n = 4), Staphylococcus aureus (n = 3), and Streptococcus faecalis (n = 2) were positive by ELISA but only 71.4% of Proteus sp (n = 7), 61.4% coliforms (n = 70), and 25% of coagulase negative staphylococci (n = 4).
 It is concluded that further development is required before the ELISA can be used for routine screening for urinary tract infection.
",11
1867,"Percutaneous nephrolithotomy for calculi in horseshoe kidneys.
 Between 1983 and 1988, 15 patients (18 kidneys) underwent percutaneous nephrolithotomy at this unit for calculi in horseshoe kidneys.
 A standard 1-stage percutaneous access technique with minor modifications was used.
 In situ disintegration with ultrasound or electrohydraulic lithotripsy was necessary in 15 moieties (83.3%) and nephrostomy drainage was required in 12 (66.7%).
 Percutaneous access was not a problem and there were minimal perioperative problems.
 Blood transfusion was required postoperatively in 2 patients.
 A total of 14 kidneys (77.8%) were rendered free of stone with percutaneous nephrolithotomy alone and 2 kidneys were left with asymptomatic stone fragments of 2 mm.
 or less.
 Another 2 kidneys became free of stone after extracorporeal shock wave lithotripsy, thus giving an over-all stone clearance rate of 88.8%.
 We conclude that percutaneous nephrolithotomy is an acceptable treatment for stones in horseshoe kidneys and it is the treatment of choice for patients in whom imaging is difficult or impossible.
",11
1868,"Extracorporeal shock wave lithotripsy of urinary calculi: experience in treatment of 3,278 patients using the Siemens Lithostar and Lithostar Plus.
 Between March 1986 and June 1989, 3,278 patients with upper urinary tract calculi were treated at our medical center with the Lithostar lithotriptor.
 The stones were located in the calices in 41.9% of the cases, renal pelvis in 25.7% and ureter in 32.4%.
 Perirenal hematoma was noted in 0.5% of the patients but this resolved spontaneously within a few days.
 Auxiliary procedures were performed in 37.3% of the cases, including Double-J stent and ureteral catheter in 26.8%, ureterorenoscopy in 2.1%, percutaneous nephrostomy in 1.6%, Zeiss loop in 4.3% and percutaneous nephrolithotripsy in 3.5%.
 Of the treatments 83.1% were performed without general or regional anesthesia.
 Followup after 3 months showed a 63.8% rate free of stone.
 The Lithostar upgraded with the overhead lithotripsy module is called Lithostar Plus.
 A total of 25 patients with upper urinary stones underwent treatment with the overhead module.
 Initial experience revealed fragmentation of stones after the first session in 20 patients, while a second session was necessary in 5.
 Analgesic sedation was used in 4 patients in whom a Double-J stent was inserted.
",11
1869,"Treatment of steinstrasse with repeat extracorporeal shock wave lithotripsy: experience with piezoelectric lithotriptor.
 Among 958 patients with renal stones who underwent extracorporeal shock wave lithotripsy (ESWL) monotherapy using an EDAP-LT01 piezoelectric lithotriptor steinstrasse developed in 55 (5.7%).
 Of these 55 cases stone fragments passed spontaneously in 35 (63.6%) and were treated successfully (no residual stone fragment in ureter) with repeat ESWL in 18 (32.8%).
 Only 2 patients (3.6%) required ureteroscopic management or open ureterolithotomy.
 Therefore, repeat ESWL is considered a good initial method to treat complicated steinstrasse.
",11
1870,"Cystourethrometric findings in patients with detubularized right colonic segment for bladder replacement.
 Urodynamic evaluation was performed in 13 men 4 to 18 months after cystoprostatectomy and bladder replacement using a detubularized right colonic segment.
 All patients are continent by day and only 3 are incontinent during the night to a degree that necessitates use of a condom catheter.
 Two patients awaken every 2 to 3 hours to void and the remainder have nocturia comparable to normal men of their age.
 The residual volume was 0 to 70 ml.
 The urethral closure pressure was normal, and in 3 patients studied preoperatively and postoperatively no significant change was observed other than shortening of the profile length.
 Maximal flow rates were normal although the pattern was intermittent.
 In 2 patients no cystoplasty contractions were recorded and in all but 2 patients the amplitude of the contractions was less than 40 cm.
 water.
 Simultaneous bladder and urethral pressure recordings during bladder filling demonstrated no change in urethral pressure in 10 patients.
 Although creation of a reservoir with a low pressure and careful preservation of the infraprostatic urethra are important for continence in these patients, we believe that the absence of normal sacral route reflexes after cystoprostatectomy is an important contributing cause to nocturnal incontinence.
",11
1871,"The detection of reflux nephropathy in infants by 99mtechnetium dimercaptosuccinic acid studies.
 Dimercaptosuccinic acid (DMSA) studies were performed in 113 infants less than 1 year old at risk of renal scarring.
 Of these patients 86 presented with urinary tract infection and 27 were asymptomatic.
 A voiding cystourethrogram was performed in all cases and excretory urography (IVP) was done in 99.
 More abnormalities were detected by DMSA study when compared to scars on IVP.
 When both studies were abnormal there was an excellent correlation on a site by site basis.
 Fever or systemic disorder was not a reliable sign to determine whether there was upper tract involvement with infection.
 The incidence of DMSA abnormalities in infants increased with high grade vesicoureteral reflux and decreased with low grade reflux.
 There was no significant difference in the incidence of abnormal kidneys between the infected and noninfected groups, suggesting that renal scarring may occur with sterile reflux.
",11
1872,"A continuous intravesical drug delivery system for the rat.
 We describe a self-contained system for the continuous infusion of drugs into the rat urinary bladder.
 A reversible model of hydronephrosis is used to prepare one renal unit for nephrostomy tube placement.
 An 0.8 mm.
 silastic nephrostomy tube is introduced into the hydronephrotic kidney via a 16 gauge angiocath.
 The nephrostomy tube is then connected to an Alzet mini osmotic pump which is implanted in a subcutaneous location.
 The ability of this system to deliver a continuous dose of a test agent into the bladder was evaluated.
 Pumps were filled with a 1% solution of methylene blue in phosphate buffered saline.
 Following pump implantation, urinary samples were collected on a daily basis and subsequently analyzed for their concentration of methylene blue.
 At the completion of the experiment, specimens of the kidney, ureter, and bladder were histologically examined.
 Results demonstrated an average of 102% recovery of the theoretically delivered dose over a 14-day period.
 Renal histology demonstrated chronic inflammatory changes at the site of nephrostomy tube placement.
 No upper or lower tract urothelial changes were identified.
 This model provides a system for the continuous delivery of drugs in the rat urinary tract and results in no histological alteration to the lower urinary tract.
",11
1873,"Determination of the coefficient of kinetic friction of urinary catheter materials.
 The coefficient of kinetic friction plays an important role in the biocompatibility of urinary catheters.
 A method for determination of the in vivo coefficient of kinetic friction is described that allows the comparison of the catheter-urethral interaction of the various materials used in the production of urinary catheters and the different types of lubricants.
",11
1874,"Radio-contrast enhancement of urinary tract stones.
 Most urologists treating stone disease with any method (ESWL, PCL, URS) have encountered problems of poor stone visualization with fluoroscopy.
 This difficulty to localize urinary tract (UT) stones or fragments may result in incomplete stone extraction, prolonged surgery and increased risk of recurrence and post-operative complications.
 We have sought and found means to increase the radioopacity of mineral UT stones by a simple pre-operative perfusion technique.
 The capacity of radioopacification has first been demonstrated in in vitro incubations of fragments of human mineral stones with aqueous solutions of barium, of the lanthanides and of the two natural actinides.
 Most of the incubations led to considerable radio-contrast enhancement and heavy metal incorporation, measured by X-ray fluorescence analysis.
 Dogs with implanted human stone fragments were used as an in vivo model.
 The UT were perfused through a retrograde pyelic catheter with heavy metal salts solutions, the ensuing radioopacification of the implanted UT-stones was estimated by abdominal radiographies and the metal incorporation was measured on the retrieved stones.
 Considerable radioopacity enhancement together with heavy metal incorporation was observed for the following elements: Sr, Ba and the lanthanides Gd and Yb.
 The pathological evaluation of the urothelial linings from animals treated with lanthanide salt showed no toxic effects.
",11
1875,"Cytostatic effects of suramin on prostate cancer cells cultured from primary tumors.
 Suramin is currently undergoing clinical trials as a chemotherapeutic agent for prostate cancer.
 The effects of suramin on cultured human epithelial cells derived from normal, benign hyperplastic, and malignant prostate tissues were examined.
 In serum-free medium, suramin inhibited the clonal growth of prostate cells at a half-maximal dose of approximately 10 micrograms/ml.
 Growth inhibition by suramin was completely reversible even after 24 hours of exposure.
 In conjunction, suramin did not alter cellular phenotype with regard to expression of keratins and prostate-specific antigens.
 Although suramin is reportedly an antagonist of growth factor-mediated mitogenesis, ten-fold excesses of growth factors did not appreciably suppress the cytostatic activity of suramin.
 In comparison to the activities of other possible chemotherapeutic agents, suramin would appear suboptimal because its inhibitory effects are reversible and it does not induce a terminally differentiated cellular phenotype.
",11
1876,"Chronic effects of focused electrohydraulic shock waves on renal function and hypertension.
 The chronic effects of focused electrohydraulic shock waves were studied in a minipig model.
 Fifteen animals underwent a unilateral nephrectomy and compensatory renal hypertrophy was allowed to take place over a minimum of six months.
 Baseline studies were then carried out consisting of 1) serum creatinine, blood urea nitrogen, and plasma renin levels 2) intra-arterial blood pressure measurement and 3) 3H-inulin clearance.
 Ten of the animals then underwent 8 shockwave treatments (2500 shocks per treatment), alternately to the upper and lower pole of the kidney, at two weeks intervals.
 A total of 20,000 shock waves were administered to each minipig over the four month period.
 The five control pigs underwent sham procedures.
 The renal function and blood pressure evaluations were then repeated.
 No significant decrease in renal function was noted in the experimental animals when compared to the controls.
 In addition, renin mediated hypertension was not observed despite the excessive number of total shock waves delivered to the kidney.
",11
1877,"Renal arterial duplex Doppler ultrasound in dogs with urinary obstruction.
 Recent clinical studies using duplex Doppler sonography identified an alteration in renal arterial blood flow in obstructed hydronephrotic kidneys that reportedly can be used to distinguish obstructive from nonobstructive collecting system dilatation.
 We attempted to verify these clinical findings and establish the temporal relationship of the alteration in the Doppler spectrum to the onset of urinary obstruction by evaluating surgically induced urinary obstruction in dogs.
 We performed laparotomies on 11 dogs, with the left ureter isolated and ligated in five dogs, and left intact in six dogs (control group).
 Duplex Doppler examination of the left renal arteries performed nine times during the first postoperative month identified a statistically significant difference (p less than .05) in the Doppler resistive index calculation between the two groups on days 1, 2, 4, and week 4.
 A resistive index discriminatory threshold of 0.7 (greater than 0.7, obstructed; less than 0.7, nonobstructed) produced a test sensitivity of 74% and specificity of 77%.
 We conclude from our study that renal arterial duplex Doppler sonography can detect a change in renal perfusion as a result of urinary obstruction and that this change can be detected as early as 24 hours after obstruction.
 However, high false-positive and false-negative rates may limit the ability of this modality to reliably distinguish obstructive from nonobstructive collecting system dilatation.
",11
1878,"The effect of radiation therapy and hyperthermia on a human prostatic carcinoma cell line grown in athymic nude mice.
 The effect of radiation and/or hyperthermia on a human prostatic carcinoma xenograft in athymic nude mice was investigated.
 A human prostate carcinoma subline (1-LN-PC-3-1A) was inoculated subcutaneously in the thigh of male athymic nude mice.
 When tumors reached a size of approximately 200 mm.3, they were treated with either radiation (X) or hyperthermia (H) alone, or in combination (X + H).
 In the combined treatment, hyperthermia was delivered immediately after radiation exposure.
 Comparison of the time required to reach twice the tumor volume observed at the time of treatment was used to define therapeutic impact on tumor growth.
 The combined treatment resulted in median tumor volume doubling time of 35.5 days, compared to 18 days and 25.5 days, respectively, for hyperthermia or radiation alone.
 Analysis of tumor doubling time using a proportional hazards regression indicates that under the conditions of this experiment, the effect of radiation and hyperthermia for 1-LN-PC-3-1A tumors is additive.
 The impact of this treatment regimen in the management of prostatic cancer requires further investigation.
",11
1879,"Image guided localized 31P magnetic resonance spectroscopy of acute urinary tract obstruction.
 Using 31P magnetic resonance spectroscopy, localized spectroscopy and magnetic resonance imaging we studied effects of acute urinary obstruction in the in vivo pig kidney.
 Accumulation of urine in the renal pelvis and collecting ducts resulted in the appearance of a new peak in the localized phosphorus spectra originating in the renal papilla, resonating at 3.43 to 4.56 ppm.
 This was inorganic phosphate with a pH of 5.60 to 6.79 (urine pH).
 Imaging did not show any dilatation of renal pelvis.
 There was a significant time dependent fall in renal [ATP] during urinary obstruction followed by a rapid ""overshoot"" of [ATP] and disappearance of the phosphate peak after release of obstruction.
 Possible mechanisms for this phenomenon are discussed.
 We conclude that 31P magnetic resonance spectroscopy provides early evidence of urinary obstruction in vivo and could be of value in clinical diagnosis.
",11
1880,"Preliminary experience with the pulsed dye laser for treatment of urolithiasis.
 We report our initial experience using the pulsed dye laser in 26 patients with urolithiasis.
 The patients ranged in age from 27 to 82 years; 11 patients were female and 15 were male.
 Of the 26 patients, 4 stones were in the kidney, 21 were in the ureter, and one was in the bladder.
 Surgical time ranged from 32 to 130 minutes.
 All patients were treated under spinal or general anesthesia.
 The size of ureteral stones ranged from 0.2 to 1.5 cm, and the renal stones 3.0 to 4.0 cm.
 Chemical analysis of the stones was not available on all patients, but when available, chemical analysis revealed the stones to be calcium monohydrate, calcium dihydrate, or struvite.
 The use of the Candela miniscope in 11 patients permitted access without ureteral dilation.
 In 19 patients, ureteral stents were placed.
 One patient suffered a ureteral perforation.
 Success was defined as adequate disintegration of the stone for passage of the fragments without the necessity of a secondary procedure.
 Using this criterion, 22 of 26 patients were successfully treated for an overall success rate of 85%.
",11
1881,"Diagnosis of heterozygous states for adenine phosphoribosyltransferase deficiency based on detection of in vivo somatic mutants in blood T cells: application to screening of heterozygotes.
 An accurate diagnosis of heterozygotes for autosomal recessive disorders with unknown mutations can be difficult.
 Using a unique phenomenon occurring in vivo, we designed a method for the diagnosis of heterozygotes for adenine phosphoribosyltransferase (APRT) deficiency which makes way for a qualitative distinction between normal and heterozygous subjects.
 We cultured peripheral blood mononuclear cells with 2,6-diaminopurine, an APRT-dependent cytotoxin, to search for in vivo mutational cells.
 Fifteen putative heterozygotes examined were found to possess such mutant cells at rather high frequencies; thus, a false negative diagnosis is unlikely.
 The analysis of genomic DNA in 82 resistant clones from two of the heterozygotes clarified that 64 (78%) had lost the germinally intact alleles.
 Thirteen members of APRT-deficient families were examined; eight proved to be heterozygotes.
 Among 425 individuals from two separate residential areas of Japan, two heterozygotes were found.
 The authenticity of the heterozygosity was validated by two separate methods for the two heterozygotes; hence, a false positive diagnosis can be ruled out.
 Our data showed a calculated heterozygote frequency of 0.47% (95% confidence limits; 0.05%-1.7%), a value compatible with that (1.2%) calculated from data concerning the incidence of 2,8-dihydroxyadenine urolithiasis.
 This novel genetic approach for identifying heterozygotes is now being tested to search for other enzyme deficiencies in humans.
",11
1882,"Pharmacokinetics and bioavailability of intravenous-to-oral enoxacin in elderly patients with complicated urinary tract infections.
 The pharmacokinetics of oral fluoroquinolone antibiotics in normal volunteers have been studied extensively; however, limited patient data exist.
 Enoxacin steady-state pharmacokinetics and bioavailability were determined following repeated 400-mg intravenous (i.v.) and oral dosing by using compartmental and noncompartmental methods in 10 elderly (mean age, 73.8 years) men with complicated urinary tract infections.
 Average peak enoxacin concentrations following i.v.
 and oral dosing were 8.15 and 5.45 mg/liter, respectively.
 Mean values for major pharmacokinetic parameters (noncompartmental) were similar following i.v.
 and oral administration, respectively: area under the concentration-time curve from 0 to 12 h, 47.6 and 41.0 mg.h/liter; volume of distribution or volume of distribution/bioavailability, 1.61 and 1.99 liters/kg; total body clearance or total body clearance/bioavailability, 2.58 and 3.01 ml/min per kg; and half-life, 8.2 and 9.1 h.
 Parameters from analysis of enoxacin plasma concentration data by using a two-compartment pharmacokinetic model also revealed marked similarities between the two administration routes.
 Enoxacin was highly bioavailable (mean, 86.97%) following oral administration.
",11
1883,"Distal urethral electrical conductance (DUEC)--a preliminary assessment of its role as a quick screening test for incontinent women.
 Measurement of distal urethral electrical conductance (DUEC) has been used to detect the movement of urine along the distal urethra.
 DUEC was used as a screening test in 100 women attending the urodynamic clinic with incontinence and in the 33 women who voided over 250 ml, the findings correlated well with subsequent urodynamic diagnosis of urethral sphincter incompetence and detrusor instability.
",11
1884,"Regulation of pulsatile luteinizing hormone secretion in experimental uremia.
 Previous studies have shown that male rats with experimental uremia manifest profound suppression of circulating LH and testosterone levels, yet, paradoxically, after castration gonadotropin levels are elevated greatly above those of nonuremic castrate control rats.
 To investigate further this phenomenon, we characterized pulsatile LH secretion in experimental uremia.
 Mature orchidectomized male Wistar rats with subtotal nephrectomy demonstrated a 43% reduction of LH pulse frequency, but a 157% increase in pulse amplitude and a 335% increase in mean LH levels compared with sham-operated controls.
 All pulse parameters were highly correlated with plasma creatinine (r = 0.53-0.75).
 To determine the mechanism of the increased pulse amplitude, we tested responsiveness of the postcastration uremic pituitary to exogenous GnRH (0.01-10 micrograms/kg) in a Latin square design.
 Plasma LH response was linearly related to the logarithm of the GnRH dose in uremic and control rats, but was markedly increased in uremic rats.
 We conclude that the uremia causes decreased LH pulse frequency independent of testicular feedback.
 Pituitary hypersensitivity to GnRH magnifies LH pulse amplitude and thereby is the major factor causing the paradoxical LH hyperelevation after castration.
",11
1885,"Small artery resistance increases during the development of renal hypertension.
 Vascular pressures were measured in the principal (A1) arteriole and in upstream small arteries of the rat cremaster muscle to investigate vascular resistance changes associated with one-kidney, one clip Goldblatt hypertension.
 Pressure measurements were made at a proximal and distal site of each vessel using a servonull micropipette system.
 Vessel diameters were measured using video microscopy.
 A1 arteriole and external spermatic artery diameters were both decreased after 2 and 4 weeks of hypertension.
 Mean arterial pressure was elevated after 2 weeks of hypertension (106 +/- 4 mm Hg versus 140 +/- 5 mm Hg).
 Likewise, vascular pressures were elevated at every site: pudicepigastric artery (36%), external spermatic artery (47%), and A1 arteriole (38%).
 The pressure drop along the external spermatic artery was increased (87%) after 2 weeks of hypertension.
 Mean arterial pressure was further elevated from 2-4 weeks of hypertension (105 +/- 4 mm Hg versus 162 +/- 7 mm Hg) but only the proximal pudic-epigastric artery pressure was further elevated during this time from 2 to 4 weeks (131 +/- 5 mm Hg versus 147 +/- 7 mm Hg) of hypertension development.
 This was associated with an increased pressure drop (87%) along the artery compared with the situation at 2 weeks.
 These data indicate that small arteries upstream from the microcirculation contribute significantly to the increase in vascular resistance during hypertension.
 In addition, these data indicate that the increases in small artery resistance do not develop uniformly throughout all vessel branches.
",11
1886,"Renal nerves modulate renin gene expression in the developing rat kidney with ureteral obstruction.
 Chronic unilateral ureteral obstruction (UUO) in newborn rats activates renin gene expression in the obstructed kidney, and increases renin distribution along afferent glomerular arterioles in both kidneys.
 To investigate the role of the renal nerves in this response, 2-d-old Sprague-Dawley rats were subjected to UUO or sham operation.
 Chemical sympathectomy was performed by injection of guanethidine, whereas, control groups received saline vehicle.
 At 4-5 wk, renal renin distribution was determined by immunocytochemistry, and renin mRNA levels were determined by Northern blot hybridization.
 Compared to the saline-treated rats with UUO, renin remained localized to the juxtaglomerular region in both kidneys of rats with UUO receiving guanethidine (P less than 0.05).
 Moreover, renin mRNA levels were eightfold lower in obstructed kidneys of rats receiving guanethidine than in those receiving saline.
 Additional groups of rats with UUO were subjected to unilateral mechanical renal denervation: renin gene expression in the obstructed kidney was suppressed by ipsilateral but not by contralateral renal denervation.
 These findings indicate that either chemical or mechanical denervation suppressed the increase in renin gene expression of the neonatal kidney with ipsilateral UUO.
 We conclude that the renal sympathetic nerves modulate renin gene expression in the developing kidney with chronic UUO.
",11
1887,"Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation.
 Mesangial cell proliferation is common in glomerulonephritis but it is unclear if proliferation is associated with any in vivo alteration in phenotype.
 We investigated whether mesangial of mesangial proliferative nephritis induced with antibody to the Thy-1 antigen present on mesangial cells.
 At day 3 glomeruli displayed de novo immunostaining for alpha-smooth muscle actin in a mesangial pattern, correlating with the onset of proliferation, and persisting until day 14.
 An increase in desmin and vimentin in mesangial regions was also noted.
 Immunoelectron microscopy confirmed that the actin-positive cells were mesangial cells, and double immunolabeling demonstrated that the smooth muscle actin-positive cells were actively proliferating.
 Northern analysis of isolated glomerular RNA confirmed an increase in alpha and beta/gamma actin mRNA at days 3 and 5.
 Complement depletion or platelet depletion prevented or reduced proliferation, respectively; these maneuvers also prevented smooth muscle actin and actin gene expression.
 Studies of five other experimental models of nephritis confirmed that smooth muscle actin expression is a marker for mesangial cell injury.
 Thus, mesangial cell proliferation in glomerulonephritis in the rat is associated with a distinct phenotypic change in which mesangial cell assume smooth muscle cell characteristics.
",11
1888,"Percutaneous needle biopsy preceding preoperative chemotherapy in the management of massive renal tumors in children.
 While the National Wilms' Tumor Study (NWTS) Group in the United States puts an emphasis on accurate staging and histology before any therapy is given for Wilms' tumor, the International Society of Pediatric Oncology (SIOP) in Europe focuses on preoperative therapy and safer surgery.
 Our current approach combines the benefits of both policies in the management of massive renal tumors in children.
 In seven consecutive patients we first obtained a percutaneous posterior needle biopsy to obtain adequate tissue for histology, and proceeded with preoperative chemotherapy with vincristine and dactinomycin until tumor shrinkage was sufficient.
 Tumor removals were feasible and uneventful.
 At the time of operation, two tumors were found to be totally or almost totally necrotic.
 In the others, which still included viable tumor, the histology corresponded well to the needle biopsy findings.
 One case with unfavorable histology and one with rhabdoid sarcoma would have been missed and given suboptimal therapy without the primary needle biopsy.
 As possible biopsy-related complications, subcapsular intratumoral bleeding was recognized in two patients.
 We conclude that percutaneous posterior needle biopsy is safe and yields definite, detailed histology in massive renal tumors in children.
 Preoperative chemotherapy facilitates surgery in these patients.
",11
1889,"Molecular characterization of a major nephritogenic domain in the autoantigen of anti-tubular basement membrane disease.
 Anti-tubular basement membrane (alpha TBM) disease is a form of primary interstitial nephritis mediated by autoimmune T cells and alpha TBM antibodies.
 In mice and humans the nephritogenic immune response is directed to a glycoprotein (3M-1) found along the proximal tubule of the kidney.
 We have isolated cDNAs from an expression library that encodes for the common framework domain of the 3M-1 antigen.
 This common domain was once related evolutionarily to a family of intermediate filament-associated proteins.
 Northern hybridization revealed that all isoforms of 3M-1 range between 1700 and 1900 base pairs and in situ hybridization studies indicate that transcripts are found in tubular epithelium.
 Candidate peptide fragments were deduced and synthesized from the sequence encoding this common framework domain, and one of the peptide residues was able to bind a monoclonal 3M-1-reactive alpha TBM antibody, stimulate the growth of 3M-1-reactive helper T cells, and induce nephritogenic effector T cells capable of producing interstitial nephritis.
 Our results indicate that a unique, immunodominant region of the 3M-1 antigen is an informative participant in the emergence of autoimmune injury to certain basement membranes.
",11
1890,"Early detection program for prostate cancer: results and identification of high-risk patient population.
 Three hundred sixty-two men underwent transrectal ultrasound of the prostate (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen (PSA) determination as part of an early detection program for prostate cancer.
 Thirty-seven (10%) cancers were detected.
 DRE had the highest sensitivity and specificity, 89 percent and 84 percent, respectively.
 TRUS and PSA had comparable sensitivities (84% and 81%) and specificities (82% and 82%).
 The positive predictive values of DRE, TRUS, and PSA determination were 39 percent, 35 percent, and 33 percent, respectively.
 We found a cancer detection rate of 16 percent among patients with symptoms of bladder outlet obstruction and 5 percent in patients without these symptoms.
 The detection rate was 36 percent for physician-referred patients and 3 percent for self-referred patients.
 This suggests to us that at the present time the best utilization of medical resources to increase prostate cancer detection is to educate men to have annual medical evaluations by primary-care physicians who are encouraged to incorporate risk assessment and screening DRE as part of their routine practice.
 Any man with either abnormal findings on examination or increased risk should be referred to a urologist for further evaluation.
",11
1891,"Incontinence management scale for elderly inpatient men.
 For many elderly inpatients, urinary incontinence cannot be successfully treated and the management objective is identifying a suitable method for containment of urine loss.
 In elderly inpatient men, an external catheter is utilized in many cases for incontinence management.
 The role of the severity of incontinence and the use of an external catheter was investigated in 66 elderly inpatient men.
 Quantitative incontinence measurements showed incontinent patients having an external catheter had approximately 6.3 (SD = 2.5) episodes per day compared with 3.2 (SD = 2.0) episodes per day in the noncatheter incontinent patients.
 The clinical management method used in these patients was associated with the measured severity of incontinence.
",11
1892,"Endoscopic treatment of vesicoureteral reflux in children with neurogenic bladders.
 Endoscopic subureteral injection of Teflon was performed in 12 children (20 ureters) with neurogenic bladders and vesicoureteral reflux (grades III-IV).
 Follow-up evaluation by ultrasonography and voiding cystourethrogram at three-month intervals up to two years revealed successful correction of the reflux in 70 percent of the ureters.
",11
1893,"Pediatric testicular tumors: the Johns Hopkins experience.
 Testicular neoplasms constitute 1 percent of all childhood malignancies and rank eighth in childhood cancer mortality.
 From 1970 to 1988, 25 testicular tumors in children eighteen years and under were seen.
 The majority of the patients were white (88%).
 Pathologic analysis of the tumors revealed that 68 percent were germinal and 32 percent were nongerminal.
 Staging was undertaken in all patients with serum markers, chest x-ray film, and computerized tomography scans or lymphangiography.
 All patients underwent radical orchiectomy, and further therapy was given dependent on tumor type and stage.
 The survival among this cohort was excellent, with only 3 patients succumbing to their disease.
 Detailed results of treatment, and approaches to avoid excess treatment morbidity are reviewed.
",11
1894,"Causes of post-prostatectomy retention.
 Forty-eight patients in urinary retention following prostatectomy underwent urodynamic evaluation.
 Fifteen patients (31%) were found to have persistent residual obstruction, while 14 patients (29%) had detrusor hyporeflexia.
 In 9 patients (19%) a combination of outflow obstruction and detrusor hyporeflexia was demonstrated.
 In 6 patients (13%), urinary retention was due to compromised mental status.
 No abnormality was detected in remaining 4 patients (8%) on urodynamic evaluation.
 For proper evaluation of unsatisfactory voiding after prostatectomy cystoscopy is of limited value while urodynamic testing is essential.
",11
1895,"Stripping the fetal membranes at term. Is the procedure safe and efficacious?
 A prospective, randomized investigation was undertaken in a low-risk group of pregnant women at term (38-42 weeks' gestation) to determine if stripping the fetal membranes would safely result in earlier delivery.
 Ninety-nine patients entered the study; 51 underwent stripping of the membranes, and 48 controls did not.
 Fifty-nine percent of the patients in the stripped group delivered within one week as compared to 21% in the nonstripped group (P less than .0003).
 Two pregnancies in the stripped group advanced beyond 42 weeks' gestation as compared to six pregnancies in the control group (P = .12).
 A single gravida in the control group developed chorioamnionitis during labor.
 There were no other infections or other complications.
 Stripping the membranes was associated with earlier delivery and was not associated with any complications.
",12
1896,"Coexistence of an intrauterine pregnancy with both an ectopic pregnancy and salpingitis in the right fallopian tube. A case report.
 The current epidemic of pelvic inflammatory disease and recent advances in gynecologic techniques have resulted in a marked increase in the incidence of combined pregnancy.
 In the case reported on here the coexistence of an intrauterine pregnancy with acute salpingitis and an ectopic gestation in the same fallopian tube led to early diagnostic errors.
",12
1897,"Transcervical balloon tuboplasty. A multicenter study 
 Transcervical balloon tuboplasty represents a noninvasive technique to treat proximal tubal occlusion.
 In a multicenter study, 77 women with confirmed bilateral proximal tubal occlusion underwent the procedure.
 In 71 patients (92%), at least one proximally obstructed fallopian tube was recanalized.
 Concomitant distal bilateral tubal occlusions were diagnosed after successful proximal tubal balloon recanalizations in 13 patients (17%).
 In the remaining 64 patients, 22 clinical pregnancies (34%) have been confirmed during a median follow-up period of 12 months.
 Among those, 17 (77%) resulted in normal deliveries and five (23%) resulted in a first-trimester miscarriage.
 One patient was diagnosed with an ectopic pregnancy.
 Among 25 patients who had not conceived within 6 months of the procedure, 17 (68%) demonstrated continuing tubal patency on repeated hysterosalpingogram.
 We conclude that transcervical balloon tuboplasty is a safe outpatient technique that may represent an alternative to in vitro fertilization or microsurgical reanastomosis of fallopian tubes.
",12
1898,"Hypothesis: inhibition of endothelium-derived relaxing factor by haemoglobin in the pathogenesis of pre-eclampsia 
 Although the aetiology of pre-eclampsia is unknown, haemodynamic studies suggest that many of the clinical findings may be explained by a generalised vasoconstrictive disorder and abnormal endothelial cell function.
 Vasoconstriction may be attributed to the increased concentrations of haemoglobin found in pre-eclampsia compared with normal pregnancy.
 Free haemoglobin may be derived from haemolysis and placental haemorrhage and, at concentrations known to be present in pre-eclampsia, vasodilatation mediated by endothelium-derived relaxing factor is inhibited.
 Infusion of oxyhaemoglobin into human coronary arteries inhibits acetylcholine-induced vasodilatation.
 We suggest that an increased free haemoglobin concentration is the cause of vasoconstriction in pre-eclampsia.
",12
1899,"A preliminary report on oocyte donation extending reproductive potential to women over 40 
 BACKGROUND.
 Fertility in women 40 years of age or older is decreased, and in those with ovarian failure it is thought to be irrevocably lost.
 The donation of oocytes to young (less than 35 years old) women with ovarian failure has allowed many considered infertile a chance to become pregnant.
 In these women gonadal hormone replacement results in an endometrium receptive to implantation.
 It is not known whether the endometrial response to such replacement is decreased in women over the age of 40.
 METHODS.
 To test the efficacy of oocyte donation to older women, we enrolled seven women 40 to 44 years old with ovarian failure in a trial of hormone replacement and embryo transfer, using oocytes obtained from women undergoing ovarian hyperstimulation solely for gamete donation.
 RESULTS.
 Seven stimulated cycles in the donors that were synchronized with nine cycles in the recipients resulted in eight embryo transfers.
 Five viable pregnancies were established, one with twins.
 A sixth pregnancy ended in miscarriage.
 Five normal infants were delivered by cesarean section, and one stillborn infant was delivered vaginally.
 The outcomes were compared with those in women under the age of 40 with ovarian failure who were also participating in our donor-oocyte program and in infertile ovulating women 40 or older who were undergoing standard in vitro fertilization.
 No significant differences in rates of implantation or ongoing pregnancy were noted in older women as compared with younger women receiving donated embryos.
 These rates, however, were higher than the rates in the infertile ovulating women of similar age who were undergoing standard in vitro fertilization.
 CONCLUSIONS.
 These preliminary results suggest that the endometrium retains its ability to respond to gonadal steroids and provides a receptive environment for embryo implantation and gestation even in older women.
",12
1900,"Premature rupture of membranes at term in nulliparous women: a hazard?
 One hundred five consecutive women with premature rupture of the membranes (PROM) at term were managed expectantly for at least 24 hours.
 Seventy-six went into spontaneous labor, of whom 38 were augmented with oxytocin.
 Twenty-nine had labor induced.
 Subjects who delivered during the same study interval after artificial rupture of the membranes served as controls.
 There were no statistically significant differences in the frequency of amnionitis, endometritis, cystitis, neonatal infection, low Apgar score, low cord arterial blood pH, instrumental delivery, or cesarean delivery.
 Morbidity was seen most often in induced labor whether or not the membranes were ruptured for a long time.
 It is concluded that expectant management of PROM at term does not increase perinatal morbidity.
",12
1901,"Zinc status in women with premature rupture of membranes at term.
 Zinc concentrations were measured by atomic absorption spectrometry in whole blood, scalp hair, pubic hair, and colostrum from patients at term with and without premature rupture of membranes (PROM).
 A maternal zinc index was established for each patient, expressed as an average ranking of the four determinations.
 The mean +/- SD value of the maternal zinc index in patients with PROM was significantly lower than in patients without this complication (4.33 +/- 1.18 versus 5.97 +/- 1.39, respectively; P = .0002).
 The inverse relationship between maternal zinc index and parity was statistically significant (r = -0.61; P = .04).
 These results suggest that the subnormal tissue zinc content in pregnancy may play a role as a causative factor in PROM at term.
",12
1902,"Real-time microcomputer-based analysis of spontaneous and augmented labor 
 In an attempt to develop a reproducible, objective measure of adequate uterine activity in labor, real-time measurements of intrauterine pressure amplitude and contraction frequency, interval, duration, and integral were made in 54 patients, 11 of whom received oxytocin augmentation.
 We determined the active pressure integral required per centimeter of cervical dilatation, expressed in kPa seconds, and the mean active pressure, expressed in kPa.
 The augmented group had a significantly higher mean active pressure integral per centimeter than those in normal labor (P less than .01).
 There was a trend, which did not reach statistical significance, for subjects who required oxytocin augmentation of labor to develop a higher mean active pressure than those in normal labor.
 However, the correlation of any uterine contractility index (Montevideo units, Alexandria units, mean active pressure) with progress in labor was poor.
 We conclude that women with dysfunctional labor require more uterine activity for progress in labor than women with normally progressing labor, and that the computer-derived ""area under the curve"" is not a better predictor of labor progress than Montevideo units.
",12
1903,"Accuracy and safety of transvaginal sonographic placental localization.
 Transvaginal sonographic localization of the placenta was performed in 100 patients suspected of having placenta previa.
 Except in one patient, the diagnosis was confirmed at cesarean delivery in all cases of placenta previa found by sonography before delivery, resulting in a 93.3% predictive value of a positive test.
 The predictive value of a negative test was 97.6%; in two patients a low-insertion placenta diagnosed by sonography was found to be a placenta previa at delivery.
 The sensitivity and specificity of the technique were 87.5 and 98.8%, respectively.
 Although in some instances transvaginal sonography was performed during vaginal hemorrhage, aggravation of bleeding was never observed.
 Transvaginal sonographic localization of the placenta proved to be an accurate and safe diagnostic procedure.
",12
1904,"Effect of peritoneal fluid from endometriosis patients on endometrial stromal cell proliferation in vitro.
 Late proliferative phase endometrial stromal cells grown in short-term culture were used as a model for the stromal component of endometriotic implants.
 Cells were grown in medium alone and in medium supplemented by 5, 10, and 20% concentrations of the cell-free fractions of peritoneal fluid obtained from patients with and without endometriosis.
 Nine fluid-sample pairs were matched based on the presence or absence of endometriosis at laparoscopy and the similarity of peritoneal fluid estradiol concentrations.
 Stromal cell proliferation as reflected by 3H-thymidine incorporation during sequential cell harvests over 72 hours was greater for cells exposed to endometriosis peritoneal fluid than for those exposed to non-endometriosis peritoneal fluid.
 This reached statistical significance with exposure to peritoneal fluid concentrations of 10 and 20% (P less than .05).
 A linear dose-response relationship between 3H-thymidine incorporation and peritoneal fluid concentration could be derived only for stromal cells exposed to fluid samples obtained from endometriosis patients (r = 0.51; P less than .001).
 In addition, proliferation over 72 hours was significantly greater for cells grown in 20% endometriosis peritoneal fluid than for those grown in nutrient medium alone (P less than .001).
 These data imply that factor(s) secreted into the peritoneal fluid of endometriosis patients may play a role in the proliferation or maintenance of disease implants.
",12
1905,"Antepartum and intrapartum events in women exposed in utero to diethylstilbestrol.
 Using a retrospective cohort design, we analyzed the effects of intrauterine diethylstilbestrol (DES) exposure on various antepartum and intrapartum events.
 Gravidas exposed to DES had a higher likelihood of being delivered abdominally, undergoing manual removal of the placenta, and hemorrhaging in the postpartum period.
 The increased risk for these events remained after controlling for age, race, and parity.
 We also constructed labor curves in DES-exposed women by plotting cervical dilation against time.
 The curves were similar for nulliparous DES-exposed women and nulliparous controls, but DES-exposed parous women experienced prolonged labors.
 These findings suggest that, in addition to the well-known adverse effects of intrauterine DES exposure, the interaction between the uterus and placenta is altered in some DES-exposed patients.
",12
1906,"Experimental and clinical studies with radiofrequency-induced thermal endometrial ablation for functional menorrhagia.
 A method of ablating the endometrium has been introduced into clinical practice that uses radiofrequency electromagnetic energy to heat the endometrium, using a probe inserted through the cervix.
 Preliminary studies suggest that over 80% of patients treated will develop either amenorrhea or a significant reduction in flow.
 The advantages of radiofrequency endometrial ablation over laser ablation or resection are the avoidance of intravascular fluid absorption, simplicity (no special operative hysteroscopic skills are required), speed of operation, and reduced cost compared with the Nd:YAG laser.
 In this paper, we describe the experimental studies performed during development of this new technique.
",12
1907,"Preoperative angiographic uterine artery embolization in the management of cervical pregnancy.
 The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of extensive hemorrhage during attempted evacuation.
 In some cases, hysterectomy has been the necessary treatment to control bleeding.
 We report two cases of cervical pregnancy detected by ultrasound.
 Before pregnancy termination, the uterine arteries were successfully embolized using angiographic techniques.
 As a result, surgical evacuation was performed with minimal hemorrhage; hysterectomy was not required and the patients' potential fertility was retained.
",12
1908,"Successful treatment of cervical pregnancy with oral etoposide.
 Cervical ectopic pregnancy is an uncommon entity associated with significant morbidity and devastating effects on future fertility.
 A woman with a cervical gestation with quantitative serum beta-hCG levels higher than 46,000 mIU/mL and fetal cardiac activity on ultrasound was treated successfully with one course of oral etoposide, a fetocidal agent, which avoided operative intervention and preserved the patient's fertility.
",12
1909,"Pregnancy associated with Friedreich ataxia.
 The pregnancy of a woman with Friedreich ataxia was complicated by the onset of preterm labor and preeclampsia.
 Administration of magnesium sulfate (MgSO4.7H2O) in the usual intravenous dosage resulted in the dramatic development of profound motor weakness and respiratory distress.
 Magnesium acts to antagonize the action of acetylcholine at the motor end plate of the neuromuscular junction and may operate synergistically with underlying neuromuscular disorders.
 Therefore, the use of magnesium sulfate in patients with Friedreich ataxia and other similar neurodegenerative diseases is contraindicated.
",12
1910,"Fetal levels of tobramycin following maternal administration.
 A single dose of tobramycin 2 mg/kg was given intravenously to a woman who presented a 22-week heterotopic pregnancy with both intrauterine and ovarian gestations and two living fetuses.
 After excision of the adnexum, tobramycin levels were measured in the maternal serum and in the fetal fluids and tissues.
 Antibiotic levels were especially high in the fetal spleen and kidney.
",12
1911,"The UCLA-University of Utah epidemiologic survey of autism: prenatal, perinatal, and postnatal factors.
 In a recent epidemiologic survey conducted in Utah, 241 autistic patients (DSM-III criteria) were found.
 Medical records of 233 autistics were surveyed for the presence of 36 potentially pathologic prenatal, perinatal, and postnatal factors.
 These results were compared with those of an identical survey of 62 of their nonautistic siblings, with the results of four previously published surveys, and with normative data.
 No potentially pathologic factor or group of factors occurred significantly more frequently among the autistic patients.
 Also, previous observations of significant differences in the occurrence of certain factors in the histories single vs multiple siblings with autism were not confirmed, with the exception of increased viral-type illness during gestation in single-incidence cases.
 Thus, the etiology of the brain pathology that characteristically disrupts normal development and produces the syndrome of autism remains obscure.
 Other data from the epidemiologic survey, however, suggest that the role of genetic factors needs to be explored further.
",12
1912,"Barrier contraceptive methods and preeclampsia.
 Recent investigations have suggested that women who use barrier methods of contraception may be at increased risk for preeclampsia.
 We used data from two prospective pregnancy studies to examine the relationship between contraceptive use before conception and preeclampsia.
 The preeclampsia rates among women using barrier contraceptives were not significantly higher than the rates in women using nonbarrier contraceptives or the rates in women using no contraceptives in either study.
 The odds ratios for preeclampsia in barrier contraceptive users in the two studies were 0.89 (95% confidence interval [Cl], 0.71 to 1.12) and 0.85 (95% Cl, 0.49 to 1.45) compared with nonbarrier contraceptive users and 0.91 (95% Cl, 0.71 to 1.16) and 0.81 (95% Cl, 0.48 to 1.35) compared with women using no contraceptives.
 After adjusting for other risk factors, we found no association between preeclampsia and barrier contraceptive use.
 Additional studies are needed to resolve this issue; however, we would recommend that women not be advised to avoid barrier contraceptives unless more data linking their use to preeclampsia appear.
",12
1913,"Umbilical artery Doppler velocimetry as a labor admission test.
 Doppler ultrasound of the umbilical artery flow velocity waveform was studied prospectively as an admission test at the labor ward.
 Recordings were made in 575 women in various stages of labor before, during, and after uterine contractions, and evaluated in relation to intrapartum and fetal outcome variables.
 No association was found between abnormal flow velocity waveforms and cord complications, meconium-stained amniotic fluid, or abnormal fetal heart rate tracing, nor was there any association with operative delivery for fetal distress or low Apgar scores at 1 and 5 minutes.
 Small for gestational age fetuses had significantly more abnormal flow velocity waveforms than appropriate for gestational age fetuses, and so had those with umbilical artery acidemia compared with those with normal pH.
 The results indicate that Doppler recording of the umbilical artery flow velocity waveform as an admission test at the labor ward is not a good predictor of fetal distress in an unselected population.
",12
1914,"Clinical and pathologic correlation of endometrial cavity fluid detected by ultrasound in the postmenopausal patient.
 A registry of ultrasound procedures spanning nearly 5 years was searched retrospectively to discover cases of endometrial cavity fluid collections in postmenopausal women.
 Twenty cases were identified; all medical records were available for review.
 One patient was lost to follow-up.
 Seventeen patients had surgical procedures: 11 had only a D&C, and six had a primary evaluation of laparotomy with removal of the uterus and adnexa.
 Five women had cancer (two ovarian, one tubal, one endometrial, and one cervical); eight women had benign gynecologic conditions, including uterine fibroids (five), ovarian serous cystadenoma (two), and cervical dysplasia (one).
 There were two cases of apparent subclinical pyometra.
 Five women had endometrial pathology consistent with prescribed hormone therapy for breast cancer (four) or endometrial hyperplasia (one).
",12
1915,"Cocaine abuse is associated with abruptio placentae and decreased birth weight, but not shorter labor 
 Many of our patients report having ingested cocaine hoping to decrease the duration of labor.
 We reviewed the computerized records of 592 women who abused cocaine.
 Compared with 4687 controls, women who ingested cocaine were older and had higher parity.
 Birth weight, birth weight percentile, and gestational age at delivery were significantly decreased among their neonates, and the incidence of abruptio placentae was nearly doubled among these women.
 Although these factors tend to shorten labor, the total duration of labor was not significantly different between the two groups.
 These data add to the accumulating evidence that cocaine abuse is associated with increased obstetric morbidity, but do not support the belief that cocaine shortens labor.
",12
1916,"Vulvar Paget disease: fluorescein-aided visualization of margins.
 Two women with extramammary Paget disease of the vulva were given fluorescein intravenously in order to visualize disease margins with the use of an ultraviolet light.
 As a diagnostic modality, the technique was found to have a positive predictive value of 97.4% and a negative predictive value of 99.9%.
 The accuracy of the fluorescein technique was compared with gross visualization using a histologic mapping technique.
 A total of 2424 fields were mapped and the predictive accuracy of each test was determined.
 A chi 2 test demonstrated fluorescein visualization to be a significantly better predictor of a disease state.
 Fluorescein visualization is suggested as an adjunct to surgical management of patients with primary vulvar Paget disease.
",12
1917,"Successful use of gamete intrafallopian transfer does not reverse the decline in fertility in women over 40 years of age.
 To assess the impact of assisted reproductive technologies on the potential fertility of older women, we report our experience with gamete intrafallopian transfer (GIFT) in a large number of women 40 years of age and older.
 One hundred twenty-two GIFT cycles were initiated in 59 women over 18 months.
 Seventy-three tubal transfers were performed, resulting in seven clinical pregnancies, a rate of 9.6% per transfer.
 This contrasts with a 27.3% clinical pregnancy rate per transfer in women under 40.
 Thus, older patients require thorough counseling regarding the decreased likelihood of success despite the use of assisted reproductive technologies.
",12
1918,"Sensitivity and specificity of screening for Down syndrome with alpha-fetoprotein, hCG, unconjugated estriol, and maternal age [published erratum appears in Obstet Gynecol 1991 May;77(3):462] 
 The sensitivity and specificity of maternal serum screening for Down syndrome with different biochemical markers were evaluated.
 Detection rates with different combinations of maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (uE3) were established by retrieving and analyzing 54 serum specimens from women with confirmed Down syndrome pregnancies, compared with 657 specimens from women with normal outcomes.
 With a risk cutoff of 1:270 at the second trimester, the detection rate with MSAFP, hCG, and uE3 was two to three times higher than with MSAFP alone.
 With all three markers, the detection rate for Down syndrome increased from 50 to 77% as maternal age increased, and was 60% in a representative screened population.
 If uE3 was omitted, the detection rate decreased from 60 to 48%.
 One thousand women were screened prospectively, either with MSAFP or with all three markers prospectively, either with MSAFP or with all three markers and 4.1% with MSAFP.
 With the three markers, the positive predictive value for Down syndrome was 2.2% overall and as high as 5.9% in older women.
 Therefore, the addition of hCG and uE3 to the maternal serum screen increases the positive predictive value by 50-300%, depending on maternal age.
 These results confirm the efficacy of screening for Down syndrome using maternal age and three serum markers.
",12
1919,"Factors associated with postpartum hemorrhage with vaginal birth.
 A case-control study was performed to study risk factors for postpartum hemorrhage.
 Cases of hemorrhage were defined by a hematocrit decrease of 10 points or more between admission and post-delivery or by the need for red-cell transfusion.
 Patients with antenatal bleeding were excluded.
 Among 9598 vaginal deliveries, postpartum hemorrhage occurred in 374 cases (3.9%).
 Three controls were matched to each case and multiple logistic regression was used to control for covariance among predictor variables.
 Factors having a significant association with hemorrhage were prolonged third stage of labor (adjusted odds ratio 7.56), preeclampsia (odds ratio 5.02), mediolateral episiotomy (4.67), previous postpartum hemorrhage (3.55), twins (3.31), arrest of descent (2.91), soft-tissue lacerations (2.05), augmented labor (1.66), forceps or vacuum delivery (1.66), Asian (1.73) or Hispanic (1.66) ethnicity, midline episiotomy (1.58), and nulliparity (1.45).
 These data may help predict postpartum hemorrhage and may be useful in counseling patients about the advisability of home delivery, intravenous access in labor, or autologous blood donation.
",12
1920,"Hysterosalpingo-contrast sonography of the uterus and fallopian tubes: results of a clinical trial of a new contrast medium in 120 patients.
 The feasibility, diagnostic efficacy, and patient tolerance of a new diagnostic modality, hysterosalpingo-contrast sonography (HyCoSy), were evaluated in a clinical study of 120 patients with suspected infertility.
 A new echogenic contrast medium for ultrasound was administered transcervically with conventional tools for hysterosalpingography or a balloon catheter.
 The flow of multiple fractions of the contrast medium through each fallopian tube was observed in real time in appropriate imaging planes by means of a transvaginal probe.
 All patent tubes were diagnosed correctly with HyCoSy, results comparing well with findings at hysterosalpingography or laparoscopy.
 With B-mode scanning only, sensitivity was 88% for the right tube and 90% for the left; specificity was 100% for each tube.
 The supplementary use of Doppler techniques (duplex, color Doppler) provided additional information in special cases of suspected tubal occlusion and led to an improvement in diagnostic accuracy.
 The contrast agent was well tolerated.
 HyCoSy demonstrates normal anatomy and tubal patency with high reliability and permits advance selection of patients in whom more invasive diagnostic procedures may be required.
",12
1921,"Potential prenatal predictions of Down syndrome: a statistical analysis.
 To determine the feasibility of combining several screening tests for the prenatal detection of Down syndrome, we evaluated the potential relationship among three proposed predictors.
 We determined the concentration of chorionic gonadotropin in frozen serum samples from women of known maternal age and weight, fetal biparietal diameter, and femur length, and alpha-fetoprotein concentration.
 When corrected for gestational age and maternal weight, the potential predictors were independent, except for a slight correlation (r = 0.10) between maternal serum alpha-fetoprotein and maternal serum human chorionic gonadotropin.
 Both maternal serum human chorionic gonadotropin and biparietal diameter/femur length demonstrated an approximately log-normal distribution similar to maternal serum alpha-fetoprotein.
 Therefore it is scientifically sound to use any or all of these variables in combination for the identification of pregnancies at increased risk for Down syndrome.
",12
1922,"The course of labor after endurance exercise during pregnancy.
 This study was designed to test the hypothesis that continuation of a regular running or aerobics program, or both, during the latter half of pregnancy would have a negative effect on the course and outcome of labor.
 The onset, course, and outcome of labor were independently monitored in 131 well-conditioned recreational athletes who had an uneventful first half of pregnancy.
 Daily exercise performance was quantitated before conception and throughout pregnancy.
 Comparisons were made between the 87 women who continued to exercise regularly at or above 50% of their preconceptional level throughout pregnancy and the 44 who discontinued their regular exercise regimen before the end of the first trimester.
 The incidence of preterm labor was similar in the two groups (9%).
 Labor began significantly earlier in the exercise group (277 +/- 6 vs 282 +/- 6 days).
 The women who continued to exercise had a lower incidence of abdominal (6% vs 30%) and vaginal (6% vs 20%) operative delivery, and active labor was shorter (264 +/- 149 vs 382 +/- 275 min) in those who were delivered vaginally.
 Finally, clinical evidence of acute fetal stress (meconium, fetal heart pattern, and Apgar score) was less frequent in the exercise group (50% vs 26%), although birth weight was reduced (3369 +/- 318 vs 3776 +/- 401 gm).
 These data negate the initial hypothesis and indicate that, in well-conditioned women who regularly perform aerobics or run, continuation of these exercise regimens has a beneficial effect on the course and outcome of labor.
",12
1923,"Growth factor activity in the blood of women in whom preeclampsia develops is elevated from early pregnancy.
 Preeclampsia is a pregnancy-specific disorder of uncertain cause and pathophysiology that appears to be associated with endothelial cell injury.
 Our current studies demonstrate that a pregnancy growth factor activity is elevated compared with postpartum values in the blood of women with preeclampsia months before the onset of clinical manifestations of toxemia.
 A cohort of primigravid women was followed throughout pregnancy and multiple serial plasma samples from six women with preeclampsia and six matched normal women were assayed for mitogenic activity.
 The data indicated that the ratio of predelivery/postdelivery plasma mitogenic activity was greater in women predestined to meet strict criteria for the diagnosis of preeclampsia compared with matched normal primigravid women.
 Growth factor activity could distinguish women in whom preeclampsia would develop from their normal peers throughout pregnancy, and as early as the first trimester of gestation (p less than 0.05).
 Similar studies performed with plasma obtained greater than 6 weeks post partum, when the two groups of patients were clinically indistinguishable, revealed no differences in this index of mitogenic activity.
 Our results indicate that elevated mitogenic activity ratios of prepartum versus postpartum plasma antedate the clinical recognition of preeclampsia, and return to normal with the resolution of the syndrome.
",12
1924,"The effect of nifedipine therapy on fetal and placental Doppler waveforms in preeclampsia remote from term.
 Twenty patients with preeclampsia at a gestational age of 26 to 35 weeks were treated with oral nifedipine until delivery.
 The mean oral daily dose was 45.1 +/- 11 mg/day (range, 40 to 80 mg/day).
 Fetal aorta, internal carotid artery, umbilical artery, and uteroplacental Doppler flow velocity waveforms were recorded before treatment and then serially.
 The mean nifedipine concentration at the time of the Doppler studies was 60.3 ng/ml (range, 10 to 90 ng/ml).
 The use of nifedipine therapy was associated with a significant decrease in both maternal systolic blood pressure (baseline, 154 to 135 mm Hg, p less than 0.001) and diastolic blood pressure (baseline, 100 to 88 mm Hg, p less than 0.001).
 However, there was no significant difference in the resistance index between baseline and postnifedipine Doppler studies in either the fetal or uteroplacental vessels.
 The use of oral nifedipine to control blood pressure in preeclampsia does not affect the resistance indices in fetal or uteroplacental vessels as measured by the Doppler technique.
",12
1925,"Inhibition of spontaneous uterine contractions during the last trimester in pregnant baboons by an oxytocin antagonist.
 The effect of a potent oxytocin antagonist, produced in our laboratories, on spontaneous uterine contractions in the pregnant baboon was examined.
 Three types of uterine contractions were studied: immediately after operation, during the nocturnal period, and near or at labor.
 Bolus intravenous injections of oxytocin antagonist were given and uterine activity was examined +/- 1 hour after the injection.
 The oxytocin antagonist caused a precipitate decrease (approximately 70%) in contractile force (mean amplitude x frequency) in the first 15 minutes after injection (p less than 0.05); this force diminished to approximately 90% at the end of 1 hour for both nocturnal and labor contractions.
 In contrast, uterine contractions immediately after operation were diminished by only 60% within 60 minutes after the oxytocin antagonist.
 These results indicate that the oxytocin antagonist is a potent inhibitor and suggest that oxytocin is a primary regulator of spontaneous nocturnal and labor uterine contractions in the pregnant baboon.
",12
1926,"Observations on the cause of oligohydramnios in prolonged pregnancy.
 There is increasing evidence that implicates reduced amnionic fluid volume as a major determinant of fetal risk in prolonged pregnancy.
 We sought to determine whether reduced fetal urine production might be associated with oligohydramnios in pregnancies that reach 42 weeks or more.
 Ultrasonographic measurements of the fetal bladder were obtained every 2 to 5 minutes for 1 hour in 38 gestations verified to be at least 42 weeks.
 Oligohydramnios was present in eight of the prolonged pregnancies.
 Similar measurements were performed in 15 normal pregnancies delivered by elective repeat cesarean section between 38 and 40 weeks' gestation.
 Hourly fetal urine production rates were calculated with sequential bladder volume measurements.
 The result of this investigation suggest that diminished fetal urine production is associated with oligohydramnios in prolonged pregnancy.
 The mechanism by which fetal urine production is reduced in prolonged pregnancy remains unknown.
 A likely possibility is reduced fetal swallowing because of already diminished amnionic fluid volume, the latter a result of placental senescence.
",12
1927,"A mechanism leading to reduced lung expansion and lung hypoplasia in fetal sheep during oligohydramnios.
 Our aim was to determine the mechanism whereby oligohydroamnios causes reduced fetal lung expansion and eventual lung hypoplasia.
 We studied 20 fetal sheep during 2 to 9 days of oligohydramnios produced by drainage of amniotic and allantoic fluids during the last third of gestation.
 Oligohydramnios led to a reversible reduction in lung liquid volume of 19.5% within 48 hours.
 During oligohydramnios tracheal pressure, relative to amniotic pressure, rose by 1.7 mm Hg (p less than 0.001); pressures also tended to rise in the fetal pleural space and abdomen, relative to amniotic pressure, and to fall in the amniotic sac.
 Pressure increments, relative to amniotic pressure, which normally occur in the fetal trachea, pleural cavity, and abdomen during nonlabor uterine contractions, were significantly increased by 1.9 to 2.5 mm Hg during oligohydramnios.
 Oligohydramnios increased flexion of the fetal thoracolumbar spine, quantified as a reduction in the ratio of spinal radius of curvature to spine length (0.76 in controls vs 0.40 after oligohydramnios, p less than 0.001).
 In three sets of twins, only the fetus exposed to oligohydramnios was affected.
 A similar degree of spinal flexion imposed on normal fetal sheep cadavers increased abdominal (1.6 mm Hg), pleural (1.5 mm Hg), and tracheal (2.0 mm Hg) pressure, and caused a significant reduction in fetal lung expansion.
 We conclude that oligohydramnios in fetal sheep increases spinal flexion, leading to compression of abdominal contents, upward displacement of the diaphragm, and lung compression, favoring loss of fetal lung liquid.
 These changes, which are accentuated during nonlabor uterine contractions and are reversible, may lead to pulmonary hypoplasia if prolonged.
",12
1928,"Isolation and characterization of the gene from a human genome encoding 17 beta-estradiol dehydrogenase: a comparison of Jar and BeWo choriocarcinoma cell lines.
 17-beta-Estradiol dehydrogenase is required for the enzymatic interconversion of estradiol and its weaker related sex steroid, estrone.
 We isolated and sequenced a complementary deoxyribonucleic acid clone for 17 beta-estradiol dehydrogenase from the BeWo choriocarcinoma cell line.
 Comparison of the BeWo complementary deoxyribonucleic acid sequence to a previously derived placental complementary deoxyribonucleic acid sequence yields greater than 98% homology.
 We also isolated the gene for 17 beta-estradiol dehydrogenase from the Jar human choriocarcinoma cell line and elucidated its primary nucleic acid structure.
 Significant differences in the Jar-deduced complementary deoxyribonucleic acid sequence clearly differentiate it from both the human placental and BeWo forms of 17 beta-estradiol dehydrogenase, indicating the existence of two genes for 17 beta-estradiol dehydrogenase in the human genome.
 Evaluation of 17 beta-estradiol dehydrogenase gene expression in BeWo and Jar cells was compared with expression in luteinized granulosa cells.
 Messenger ribonucleic acid for human placental 17 beta-estradiol dehydrogenase was identified in all three cell types as a 1.3 kilobase band on Northern blot analysis.
 A second messenger ribonucleic acid species measuring 2.1 kilobase was abundantly present in the granulosa cells.
 Whether these two species of messenger ribonucleic acid are involved in the regulation of the estradiol dehydrogenase genes is yet to be determined.
",12
1929,"Turner syndrome and its variants.
 Turner syndrome is suspected in females with short stature, gonadal dysgenesis, and lymphedema; however, there are no pathognomonic features of Turner syndrome, and the disorder should be considered in any girl with short stature or delayed puberty.
 This article discusses the natural history of Turner syndrome and complications that occur in various organ systems; it reviews the physical features and complications seen with various karyotypic changes in Turner syndrome.
 Age-specific screening and therapies are covered.
",12
1930,"Almitrine mimics hypoxia in fetal sheep with lateral pontine lesions.
 Almitrine bimesylate is a potent and long-lasting respiratory stimulant in adult species.
 It acts by stimulating the peripheral chemoreceptors, where it has been shown to accumulate specifically, although its exact mechanism of action is uncertain.
 In the fetal lamb, however, it produces a profound inhibition of breathing even after denervation of the peripheral chemoreceptors.
 In this respect its action is similar to hypoxia.
 To investigate whether almitrine is hypoxia mimetic, we examined the effect of almitrine in nine fetal lambs of 120-130 days gestation.
 Five had lesions in the lateral pons that changed the fetal depressive response to hypoxia to one of stimulation.
 In the remaining four fetuses, the lesions did not bilaterally encompass the appropriate area of the pons; thus they still showed the normal fetal depressive response to hypoxia and so acted as controls.
 Almitrine (10 mg iv) caused a pronounced stimulation of breathing that lasted 406 +/- 26 min in all five fetuses with lesions that caused a stimulatory response to hypoxia.
 However, in the remaining four fetuses, in which the response to hypoxia was inhibitory, almitrine caused an inhibition of breathing that lasted 184 +/- 28 min.
 We conclude that the action of almitrine is like that of hypoxia and that, because it acts specifically on the chemoreceptors, it may prove to be a useful tool in the study of possible central chemoreceptor mechanisms.
",12
1931,"Elevated plasma norepinephrine levels in infants of substance-abusing mothers.
 Infants of substance-abusing mothers (ISAM) have significant growth and neurodevelopmental abnormalities.
 The origin of these abnormalities is unknown.
 We postulated that ISAM have increased sympathetic nervous system tone and altered catecholamine levels.
 Therefore, we measured plasma norepinephrine, epinephrine, and dopamine levels and the number and receptor affinity of beta-adrenoreceptor binding sites on lymphocytes and alpha-adrenoreceptor binding sites on thrombocytes in 22 otherwise healthy ISAM (age, 2.1 +/- 0.5 months; mean +/- SD) and 15 healthy controls (age, 2.5 +/- 0.8 months).
 Norepinephrine levels in venous blood were 1.8-fold higher in ISAM than in control infants (6.30 +/- 3.85 nmol/L vs 3.55 +/- 2.45 nmol/L).
 There were no differences in plasma epinephrine or dopamine levels.
 There were no differences in the number of binding sites or receptor affinity for beta- and alpha-adrenoreceptors.
 We conclude that ISAM have elevated circulating norepinephrine levels compared with controls.
 We speculate that this is associated with increased sympathetic nervous system tone in ISAM and that the absence of adrenoreceptor down-regulation may create catecholamine suprasensitivity.
",12
1932,"Attention deficits in children exposed to alcohol prenatally.
 Twenty children with fetal alcohol syndrome or fetal alcohol effect (FAS/FAE) were compared with 20 attention deficit disorder (ADD) children and 20 normal controls on three experimental tasks designed to isolate four different components of attention.
 Parents completed three questionnaires regarding their child's activity level and overall functioning, and the children completed a short form of an IQ test.
 The children in each group ranged from 5 to 12 years.
 Results indicate that although the children with FAS/FAE are significantly more impaired intellectually, their attentional deficits and behavioral problems are similar to those of children with ADD.
 These findings imply that the treatments known to facilitate learning in children with ADD may also benefit children with FAS/FAE.
",12
1933,"The long-term behavioral effects of prenatal alcohol exposure in rats.
 Prenatal exposure to alcohol can cause a variety of behavioral disturbances later in life.
 Many of the reports in animals of the behavioral teratogenic effects of alcohol have focused on assessing younger animals.
 The purpose of this paper is to review some of the longer lasting behavioral consequences of gestational alcohol exposure in animals.
 It is not meant as a comprehensive review, but rather focuses on selected studies.
 It is concluded that prenatal alcohol exposure does have long lasting effects, although some of these might only occur under challenging or stressful circumstances.
 It is hypothesized that as the animal matures compensatory mechanisms or strategies develop to compensate for these dysfunctions.
 Thus, behavioral problems may only be detected when these compensatory systems break down, either as a result of stress, because of complex testing procedures, or old age.
",12
1934,"Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation.
 Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3 or 4.1 gm/kg from the 5th week.
 Mean maternal peak plasma ethanol concentrations (MPPEC's) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose.
 Thirty-three live born infants were assessed for abnormalities of physical and behavioral development.
 Ocular pathology, neuropathologic and neurochemical assessements were done on 31 animals at 6 months postnatal age.
 Microphthalmia was noted in three of the 26 animals exposed to ethanol.
 Retinal ganglion cell loss was significantly associated with intra-uterine ethanol exposure.
 Microphthalmia and retinal ganglion cell loss was observed in both the delayed and full-gestational exposed animals.
 No structural anomalies were found in the brains via gross inspection or light microscopy.
 Chemical abnormalities in the striatal nuclei were identified.
 Striatal dopamine concentrations increased with increasing MPPEC exposure (0-249 mg/dl) among animals exposed weekly to ethanol throughout gestation.
 Striatal dopamine concentrations decreased with increasing MPPEC exposure (260-540 mg/dl) among animals whose weekly exposure to ethanol was delayed until the 5th week of gestation.
 The same pattern of association was also noted between MPPEC and ultrastructural alterations in the caudate nucleus.
 The extent of ultrastructural alterations increased with increasing MPPEC among the full-gestational exposed animals and decreased with increasing MPPEC among the delayed-dose animals.
",12
1935,"Effects of ethanol on hexose uptake by cultured rat brain cells.
 The effects of ethanol on hexose uptake by glial cells was investigated using primary cultures prepared from term rat fetuses.
 Specific 3H 2-deoxy-D-glucose (2DG) uptake was significantly reduced by a 4-hr exposure to ethanol at concentrations of 25, 50, and 100 mM, but not 200 or 300 mM.
 The inhibitory effect of 50 mM ethanol increased with the duration of exposure, with 2DG uptake inhibited by 36% after 18 hr.
 Astrocytes cultured from the brains of term fetuses of rats fed ethanol during pregnancy showed essentially the same 2DG uptake response to in vitro ethanol treatment.
 Kinetics of 2DG uptake showed a significant decrease of Vmax in the presence of ethanol.
 No interaction was found between ethanol and insulin, which stimulated 2DG uptake and protein content of the cultures.
 The data suggest that ethanol can modulate hexose uptake by astrocytes cultured from fetal rat brain.
 However, insulin actions on glial cells were not affected by ethanol.
",12
1936,"Factor analysis in patients with a history of failed tracheal intubation during pregnancy.
 Eight patients with a history of failed tracheal intubation during pregnancy were investigated by x-ray laryngoscopy after delivery.
 Partial elevation of the epiglottis with no view of glottic structures was found in five patients who were therefore considered to still present difficulty.
 In each of these five patients the blade tip failed to make contact with the hyoid and in four this was explained by the tongue being compressed into a pear shape such that it prevented sight of the larynx.
 Relatively few abnormal anatomical indices were seen in these patients and this was in keeping with the level of difficulty encountered.
 An angular measure of jaw protrusion from a line joining the upper incisors and a point just above and anterior to the vocal cords, to the mid-point on the inner surface of the mandible was useful: the lower angle of this triangle was as important as the angle at the incisors.
",12
1937,"Comparison of two preparatory techniques for urine cytology.
 Two methods of preparation of urine for cytology were compared retrospectively.
 In method 1 cells in the urine were fixed after the preparation of the smear; in method 2 the cells were fixed before smear preparation.
 Urine cytology reports were correlated with subsequent histological analysis.
 The specificities of urine cytology using both methods were high (99%).
 The sensitivity using method 1 was 87%; using method 2 it was 65%.
 This difference was significant.
 The cell preparation technique therefore significantly changes the sensitivity of urine cytology.
 Cellular fixation after smear preparation is preferable to smear preparation after fixation.
",12
1938,"Gene mapping in Alport families with different basement membrane antigenic phenotypes.
 The present study was undertaken to determine whether differences among Alport kindreds in the antigenic phenotypes of their basement membranes result from defects at distinct genetic loci or from allelic mutations at a single locus.
 We analyzed linkage of the Alport gene to polymorphic loci on the X chromosome in three families with Alport syndrome.
 In two of the families, epidermal basement membranes of affected members showed altered immunohistologic reactivity with a discriminating antibody (FNS1) that identified a 26 kD peptide in the NCl domain of basement membrane collagen.
 In the third family epidermal basement membranes of affected individuals reacted normally with the antibody.
 The disease gene mapped to the Xq21-q22 region of the long arm of the X chromosome in the two families with altered basement membrane antigenicity and in the family with normal basement membrane antigens.
 We conclude that Alport syndrome in each of these kindreds arose from allelic mutations at a single genetic locus, although we cannot at this time exclude the possibility that two or more tightly linked genes are involved.
 As the genes for the known chains of type IV collagen are on chromosome 13, our findings suggest that the Alport gene may encode a new basement membrane collagen chain.
",12
1939,"Obstetric complications in young teenagers.
 We compared pregnancy outcome in 286 teenaged primigravidas (less than or equal to 16 years old) and 267 adult primigravidas (21 to 25 years old) who had similar prenatal care, socioeconomic status, and racial balance.
 The incidence of preterm labor and delivery of a low birthweight infant was significantly higher in the teenagers.
 The incidence of preeclampsia was significantly higher in the adults.
 Cesarean delivery was not done more frequently in teenagers, nor was there a higher incidence of infants small for gestational age, anemia, and abnormal presentation in labor.
 The birthweight of infants of black teenagers was significantly lower than the birthweight of those of white teenagers, and overall birthweight was significantly lower in infants of teenagers than those of adults.
 Although prenatal care, socioeconomic factors, and racial balance were comparable for young teenagers and adults, teenagers were still at a significantly greater risk for delivery of smaller infants, preterm labor, and low birthweight infants.
",12
1940,"The accuracy of clinical findings and laparoscopy in pelvic inflammatory disease.
 The accuracy of clinical diagnosis for pelvic inflammatory disease was determined in 95 women who presented with pelvic pain to primary care physicians and then were referred to gynecologists.
 Laparoscopy or laparotomy with endometrial biopsy and fimbrial minibiopsy revealed that prevalence of pelvic inflammatory was 46% (44/95) and positive and negative predictive values of gynecologists were 74% (23/31) and 67% (43/64) (p = 0.0002).
 If histopathologic diagnosis was the standard, clinical accuracies of the gynecologists were no better than chance (p = 0.43), suggesting an expectation bias for visual diagnosis.
 Laparoscopy had a sensitivity of 50% (12/24) and a specificity of 80% (40/50) for salpingitis if the standard was fimbrial histopathologic diagnosis (p = 0.01).
 These results support the routine use of laparoscopy, supplemented when negative by endometrial and fimbrial minibiopsy, to accurately diagnose pelvic inflammatory disease.
",12
1941,"Heterotopic pregnancies after in vitro fertilization and embryo transfer.
 Seventeen cases of heterotopic pregnancies are reported among 1648 clinical pregnancies after in vitro fertilization.
 The high prevalence of tubal damage among IVF patients and the use of superovulation and multiple embryo transfer might predispose patients to the condition.
 Nine patients reported abdominal pain and vaginal bleeding, five patients did not have symptoms, and three had acute abdominal emergencies.
 Transvaginal ultrasonography was superior to transabdominal ultrasonography in the diagnosis of extrauterine pregnancies.
 The presence of an intrauterine gestation sac in a patient without symptoms should not exclude the diagnosis of a concomitant extrauterine pregnancy until the pelvis is carefully visualized.
 Early diagnoses of viable ectopic pregnancies before rupture abolishes mortality and morbidity and offers the chance of patient selection for conservative treatment.
 In two patients the extrauterine gestation sac was treated by transvaginal aspiration and injection of potassium chloride under ultrasonographic guidance.
 The outcome of the intrauterine pregnancy was favorable regardless of the method of treatment of the ectopic pregnancy.
",12
1942,"Forskolin and methotrexate induce an intermediate trophoblast phenotype in cultured human choriocarcinoma cells.
 The human placenta and its associated membranes are vital to the maintenance, nutrition, and protection of the developing fetus.
 During placental development some cytotrophoblasts give rise to the chorionic membrane whereas others fuse to form a differentiated syncytium of cells that are responsible for placental protein and steroid hormone production.
 The mechanisms involved in the differentiation of the trophoblasts are unknown; however, an intermediate stage with a characteristic phenotype has been documented in vivo.
 We have observed that chemically dissimilar xenobiotic agents induced BeWo choriocarcinoma cells to change their usual cytotrophoblastic phenotype and acquire morphologic and functional characteristics typical of intermediate trophoblast.
 Incubation of BeWo cell cultures in the presence of 1 mumol/L methotrexate for 48 hours stimulated human chorionic gonadotropin secretion (2.3-fold) and aromatase activity (4.9-fold).
 Morphologic findings associated with these hormonal changes, including increased nuclear size and cytoplasmic expansion, were also observed.
 With the use of a computer-interfaced image analyzer, planimetric morphometry of the nuclear area of the cells revealed a 1.8-fold increase after incubation with methotrexate.
 The effect of forskolin, a direct activator of adenylyl cyclase, was also evaluated by means of this model of cytotrophoblast differentiation.
 The addition of 10 mumol/L forskolin to BeWo cultures also resulted in dramatic changes in trophoblast cell phenotype.
 Increases in human chorionic gonadotropin synthesis (7.3-fold), aromatase activity (13.5-fold), and nuclear area (3.0-fold) were induced over those of untreated cells.
 In addition, increases in [3H]thymidine incorporation (1.7-fold) were afforded by both treatments.
 These results suggest that biochemical and cytologic changes associated with human trophoblast differentiation can be induced in vitro via activation of the adenylyl cyclase pathway by forskolin and through unknown and apparently independent signals by methotrexate.
",12
1943,"Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality.
 Diagnostic curettage has for many years been the method of choice to diagnose endometrial cancer in women with postmenopausal bleeding.
 The costs for curettage performed today are huge, and approximately only 10% in this group of women will be diagnosed with endometrial cancer.
 Thus less expansive techniques to obtain endometrial samples have been evaluated, but all of them are invasive.
 The value of endovaginal ultrasonography for identifying endometrial abnormality in this group of women has not been evaluated until now.
 This study used endometrial thickness as measured by endovaginal ultrasonography as an indicator of endometrial abnormality.
 It was demonstrated in 205 women with postmenopausal bleeding that if the endometrium was less than 9 mm thick, no endometrial cancer was found at curettage.
 The mean endometrial thickness in those women with endometrial cancer was 18.2 +/- 6.2 mm as compared with 3.4 +/- 1.2 mm in those women with atrophic endometrium.
 If the cutoff limit for endometrial abnormality was 5 mm, the positive predictive value for identifying endometrial abnormality was 87.3%.
 If this limit had been used in this study, 70% of the curettage procedures could have been avoided.
",12
1944,"Fetal urine output does not influence residual amniotic fluid volume after premature rupture of membranes.
 Fetal urine production in 12 women with premature rupture of membranes did not differ from that of a control group, and there was no correlation between fetal urine output and residual amniotic fluid volume.
 Residual amniotic fluid volume after premature rupture of membranes does not appear to depend on or alter fetal renal function.
",12
1945,"The clinical implications of subchorionic placental lucencies.
 Forty-six patients were identified at a perinatal diagnostic referral center as having subchorionic placental lucencies.
 These lucencies varied from simple to multicystic and covered up to 50% of the subchorionic placental surface.
 Clinical follow-up of 40 patients demonstrated no increase in the incidence of adverse pregnancy outcome.
 We conclude that these pregnancies are not at higher risk when the subchorionic placental lucencies are not associated with other intraplacental or fetal anomalies.
",12
1946,"Evidence that human chorionic gonadotropin/luteinizing hormone receptor down-regulation involves decreased levels of receptor messenger ribonucleic acid.
 Injection of pseudopregnant rats with pharmacological doses of hCG leads to a characteristic decrease in LH/hCG binding by the isolated luteal cells.
 The steady state levels of LH/hCG receptor mRNA were determined in rat ovaries during hCG-induced down-regulation of the receptor.
 Northern blots were performed using a 20-mer probe corresponding to a guanine cytosine-rich carboxyl-terminal untranslated region of the LH/hCG receptor cDNA.
 The hybridization of the probe to LH/hCG receptor mRNA was highly specific, since the probe hybridized only to rat luteal cell RNA fraction, with no signal detected in nontarget tissues.
 The LH/hCG receptor level was quantitated by [125I]hCG binding to the isolated membrane fractions from the corresponding treatment and control groups.
 Examination of mRNA levels of the receptor during hCG-induced down-regulation showed a steady decrease from 0-24 h, followed by a gradual increase to control levels from 24-72 h corresponding to days 8-9 of pseudopregnancy.
 The [125I]hCG-binding activity during down-regulation paralleled the mRNA profile in both the experimental and control groups.
 Examination of the levels of mRNA for alpha-actin showed no change during this period, suggesting that the loss of LH/hCG receptor mRNA at 24 h was not due to a general loss of mRNA in luteal cells.
 These results suggest that hCG-induced down-regulation of the LH/hCG receptor in luteal cells involves regulation of the receptors at the message level.
",12
1947,"Retinoic acid stimulates placental hormone secretion by choriocarcinoma cell lines in vitro.
 Retinoic acid (RA), an active metabolite of vitamin A, is an important mediator of cellular differentiation and has been shown to stimulate human CG (hCG) secretion by JEG-3 choriocarcinoma cells in vitro.
 In order to determine whether RA stimulates the hCG secretion by other trophoblastic cell lines, we evaluated the effect of RA on hCG, hCG-alpha subunit (hCG-alpha), and progesterone secretion in three choriocarcinoma cell lines: JEG-3, JAR, and BeWo.
 RA stimulated hCG and hCG-alpha secretion in a dose-dependent fashion by each of the three cell lines.
 The time required to give a statistically significant increment of hCG and hCG-alpha over control cells was 48 h.
 The addition RA to cholera toxin (10 micrograms/ml) resulted in an additive or synergistic stimulation of hCG and hCG-alpha secretion by the three cell lines.
 Cycloheximide (1 microM) abolished the effect of RA on hCG and hCG-alpha secretion in the BeWo cell line.
 Progesterone secretion in response to RA was inconsistent.
 Progesterone secretion by both JEG-3 and BeWo cell lines were stimulated at high concentrations of RA (1 x 10(-6], whereas progesterone secretion by JAR cells was not stimulated.
 Intracellular levels of cAMP were not affected by RA treatment in the JEG and JAR cells.
 In the dosages used, RA did not significantly alter cell number in any of the cell lines.
 RA in physiologic concentrations stimulates hCG and hCG-alpha secretion by three choriocarcinoma cell lines in vitro.
 Whether RA is a physiologic mediator of placental hormone production is unknown.
",12
1948,"In vitro fertilization-embryo transfer (IVF-ET) in the United States: 1989 results from the IVF-ET Registry. Medical Research International, Society for Assisted Reproductive Technology, The American Fertility Society.
 This is the fourth annual report of the United States Registry of in vitro fertilization-embryo transfer (IVF-ET) and related practices.
 The present report describes the 1989 experiences of 163 United States member clinics with respect to treatments and outcomes.
 During 1989, the clinics reported performing 24,183 ovarian stimulation cycles.
 From all treatments, including frozen ET and IVF with donor oocytes, there were with 4,598 clinical pregnancies and 3,472 live deliveries.
 Ninety-eight percent of the clinics had at least one delivery, and overall a total of 4,736 babies were born.
 The overall live delivery rates were 14% for IVF (based on 15,392 retrievals), 23% for gamete intrafallopian transfer (GIFT) (based on 3,652 retrievals), 26% for IVF and GIFT in combination (based on 452 retrievals), and 17% for zygote intrafallopian transfer (ZIFT) and related practices (based on 908 retrievals).
 In addition to these treatments, results are presented for frozen ETs and IVF of donated oocytes.
",12
1949,"Handling of tubal infertility after introduction of in vitro fertilization: changes and consequences.
 This study aimed at quantifying some important social and economic consequences of the altered handling of tubal infertility after the establishment of IVF treatment.
 The number of tubal operations was reduced by 50%.
 This had most important and positive implications on the availability of the operating theater for other elective operations, on the availability of hospital beds for other patient groups, and on the total duration of the certificate of illness.
 The calculated costs per live birth were $17,000 after tubal surgery, compared with $12,000 after IVF treatment.
 Life table analyses demonstrated a highly significant increased rate of deliveries after a complete IVF treatment (72.3% per patient) compared with tubal surgery (23.7%, P less than 0.001).
",12
1950,"Fertility before and after surgery for primary ovarian pregnancy.
 Primary ovarian pregnancy usually occurs in parous fertile women.
 It is an accidental event probably related to the presence of the IUD affecting implantation rather than an indicator of altered fertility.
 Reproductive performance postoperatively remains unmodified.
",12
1951,"Oocyte and pre-embryo donation to women with ovarian failure: an extended clinical trial.
 The outcome of a series of pre-embryo transfers to 31 women with ovarian failure is described.
 Twenty six fertile women functioned as nonanonymous donors, providing oocytes for in vitro fertilization after undergoing controlled ovarian hyperstimulation and transvaginal ultrasound directed oocyte aspiration.
 Recipients, 24 to 44 years of age, received hormone replacement therapy before pre-embryo transfer (ET).
 A mean of 13.7 +/- 1.1 oocytes were obtained per aspiration resulting in the transfer of 4.5 +/- 0.2 pre-embryos to each recipient couple.
 Twenty-five of 47 ET resulted in pregnancy (53.2% per ET); 5 preclinical, and 20 clinical, of which 18 are ongoing or delivered.
 The overall implantation rate per individual transferred fresh pre-embryo was 21.1%.
 We conclude that oocyte donation is a safe and highly efficient means of achieving pregnancy for women with ovarian failure.
",12
1952,"Treatment of tubal ectopic pregnancy by salpingotomy with or without tubal suturing and salpingectomy [published erratum appears in Fertil Steril 1991 Jun;55(6):1213-4]
 Thirty-four women with unruptured tubal ectopic pregnancy (EP) were randomly assigned to undergo salpingotomy without tubal suturing (n = 15) or salpingotomy with tubal suturing (n = 19).
 The reproductive performance of these patients was compared with 24 patients who underwent salpingectomy for their EP (historical control).
 Using life table analysis, the cumulative probability of intrauterine pregnancy (IUP) at 12 and 24 months was 45% and 45% after salpingotomy without tubal suturing and 21% and 47% after salpingotomy with tubal suturing, respectively.
 The cumulative probability of IUP after salpingectomy (21% and 26% at 12 and 24 months, respectively) was significantly lower than after salpingotomy with or without tubal suturing.
 There was no difference in the cumulative probability of EP after salpingotomy with or without tubal suturing, but it was significantly higher than after salpingectomy.
 In 18 women who subsequently underwent laparoscopy or laparotomy, no significant difference was found between the degree of adhesions after salpingotomy with or without tubal suturing.
 These findings suggest that IUP after conservative treatment is higher than after salpingectomy, but recurrent EP is also higher.
 Intrauterine pregnancy occurs earlier after salpingotomy without tubal suturing than after salpingotomy with tubal suturing.
 This might be because of rapid return of tubal function after healing by secondary intention.
",12
1953,"Ovarian hyperandrogenism: the role of and sensitivity to gonadotropins.
 To determine if ovarian hyperandrogenism represents enhanced gonadotropic stimulation, augmented ovarian sensitivity to gonadotropins, or both, we have undertaken to evaluate (1) the 24-hour integrated concentrations of serum total testosterone (T) and luteinizing hormone (LH) and (2) the ovarian response of T to exogenous gonadotropic stimulation.
 To this end, two groups of women, hyperandrogenic anovulatory (n = 4) and early follicular phase (n = 4) normally-cycling controls, were subjected to continuous blood withdrawal over 24 hours with a portable Cormed pump (Cormed Inc., Middleport, NY) and to exogenous stimulation with human chorionic gonadotropin.
 Our current observations support the notion that ovarian hyperandrogenism represents the combined impact of an overall increase in gonadotropic support coupled with augmented ovarian sensitivity to gonadotropic stimulation.
",12
1954,"Endometrial antibodies versus CA-125 for the detection of endometriosis.
 Detection of endometrial antibodies using an indirect immunofluorescence method along with a well-established human endometrial carcinoma cell line was evaluated and compared with CA-125 for detecting endometriosis.
 Two hundred two patient sera from the infertility, gynecological, and gynecological oncology services were evaluated.
 The sensitivity for antibody testing was 83.1% with a specificity of 78.8%, in contrast to a sensitivity of 27.3% and a specificity of 82.6% for CA-125.
 These preliminary findings offer promise that antibody detection methods may be a useful adjunct in the diagnosis of endometriosis.
",12
1955,"Maturation of immature oocytes by coculture with granulosa cells.
 To increase the number of embryos available for transfer, immature human oocytes were cocultured with granulosa cells from preovulatory follicles.
 Greater numbers of immature oocytes incubated with granulosa cells had dispersion of the cumulus and corona cells compared with immature oocytes cultured in media alone.
 Fifty-four percent of immature oocytes were fertilized after coculture with granulosa cells compared with 20% fertilization of immature oocytes cultured without granulosa cells.
 There were no cases in which only embryos developed from immature oocytes were transferred, and thus we could not determine if the immature oocytes could contribute to a pregnancy.
",12
1956,"A comparison of Doppler flow velocity waveforms, amniotic fluid columns, and the nonstress test as a means of monitoring post-dates pregnancies.
 Five hundred thirty-four pregnancies exceeding 294 days were monitored by weekly sonographic estimations of amniotic fluid columns, daily maternal recordings of fetal movements, and thrice-weekly nonstress tests.
 In addition, each woman received twice-weekly studies of the uteroplacental and umbilical circulations by means of Doppler ultrasound.
 There were no fetal deaths in the study.
 Of the individual methods of fetal surveillance, absence of end-diastolic frequencies in the umbilical artery was the most sensitive, predicting 91% of fetuses who developed fetal distress in the first stage.
 Combining the test with sonographic estimation of amniotic fluid columns improved the prediction to 100%, with only a minimal fall in the specificity.
 These results strongly suggest that a combination of umbilical artery Doppler waveforms and amniotic fluid determinations is an adequate method of monitoring the post-dates pregnancy.
",12
1957,"Low incidence of positive amnionic fluid cultures in preterm labor at 27-32 weeks in the absence of clinical evidence of chorioamnionitis.
 In order to determine the utility of amniocentesis for detecting subclinical chorioamnionitis in asymptomatic afebrile women in preterm labor with intact membranes, we enrolled 47 women between 27-32 weeks' gestation in a prospective study.
 After enrollment, 38 women fulfilled all clinical and laboratory criteria for the study; nine women were excluded because they had a leukocyte count exceeding 15,000/microL.
 None of the 38 asymptomatic afebrile women had a positive culture from the amnionic fluid for bacteria, fungi, Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, or any viruses.
 Sepsis was not proved in any of the 38 infants delivered to these patients.
 There was a clear relationship between histologic evidence of chorioamnionitis and failure of tocolytic therapy.
 Fetal lung profiles were mature in 29% of the amnionic fluid samples from 30-32 weeks' gestation, but in none of the amnionic fluid samples before 30 weeks.
 Amniocentesis does not seem useful to detect chorioamnionitis in asymptomatic afebrile women with preterm labor and intact membranes at 27-32 weeks' gestation, and should be reserved for those cases in which information about fetal lung maturity would be helpful.
",12
1958,"Comparison of continuous versus sequential estrogen and progestin therapy in postmenopausal women.
 A pilot study was performed comparing the efficacy and safety of continuous versus sequential schedules of the two most commonly prescribed medications for ovarian hormone replacement, conjugated equine estrogens and medroxyprogesterone acetate.
 Bleeding patterns, endometrial histology, and metabolic parameters were studied in 48 postmenopausal women prospectively randomized to a continuous schedule (daily estrogen and progestin) or a sequential schedule (conjugated estrogen on days 1-25, medroxyprogesterone acetate on days 16-25).
 Doses studied were 0.625 and 1.25 mg of conjugated estrogens and 10 mg of medroxyprogesterone acetate.
 Significantly greater bleeding was observed with the 1.25-mg dosage of conjugated estrogens.
 Bleeding patterns were similar between schedules, with the exception that amenorrhea was more prevalent in the women using the 1.25-mg dosage of estrogen and the continuous progestin schedule.
 More frequent endometrial atrophy was observed with the continuous schedule, supporting the concept that prolonged use of this schedule may promote amenorrhea in most patients.
 Both doses and schedules were associated with modest and insignificant increases in high-density lipoprotein cholesterol.
 Sequential therapy did not prevent the estrogen-induced decrease of low-density lipoprotein cholesterol, whereas the continuous schedule did, particularly with 0.625-mg dosage of conjugated estrogens.
 Significant increases of triglycerides were also seen with the continuous but not with the sequential schedule.
 Because of reports that the continuous schedule using the 2.5-mg dosage of medroxyprogesterone acetate does not elicit these actions on circulating lipids, attention should be directed toward examining the long-term effects of this lower dosage given continuously.
",12
1959,"Endotoxin in vaginal fluid of women with bacterial vaginosis.
 The concentration of endotoxin in vaginal fluid was measured in 19 women with bacterial vaginosis and in nine controls with normal vaginal flora.
 The vaginal fluid of the women with bacterial vaginosis contained significantly greater amounts of endotoxin: 0.308 +/- 0.396 versus 0.008 +/- 0.002 endotoxin units/mg vaginal fluid.
 Endotoxin in vaginal fluid may contribute to the activation of the prostaglandin system, which could provoke premature labor.
",12
1960,"Persistent tubal pregnancy.
 Persistent tubal pregnancy may be manifest by either acute symptoms or a persistent or rising beta-hCG titer following conservative surgery.
 This condition is a relatively new complication, related to the recent practice of conservative surgical management of tubal pregnancy.
 Much has been written on the identification and possible therapy for this condition but little is known about its pathophysiology.
 Eight cases of persistence were studied, as well as three cases of failed conservative procedures.
 In nine instances, the surgeon had concentrated appropriately on the maximally dilated portion of the tube, which contained the blood clot and aborted products of conception.
 Unfortunately, the implantation site was located medially, toward the uterus.
 Ways of avoiding this complication include medial exploration or possibly the use of mesosalpingeal injection of vasopressin.
 An understanding of the natural history of the pathologic process might also be valuable in the management of cases of ""persistence"" identified solely by a continuing beta-hCG titer.
",12
1961,"Regulation of gene expression in choriocarcinoma by methotrexate and hydroxyurea.
 Choriocarcinoma, a highly malignant neoplasm of trophoblastic origin, is remarkable for its marked degree of sensitivity to chemotherapeutic agents.
 We treated two cell lines derived from choriocarcinoma patients with two antineoplastic agents, methotrexate and hydroxyurea (HU), both of which cause nucleotide depletion and have been previously shown to be effective against choriocarcinoma, and found pleiotropic regulation of several genes.
 Three genes, hCG alpha-subunit, beta-subunit, and placental alkaline phosphatase, were all strongly induced by methotrexate and HU.
 Expression of c-myc, an oncogene associated with proliferation, was reduced to nearly undetectable levels by the drug treatment, while expression of beta 2-microglobulin, a component of the class 1 major histocompatibility locus, was unchanged.
 In addition, the mechanism of induction by HU of one of these genes, the hCG alpha-subunit gene, was found to occur at the level of transcription.
 The similar effects of methotrexate and HU, two mechanistically unrelated antimetabolites, on the induction of specific gene expression in choriocarcinoma cells suggest that these effects are due to nucleotide pool alteration, rather than specific ligand effects.
 Furthermore, the hCG alpha-subunit promoter contains a transcriptionally regulated HU-responsive element.
",12
1962,"Changes in women's mental and physical health from pregnancy through six months postpartum.
 A longitudinal study was conducted to investigate changes in women's mental and physical health around the time of childbirth, and to determine whether health was related to length of maternity leave.
 Thirty-seven married, employed first-time mothers completed questionnaires during pregnancy, and again at 6 weeks, 3 months, and 6 months postpartum.
 Results showed that, from pregnancy to the 6th postpartum month, the number of days that mothers were ill because of infections steadily increased.
 In addition, depressive symptoms for new mothers rose from pregnancy to the 6th week postpartum, and declined thereafter.
 For women who did not return to work during the period of the study, a significant decline in depressive symptoms was observed from the prenatal period through the 6th postpartum month.
 These findings demonstrate significant changes in mental and physical health for this group of first-time mothers.
",12
1963,"Endometrial ablation with the roller ball electrode.
 Endometrial ablation for control of menorrhagia is a safe, effective alternative to hysterectomy in selected patients.
 Endometrial ablation with a resectoscope equipped with a roller ball electrode was used on 12 patients.
 The technique appears to be as effective as Nd:YAG laser endometrial ablation and offers gynecologists the advantages of speed, low cost and safety when compared to the laser approach.
",12
1964,"Increased risk of ectopic pregnancy with maternal cigarette smoking.
 As part of a case-control study of ectopic pregnancy, we evaluated the potential etiologic role of cigarette smoking.
 Maternal cigarette smoking at the time of conception was associated with an increased risk of ectopic pregnancy with a dose-response relationship (adjusted odds ratios: 1.30 to 2.49).
 On the other hand, partner's smoking was not associated with ectopic pregnancy.
 The study provides a supplementary argument towards a causal effect of smoking in the development of ectopic pregnancy.
",12
1965,"Carcinoma of the female reproductive organs. Value of cross-sectional imaging.
 Cross-sectional imaging techniques i.e., computed tomography (CT) and magnetic resonance imaging (MRI), play an integral role in the evaluation of patients with carcinoma of the female reproductive system.
 Neither CT nor MRI, however, are tissue-specific, and benign and malignant disease cannot be differentiated using these techniques alone.
 Therefore, the diagnosis is clinical and is based on history, physical examination, and histology.
 After the diagnosis has been made, CT and MRI are recommended for noninvasive evaluation of tumor extent, often helping in designing optimal therapy, thus facilitating more effective treatment and ultimately influencing patient prognosis.
 In evaluating tumors of the uterus, including endometrial and cervical carcinomas, CT is limited to the evaluation of more extensive disease.
 It is believed that the value of CT rises proportionately to the size and extent of disease.
 Its major limitation is suboptimal tissue contrast resolution, making differentiation between a small tumor and the surrounding normal tissue difficult.
 MRI renders excellent soft tissue contrast, allowing direct tumor visualization and assessment of tumor volume, depth of penetration, and extension to adjacent tissues.
 Assessment of these parameters is crucial in deciding on the choice of therapy, whether surgery, radiation, chemotherapy, or their combination.
 The initial management of ovarian cancer usually includes surgical staging with tumor debulking.
 CT remains the primary staging technique; its value resides primarily in identification of tumor metastases and in patient follow-up.
 Despite progress in the use of CT and MRI, second-look laparotomy for ovarian cancer has not been superseded.
 Technical advances in radiologic cross-sectional imaging have significantly improved the accuracy of noninvasive tumor staging.
 Although there are still limitations to these techniques, additional technical improvement and better tissue characterization are imminent.
",12
1966,"Laparoscopic cautery in the treatment of endometriosis-related infertility.
 Life table analysis and the two-parameter exponential method have been applied to pregnancy rates in 72 patients undergoing laparoscopic cautery exclusively.
 Patients with male factor infertility were excluded.
 Estimated cure rates for patients with stage I and II disease were 98.2% and 76.6%, respectively (not significantly different).
 No significant difference was seen when anovulation complicated the endometriosis (68.6%).
 When greater than one infertility factor was present, a significant difference was observed (50.6%).
 Patients with stage I disease had an average fecundity of 10.30% with decreasing values observed in stage II (7.59%), anovulation (6.67%), and more than one infertility factor (3.33%).
 We conclude that laparoscopic cauterization is an effective mode of therapy for the treatment of stage I and II endometriosis associated with infertility.
",12
1967,"Endometrial epithelial cells in peritoneal fluid during the early follicular phase.
 Peritoneal fluid (PF) was obtained during the early follicular phase in 24 women at laparoscopy as part of infertility investigation.
 The cells present in PF were pelleted and cultured.
 Developing endometrial epithelial cell colonies were identified in 19 women (79%).
 Identification of these cell colonies was facilitated using the monoclonal antibody BW 495/36 as specific marker.
 The number of endometrial epithelial cell colonies showed a large variation (1 to 200 or more PF sample).
 No significant distinction in incidence and number of cell colonies was found between women with minimal (n = 11) and without endometriosis (n = 12).
 A significant correlation with number of cell colonies was found in women with infertility and no mechanical and male infertility factors.
 These data indicate that retrograde transport of viable endometrial cells during menstruation occurs in most women with patent tubes.
 Implications of the results for the relation between retrograde menstruation, endometriosis, and infertility are discussed.
",12
1968,"Detection of a progesterone-induced secretory protein synthesized by the uteri but not the endometriotic implants of rats with induced endometriosis.
 Steroids modulate the secretory activity of the uterus, but little is known of their effect on ectopic endometrium protein synthesis and secretion.
 We utilized two-dimensional electrophoresis to visualize proteins produced by the uteri and endometriotic implants of both steroid-treated and reproductively cyclic rats with and without surgically induced endometriosis.
 Of the greater than 300 proteins visualized, only the uterine cultures from progesterone (P)-stimulated, estrogen-suppressed rats contained a distinctive glycoprotein (P-induced uterine protein-1; molecular weight [Mr] 70,000; isoelectric point [pI] 5.7).
 This protein was not detected in any of the endometriotic implant cultures.
 Progesterone-induced uterine protein-1 could play a role in luteal or endometrial physiology and may be valuable in assessing endometrial function.
 The aberrant secretory behavior of the ectopic endometrium suggests a possible involvement in the reproductive dysfunction associated with endometriosis.
",12
1969,"Intraoperative management of ureteral injury during operative laparoscopy.
 Injury to the ureter from operative laparoscopy is rare.
 The diagnosis is usually made radiologically, in the postoperative period, when the patient presents with symptoms and signs suggestive of ureteral injury.
 We report herein a case of ureteral injury resulting from operative laparoscopy for endometriosis.
 The injury was diagnosed and treated via laparoscopy during the same procedure.
 The increased utilization of operative laparoscopy to perform more complex procedures increases the potential for operative injury to the ureter.
 Prior visualization or retroperitoneal dissection of the ureter, in appropriate cases, will help reduce this complication and/or permit a prompt diagnosis in the event of such injury.
",12
1970,"Predictive value of the active renin assay for the diagnosis of ectopic pregnancy.
 The increasing frequency of EP and the need for its early diagnosis have focused our interest on the research of biochemical markers.
 We have established hormonal values in the plasma of 99 spontaneous ongoing pregnancies between the 4th and 10th weeks of amenorrhea, in 21 EPs, and 20 cases of early abortion.
 We have examined the predictive values of trophoblastic and CL production in pathological pregnancies.
 The association of low hCG and low active renin appears to be able to discriminate between ectopic and abortive spontaneous gestations.
",12
1971,"Bone mineral density of the lumbar spine in endometriosis subjects compared to an age-similar control population.
 The purpose of this study was to compare the lumbar bone mineral density (BMD) between women with endometriosis and age-similar controls.
 Eighty-five women from nine North American centers (mean age, 30.7 yr) with laparoscopically proven endometriosis (study patients) were enrolled in a study of the efficacy of nafarelin, a GnRH agonist.
 Fifty-two women (mean age, 32 yr) from the Palo Alto area, with regular menstrual cycles and no major medical problems, served as age-similar controls.
 Both groups were predominantly (greater than 92%) white.
 The mean BMD of the lumbar spine was 1.1 g/cm2 in both the study subjects and the controls.
 Study patients were 104.8% and controls were 104.8% of normal values for age.
 BMD was not significantly different in the two groups.
 BMD was not correlated with severity or time from diagnosis of endometriosis.
 BMD was positively correlated with weight (r = 0.28; P less than 0.05) in both groups, with height (r = 0.30; P less than 0.01) in study patients, and marginally with height (r = 0.26; P less than 0.07) in controls.
 This study showed no difference in BMD between endometriosis patients and age-similar controls; both groups had normal BMD.
",12
1972,"Nifedipine in the treatment of severe preeclampsia.
 We conducted a randomized clinical trial in which patients with severe preeclampsia between 26-36 weeks of gestation received either nifedipine (10-30 mg sublingually, then 40-120 mg/day orally; N = 24) or hydralazine (6.25-12.5 mg intravenously, then 80-120 mg/day orally; N = 25).
 Effective control of blood pressure was achieved with nifedipine in 95.8% of subjects and with hydralazine in 68%, a statistically significant difference (P less than .05).
 Maternal side effects were minor in both groups.
 Acute fetal distress developed in one nifedipine subject and in 11 treated with hydralazine.
 Mean prolongation of gestation was 15.5 +/- 10 days with nifedipine and 9.5 +/- 11 days with hydralazine, a difference that did not reach statistical significance (P less than .07).
 Infants born to women treated with nifedipine were delivered at more advanced gestational ages (34.6 +/- 2.3 versus 33.6 +/- 2.4 weeks; statistically not significant), weighed more (1826 +/- 456 versus 1580 +/- 499 g; statistically not significant), and tended to have fewer, mainly minor, complications.
 The average number of days spent in the neonatal intensive care unit was significantly lower in the nifedipine group (15.1 versus 32.7 days; P less than .005), leading to an average 31% reduction in total (maternal and neonatal) hospitalization-related charges for each nifedipine-treated pregnancy.
 We conclude that nifedipine is an effective, convenient, and low-cost treatment for patients with severe preeclampsia, and is not associated with undesirable side effects.
",12
1973,"Etiologies of preterm birth in an indigent population: is prevention a logical expectation?
 To assess the expectations of preterm birth prevention, we determined the causes of preterm birth in a population of indigent women.
 We studied 13,119 singleton births in a predominantly black, indigent population occurring between November 1982 and April 1986 to identify the proportion of preterm births that may have been prevented using current treatment modalities.
 Forty-four percent of the preterm births occurred at 35 to 36 weeks' gestational age, a time when most practitioners do not attempt tocolysis.
 Of the remainder, 17% occurred before 35 weeks but were indicated for maternal medical or obstetric complications, and another 17% occurred before 35 weeks but followed spontaneous premature rupture of the membranes.
 Therefore, of the 1445 preterm births, we calculated that only 336 (23.2%) were theoretically preventable.
 A fourth of these presented at less than 3 cm cervical dilatation and were treated appropriately with tocolytics, but delivered anyway.
 Therefore, most of the potentially preventable births occurred in the group that presented with cervical dilatation of more than 3 cm.
 We conclude that improving the preterm birth rate significantly below current levels may be difficult to achieve.
",12
1974,"Risk factors for shoulder dystocia: an engineering study of clinician-applied forces.
 We report on engineering risk factors associated with clinician-applied forces during vaginal delivery of newborns.
 Specifically, we present and interpret data from a series of experiments using force-sensing devices on 29 randomly selected vaginal births, including two shoulder dystocia deliveries and one birth injury.
 The results indicate that clinician-applied peak forces are typically about 47 N for routine deliveries, 69 N for difficult deliveries, and 100 N for a shoulder dystocia delivery (P less than .01).
 The time required to deliver fetal shoulders doubles for nonroutine deliveries (P less than .01).
 In addition, impulse and rate of application of force distinguish between routine and nonroutine deliveries (P less than .03).
 We conclude that, if properly perceived, force, force rate, and the duration of force are objective parameters that can be used in recognizing and managing shoulder dystocia and in predicting thresholds for birth injury.
",12
1975,"Salpingoscopy: light microscopic and electron microscopic correlations [published erratum appears in Obstet Gynecol 1991 May;77(5):809-10]
 In order to examine the ability of salpingoscopy to diagnose intratubal pathology, 32 fallopian tubes were evaluated salpingoscopically and histologically.
 Both flexible and rigid salpingoscopes were used, and observations were documented by intratubal photography.
 Salpingoscopic criteria were established and each criterion assigned a numerical value.
 Each tube was evaluated for patency, mucosal fold architecture, erythema, adhesions, and dilatation.
 Based on these criteria, tubes were graded as normal or as abnormal with mild, moderate, or severe changes.
 Histologically, each tube was evaluated for patency, epithelial changes, vascularity, dilatation, adhesions, and active inflammation.
 Six tubes with significant histologic findings and two histologically normal fallopian tubes were also examined by transmission electron microscopy.
 In five discordant cases, histology revealed epithelial and stromal changes not detected by salpingoscopy.
 Fallopian tubes with severe disease were diagnosed by both methods.
 Transmission electron microscopy of histologically abnormal tubes showed flattening of the epithelium with markedly reduced ciliary distribution, degenerating secretory epithelial cells with large intracellular vacuoles, and swollen nuclei containing sparse chromatin.
 Our results indicate that salpingoscopic observations are consistent with histologic findings when endotubal disease is severe.
 However, moderate pathologic changes as documented by light microscopy and transmission electron microscopy were frequently not diagnosed salpingoscopically, even with magnification.
",12
1976,"Serial endovaginal sonography of ectopic pregnancies treated with methotrexate.
 Methotrexate therapy is a newly established treatment modality for ectopic pregnancy.
 We performed this study to determine the time frame for resolution of the sonographically identifiable mass during such therapy and to determine the role of sonography in the management of these patients.
 Eighteen patients treated with methotrexate for laparoscopically proven ectopic pregnancy consented to long-term follow-up with endovaginal sonography.
 These 18 patients constitute the study group.
 The time required for sonographic resolution of the mass was variable, although poor patient compliance with sonographic follow-up affected the conclusions regarding resolution time.
 One hundred eight days was the longest period accurately known for resolution of a mass.
 In seven patients, the mass persisted after a negative hCG titer.
 Enlargement of the adnexal mass during therapy did not necessarily predict treatment failure, as only two of ten such patients required surgery for rupture.
 Serial sonography did not alter the management of most patients and appears not to be warranted on a routine basis.
 Follow-up sonography was most useful when complications were suspected.
 All patients considered for methotrexate therapy should first have an endovaginal sonogram, as cardiac activity remains a relative contraindication to this treatment.
 We have determined that the mass of an ectopic pregnancy may remain after the hCG is negative.
 Therefore, a persistent mass should not be interpreted as treatment failure.
",12
1977,"Measures of sexual behavior and the risk of pelvic inflammatory disease.
 A women's sexual behavior affects her risk of acquiring pelvic inflammatory disease, but the risks have not been well characterized.
 To study the association between pelvic inflammatory disease and sexual behavior, we analyzed data from a multicenter, case-control study involving 712 women hospitalized with an initial episode of pelvic inflammatory disease and 2719 hospitalized control women without a history of pelvic inflammatory disease.
 Study participants provided information on their frequency of intercourse, number of recent sexual partners, and previous history of gonorrhea.
 Logistic regression methods were used to adjust for confounding factors.
 Women who reported having four or more sexual partners were over three times more likely to be hospitalized for pelvic inflammatory disease (relative risk 3.4; 95% confidence interval 2.2-5.3) than were women who reported only one recent sexual partner.
 To a lesser extent, frequent sexual intercourse and history of gonorrhea also increased a woman's risk of pelvic inflammatory disease.
 Frequent intercourse was a strong risk factor for pelvic inflammatory disease among a subgroup of women who were at low risk for acquiring a sexually transmitted disease: Married women with one recent sexual partner with intercourse six or more times per week had a risk of pelvic inflammatory disease of 3.2 (1.4-7.2) compared with similar women having intercourse less than once per week.
 Frequent intercourse, which does not by itself increase the risk of acquiring a sexually transmitted disease, may increase a woman's risk of pelvic inflammatory disease.
",12
1978,"Epidemiologic characteristics of preterm delivery: etiologic heterogeneity.
 Preterm delivery (less than 37 weeks completed gestation) is known to result from diverse etiologic pathways, which can be grouped into idiopathic preterm labor, preterm premature rupture of the membranes, and medical complications.
 Data from publications providing sufficient detail to subdivide preterm delivery cases into these groups were tabulated.
 In spite of inconsistent terminology and incomplete reporting, patterns were identified.
 Black women have a markedly higher risk of preterm delivery, which is especially pronounced for preterm premature rupture of the membranes.
 Idiopathic preterm labor is predominant in lower-risk, white populations.
 These observations encourage consideration of subcategories of preterm delivery in studies of etiology and prevention.
",12
1979,"Investigation of placental circulations by color Doppler ultrasonography.
 The placental circulations of 25 normal and five complicated pregnancies were studied by color Doppler ultrasonography.
 Flow velocity waveforms were obtained in all 30 pregnancies and could discriminate between fetal and maternal intraplacental blood flow.
 We believe that color Doppler ultrasonography will improve our understanding of the pathophysiology of various pregnancy disorders that alter the placental circulations and that color ultrasonography is useful for the prenatal differential diagnosis of intrauterine masses.
",12
1980,"Reproductive factors and risk of endometrial cancer.
 The role of reproductive factors in endometrial cancer risk has been analyzed in a case-control study conducted since 1983 in the greater Milan area on 568 women (cases) with histologically confirmed endometrial cancer and 1925 women (controls) who were admitted for acute, nonmalignant, hormonal, gynecologic conditions to hospitals that cover a comparable catchment area.
 Compared with nulliparous women, parous women had a 30% lower risk of endometrial cancer, but there was no evidence of a decline in risk with increasing number of births.
 The risk of the disease decreased with number of spontaneous or induced abortions; the multivariate relative risk estimates were, compared respectively with no spontaneous or induced abortions, 0.5 for women with two or more spontaneous abortions and 0.3 for women with two or more induced abortions; both trends in risk were statistically significant.
 When parous women only were considered, no association emerged between endometrial cancer and age at first birth, but the risk decreased with increasing age at last birth: compared with women whose last birth occurred before age 25, the relative risk was 0.5 for women who were greater than or equal to 35 years old at last birth, and the multivariate trend in risk was statistically significant.
 For most of the reproductive factors that were considered, the risk estimates tended to be greater at younger age or among premenopausal women and to flatten off in subsequent strata of age.
 An association between endometrial cancer and age at first birth was observed in women who were less than or equal to 49 years old, but not in older groups.
 The observation that later age at last birth as well as later first birth in younger women decreases the risk of endometrial cancer suggests a short-term protective effect of pregnancy.
 This finding is consistent with a late-stage (promotional) effect of reproductive factors on endometrial carcinogenesis.
",12
1981,"Pregnancy-related mortality in New York City, 1980 to 1984: causes of death and associated risk factors.
 To identify causes and risk factors for pregnancy-related mortality in New York City, we analyzed 224 pregnancy-related deaths that occurred from 1980 to 1984.
 The leading causes of death were ectopic pregnancy complications, embolism, intrapartum cardiac arrest, and hypertension.
 Mortality ratios were determined by comparing the characteristics of the women whose death was pregnancy-related with those of women who had survived delivery of a live infant in New York City during the same period.
 Black and Hispanic women had mortality ratios that were respectively 4.2 and 2.0 times higher than those for white, non-Hispanic women.
 In comparison with women aged 20 to 24, those older than 30 were more than twice as likely to die from pregnancy-related causes, and those older than 40 were five times as likely to do so.
 Other factors that were associated with an increased risk of pregnancy-related mortality included 9 to 11 years of education, lack of private medical insurance, more than five previous pregnancies, and fewer than five prenatal visits.
 This study suggests that changes in current maternal-health and family-planning services will be required to achieve further reductions in preventable pregnancy-related mortality.
",12
1982,"Human amniotic fluid modulation of collagenase production in cultured fibroblasts. A model of fetal membrane rupture.
 The participation of a mechanical factor as the only cause of rupture of fetal membranes during normal labor or premature rupture has been criticized, and the involvement of an enzymatic mechanism has been proposed.
 In this study we analyzed the effect of human amniotic fluids at different gestational ages on the collagenase synthesis of cultured fibroblasts.
 Our results show that term amniotic fluids are capable of inducing the synthesis of collagenase and other proteases in fibroblasts, as revealed by selective increases in collagenase activity and in immunoreactive collagenase.
 Nonterm amniotic fluids failed to do the same.
 This phenomenon is proposed as a model for studying the collagen degradation of fetal membranes during term gestation.
",12
1983,"Early diagnosis of vulvar neoplasia as a result of vulvar self-examination.
 Vulvar self-examination was used to facilitate early diagnosis and treatment of vulvar neoplasia in eight patients.
 Five of them were found to have invasive squamous cell carcinoma of the vulva, two had carcinoma in situ, and one had a vulva melanoma.
 All eight patients benefited from early diagnosis, which allowed definitive treatment and vulvar conservation.
",12
1984,"Prevalence of marijuana use during pregnancy. A pilot study.
 We examined the prevalence of marijuana use in a group of pregnant women using a qualitative, rapid urine screen to detect marijuana metabolites.
 Between July 1, 1987, and Aug 15, 1987, 322 consecutive patients underwent an anonymous urine toxicology screen at the time of admission to the labor-and-delivery unit.
 Patients were identified only by a consecutive number and by their age, race, marital status, gravidity, parity and obstetric service (clinic vs.
 private).
 The prevalence of positive urine toxicologic screens for marijuana was 19.9% among the study population (64 positive tests among 322 women screened).
 The prevalence was greater among the clinic patients than the private patients (52 of 161, or 32.3%, vs.
 12 of 161, or 7.5%, respectively).
 The distribution of race and marital status among the marijuana-positive and -negative groups were also significantly different.
 Specifically, the proportions of black and single women were higher among the marijuana-positive group.
 Our findings suggest that marijuana use is common in our obstetric patients.
 The possible association between marijuana use during pregnancy and perinatal morbidity, as well as the unreliable nature of patient drug histories, may support the use of rapid, inexpensive screening techniques, especially if general screening is considered.
",12
1985,"Early recourse to laparoscopy in the management of suspected ectopic pregnancy. Accuracy and morbidity.
 Ninety-nine patients with suspected ectopic pregnancy (EP) who were subjected to laparoscopy/laparotomy over an 18-month period at Greenwich District Hospital, London, were audited.
 A third (32/99) of the cases had an EP, and 67 potentially avoidable laparoscopies were performed.
 A potentially avoidable laparoscopy was followed by a laparotomy in 27% of cases (18/67), and at least 13 of those laparotomies were unnecessary.
 In addition, two false-positive diagnoses of EP were made at laparoscopy, resulting in the avoidable loss of part or all of a single remaining fallopian tube.
 With the use of sensitive pregnancy testing at least 62 laparoscopies, 13 laparotomies and 1 case of pulmonary embolus might have been avoided in these patients and up to 195 days' hospitalization saved.
",12
1986,"Ascertainment of maternal deaths in New York City.
 Maternal deaths in New York City are defined as deaths from any cause in a woman while pregnant or within six months of pregnancy termination.
 Pilot studies seeking to improve maternal death ascertainment found that selected medical examiner reports contributed an additional 10.5 percent of the total maternal deaths, vital statistics review contributed 6.3 percent, linkage of death tapes of women of reproductive age to live birth and fetal death tapes contributed 1.0 percent.
 Medical examiner cases should be incorporated into surveillance data for accurate ascertainment of pregnancy associated deaths.
",12
1987,"Effects of maternal iodine supplementation during pregnancy.
 Reduced maternal thyroid hormone concentrations during pregnancy can adversely affect fetal neurological development.
 In the context of national iodine supplementation programmes, concern has been expressed over the theoretical possibility that iodine supplementation during pregnancy might adversely affect fetal development as a result of maternal thyroid inhibition from the Wolff-Chaikoff effect.
 In a double blind controlled trial in five villages in Papua New Guinea, several measures of motor and cognitive function showed no significant differences at either age 11 or 15 years between those children whose mothers had received supplementary iodine during pregnancy and the control children whose mothers had received the placebo.
",12
1988,"Suicide during pregnancy and in the first postnatal year 
 OBJECTIVES--To calculate age adjusted mortality ratios for suicide by women in the first year after childbirth and during pregnancy, and to identify characteristics of postnatal suicide in childbearing women.
 DESIGN--Retrospective study based on population data for England and Wales from 1973 to 1984.
 SUBJECTS--Women aged 15-44 who committed suicide in the year after childbirth or during pregnancy.
 MAIN OUTCOME MEASURES--Observed to expected mortality ratios for the total postnatal sample, for five year age groups, for unmarried mothers, and for suicide after stillbirth; observed to expected mortality ratios for all suicides during pregnancy and for five year age groups; the timing of suicides in relation to delivery; and the frequency of the various methods of suicide.
 RESULTS--The standardised mortality ratio for postnatal suicide was calculated to be 0.17--that is, the actual total was only one sixth of that expected.
 The low ratio was not found after stillbirth, which was associated with a rate six times that in all women after childbirth.
 The low ratio was less pronounced, but still present, in teenage mothers and in unmarried mothers.
 Women who committed suicide after childbirth most often did so in the first month, and there was a tendency to use violent methods.
 The standardised mortality ratio for suicide during pregnancy was calculated to be 0.05 of all pregnant women.
 Teenagers were at substantially increased risk.
 CONCLUSIONS--Women in the first year after childbirth and during pregnancy have a low risk of suicide despite their high rate of psychiatric morbidity.
 Underreporting of maternal suicides is unlikely to explain the findings, though it may affect their magnitude.
 Motherhood seems to protect against suicide.
 Concern for dependants may be an important focus for suicide prevention in clinical practice.
",12
1989,"Duchenne and Becker muscular dystrophies: genetics, prenatal diagnosis, and future prospects.
 DMD and BMD are now understood at the genetic, biochemical, and molecular levels.
 At the genetic level, both disorders result from mutations of the X-linked gene encoding dystrophin.
 At the biochemical level, DMD results from the deficiency of a large protein called dystrophin, whereas BMD results when dystrophin is present, though abnormal in either amount or molecular structure.
 To date, thousands of patients have been analyzed for mutations of the dystrophin gene in peripheral blood DNA or alterations of the dystrophin protein in muscle tissue.
 The severity of the clinical phenotype of these patients has been compared with their dystrophin gene mutations and corresponding dystrophin protein alterations, revealing an unexpectedly high degree of correlation.
 Thus, information derived from the molecular analysis (DNA or protein) of a particular patient provides a ""molecular diagnosis,"" which is highly predictive of the clinical course that patient can be expected to follow.
 Because molecular diagnoses are independent of the patient's age, they provide a prognosis for the large majority of muscular dystrophy patients even before clinical symptoms of their disease become apparent.
 Such prognostic molecular diagnoses have proven particularly valuable when the patient is an isolated case, with no family history for the disorder.
 Prenatal genetic diagnosis of DMD or BMD may involve use of Southern blot or PCR techniques to search for a deletion in the DNA of at-risk fetuses or more complicated family linkage studies using intragenic and flanking RFLPs.
 More recently, assay of dystrophin content in fetal skeletal or cardiac muscle from at-risk abortuses has been accomplished, allowing definitive discrimination of affected and normal fetuses in cases in which deletion analyses and family DNA studies were equivocal.
 In utero fetal skeletal muscle biopsy for dystrophin protein assay has actually been accomplished in at least one at-risk pregnancy in which family DNA studies were uninformative.
 Dystrophin was present in skeletal muscle from this 20-week-old male fetus, and the pregnancy continued, resulting in the term birth of a healthy male infant.
 The future holds exciting opportunities for neonatal screening and treatment of these devastating neuromuscular diseases.
",12
1990,"The intrauterine device and pelvic inflammatory disease: the Women's Health Study reanalyzed 
 The Women's Health Study (WHS) was a large, widely accepted and influential case-control study of the relationship between the use of intrauterine contraceptive devices (IUDs) and pelvic inflammatory disease (PID).
 The data were collected at 16 hospitals in 9 cities across the U.S.A.
 from October 1976 through August 1978.
 The first paper on this research was published in 1981 and concluded that IUDs increase the risk of PID.
 The report cited an estimated RR (relative risk) of PID for current IUD users vs nonIUD users of 1.6 with a 95% confidence interval of (1.4, 1.9).
 However, careful examination of the report reveals that the data support conclusions antithetical to those at which the author arrived.
 When the second report on the WHS was published in 1983, it was anticipated that many of the shortcomings of the first report would be corrected, but they were not.
 In 1983 we undertook a complete reanalysis of the same WHS data using more appropriate criteria and the results were compared to the first two published reports.
 The reanalysis revealed an RR of 1.02 (0.86, 1.21) for current IUD users compared to noncontraceptors.
 The conclusion of the WHS should have been that IUDs do not increase the risk of PID.
",12
1991,"Coagulation screening before epidural analgesia in pre-eclampsia.
 A questionnaire survey of current practice at a small cross-section of obstetric units, covering 22% of all United Kingdom deliveries, revealed a marked lack of standard practice regarding requests for coagulation screens on pre-eclamptic patients who require epidural procedures.
 A retrospective audit was therefore carried out on 434 coagulation screens requested for pre-eclamptic patients in whom epidural analgesia might have been considered.
 Borderline abnormalities of coagulation were found in only 10 patients (2%).
 Platelet counts of less than 150 x 10(9)/litre were present in 28% of cases.
 'Significant' thrombocytopenia (less than 100 x 10(9)/litre) and all coagulation abnormalities were only encountered in severe pre-eclampsia (diastolic blood pressure of greater than 110 mmHg and proteinuria of + + or greater).
 Furthermore, coagulation abnormality was always associated with a reduced platelet count (mean, 97 x 10(9)/litre).
 This study would therefore support anaesthetic practice which restricted any requests for coagulation testing to severe pre-eclamptic patients only.
 For these patients first line testing could be limited to a platelet count.
",12
1992,"Comparison of a food frequency questionnaire using reported vs standard portion sizes for classifying individuals according to nutrient intake.
 Individual intakes of retinol, carotene, vitamin C, and folacin calculated from a food frequency questionnaire using reported portion size were compared with intakes calculated using standard portion size information.
 Data from a case-control study to determine the association of nutrient intake and risk of cervical dysplasia were supplemented by standard portion size information from the US Department of Agriculture and reanalyzed.
 Significant mean differences were found between intake calculated from reported portion size data and that calculated from standard portion size data for all nutrients.
 Correlation of nutrient intakes obtained by the two methods of data collection ranged from .73 to .92.
 Calculation of the rho statistic, measuring the consistency of classification of participants into groups of high, medium, and low nutrient intake, led to values ranging from .55 to .71, indicating some misclassification of study participants.
 To determine the effect misclassification had on the study outcome, odds ratios were calculated using nutrient amounts obtained from both methods of collecting portion size data.
 Results indicate that replacing reported portion size data with standard portion size data may lead to conflicting outcomes for specific nutrients in research concerning the relationship between diet and disease.
",12
1993,"Gender roles, social support, and postpartum depressive symptomatology. The benefits of caring.
 Although women are assumed to be particularly vulnerable to depressive symptomatology after childbirth, the extent to which this symptomatology predominates over that found in men at this life cycle stage has not been addressed.
 This study examined gender differences in postpartum depressive symptomatology and the link between postpartum symptomatology and gender roles and relationships in a sample obtained from childbirth preparation classes.
 The data show no gender difference in depressive symptomatology at 2 months after childbirth.
 Women manifested a decrease in depressive symptomatology and men showed a slight increase from the preparenthood point.
 We partially link women's equivalent rather than higher distress levels to the protective effects of their varied social supports.
 By contrast, men depended primarily on their spouses, but both genders experienced a decrease in spouse support after childbirth.
 Female lack of support was more strongly associated with symptomatology in homemakers compared with employed women or women on maternity leave.
 Within the context of gender role changes, the data highlight benefits of female bonding in contrast to the ""costs of caring"" depicted by other researchers.
",12
1994,"External cephalic version at term. A randomized controlled trial using tocolysis 
 OBJECTIVE--To assess the role of external cephalic version (ECV) at term, using tocolysis.
 DESIGN--A randomized controlled trial over a 12 month period.
 SETTING--Harare Maternity Hospital, Harare, Zimbabwe.
 SUBJECTS--208 women with breech presentation at term were recruited after satisfying eligibility criteria.
 There were 103 women in the study group and 105 in the control group.
 At the end of the study a further 104 women were recruited for ECV.
 INTERVENTION--ECV attempted after intravenous injection of 10 micrograms of hexaprenaline, using either forward or backward somersault over a maximum period of 5 min.
 MAIN OUTCOME MEASURES--Success rate in terms of presentation during labour, need for caesarean section, and various variables related to fetal outcome.
 RESULTS--ECV reduced the frequency of breech presentation during labour from 83% to 17% and that of caesarean section from 33% to 13%.
 There were no troublesome complications from the procedure.
 CONCLUSION--In carefully selected women with breech presentation, ECV at term using tocolysis, safely reduced the rate of breech presentation in labour and also the caesarean section rate.
 Further research is needed to determine the role of ECV in early labour.
",12
1995,"Insulin stimulates synthesis and release of human chorionic gonadotropin by choriocarcinoma cell lines.
 Recent studies have shown that insulin regulates placental lactogen, progesterone, and estrogen production from human trophoblast cells.
 This study was performed to examine whether insulin also regulates the production of hCG by this type of cell.
 After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x 10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well) were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium for 24-96 h.
 Secretion of hCG from JEG-3 cells was stimulated by human insulin, human proinsulin, or porcine insulin in a dose-dependent manner, with lowest effective doses of 6.7, 96, and 53 mg/L, respectively.
 Time-course studies showed that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no decernable peak was seen without insulin in serum-free media.
 Exposure of JEG-3 cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3% more immunoreactive intracellular hCG (P less than 0.05).
 Cells grown in the presence of insulin and [35S]methionine had 47 +/- 21% more labeled intracellular hCG and 56 +/- 13% more immunoprecipitable [35S]methionine-hCG secreted into the medium than the control cultures (P less than 0.05).
 During this time period, human placental lactogen release and total trichloroacetice acid-precipitable [35S]methionine protein were not increased.
 The insulin-induced stimulation of hCG synthesis was inhibited by cycloheximide.
 Additionally, insulin did not significantly affect total intracellular protein during 24-96 h of incubation.
 Insulin also increased hCG release from JAR cells, but not from human term trophoblast cells.
 A mouse monoclonal antibody to the IGF-I receptor inhibited the stimulation of insulin in JEG-3 cells.
 We conclude that insulin stimulates the synthesis and secretion of hCG from JEG-3 cells and JAR cells, and that hCG regulation in choriocarcinoma cells differs from that in primary human placental trophoblast cells.
 The effect of insulin on JEG-3 cells may be mediated in part through the insulin-like growth factor-I receptor.
",12
1996,"The effect of beta-carotene on the regression and progression of cervical dysplasia: a clinical experiment.
 In order to gain insight into the causality of the relation between beta-carotene and cancer, we performed a randomized placebo-controlled trial in which the effect of beta-carotene on the regression and progression rates of cervical dysplasia were examined.
 The experimental group (n = 137) received a supplemental dose of 10 mg of beta-carotene daily for 3 months.
 The control group (n = 141) received placebo capsules.
 As the outcome parameter, two definitions of regression and progression were used, which were based on the degree of dysplasia before and after the medication period.
 The number of patients who showed progression was too small to allow conclusions.
 No effect of beta-carotene on the regression percentages was observed: OR = 0.68 (95% CI: 0.28-1.60) using the broad definition; and OR = 1.22 (95% CI: 0.43-3.41) with the strict definition.
 A secondary analysis, in which the effect of the total intake of beta-carotene (diet + medication) on the regression percentages of cervical dysplasia was studied, did not show a positive effect either.
 The paper discusses to what extent issues in the study design may have masked a potential effect and how our results affect the evidence for a causal relation between beta-carotene and cancer.
",12
1997,"Selective fallopian tube canalization.
 Infertility is an increasingly common problem.
 Occlusion of the fallopian tubes is one of the principal causes, and until recently surgery was the only available treatment.
 The success rate of surgery is often low, particularly with occlusion of the proximal tube.
 Selective fallopian tube canalization under fluoroscopic guidance has been successful in alleviating proximal tubal obstruction.
 This procedure may be performed in the outpatient setting and is a safe, cost-effective alternative to surgery.
",12
1998,"Cause of death in an emergency department 
 A retrospective review was done of 601 consecutive emergency department deaths.
 Nontrauma causes accounted for 77% of the deaths and this group had an average age of 64 years and a male to female ratio of 1.9:1.
 Trauma caused 23% of the fatalities and this group had a younger average age of 29 years and a male to female ratio of 4.6:1.
 The most common causes of nontrauma death were sudden death of uncertain cause (34%), coronary artery disease (34%), cancer (5%), other heart disease (4%), chronic obstructive lung disease (3%), drug overdose (3%), and sudden infant death syndrome (2%).
 The most common causes of trauma death were motor vehicle accidents (61%) and gunshot wounds (16%).
 The overall autopsy rate was 40%.
 Death certificates were often in error.
",13
1999,"Efficacy of potassium and magnesium in essential hypertension: a double-blind, placebo controlled, crossover study 
 OBJECTIVE--To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension.
 DESIGN--A double blind, randomised, placebo controlled, crossover trial of 32 weeks' duration.
 SETTINGS--Cardiology outpatient department, Sassoon General Hospitals, Pune, India.
 PATIENTS--37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg).
 INTERVENTION--Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design.
 No other drug treatment was allowed.
 MEASUREMENTS--Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals.
 RESULTS--Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change.
 Magnesium did not have an additional effect.
 Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium.
 The drug was well tolerated and compliance was satisfactory.
 CONCLUSION--Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension.
 Giving magnesium as well has no added advantage.
",13
2000,"Resympathectomy of the upper extremity.
 Resympathectomy was performed in 27 patients (eight bilaterally) with ischaemic hand phenomena.
 An extended operative technique, resecting parts of the second and third intercostal nerves and their surrounding tissue, was used.
 In all 35 procedures the posterior extrapleural approach was used.
 Follow-up was from 3 to 12 years.
 Only the sympathetic ganglia had been removed during the previous surgery by the axillary approach (67 per cent of these patients had had a transient response for between 6 months and 2 years; 33 per cent had had no response at all).
 A direct subjective improvement was seen after 27 of the 35 reoperations (77 per cent).
 In 14 patients continuous wave Doppler ultrasound studies were available and showed a significant increase in peak forward frequency after operation (P less than 0.001).
 From these data it may be concluded that it is possible to obtain a resympathectomy effect, but reoperation should be reserved for special cases for whom survival of digits is essential.
",13
2001,"Oscillometric finger blood pressure versus brachial auscultative blood pressure recording.
 In this study, a recently marketed proprietary finger blood pressure monitor, the Marshall, Astro F-88, was compared with the standard auscultative brachial mercury sphygmomanometer on 125 subjects.
 Measurements were undertaken according to the standards set by the American Heart Association.
 Sensitivity of the finger blood pressure measurement was 76% for systolic and 75% for diastolic blood pressure in diagnosis of high blood pressure (systolic greater than 140 mm Hg and diastolic greater than 90 mm Hg).
 Specificity was 86% for systolic and 82% for diastolic blood pressure.
 Positive predictive values were 58% for systolic and 38% for diastolic blood pressure in the study population in which prevalence of hypertension was 12%.
 The correlation coefficient (Pearson) for systolic values between devices was 0.76 (P less than .0001) and 0.57 (P less than .0001) for diastolic pressure.
 Values obtained by the finger monitor were found to be higher than those obtained by the mercury sphygmomanometer.
 Mean differences and standard deviations (paired t test) for systolic and diastolic pressures between the two devices were 2.3 +/- 14.9 mm Hg (P less than .08) and 2.9 +/- 14.5 mm Hg (P less than .02), respectively.
 These values are not in accordance with the proposed national standards because only 48% of the systolic and 37% of the diastolic blood pressure measurements were within 5 mm Hg of the mercury sphygmomanometer measurements.
 Therefore, although these differences may well be due to different techniques of monitoring employed by the devices, this device is not recommended for evaluation of blood pressure.
",13
2002,"The leukocyte count: a predictor of hypertension.
 In an exploratory study of 1031 persons observed to progress from normotension to essential hypertension and 1031 matched subjects who remained normotensive, the initial leukocyte count (WBC) was found to be related to the development of hypertension, with risk increased 40% (95% confidence interval 12-82%) in persons in the highest as compared to the lowest quartile of WBC.
 This relationship proved to be largely independent of body mass index, body fat distribution, alcohol and tobacco consumption, and parental history of hypertension.
 An increased WBC may reflect greater sympathetic tone or may directly increase peripheral vascular resistance by impeding circulation through small blood vessels.
 If confirmed, this study adds another condition to the growing list for which the WBC is predictive.
 This simple, cheap test should be considered for inclusion in prospective epidemiological studies of many different diseases.
",13
2003,"Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study.
 Plasma fibrinogen was measured in a sample of 8824 men and women aged 40-59 years participating in the Scottish Heart Health Study, and related to cardiovascular risk factors.
 Women had higher fibrinogen levels than men.
 In both sexes, multivariate analysis showed that fibrinogen was positively associated with age, smoking, total cholesterol and body mass index and negatively associated with alcohol consumption.
 Among women, early menopause and systolic blood pressure were also associated with fibrinogen levels.
 Univariate analyses showed weak positive associations with fish consumption for both sexes although only male white fish consumption entered the final model.
 Women with a history of contraceptive pill usage had significantly lower fibrinogen levels.
 The relationship between fibrinogen and physical activity was complex, and could largely be explained by smoking.
 These findings support the hypothesis that raised fibrinogen is one mechanism by which several major risk factors may promote coronary heart disease.
 However, known risk factors explained, at most, 10% of the total variance in fibrinogen levels among the general population.
",13
2004,"The effects of generation and gender on the joint distributions of lipid and apolipoprotein phenotypes in the population at large.
 The generation and gender effects on the joint distributions of total plasma cholesterol (Total-C), ln triglycerides (lnTrig), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), apolipoproteins AI (Apo AI), AII (Apo AII), and E (lnApo E) were studied in 184 male grandparents (MGP), 242 female grandparents (FGP), 237 male parents (MP), 235 female parents (FP), 202 male children (MC), and 200 female children (FC).
 Homogeneity of variance tests revealed that lipid variances were gender and/or generation specific while apolipoprotein variances were homogeneous across strata.
 In the absence of heterogeneity of variance, significant heterogeneity in LDL:lnTrig and lnTrig:Apo AII covariation was found between genders in the parental generation.
 In the presence of heterogeneity of variance, significant heterogeneity of correlation between genders and/or across generations was found for the HDL-C:LDL-C, Total-C:LDL-C, Total-C:lnTrig, lnTrig:LDL-C, Total-C:lnApo E and HDL-C:lnApo E bivariate distributions.
 Analyses of principal components revealed that the generation and gender specific cohorts have similar eigenvalues but distinct eigenvectors for the first two principal components underlying the seven dimensional lipid and apolipoprotein distribution.
 We conclude that the amount of variability explained by the first two principal components is the same across cohorts but how the interindividual variability is distributed among the lipid and apolipoprotein traits is generation and gender specific.
 This study documents the role that variance and covariance might play in determining risk of disease for special subgroups of the population at large.
 It also demonstrates how variances and covariances between risk factors traits characterize life processes of aging and sexual dimorphism.
 This study argues that future biometrical genetic and epidemiological studies of coronary artery disease must take into account age and gender effects on interindividual variability and covariability of risk factors.
",13
2005,"Risk ratios and risk differences in estimating the effect of risk factors for cardiovascular disease in the elderly.
 This article reviews the nature of the effects of hypertension, smoking and cholesterol on the incidence of cardiovascular disease and emphasizes how these effects vary by age.
 In the Methods section, we discuss briefly the concepts of additive and multiplicative statistical models as tools for summarizing data.
 In the results section, we summarize available data on the association between incident stroke and coronary heart disease in the elderly and each of these major risk factors.
 The traditional multiplicative model parsimoniously characterizes the individual and joint effects of age and high blood pressure in terms of risk ratios; but, for smoking and cholesterol, an additive model appears to be the most parsimonious.
 We discuss the consequences of these observations for the study and prevention of cardiovascular disease in the elderly.
",13
2006,"Significance of fill-in after thallium-201 reinjection following delayed imaging: comparison with regional wall motion and angiographic findings 
 To identify reversible defects, reinjection of a small amount of thallium-201 (201Tl) following 3-hr delayed imaging was performed in 60 patients with coronary artery disease who had perfusion abnormalities on their post-exercise 201Tl images.
 Thallium-201 uptake was visually scored and judged as normal (Group 1), reversible defect (Group II), new fill-in after reinjection (Group IIIa) and no fill-in even after reinjection (Group IIIb).
 New fill-in after reinjection was observed in 27 segments of the 85 segments (32%), showing persistent defect on the stress and delayed images.
 The wall motion in Group IIIa was worse than Group II but better than Group IIIb.
 Group IIIa showed Q-wave on ECG more often (69%) than Group II (27%) (p less than 0.01), but less often than Group IIIb (85%) (p less than 0.05).
 These data indicate that the reinjection 201Tl imaging often identifies new fill-in in the areas of no redistribution on the delayed images and it may hold promise for assessing tissue viability which the conventional imaging may underestimate.
",13
2007,"Effects of long-term coenzyme Q10 and captopril treatment on survival and functional capacity in rats with experimentally induced heart infarction.
 The effects of coenzyme Q10 (CoQ) and captopril on functional capacity, hemodynamics and survival were studied in 154 rats that recovered after experimental myocardial infarction.
 Rats were randomized into four groups receiving either CoQ, captopril, a combination of the two drugs or 1 ml of tap water once daily for 12 weeks from the day of coronary artery ligation.
 CoQ as well as captopril and the combined treatment significantly improved exercise capacity as evaluated by lactate production during a standardized treadmill exercise test.
 No significant changes in heart rate or mean blood pressure were observed during the study in the captopril-treated group.
 CoQ treatment increased the maximum heart rate significantly, whereas no effect on mean blood pressure was observed.
 Both captopril and CoQ decreased pulmonary congestion.
 Furthermore, the data may suggest that captopril prevents right ventricular hypertrophy seen in placebo-treated rats with large infarcts.
 This was not observed after CoQ treatment.
 Captopril treatment improved 3-month probability of survival (93%) as compared with placebo (74%) (P less than .05).
 CoQ and the combined treatment tended to improve survival, but this was, however, not statistically significant.
",13
2008,"How ancient is temporal arteritis?
 Realism is one of the characteristics of Amarnian art; some details of The Harpist represented in the tomb of Pa-Aton-Em-Heb (1350 BC, 18th Dynasty) might gives clues to a diagnosis: the eyes are closed with swollen lids, and the harpist appears to stare into space; he is round shouldered with a very wasted face, his temporal ara is heightened and hollowed by a broken line joining the extremity of the eyebrow with the corner of the eye.
 These details are not found elsewhere.
 Did the harpist's blindness result from temporal arteritis associated to polymyalgia rheumatica?.
",13
2009,"Propagation of deep venous thrombosis identified by duplex ultrasonography.
 To investigate the efficacy of anticoagulation in preventing continuing thrombosis, we prospectively evaluated 24 patients with acute deep venous thrombosis using duplex ultrasonography.
 All patients were hospitalized with conclusive ultrasonic evidence of deep venous thrombosis identified in one of four levels: I, calf only; II, calf-popliteal; III, calf-popliteal-femoral; or IV, calf-popliteal-femoral-iliac.
 Duplex scans were obtained on admission and on three subsequent occasions during therapy.
 Progression of thrombosis was defined as advancement of thrombus to the more proximal venous level.
 Demographic data, symptoms, risk factors for deep venous thrombosis, physical findings, anticoagulation regimens, and hematologic variables were ascertained.
 Adequacy of anticoagulation was defined as elevation of baseline activated partial thromboplastin time by 150%.
 Nine patients (38%) had progression of thrombosis, and 15 (62%) had stable or improving duplex scans.
 Progression occurred as follows: I----II (2), I----III (2), II----III (1), and III----IV (4).
 Of the demographic and clinical variables examined, only smoking correlated with progression of thrombus (p = 0.04).
 Average heparin dose in the stable group was 1214 +/- 294 units/hr and 1122 +/- 248 units/hr in the group that progressed (p = 0.8): activated partial thromboplastin time was 45.6 +/- 7 seconds in the stable group and 49.8 +/- 9 seconds in the progression group (p = 0.7).
 Nine patients in the stable group had consistently adequate anticoagulation, whereas six did not; six in the progression group were consistently anticoagulated, and three were not.
 Two patients (one with stable thrombus and one with progressive thrombus) suffered nonfatal pulmonary emboli.
 Clot progression as determined by duplex scanning did not predict acute complications of deep venous thrombosis.
",13
2010,"Clinical spectrum of symptomatic external iliac fibromuscular dysplasia.
 External iliac fibromuscular dysplasia is a rare and usually asymptomatic disorder.
 We report eight symptomatic patients seen over a 15-year period and review pathophysiologic mechanisms accounting for the three following distinct lower extremity ischemic sequelae: (1) Emboli--episodic focal digital ischemia (blue toe) was seen in three patients.
 Resection and primary anastomosis of focal iliac ulcerative fibromuscular dysplasia (one patient) or resection and replacement (two patients) removed the embolic source and relieved the symptoms.
 (2) Chronic ischemia--gradual onset of full leg claudication in four patients was treated by operative graduated intraluminal dilation in three patients and prosthetic bypass in one.
 Arteriography subsequently showed a remodeled lumen in the three patients who underwent dilation.
 (3) Dissection--acute onset leg ischemia resulted from presumed dissection of the external iliac segment.
 After 4 months of conservative management of antiplatelet agents and exercise, symptoms resolved completely, and arteriogram showed spontaneous restoration of a normal lumen in the dissected segment.
 The clinical presentation of fibromuscular dysplasia may mimic other arterial processes such as atherosclerosis.
 Diagnosis is made only by arteriography with specific magnification views of the external iliac arteries and careful surveillance of the renal arteries.
 Appropriate treatment should be tailored to the clinical presenting symptom.
 For microembolic disease, resection and replacement are required.
 For chronic ischemia, intraluminal dilation is generally sufficient and durable and has proved to be a simpler and acceptable alternative to replacement or bypass.
 In acute dissection, surgical intervention may be deferred if the limb is viable to allow spontaneous healing and remodeling.
 Persistent symptoms may be the only indication for intervention in this ischemic manifestation of external iliac fibromuscular dysplasia.
",13
2011,"Initial clinical evaluation of carotid artery laser endarterectomy.
 Clinical study of carotid artery laser endarterectomy began April 15, 1988.
 This report describes the first 10 cases that were performed in nine patients (five men and four women, mean age 70 years).
 Indications were asymptomatic stenosis (5), transient ischemic attacks (4), and stroke in evolution (1).
 There were two emergency cases and eight elective cases (including one reoperative case).
 Surgical exposure, systemic heparinization, vascular control, and a longitudinal arteriotomy were used.
 The cleavage plane between atheromas and media was developed with argon ion laser radiation (488 and 514.5 nm) directed through a 300 microns quartz fiber at power 1.0 W.
 Laser radiation was used to cut the atheromas out of the arteries and weld the end points.
 Residual atheromatous debris were vaporized with individual laser exposures.
 Arteriotomies were closed with sutures, and blood flow was restored.
 The endarterectomies were 3.9 +/- 1.1 cm long and required 330 +/- 97 joules.
 Mean clamp time was 22.5 +/- 7.9 minutes.
 Shunts were used in two cases.
 There were no arterial perforations or injuries as a result of laser light.
 Complications were hematoma (1), respiratory arrest (1), and transient neurologic deficit (1).
 Carotid endarterectomy is technically feasible with argon ion laser radiation.
 In the present series, postoperative observations, averaging 12 months and ranging from 5 to 19 months, have shown satisfactory results.
 No angiographic follow-up examinations were carried out.
",13
2012,"The influence of extracorporeal circulation on erythrocytes and flow properties of blood.
 The influence of extracorporeal circulation on red blood cells and flow properties of blood was studied in 10 patients undergoing aorta-coronary bypass grafting.
 Blood samples were drawn on admission, under general anesthesia before the operation, during extracorporeal circulation, immediately after extracorporeal circulation, and 24 hours after extracorporeal circulation.
 Echinocytes were found during and shortly after extracorporeal circulation, but disappeared within 24 hours.
 Washing the cells in buffer restored the normal discocytic shape, which indicated that a plasma factor was responsible.
 Red cell membrane lipids were not affected.
 Analysis of the membrane proteins revealed a decrease of ankyrin after extracorporeal circulation, which was prevented by protease inhibitors during preparation.
 This suggests an increased proteolytic activity of the plasma after extracorporeal circulation.
 Red cell deformability was not altered.
 Plasma viscosity and hematocrit were markedly reduced by hemodilution with the priming solution.
 Their low levels resulted in a low blood viscosity during extracorporeal circulation, which was even lower at 26 degrees C than before or after the operation at 37 degrees C.
 We conclude that the red cell is affected by extracorporeal circulation.
 The flow properties of blood, however, are not impaired, but are improved by hemodilution.
",13
2013,"Prostacyclin and prostaglandin E2 mediate reduction of increased mean arterial pressure during cardiopulmonary bypass by aspiration of shed pulmonary venous blood.
 Increased mean arterial pressure during the aortic crossclamp period while on cardiopulmonary bypass was usually treated by us with hypotensive drugs.
 We noticed, however, that aspirating shed excess pulmonary venous blood from the open pleural cavities causes an immediate reduction in mean arterial pressure, obviating the need for any further pharmaceutical intervention.
 In this study we investigated the relationship between the reduction in mean arterial pressure and the levels of prostacyclin and prostaglandin E2 in the peripheral and pulmonary venous blood.
 Ten men undergoing coronary bypass operations had 21 episodes of increased mean arterial pressure (106.9 +/- 11.4 mm Hg) during aortic crossclamping, which was reduced to 67.4 +/- 11.4 mm Hg (p less than 0.001) only by aspirating a mean of 490 ml (range 150 to 1100 ml) of pulmonary venous blood from the pleurae back into the circulation.
 Mean peripheral prostacyclin level, measured as 6-keto-prostaglandin F1 alpha, and prostaglandin E2 level, both measured by radioimmunoassay technique, were significantly lower at peak mean arterial pressure (419 +/- 180 and 59.5 +/- 21.2 pg/ml) than at lowest mean arterial pressure (632 +/- 271 and 96.7 +/- 52.4 pg/ml for 6-keto-prostaglandin F1 alpha and prostaglandin E2, respectively; p less than 0.001).
 Prostaglandin F1 alpha and prostaglandin E2 levels in the aspirated pulmonary venous blood were 2309 +/- 3098 pg/ml and 749 +/- 909 pg/ml, respectively.
 The hypotensive effect of shed pulmonary venous blood that is aspirated back from the pleurae into the circulation seems to be mediated by the high levels of prostacyclin and prostaglandin E2, both powerful vasodilators.
",13
2014,"Myocardial temperature during cardiac operations: influence on right ventricular function.
 Maintenance of right heart integrity is frequently neglected during coronary operations.
 Right ventricular dysfunction sometimes limits the success of the surgical procedure, however.
 In addition to the use of cardioplegic solutions, myocardial hypothermia during ischemic cardiac arrest seems to be an important factor for guaranteeing right ventricular performance thereafter.
 This study was designed to measure myocardial temperature in patients with coronary artery disease who have significant stenosis of the right coronary artery in comparison with those who do not have stenosis of the right coronary artery and to evaluate the influence of myocardial temperature on right ventricular hemodynamics after cardiopulmonary bypass.
 Right ventricular function was assessed by thermodilution technique, which allows measurement of right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume.
 Right ventricular temperature differed significantly between the two groups, with the lowest value of 15.1 degrees +/- 1.8 degrees C in the group without stenosis of the right coronary artery and a value of 22.2 degrees +/- 2.1 degrees C in the group with stenosis of the right coronary artery.
 Left ventricular and septal temperatures were without group differences within the investigation period.
 Right ventricular hemodynamics were impaired only in the group with stenosis of the right coronary artery with a decrease in right ventricular ejection fraction from 44.2% to 34.1% immediately after termination of bypass and an increase in right ventricular end-diastolic volume index (+38%) and right ventricular end-systolic volume index (+70%).
 Cardiac index decreased only in this group, too (-22.5%).
 Analysis of covariance revealed a significant correlation only between changes in right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume and the course of right myocardial temperature.
 It is concluded that right ventricular hypothermia is more difficult to achieve in patients with a diseased right coronary artery.
 Constant myocardial hypothermia, however, seems to be important in guaranteeing right ventricular function, which easily can be evaluated by the thermodilution technique.
",13
2015,"Intraoperative coronary artery endarterectomy with excimer laser.
 Compared with continuous-wave lasers, excimer lasers exhibit several in vitro advantages: nonthermal ablation process and linear relation between the number of pulses and the depth of the crater.
 A 308 nm, 20 nsec pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application.
 At the time of cardiopulmonary bypass in 10 symptomatic patients, before bypass grafting, a 1 mm diameter core specifically ultraviolet-tipped fiberoptic scope was introduced via the coronary arteriotomy and placed upstream (seven patients) and downstream (three patients) in contact with the stenosis.
 Laser power was increasingly delivered up to the clearing of the stenosis or occlusion.
 Quality of angioplasty was controlled by calibration of the neolumen, cardioplegic solution output through the laser-treated segment, and an eighth day or sixth month coronary arteriogram.
 In the first three patients studied on the eighth day, all laser-treated coronary artery segments showed an early parallel-linked patent neolumen despite competitive bypass graft flow.
 In the patients studied after 6 months, all recanalized segments were patent except one; in one patient the venous graft was occluded, but the upstream laser angioplasty was patent.
 The main limitation of the method lies in the fact that laser coronary recanalization is confined to the fiber core diameter.
 We conclude that (1) excimer laser angioplasty may be safe and efficient during surgical procedure and (2) as catheter flexibility remains the most critical problem, we are now assuming an appropriate tool with a multifiber system that is suitable for intraoperative as well as percutaneous routes.
",13
2016,"Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group 
 796 men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction [MI] ), were randomised to double-blind placebo-controlled treatment with oral aspirin 75 mg/day and/or 5 days of intermittent intravenous heparin.
 The risk of MI and death was reduced by aspirin.
 After 5 days the risk ratio was 0.43 (confidence intervals, 0.21-0.91), at 1 month 0.31 (0.18-0.53), and at 3 months 0.36 (0.23-0.57).
 Aspirin reduced event rate in non-Q-wave MI and unstable angina, independently of electrocardiographic abnormalities or concurrent drug therapy.
 Heparin had no significant influence on event rate, although the group treated with aspirin and heparin had the lowest number of events during the initial 5 days.
 Treatment had few side-effects and high patient compliance.
",13
2017,"The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease 
 BACKGROUND.
 A high incidence of hypertension (50 to 75 percent) occurs early in the course of autosomal dominant polycystic kidney disease.
 Cyst enlargement, causing bilateral renal ischemia and subsequent release of renin, is proposed as the cause of this form of hypertension.
 METHODS.
 To investigate this hypothesis, we measured plasma renin activity and aldosterone concentrations during short-term and long-term converting-enzyme inhibition in 14 patients with hypertension due to polycystic kidney disease, 9 patients with essential hypertension, 11 normotensive patients with polycystic kidney disease, and 13 normal subjects.
 The groups were comparable with respect to age, sex, body-surface area, degree of hypertension, sodium excretion, and renal function.
 RESULTS.
 During the short-term study, the mean (+/- SE) plasma renin activity was significantly higher in the hypertensive patients with polycystic kidney disease than in the patients with essential hypertension, in the supine (0.36 +/- 0.06 vs.
 0.22 +/- 0.06 ng per liter.second, P = 0.05) and upright positions (1.03 +/- 0.14 vs.
 0.61 +/- 0.08 ng per liter.second, P less than 0.03) and after converting-enzyme inhibition (1.97 +/- 0.28 vs.
 0.67 +/- 0.17 ng per liter.second, P less than 0.0006).
 The mean arterial pressures measured in the supine and upright positions and the plasma aldosterone concentrations measured in the upright position were significantly higher in the normotensive patients with polycystic kidney disease than in the normal subjects.
 After six weeks of converting-enzyme inhibition, renal plasma flow increased (P less than 0.005), and both renal vascular resistance (P less than 0.007) and the filtration fraction (P less than 0.02) decreased significantly in the hypertensive patients with polycystic kidney disease but not in the patients with essential hypertension.
 CONCLUSIONS.
 The renin-angiotensin-aldosterone system is stimulated significantly more in hypertensive patients with polycystic kidney disease than in comparable patients with essential hypertension.
 The increased renin release, perhaps due to renal ischemia caused by cyst expansion, probably contributes to the early development of hypertension in polycystic kidney disease.
",13
2018,"Predicting the appropriate use of carotid endarterectomy, upper gastrointestinal endoscopy, and coronary angiography 
 BACKGROUND AND METHODS.
 In a nationally representative population 65 years of age or older, we have demonstrated that about one quarter of coronary angiographies and upper gastrointestinal endoscopies and two thirds of carotid endarterectomies were performed for reasons that were less than medically appropriate.
 In this paper we examine whether specific characteristics of patients (age, sex, and race), physicians (age, board-certification status, and experience with the procedure), or hospitals (teaching status, profit-making status, and size) predict whether a procedure will be performed appropriately.
 RESULTS.
 In general, we found that little of the variability in the appropriateness of care (4 percent or less) could be explained on the basis of standard, easily obtainable data about the patient, the physician, or the hospital.
 For all three procedures, however, performance in a teaching hospital increased the likelihood that the reasons would be medically appropriate (P = 0.09 for angiography, P = 0.30 for endoscopy, and P less than 0.01 for endarterectomy).
 In addition, angiographies were more often performed for appropriate reasons in older or more affluent patients (P less than 0.01 for both).
 Being treated by a surgeon who performed a high rather than a low number of procedures decreased the likelihood of an appropriate endarterectomy by one third, from 40 to 28 percent (P less than 0.01).
 CONCLUSIONS.
 Appropriateness of care cannot be closely predicted from many easily determined characteristics of patients, physicians, or hospitals.
 Thus, for the present, if appropriateness is to be improved it will have to be assessed directly at the level of each patient, hospital, and physician.
",13
2019,"Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B 
 BACKGROUND AND METHODS.
 The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography.
 Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment.
 Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated).
 RESULTS.
 The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, -7 and +5 percent, respectively), but more substantially among patients treated with lovastatin and colestipol (-46 and +15 percent) or niacin and colestipol (-32 and +43 percent).
 In the conventional-therapy group, 46 percent of the patients had definite lesion progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11 percent.
 By comparison, progression (as the only change) was less frequent among patients who received lovastatin and colestipol (21 percent) and those who received niacin and colestipol (25 percent), and regression was more frequent (lovastatin and colestipol, 32 percent; niacin and colestipol, 39 percent; P less than 0.005).
 Multivariate analysis indicated that a reduction in the level of apolipoprotein B (or LDL cholesterol) and in systolic blood pressure, and an increase in HDL cholesterol correlated independently with regression of coronary lesions.
 Clinical events (death, myocardial infarction, or revascularization for worsening symptoms) occurred in 10 of 52 patients assigned to conventional therapy, as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol (relative risk of an event during intensive treatment, 0.27; 95 percent confidence interval, 0.10 to 0.77).
 CONCLUSIONS.
 In men with coronary artery disease who were at high risk for cardiovascular events, intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions, increased the frequency of regression, and reduced the incidence of cardiovascular events.
",13
2020,"Outcome and predictors of outcome in pediatric submersion victims receiving prehospital care in King County, Washington 
 Predictors of outcome in pediatric submersion victims treated by Seattle and King County's prehospital emergency services were studied.
 Victims less than 20 years old were identified from hospital admissions and paramedic and medical examiners' reports.
 The proportion of fatal or severe outcomes in patients were compared with various risk factors.
 Of 135 patients, 45 died and 5 had severe neurologic impairment.
 A subset of 38 victims found in cardiopulmonary arrest had a 32% survival rate, with 67% of survivors unimpaired or only mildly impaired.
 The two risk factors that occurred most commonly in victims who died or were severely impaired were submersion duration greater than 9 minutes (28 patients) and cardiopulmonary resuscitation duration longer than 25 minutes (20 patients).
 Both factors were ascertained in the prehospital phase of care.
 Submersion duration was associated with a steadily increasing risk of severe or fatal outcomes: 10% risk (7/67) for 0 to 5 minutes, 56% risk (5/9) for 6 to 9 minutes, 88% risk (21/25) for 10 to 25 minutes, 100% risk (4/4) for greater than 25 minutes.
 None of 20 children receiving greater than 25 minutes of cardiopulmonary resuscitation escaped death or severe neurologic impairment.
 Our rates for saving all victims, particularly victims in cardiopulmonary arrest, are considerably higher than has been reported before the children.
 Prompt prehospital advanced cardiac life support is the most effective means of medical intervention for the pediatric submersion victim.
 Prehospital information provided the most valuable predictors of outcome.
",13
2021,"Histologic investigation of vascular malformations of the face after transarterial embolization with ethibloc and other agents.
 Twenty-one vascular malformations located in the facial area, 11 high-flow arteriovenous malformations and 10 slow-flow malformations, underwent combined treatment by embolization and later surgery.
 Embolization was performed simultaneously with superselective angiography of the branches of the external carotid artery.
 The new biodegradable fibrosing agent Ethibloc was used in 16 cases.
 Histologic examination of the surgical specimens confirmed the good target orientation by the transarterial injection of Ethibloc.
 Limitations of this technique are discussed.
 The agent proved to have thrombogenic and fibrogenic properties.
 Some of the vascular walls degenerated and ruptured following the embolization, but there were no instances of necrosis of interstitial tissue or skin.
 Embolization treatment of vascular malformations of the face was not curative, but it facilitated subsequent surgery in all examined cases.
",13
2022,"Surgical augmentation of skin blood flow and viability in a pig musculocutaneous flap model.
 A porcine rectus abdominis musculocutaneous (TRAM) flap model was designed and validated in nine pigs.
 This TRAM flap was based on the deep inferior epigastric (DIE) vessels with an 8 x 18 cm transverse skin paddle at the superior end of the rectus abdominis muscle.
 The model was subsequently used to test our hypothesis of surgical augmentation of flap viability by vascular territory expansion.
 Specifically, we observed that ligation of the superior epigastric (SE) vessels at 4, 7, 14, and 28 days (N = 6 to 8) prior to raising the TRAM flaps significantly increased (p less than 0.05) the length and area of the viable skin in the transverse skin paddles of the treatment flaps compared with the contralateral shammanipulated control flaps.
 This significant increase in skin viability was seen to be accompanied by a significant increase (p less than 0.05) in skin and muscle capillary blood flow in the treatment TRAM flaps compared with the controls (N = 9).
 The mechanism of vascular territory expansion is unclear.
 We postulate that hypoxia resulting from the ligation of the superior epigastric vessels prior to the flap surgery may play a role in the triggering of the deep inferior epigastric artery to take over some of the territory previously perfused by the superior epigastric artery.
 This would then increase the skin and muscle capillary blood flow in the transverse paddle when the TRAM flap was raised on the deep inferior epigastric vascular pedicle.
",13
2023,"Critical ischemia times and survival patterns of experimental pig flaps.
 Previous work on critical ischemia time suggested (1) a greater susceptibility of myocutaneous flaps over skin flaps to the ischemia reperfusion injury and (2) that duration of ischemia may affect the survival area of a flap.
 Using a pig model, 55 animals were operated on and the critical ischemia times and survival patterns of the buttock skin (n = 85) and latissimus dorsi myocutaneous (n = 88) island flaps were determined after being submitted to 0, 2, 4, 6, 8, 10, 12, 14, and 16 hours of normothermic ischemia.
 The average critical ischemia times (CIT50) were determined to be 9 and 10 hours for the buttock skin and latissimus dorsi myocutaneous flaps, respectively.
 Percentage of total area surviving (%TAS) in those flaps which did survive was adversely affected by increases in the ischemic interval in both flap models.
 A statistically significant decrease in percentage of total area surviving was found after 6 and 8 hours of ischemia for the buttock skin and latissimus dorsi myocutaneous flaps, respectively.
",13
2024,"Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase.
 A brother and sister with long-standing symptoms of postural hypotension are described.
 They were considerably worse in the morning, after exercise and in warm weather.
 In the male, erection was unaffected but ejaculation was prolonged or absent.
 Both had nocturia, but there were no urinary bladder, bowel or sweating abnormalities.
 Autonomic function tests confirmed sympathetic adrenergic failure with spared sympathetic cholinergic and intact parasympathetic function.
 There were no other neurological abnormalities.
 Noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was elevated.
 Urinary levels of noradrenaline and adrenaline metabolites were below detection limits, but dopamine metabolites were normal or elevated.
 Dopamine beta-hydroxylase activity was undetectable in the plasma.
 Immunohistochemical studies of perivascular cutaneous tissue confirmed normal peptidergic and tyrosine hydroxylase immunoreactivity, with absent dopamine beta-hydroxylase immunoreactivity.
 The findings were consistent with an enzymatic deficit in the conversion of dopamine to noradrenaline.
 The parents were clinically and biochemically normal.
 Treatment of both patients with the synthetic amino acid, d-l-threo-dihydroxyphenylserine, which contains a hydroxyl group and is converted to noradrenaline by dopa-decarboxylase, reduced symptoms and signs of postural hypotension and increased levels of plasma noradrenaline and its urinary metabolites.
 In the male, ejaculation became possible.
 Behavioural changes included a feeling of confidence and optimism, with a tendency to be argumentative.
 The laevo isomer also raised blood pressure and plasma noradrenaline levels.
 The drug had no direct pressor effects, as its actions were prevented by the dopa-decarboxylase inhibitor, carbidopa.
",13
2025,"Clinical diagnosis of tamponade in Malawi.
 A consecutive series of 25 Malawian patients with tamponade secondary to tuberculosis were compared to 25 patients with congestive cardiac failure, without pericardial effusion in a retrospective study.
 More patients with tamponade had an impalpable apex beat (21/1), pulsus paradoxus (13/0), soft heart sounds (13/2), paradoxical rise in jugular venous pressure (6/0), and fewer had a murmur (1/14).
 All these results are significant (p less than 0.05) by the chi 2 test with Yates' correction.
 The presence of two or more of these discriminating physical signs has a positive predictive value of 75 per cent, and a negative predictive value of 99.5 per cent for the diagnosis of tamponade.
 Clinical diagnosis of tamponade by primary health care personnel in Malawi should be possible, and lead to earlier treatment.
",13
2026,"Effects of long-term verapamil therapy on serum lipids and other metabolic parameters.
 Calcium antagonists have been used successfully in the management of hypertension for more than a decade, but less is known about their long-term metabolic effects.
 To define the impact of one calcium antagonist, verapamil, on serum lipids and other metabolic parameters, we placed 45 hypertensive patients on verapamil monotherapy and followed them for 4 to 8 years.
 After a mean treatment period of 5.3 years, total cholesterol and triglyceride levels were not significantly different from baseline, whereas the mean high-density lipoprotein cholesterol value increased significantly from 1.17 +/- 0.41 mmol/L at the initiation of treatment to 1.39 +/- 0.36 mmol/L at 5.3 years (p less than 0.05).
 Other important biochemical parameters, including serum glucose, potassium and uric acid levels were unaffected by verapamil therapy.
 No serious side effects or adverse cardiovascular events occurred during verapamil therapy, and there were no study dropouts.
 It therefore seems likely that this agent will become increasingly useful in the long-term management of essential hypertension.
",13
2027,"Anti-atherosclerotic and vasculoprotective actions of calcium antagonists.
 Treatment of hypertension may prevent many of the complications attributable to blood pressure elevation, particularly those that are ""pressure-related,"" such as stroke.
 However, the atherosclerotic complications of hypertension, e.g., coronary artery disease manifested as coronary morbidity and mortality, have not been reduced significantly with antihypertensive therapy.
 This disappointing outcome may reflect the adverse metabolic effects of the traditional therapies, diuretics and beta blockers, and their lack of specific vasoprotective properties.
 Increasing attention is thus being paid to the newer antihypertensive agents, which typically have fewer adverse effects and perhaps more physiologic mechanisms of antihypertensive action.
 Since calcium plays a key role in the genesis of atherosclerosis, calcium antagonists may positively affect the course of vascular disease.
 Investigators have observed that calcium antagonists display clear antiatherosclerotic properties in experimental as well as clinical studies.
 In one recently published clinical study, coronary artery disease was shown to develop more slowly, with a slower progression of individual stenoses, higher regression rate and less frequent occurrence of new lesions in patients treated chronically with verapamil compared to those receiving conventional therapies.
 Other similar investigations are currently under way to evaluate the antiatherogenic properties of calcium antagonists, including the Frankfurt Isoptin Progression Study (FIPS), the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS), the International Nifedipine Trial on Atherosclerosis Coronary Therapy (INTACT), and the large-scale Montreal Heart Institute Study.
 Results of these studies, which use precise end points such as myocardial infarction, cerebral infarction and peripheral vascular disease, may revolutionize the treatment of hypertension by identifying therapeutic approaches that control both the pressure-related and atherosclerotic complications of the disease.
",13
2028,"Secondary prevention with verapamil after myocardial infarction. The Danish Study Group on Verapamil in Myocardial Infarction.
 The effect of verapamil on death and major events (i.e., death or reinfarction) after an acute myocardial infarction was studied in a double-blind, randomized, placebo-controlled, multicenter trial, the Danish Verapamil Infarction Trial II (DAVIT II).
 Eight hundred seventy-eight patients started treatment with verapamil 360 mg/day and 897 patients with placebo.
 Treatment continued for up to 18 months (mean 16 months).
 Ninety-five deaths and 146 major events occurred in the verapamil group and 119 deaths and 180 major events in the placebo group.
 Eighteen-month mortality rates were 11.1 and 13.8% (hazard ratio 0.80, 95% confidence limits 0.63 to 1.05, p = 0.108), and major event rates 18.0 and 21.6% (0.80, 0.64 to 0.99, p = 0.027) in the verapamil and placebo groups respectively.
 When combining the results of this trial with the results of the first Danish study on verapamil in myocardial infarction, the meta-analysis demonstrated that treatment with verapamil from the second week after an acute myocardial infarction resulted in a reduction of pooled odds ratios of 0.22 (95% confidence interval 0.01 to 0.37, p = 0.04) for death, 0.21 (0.05 to 0.35, p = 0.02) for major events, and 0.27 (0.06 to 0.43, p = 0.02) for first reinfarctions.
 It is concluded that long-term treatment with verapamil after an acute myocardial infarction is associated with a significant reduction in overall mortality as well as major event and reinfarction rates.
",13
2029,"Relation between lipids and atherosclerosis: epidemiologic evidence and clinical implications.
 Coronary artery disease (CAD) is the leading cause of death in most developed countries.
 Therefore, elucidation of risk factors and associated mechanisms for CAD has been a high priority.
 Data from the Framingham Heart Study and other large-scale epidemiologic studies have identified major risk factors associated with CAD, demonstrating the adverse effects of increased total and low-density lipoprotein cholesterol levels and the protective effect of high-density lipoprotein cholesterol.
 Other more recent investigations, including the Lipid Research Clinics Trial and the Helsinki Heart Study, have shown that lowering total cholesterol and raising high-density lipoprotein cholesterol significantly reduce the risk for CAD.
 Because hypertension is also a significant risk factor for CAD, the assumption has been that blood pressure reduction should offer significant benefits in terms of CAD risk.
 However, despite their antihypertensive efficacy, diuretics and beta blockers have failed to significantly reduce CAD morbidity or mortality.
 The adverse effects of these antihypertensive agents on lipid profiles, glucose metabolism and other metabolic parameters may account for their disappointing performance in reducing CAD morbidity and mortality.
 As a result, newer agents such as angiotensin-converting enzyme inhibitors and calcium antagonists that appear to be free of such adverse effects have garnered considerable attention for their potential to reduce CAD risk.
",13
2030,"Effects of hydralazine and prostaglandin E1 on regional myocardial function in the ischemic canine heart.
 The effects of hydralazine and prostaglandin E1 on regional myocardial function were studied in dogs.
 Sixteen dogs were randomly assigned to one of two drug treatment groups of eight dogs each.
 The first group (G1) was treated with 0.4 mg/kg hydralazine administered as a bolus.
 The second group (G2) received prostaglandin E1 given as an infusion for a total dose of 0.8 micrograms/kg.
 Regional myocardial function was assessed through the measurement of myocardial segment shortening during systole.
 We call this index percent systolic shortening (%SS).
 An ischemic heart preparation was created by partial occlusion of coronary blood flow.
 The degree of induced ischemia was determined by following the reduction in %SS.
 Hydralazine reduced %SS of the ischemic myocardium while increasing the cardiac index, stroke volume index, and coronary blood flow.
 Prostaglandin E1 increased %SS, cardiac index, and stroke volume index in the ischemic heart preparation.
 Hydralazine, therefore, induced dissociation between global ventricular function and regional myocardial function whereas prostaglandin E1 did not.
 The present findings emphasize that evaluation of vasoactive drugs should consider their effects on regional myocardial function as well as on global hemodynamics.
",13
2031,"An increase in plasma cholesterol independent of thyroid function during long-term amiodarone therapy. A dose-dependent relationship.
 OBJECTIVE: To determine whether long-term amiodarone treatment is associated with a rise in plasma cholesterol, and, if so, to analyze its relation with thyroid function.
 DESIGN: Consecutive entry trial, including cardiac patients who initiated amiodarone medication but excluding those with abnormal thyroid function (defined as peak thyroid-stimulating hormone [TSH] response to thyrotropin-releasing hormone [TRH] less than 2.8 or greater than 22.0 mU/L) either before or during amiodarone treatment.
 PATIENTS: Twenty-three patients who remained euthyroid were studied.
 INTERVENTION: Oral administration of amiodarone (mean duration of treatment, 17 months; range, 6 to 30 months).
 MEASUREMENTS: Fasting plasma lipids, thyroid hormones, and peak TSH to TRH values were recorded before and every 6 months during amiodarone treatment.
 RESULTS: Plasma cholesterol gradually increased from 5.1 +/- 0.2 mmol/L before treatment to 6.9 +/- 0.8 mmol/L after 30 months of amiodarone medication (P less than 0.001); the peak TSH response to TRH did not change.
 When age- and sex-specific reference values were applied, 30% of the patients had cholesterol values above the 75th percentile before treatment; this number rose to 69% after 2 years of treatment.
 The rise in plasma cholesterol was associated with an equal increase in apoprotein B.
 Plasma cholesterol was not related to the daily dose of amiodarone or to plasma concentrations of amiodarone, desethylamiodarone, thyroxine (T4), triiodothyronine (T3), or reverse triiodothyronine (rT3).
 Linear regression analysis indicated a positive relation between plasma cholesterol and the cumulative dose of amiodarone (r = 0.25, P less than 0.05).
 CONCLUSION: Long-term amiodarone treatment is associated with a dose-dependent increase in plasma cholesterol that is independent of thyroid function.
",13
2032,"Cardiac rehabilitation after coronary artery bypass grafting: effects on exercise performance and risk factors.
 After coronary artery bypass grafting (CABG), 49 nonselected patients followed a cardiac rehabilitation program that included medical follow-up and physical training, both in outpatient groups and on an individual basis at home.
 The effect of the program on exercise test variables, coronary risk factors, and medication one year after surgery was compared to a nonexercised control group (n = 98).
 The study group showed less increase in the rate-pressure product, indicating a favorable effect on myocardial oxygen consumption (0.7 +/- 5.4 vs 2.8 +/- 5.6, p less than .05); a lower frequency of angina at exercise testing (6% vs 18%, p less than .01); a reduction in resting systolic and diastolic blood pressure (9/4mmHg, p less than .01); fewer smokers (6% vs 17%, p less than .05); and fewer patients taking long-acting nitrates (0% vs 10.2%, p less than .05).
 It is suggested, therefore, that an organized cardiac rehabilitation program may be advantageous after CABG.
",13
2033,"A frameshift mutation leading to type 1 antithrombin deficiency and thrombosis.
 Type 1 antithrombin III (ATIII) deficiency, which is the commonest form of inherited ATIII defect, is characterized by a quantitative reduction in both immunologically and functionally detectable protein.
 This condition is associated with a high incidence of thromboembolic disorder.
 Previous investigations have shown that the ATIII genes in the majority of cases are grossly intact, but the precise underlying molecular defects remain unknown.
 We have investigated the molecular basis of a type 1 ATIII deficiency in an Italian kindred by enzymatic amplification of the ATIII gene sequences in affected family members and direct sequencing of the amplified genomic DNA.
 A novel mutation, the deletion of a single T in the second position of codon 119, was identified in each of the affected individuals.
 The resulting frameshift leads to a premature termination in codon 126, effectively resulting in a null allele.
",13
2034,"Cardiac myosin-induced myocarditis. Heart autoantibodies are not involved in the induction of the disease.
 We recently demonstrated that cardiac myosin is capable of inducing autoimmune myocarditis in genetically predisposed mice.
 This disease parallels coxsackievirus B3-induced autoimmune myocarditis in many respects and is associated with high-titer autoantibodies specific for cardiac myosin.
 The following lines of evidence suggest that these autoantibodies are not involved in the induction of autoimmune myocarditis: 1) immunoperoxidase staining of heart sections from cardiac myosin-immunized A/J and A.SW mice revealed IgG depositions only along damaged muscle fibres in infiltrated areas, but not in intact tissue; 2) myosin autoantibodies did not bind to the surface of viable cardiac myocytes isolated from mice, but only reacted with myocytes permeabilized with detergent; 3) mice treated with a single high dose of cyclophosphamide, which reduces the humoral immune response, still developed severe myocarditis, despite the fact that their autoantibody titers were reduced to the level of adjuvant-injected controls; and 4) passive transfer of high-titer myosin autoantibodies failed to induce myocarditis, although the titers in the recipients were comparable to those found in mice with cardiac myosin-induced disease.
 Together, the results suggest that high-titer myosin autoantibodies are secondary rather than primary to the disease.
",13
2035,"Circadian variations in myocardial ischemia. Implications for management.
 Extended ambulatory electrocardiographic monitoring in the patient's customary environment provides clear evidence of circadian patterns in myocardial ischemic episodes.
 In patients with effort angina, the highest activity occurs between 6 AM and noon.
 This coincides with peaks in diurnal variation of frequency of acute myocardial infarction, stroke, and sudden death.
 A number of potential underlying common triggering mechanisms, including catecholamine secretion, sympathetic nervous system activity, blood pressure, heart rate, cortisol secretion, and aggregability of platelets, exhibit similar surges.
 As a result of these coinciding morning peaks, myocardial oxygen demand is increased and oxygen supply reduced after a person arises in the morning.
 Attention to this vulnerable period is merited in the timing and choice of medication, both to prevent or reduce ischemia and to modify potential disease-triggering mechanisms.
",13
2036,"Angiotensin I-forming angiotensinogenases in extrarenal vasculature and in the kidney.
 The intention of this study was to characterize angiotensin I-forming angiotensinogenases (AIFAs) in rat extrarenal arterial walls and to clarify whether these enzymes are also present in the kidney.
 A further aim was to identify AIFAs in human vasculature and to establish whether they are affected in essential hypertension.
 Sprague-Dawley rats and vascular sections of patients undergoing corrective surgery were studied.
 Enzyme kinetic assays were performed using angiotensin I radioimmunoassay and purified natural angiotensinogens.
 Fast protein liquid chromatography was employed for biochemical characterization.
 A series of AIFAs with various isoelectric points, molecular weights and pH optima was detected in rat extrarenal vascular and, with differing distributions of enzyme activities, in renal tissues.
 In extrarenal arteries the main form of renal renin was present with a relatively low activity only.
 AIFAs were also demonstrable in human extrarenal vasculature and behaved like plasma renin in essential hypertension.
 The results indicate the existence of an intrinsic human vascular RAS in extrarenal (and renal) arteries.
 Extrarenal arterial AIFAs are not generally stimulated in essential hypertensives, as previously postulated.
",13
2037,"Role of angiotensin in the renal vasoconstriction observed during the development of genetic hypertension.
 Studies have examined renal function to determine the role of the kidney in the pathogenesis and maintenance phases of hypertension in the Okamoto-Aoki strain of spontaneously hypertensive rat (SHR).
 As compared to age-matched Wistar-Kyoto rats (WKY), 4- to 6-week old SHR are moderately hypertensive and have a reduced glomerular filtration rate (GFR) and renal blood flow (RBF), and an increased renal vascular resistance.
 Cross-breeding studies indicate the reduction in RBF and GFR in young SHR is genetically linked to the hypertension and thus may be of primary pathogenetic importance.
 The combination of an elevated vascular resistance and reduced RBF and GFR in young SHR implicates increased activity of a vasoconstrictor system(s), decreased activity of a vasodilator system(s), or both.
 Observations from several laboratories support the notion that endogenous angiotensin II contributes to the renal vasoconstriction in young SHR during the developmental phase of hypertension.
 Acute and chronic inhibition of angiotensin converting enzyme reduce arterial pressure, reduce renal vascular resistance and increase renal blood flow in young and adult SHR.
 Renal vascular tone in SHR is more dependent on angiotensin converting enzyme activity than that in WKY.
 The ability of angiotensin converting enzyme inhibitors to produce renal vasodilation may be responsible, at least in part, for its antihypertensive effects.
 Other studies indicate that renal vascular reactivity to angiotensin II is exaggerated in young SHR.
 The strain differences in renal reactivity to angiotensin II can be abolished by cyclooxygenase inhibition with indomethacin, indicating that endogenous prostanoids counteract some of the constrictor action of angiotensin II, with more pronounced buffering activity in WKY.
",13
2038,"Influences of angiotensin on renal function in renal vascular hypertension.
 The scope and the magnitude of the roles which angiotensin plays in the generation and maintenance of elevated blood pressure in models of renal vascular hypertension are continuing to expand.
 It is now clear that specific angiotensin dependent mechanisms contribute importantly to the pathophysiology of hypertension and altered renal function in models of two-kidney, one clip hypertension in rats.
 The generation of angiotensin in the local intrarenal environment of the kidney is a new and potentially important mechanism contributing to altered renal function in these models.
 Application of antagonists of the renin-angiotensin system to rat models of renal vascular hypertension indicate that the effects of angiotensin attenuate renal hemodynamic and excretory behavior, particularly in the nonclipped kidney.
 Further, angiotensin may attenuate the efficiency of autoregulation of renal hemodynamics in the nonclipped kidney.
 Evidence that inhibition of angiotensin reverses or improves these altered hemodynamic and excretory functions indicate that angiotensin may contribute importantly to the pathophysiology of hypertension in these models by altering or impairing the ability of the nonclipped or normal kidney to excrete sodium and volume.
",13
2039,"Thromboxane biosynthesis in cardiovascular diseases.
 Sudden fissuring of an atherosclerotic plaque has been suggested as the primary trigger of transient spontaneous ischemia in both the coronary and cerebral circulation.
 Measurements of urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2, as well as results of Aspirin trials, have suggested that episodic platelet activation at the site of this acute vascular lesion is mediated, at least partly, by enhanced thromboxane (TX) A2 biosynthesis.
 Thus, episodic increases in metabolite excretion have been detected in unstable angina.
 Aspirin (75-325 mg/day) prevents about one third of all fatal and nonfatal thrombotic events in this setting.
 That a similar ""dynamic"" thrombotic process occurs during the early phase of acute myocardial infarction is suggested by thromboxane metabolite measurements and by the results of the ISIS-2 trial showing a similar impact of short-term Aspirin therapy to that seen in unstable angina.
 Percutaneous transluminal coronary angioplasty is associated with transiently enhanced TXA2 biosynthesis and Aspirin-suppressable periprocedural thrombotic complications.
 On the other hand, both non-insulin-dependent diabetes mellitus and type IIa hypercholesterolemia are associated with a relatively reproducible and persisting abnormality of TXA2-dependent platelet function.
 This association is likely to reflect a systemic rather than localized stimulus to platelet activation and a continuous rather than episodic alteration.
 Low-dose (50 mg/day) Aspirin can largely suppress thromboxane metabolite excretion in both diseases.
 Thus, low-dose Aspirin and/or selective prostaglandin H2/TXA2-receptor antagonists may be important tools to test the hypothesis that TXA2-dependent platelet activation represents an important transducer of the enhanced thrombotic risk associated with these metabolic abnormalities.
",13
2040,"Effect of Bay U 3405, a new thromboxane antagonist, on collagen-induced thromboembolism in rabbits.
 Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid] potently inhibits platelet aggregation, thromboxane A2-induced contraction of smooth muscles, and coronary artery thrombosis.
 We have previously demonstrated inhibition of arachidonic acid-induced sudden death by Bay U 3405.
 The purpose of this study was to investigate the effects of Bay U 3405 on thromboembolism provoked by collagen.
 Collagen fibrils dissolved in an isotonic glucose solution were injected into a marginal ear vein of anesthetized rabbits.
 Sudden death occurred within a few minutes due to elevated thromboxane A2 levels causing intravascular platelet aggregation and myocardial ischemia.
 In the vehicle-treated group, 100% of the animals died.
 One of the most prominent parameters was the massive fall in blood pressure.
 All animals pretreated with 10 mg/kg orally Bay U 3405 survived, showing only a transient hypotensive effect.
 Tracings of the electrocardiogram and heart rate were unchanged.
 Bay U 3405 will therefore be useful to elucidate the role of thromboxane A2 in various cardiovascular and respiratory diseases.
",13
2041,"Aspirin reduces the growth of medial and neointimal thickenings in balloon-injured rat carotid arteries.
 We analyzed the effect of Aspirin on the growth of experimentally induced vascular thickenings in rat carotid arteries.
 Vascular thickenings were induced by denudation of the endothelium in the left carotid artery with a balloon catheter.
 Administration of Aspirin-rich food (17.4 g/kg body wt/day) was started 1 week before and continued 2 weeks after injury.
 Nine rats were used.
 A control group of equal size received normal food.
 Sizes of the tunica media, the neointima, and the open vessel lumen were measured on cross sections of carotid segments with the aid of a videomorphometry system.
 The results show that in the Aspirin group, neointimal lesions are significantly smaller than in the control group (0.14 mm2 versus 0.23 mm2; p less than 0.5).
 Thickenings of the tunica media are also reduced (0.11 mm2 versus 0.12 mm2; p less than 0.5).
 It is suggested that Aspirin reduces both medial hypertrophy and neointimal outgrowth in injury-induced atherosclerosis.
",13
2042,"Effect of naproxen and sulindac on blood pressure response to atenolol.
 Twenty-eight patients with mild to moderate essential hypertension well controlled by atenolol entered a five-week, double-blind, placebo-controlled trial of the effects of sulindac and naproxen on blood pressure (BP) control.
 Atenolol alone was administered during weeks 1, 3, and 5.
 Naproxen or sulindac was administered with atenolol during week 2, with crossover during week 4.
 Data were analyzed for 27 of the patients (one dropped out after developing a skin rash).
 Naproxen significantly increased the systolic BP compared with placebo (mean 4.0 mm Hg; 95 percent confidence interval, 1.1-7.0; p less than 0.05).
 There were no significant differences in systolic BP during sulindac administration compared with placebo or naproxen.
 No significant effects on diastolic BP were observed.
 Weight was increased by naproxen and sulindac compared with placebo (mean 0.6-0.8 kg, p less than 0.05), although not to a clinically significant extent.
 One-week therapy with naproxen has a greater potential than sulindac to increase systolic BP in well-controlled hypertensive patients receiving atenolol; however, the increase is minor and unlikely to be of clinical significance.
",13
2043,"High-dose epinephrine improves outcome from pediatric cardiac arrest.
 STUDY OBJECTIVE: Animal studies suggest that the standard dose of epinephrine (SDE) for treatment of cardiac arrest in human beings may be too low.
 We compared the outcome after SDE with that after high-dose epinephrine (HDE) in children with refractory cardiac arrest.
 DESIGN: Prospective intervention versus historic control groups.
 TYPE OF PARTICIPANTS: Two similar groups of 20 consecutive patients each (median ages, 2.5 and 3 years) with witnessed cardiac arrest who remained in arrest after at least two SDEs (0.01 mg/kg).
 INTERVENTIONS: Treatment with an additional SDE versus HDE (0.2 mg/kg).
 MEASUREMENTS AND MAIN RESULTS: The rates of return of spontaneous circulation and long-term survival were compared.
 Fourteen of the HDE group (70%) had return of spontaneous circulation, whereas none of the SDE group did (P less than .001).
 Eight children survived to discharge after HDE, and three were neurologically intact at follow-up.
 No significant toxicity from HDE was observed.
 CONCLUSION: HDE provided a higher return of spontaneous circulation rate and a better long-term outcome than SDE in our series of pediatric cardiac arrest.
 HDE may warrant incorporation into standard resuscitation protocols at an early enough point to prevent irreversible brain injury.
",13
2044,"Systemic atropine administration during cardiac arrest does not cause fixed and dilated pupils.
 OBJECTIVES: Systemic administration of atropine during CPR may postpone brain death determination because of its reputed ability to produce fixed and dilated pupils.
 We studied the effect of atropine administered in the usual doses as an adjunct to endotracheal intubation and for cardiac arrest to determine if it would interfere with neurological assessment.
 DESIGN: Two groups of children were studied.
 Group 1 consisted of 28 patients who received atropine (0.03 +/- 0.003 mg/kg) prior to endotracheal intubation.
 Group 2 consisted of 21 patients previously without evidence of brainstem disease who suffered a witnessed arrest and had prompt return of spontaneous circulation and received an atropine dose of 0.03 +/- 0.01 mg/kg.
 RESULTS: In group 1, pupillary size averaged 4.02 +/- 0.78 mm before and 4.75 mm +/- .84 mm after atropine (P less than .001).
 In group 2, the pupillary examination was conducted 30 minutes after return of spontaneous circulation.
 The pupillary diameter was 4.80 +/- 0.91 mm.
 All pupils were reactive to light in both groups.
 CONCLUSION: Atropine administration in conventional dose causes slight pupillary dilation but does not abolish pupillary light reactivity.
",13
2045,"Echocardiographic left ventricular mass and electrolyte intake predict arterial hypertension.
 OBJECTIVE: To identify predictors of arterial hypertension.
 PATIENTS: One hundred thirty-two normotensive adults from a large employed population.
 METHODS: Echocardiography, standard blood tests, and 24-hour urine collection, at baseline and after an interval of 3 to 6 years (mean, 4.7 +/- 0.8 years).
 RESULTS: At follow-up, 15 subjects (11%; 7 men, 8 women) had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg or both (mean, 143 +/- 7 and 87 +/- 6 mm Hg, respectively).
 At baseline, subjects who developed hypertension had a greater left ventricular mass index than those who did not (92 +/- 25 compared with 77 +/- 19 g/m2 body surface area; P less than 0.005) and higher 24-hour urinary sodium/potassium excretion ratio (3.6 +/- 1.7 compared with 2.6 +/- 1.4; P less than 0.04); there were no differences in race, initial age, systolic or diastolic blood pressure, coronary risk factors, or plasma renin activity.
 The likelihood of developing hypertension rose from 3% in the lowest quartile of sex-adjusted left ventricular mass index to 24% in the highest quartile (P less than 0.005); a parallel trend was less regular for quartiles of the sodium/potassium excretion ratio (P less than 0.04).
 In multivariate analyses, follow-up systolic pressures in all subjects and in the 117 who remained normotensive were predicted by initial age, systolic blood pressure, black race, and sex-adjusted left ventricular mass index; final diastolic blood pressure was predicted by its initial value, plasma triglyceride levels, urinary sodium/potassium ratio, low renin activity, black race, and plasma glucose level.
 CONCLUSIONS: Echocardiographic left ventricular mass in normotensive adults is directly related to the risk for developing subsequent hypertension.
 Left ventricular mass improves prediction of future systolic pressure, whereas diastolic pressure is more related to initial metabolic status.
 Black race is also an independent determinant of higher subsequent blood pressure.
",13
2046,"Noninvasive detection of occlusive disease of the carotid siphon and middle cerebral artery.
 Recently, transcranial Doppler sonography has been introduced into clinical practice for noninvasive investigation of the large intracranial arteries.
 To determine its accuracy for detection of stenosing or occluding lesions, 133 consecutive patients were studied by both transcranial Doppler sonography and selective cerebral arteriography.
 Statistical analysis of findings was done separately for various arterial segments.
 High values for sensitivity and specificity were found for detecting obstruction of the carotid siphon and main stem of the middle cerebral artery.
 Diagnostic reliability of transcranial Doppler sonography was also confirmed by the calculation of a chance-corrected measure of agreement (kappa), which was close to + 1 in all subanalyses.
 Transcranial Doppler sonography seems to be a valuable tool for noninvasive detection of intracranial lesions of the middle cerebral artery and carotid siphon.
",13
2047,"Use of quinapril in the elderly patient.
 Quinapril hydrochloride is a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor that has been extensively tested and found effective when administered once-a-day to hypertensive patients of both sexes and all degrees of hypertension and cardiac compromise, including those with left ventricular hypertrophy, with and without congestive heart failure.
 Observations with earlier ACE inhibitors led to reports that this class of drugs was relatively ineffective in older hypertensive patients.
 To ascertain the role of quinapril (greater than or equal to 10 mg/day) in older patients, its blood pressure-lowering effects in 1,175 hypertensive patients less than or equal to 65 years of age were compared with those in 304 patients greater than 65 years of age.
 An excellent response was observed in patients greater than 65 years of age with mild to moderate hypertension (diastolic BP, 95 to 105 mm Hg) and moderate to severe hypertension (diastolic BP, 106 to 115 mm Hg).
 The reductions in blood pressure achieved with quinapril were at least comparable to those obtained in the younger hypertensives, and were numerically (but not statistically) greater in the mild to moderate group (-14 mm Hg v-12 mm Hg).
 In addition, the percentage of patients who experienced adverse experiences was lower in the greater than 65 group than in the less than or equal to 65 group (15% v 19%).
 The main adverse experiences reported included dizziness, headache, cough, fatigue, and hypotension.
 These findings indicate that quinapril is at least as safe and effective in older hypertensives as in younger patients.
",13
2048,"Quinapril in chronic heart failure.
 Angiotensin converting enzyme inhibitors are now firmly established in the treatment of patients with chronic heart failure (CHF).
 Their beneficial acute and chronic hemodynamic effects are not associated with reflex tachycardia or drug tolerance.
 Angiotensin converting enzyme inhibitors produce symptomatic improvement and improve exercise capacity in all grades of heart failure.
 They also improve the prognosis of patients with severe heart failure.
 Quinapril is a recently introduced, nonsulfhydryl ACE inhibitor, whose intermediate half-life makes it well-suited for the treatment of patients with CHF.
 The acute and chronic hemodynamic effects of quinapril are similar to those of other ACE inhibitors.
 In a large, multicenter, randomized, placebo-controlled study of 225 patients with mild to moderate CHF, 10 to 40 mg/day quinapril significantly improved clinical status and exercise capacity in a dose-related manner.
 The incidence of side effects did not differ significantly from that of placebo.
 The initial studies with quinapril are promising and warrant further clinical investigation of this compound.
",13
2049,"Elevated insulin, norepinephrine, and neuropeptide Y in hypertension.
 To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose.
 Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives.
 Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives.
 Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77).
 Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036).
 We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels.
",13
2050,"Dietary calcium, vascular reactivity, and genetic hypertension in the Lyon rat strain.
 In order to examine the relationship existing between dietary calcium and the development of hypertension, we developed a long-term study in the Lyon hypertensive rat strain (LH) and two control strains, the Lyon normotensive (LN) and low blood pressure rats (LL) given enriched (HCa, 2.5%), deprived (LCa, 0.03%) and normal (NCa, 0.6%) calcium diets.
 Evolution of body weight, systolic blood pressure (BP), plasma calcium and magnesium was monitored from 4 to 23 weeks of age.
 Total cardiovascular reactivity and contractile response of isolated aorta to norepinephrine were measured at 23 weeks of age.
 LH rats on HCa diet failed to develop hypertension (BP less than 150 mm Hg) whereas LH rats on LCa diet exhibited higher blood pressure levels than their controls fed the NCa diet.
 Moreover, in LN rats HCa diet slightly decreased BP whereas LCa had no effect.
 In the LL rats, on the contrary, only LCa diet slightly increased BP.
 In vivo responsiveness to NE was significantly higher in LH compared to LL and LN rats fed a NCa diet.
 HCa and LCa diets both induced a significant decrease in this response in LH rats.
 HCa diet increased the response in LN rats but decreased it in LL.
 In contrast, at the same age, the in vitro contractile response of isolated aorta to NE was significantly decreased in LH compared to LN and LL rats receiving NCa diet.
 Moreover in LH and LN rats on HCa diet the contractile response was markedly increased but no significant difference was observed with LCa diet.
",13
2051,"Sodium sensitive and sodium retaining hypertension.
 The differences between sodium sensitive and sodium retaining hypertension were theoretically considered using a water tank model of body fluid volume-blood pressure regulation.
 If an outlet valve is attached to a tank with a base area corresponding to the reciprocal of total peripheral resistance (TPR) and water is poured into this tank at a rate corresponding to the amount of Na+ intake, then equilibrium should be achieved at a certain water level, volume and output from the outlet, which represent mean arterial pressure (MAP), cardiac output (CO) and urinary Na+ excretion.
 The height of the outlet from the tank bottom and the size cross-sectional area, of the outlet correspond to the x-intercept and slope of the renal function (pressure-natriuresis) curve, respectively.
 In both nonsodium sensitive hypertension, due to the shift of the curve toward a higher blood pressure level (elevated height of the outlet) without change in the slope (size of the outlet), and sodium sensitive hypertension, due to the depressed slope of the curve (reduced outlet size), not only MAP (water level) but also CO (water volume) are increased, resulting in sodium retaining hypertension, if TPR (reciprocal of base area) remained unchanged, while CO is relatively unchanged, resulting in nonsodium retaining hypertension, if TPR is elevated.
 Thus, the MAP and its sensitivity to sodium intake is determined by the renal function curve.
 Since body fluid volume is determined by both the renal function curve and TPR, however, changes in TPR during the development of hypertension is a major factor in determining whether or not the body fluid volume has to change only a small amount or a large amount.
 Therefore, the sodium sensitivity of blood pressure and sodium retention must be considered separately.
",13
2052,"Hemodynamic and endocrine effects of mental stress in untreated borderline hypertension.
 Mental arithmetic and mirror tracing were compared in 40 untreated patients with borderline hypertension, tested in random sequence in standardized protocols.
 Both tasks significantly increased systolic and diastolic blood pressure, heart rate, cardiac index, plasma renin, and decreased peripheral resistance.
 Mental arithmetic also increased cholesterol, triglycerides and HDL; plasma catecholamines were not changed significantly.
 Lipid changes were correlated with blood pressure changes.
 These methods will be useful in exploring the relationships between hemodynamic reactivity to stress, and the presence and progression of atherosclerosis, as well as testing the effects of antihypertensive drugs on stress-induced changes that may influence atherosclerotic complications of hypertension.
",13
2053,"The role of protein kinase C and calcium in the regulation of norepinephrine release from the vascular adrenergic neurons in hypertension.
 This study was designed to investigate the role of protein kinase C and calcium in vascular adrenergic transmission in hypertension.
 In perfused mesenteric vasculatures of spontaneously hypertensive rats (SHR, 7 to 10 weeks old) and age-matched Wistar-Kyoto rats (WKY), we have examined the effects of the protein kinase C inhibitor H-7 on endogenous norepinephrine release and vascular responsiveness during nerve stimulation.
 Endogenous norepinephrine release and pressor responses during periarterial nerve stimulation were significantly greater in SHR than in WKY.
 The protein kinase C inhibitor H-7 inhibited the stimulation-induced norepinephrine release and pressor responses in a dose-dependent manner.
 The magnitude of these suppressive responses were more pronounced in SHR than in WKY.
 Calcium removal from extracellular fluid also reduced the norepinephrine release more strongly in SHR than in WKY.
 These results demonstrate that the regulation of norepinephrine release might be more dependent on protein kinase C and calcium in the blood vessels of SHR, which could contribute, at least partially, to the pathogenesis of this form of hypertension.
",13
2054,"Vascular renin and hypertension. Uptake versus synthesis.
 Conventional radioimmunoassay techniques demonstrated in the aortic wall a renin-like activity which is derived from plasma but has a longer half-life than plasma renin.
 Blood pressure elevation after renin injection into nephrectomized rats correlates better with aortic renin than with plasma renin.
 Vascular and other extrarenal tissue can also synthesize renin.
 Using a ribonuclease protection technique for the detection of renin messenger RNA we have been able to demonstrate that a wide variety of extrarenal tissues contain the renin message.
 In at least two of these, the brain and the liver, renin messenger RNA levels are unaffected by changes in dietary salt or by changes in systemic blood pressure.
 Functional studies using isolated human resistance vessels also demonstrate the presence of renin-like activity by a contractile response to added renin substrate.
 It is suggested that extrarenal tissues therefore contain renin-like activity derived both from uptake and from local synthesis.
 These systems may be regulated in different ways and may carry out different functions.
",13
2055,"Role of basic fibroblast growth factor in vascular lesion formation.
 In the present study we investigated whether basic fibroblast growth factor (bFGF) plays a role in the proliferative response of smooth muscle cells (SMCs) to denuding injury.
 Rat carotid smooth muscle was found to express the mRNA for bFGF, and bFGF protein was found to be present in rat aorta by immunoblot analysis.
 Systemically administered bFGF was a potent mitogen for vascular SMCs in arteries denuded with a balloon catheter, increasing replication from 11.5% in controls to 54.8%.
 Denudation with a device (filament loop), which causes only minimal damage to medial SMCs, showed a similar increase in replication (1.3% versus 43.3%) after bFGF infusion.
 In unmanipulated vessels, however, SMCs were unresponsive to infused bFGF.
 Infusion of a ""mitotoxin"" (bFGF conjugated to saporin) caused a greater than 50% decrease in the number of viable SMCs in the arterial wall after balloon injury.
 Prolonged administration of bFGF (12 micrograms/day for 2 weeks) after balloon injury caused an approximately twofold increase in intimal thickening.
 These results show that bFGF, which is synthesized by the arterial wall, could be a potent mitogen for SMCs in vivo and suggest that any release of endogenous bFGF may be capable of stimulating SMC proliferation, which may subsequently lead to intimal lesion formation.
",13
2056,"Myocardial capillary permeability after regional ischemia and reperfusion in the in vivo canine heart. Effect of superoxide dismutase.
 This study assesses the effect of the superoxide anion scavenger superoxide dismutase on myocardial capillary permeability-surface area (PS) products for small hydrophilic molecules after ischemia and reperfusion.
 Open-chest dogs underwent a 20-minute occlusion of the left anterior descending coronary artery followed by 1 hour of reperfusion.
 Myocardial plasma flow rate and capillary extraction of chromium 51-labeled EDTA or technetium 99m-labeled diethylenetriaminepentaacetic acid were measured by the single-injection, residue-detection method before ischemia and 5 and 60 minutes after the start of reperfusion.
 In 13 dogs, no scavenger treatment was given (nonprotected control group), whereas eight dogs were treated systemically with 15,000 units/kg superoxide dismutase during 1 hour, starting 20 minutes before ischemia.
 In the control group, three dogs developed reperfusion ventricular fibrillation in contrast to none in the superoxide dismutase group.
 Before ischemia, plasma flow rate, myocardial capillary extraction fraction, and PS values were similar in the two groups.
 Five minutes after the start of reperfusion, plasma flow rate increased significantly (p less than 0.01) in both groups.
 In the control group, capillary extraction fraction increased by 12% (p = NS) in spite of the higher plasma flow; these increases in capillary extraction fraction and plasma flow induced a 69% increase in PS (p less than 0.01).
 In the superoxide dismutase-treated group, capillary extraction fraction decreased by 32% (p less than 0.05) in accordance with the increased plasma flow rate, resulting in an unchanged PS (p = NS).
 Sixty minutes after reperfusion, plasma flow rate, capillary extraction fraction, and PS returned to preocclusion values in both groups (p = NS).
 The increased capillary extraction fraction and PS values seen in the control group suggest an increased capillary permeability after ischemia and reperfusion.
 Superoxide anions seem to participate, directly or indirectly, in this response.
",13
2057,"Mechanism of early ischemic contractile failure. Inexcitability, metabolite accumulation, or vascular collapse?
 The basis of early ischemic contractile failure was investigated in perfused ferret hearts at 27 degrees C.
 Isovolumic left ventricular developed pressure fell by more than 50% within 30 seconds of the onset of total global ischemia and reached zero by 5 minutes.
 Monophasic action potential recordings revealed no decrease in excitability during this period.
 Phosphorus nuclear magnetic resonance spectra obtained at 30-second resolution showed no significant changes in inorganic phosphate or phosphocreatine during the first 30 seconds of ischemia.
 Intracellular pH (pHi) and ATP changed even more slowly; therefore, none of these metabolites could account for the rapid fall in force.
 To gauge the contribution of intravascular pressure, we compared ordinary aortic flow occlusion with tissue-level ischemia induced by massive coronary microembolization at the level of the precapillary arterioles.
 Functional depression developed significantly more slowly in the microembolized hearts, despite accumulation of inorganic phosphate and protons comparable with that in ordinary ischemia.
 After microembolization, the time course of functional depression reflected much more closely the concomitant inorganic phosphate and pHi changes.
 Thus, our results provide novel evidence supporting the importance of vascular collapse in the mechanism of early ischemic contractile failure.
",13
2058,"Significance of the number of stimuli to initiate ouabain-induced arrhythmias in the intact heart.
 Ouabain-induced arrhythmias are a well-known model used to study triggered activity resulting from delayed afterdepolarizations.
 In the intact heart, initiation of these arrhythmias is promoted by pacing, especially at fast rates.
 However, the relevance of the number of stimuli is unknown.
 In conscious dogs with formalin-induced atrioventricular block, we investigated the effect of variations in pacing mode on 1) the behavior of nonsustained triggered rhythms at progressive levels of ouabain intoxication, and 2) the induction of sustained ventricular tachycardia (VT).
 Twenty experiments were analyzed.
 Ouabain was administered as a bolus of 40 micrograms/kg followed by continuous infusion.
 Every 15 minutes the pacing protocol was repeated, with a maximum of 10, until completion or induction of VT.
 When VT could not be initiated, the experiment was repeated at least 1 week later, adding 5-10 micrograms/kg ouabain to the bolus and increasing the infusion rate correspondingly.
 This was repeated until VT could be induced.
 Four interstimulus intervals (200, 400, 600, and 800 msec) and seven numbers of stimuli (5, 10, 20, 35, 50, 100, and 150) were given in two pacing protocols.
 The effect of these protocols on 1) the number of induced beats per stimulation train, 2) their first postpacing interval, and 3) induction of VT were studied.
 Initiation of VT occurred after 75 +/- 42 minutes.
 The bolus of ouabain needed to induce VT was inversely related to the body weight of the animals.
 Progression of ouabain intoxication resulted in 1) a significant increase in the number of induced beats per stimulation train and 2) a significant shortening of the first postpacing interval.
 Stimulation at a faster rate and/or more stimuli resulted in 1) a significantly pronounced increase in the number of induced beats at the higher levels and 2) a significantly shorter first postpacing interval at successive levels of ouabain intoxication.
",13
2059,"[Ca2+]i transients in the cardiomyopathic hamster heart.
 Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate.
 Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]i transients were comparable in amplitude when perfused with either substrate.
 On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose.
 The amplitude of [Ca2+]i transients fell severely and was associated with a high diastolic [Ca2+]i in cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose.
 The high phosphomonoester sugars as evidenced by 31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity.
 Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]i homeostasis.
",13
2060,"Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat.
 Severe arrhythmias occur predictably on reperfusion after 5 minutes of coronary occlusion in the rat.
 There is little data available on whether ischemic preconditioning (PC) of hearts can reduce the incidence of such arrhythmias.
 The effect of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on development of arrhythmias after a subsequent 5-minute coronary artery occlusion and reperfusion was studied.
 Rats (n = 16 each group) underwent 5-minute occlusion and reperfusion alone or preceded by PC; arrhythmias were monitored during ischemia and for 10 minutes of reperfusion, and biopsies were taken for creatine phosphate and adenosine triphosphate in ischemic and nonischemic zones of the left ventricle.
 PC reduced the incidence of ventricular tachycardia (VT) during occlusion (81% control versus 13% PC, p less than 0.001).
 On subsequent reperfusion, ventricular fibrillation (VF) developed in zero PC animals versus 13 (81%) of controls (p less than 0.001), and irreversible VF in zero of PC versus seven (44%) of controls (p = 0.007).
 VT occurred in four (25%) of PC versus all (100%) of controls (p less than 0.001).
 PC reduced mean duration of VT plus VF from 320 +/- 54 to 5 +/- 1 seconds (p less than 0.001) and delayed arrhythmia onset from 8 +/- 2 to 85 +/- 35 seconds after reperfusion.
 There was no difference in creatine phosphate levels in the ischemic zone at the end of reperfusion in PC animals compared with controls without irreversible VF (16.2 +/- 4.1 versus 15.5 +/- 3.9 nmol/mg protein, p = NS).
",13
2061,"Passive smoking and heart disease. Epidemiology, physiology, and biochemistry.
 The evidence that ETS increases risk of death from heart disease is similar to that which existed in 1986 when the US Surgeon General concluded that ETS caused lung cancer in healthy nonsmokers.
 There are 10 epidemiological studies, conducted in a variety of locations, that reflect about a 30% increase in risk of death from ischemic heart disease or myocardial infarction among nonsmokers living with smokers.
 The larger studies also demonstrate a significant dose-response effect, with greater exposure to ETS associated with greater risk of death from heart disease.
 These epidemiological studies are complemented by a variety of physiological and biochemical data that show that ETS adversely affects platelet function and damages arterial endothelium in a way that increases the risk of heart disease.
 Moreover, ETS, in realistic exposures, also exerts significant adverse effects on exercise capability of both healthy people and those with heart disease by reducing the body's ability to deliver and utilize oxygen.
 In animal experiments, ETS also depresses cellular respiration at the level of mitochondria.
 The polycyclic aromatic hydrocarbons in ETS also accelerate, and may initiate, the development of atherosclerotic plaque.
 Of note, the cardiovascular effects of ETS appear to be different in nonsmokers and smokers.
 Nonsmokers appear to be more sensitive to ETS than do smokers, perhaps because some of the affected physiological systems are sensitive to low doses of the compounds in ETS, then saturate, and also perhaps because of physiological adaptions smokers undergo as a result of long-term exposure to the toxins in cigarette smoke.
 In any event, these findings indicate that, for cardiovascular disease, it is incorrect to compute ""cigarette equivalents"" for passive exposure to ETS and then to extrapolate the effects of this exposure on nonsmokers from the effects of direct smoking on smokers.
 These results suggest that heart disease is an important consequence of exposure to ETS.
 The combination of epidemiological studies with demonstration of physiological changes with exposure to ETS, together with biochemical evidence that elements of ETS have significant adverse effects on the cardiovascular system, leads to the conclusion that ETS causes heart disease.
 This increase in risk translates into about 10 times as many deaths from ETS-induced heart disease as lung cancer; these deaths contribute greatly to the estimated 53,000 deaths annually from passive smoking.
 This toll makes passive smoking the third leading preventable cause of death in the United States today, behind active smoking and alcohol.
",13
2062,"Multicenter patency trial of intravenous anistreplase compared with streptokinase in acute myocardial infarction. The TEAM-2 Study Investigators.
 Thrombolytic therapy has been shown to improve clinical outcome when administered early after the onset of symptoms of acute myocardial infarction; the mechanism of benefit is believed to be reestablishment and maintenance of coronary artery patency.
 Anistreplase is a second generation thrombolytic agent that is easily administered and has a long duration of action.
 To compare anistreplase (30 units/2-5 min) and therapy with the Food and Drug Administration-approved regimen of intravenous streptokinase (1.5 million units/60 min), a randomized, double-blind, multicenter patency trial was undertaken in 370 patients less than 76 years of age with electrocardiographic ST segment elevation who could be treated within 4 hours of symptom onset.
 Coronary patency was determined by reading, in a blinded fashion, angiograms obtained early (90-240 minutes; mean, 140 minutes) and later (18-48 hours; mean, 28 hours) after beginning therapy.
 Early total patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion) was high after both anistreplase (132/183 = 72%) and streptokinase (129/176 = 73%) therapy, and overall patency patterns were similar, although patent arteries showed ""complete"" (grade 3) perfusion more often after anistreplase (83%) than streptokinase (72%) (p = 0.03).
 Similarly, residual coronary stenosis, determined quantitatively by a validated computer-assisted method, was slightly less in patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than streptokinase (77.2%, p = 0.02).
 In patients with patent arteries without other early interventions, reocclusion risk within 1-2 days was defined angiographically and found to be very low (anistreplase = 1/96, streptokinase = 2/94).
 Average coronary perfusion grade was greater, and percent residual stenosis was less, at follow-up than on initial evaluation and did not differ between treatment groups.
 Enzymatic and electrocardiographic evolution was not significantly different in the two groups.
 Despite rapid injection, anistreplase was associated with only a small (4-5 mm Hg), transient (at 5-10 minutes) mean differential fall in blood pressure.
 In-hospital mortality rates were comparable for anistreplase and streptokinase (5.9%, 7.1%).
 Stroke occurred in one (0.5%) and three (1.6%) patients, respectively; one stroke was hemorrhagic.
 Other serious bleeding events and adverse experiences occurred uncommonly and with similar frequency in the two groups.
 Thus, for the end points of our study (patency, safety), anistreplase and streptokinase showed overall favorable and relatively comparable outcomes, with a few differences.(ABSTRACT TRUNCATED AT 400 WORDS).
",13
2063,"Detection of patients at risk for paroxysmal atrial fibrillation during sinus rhythm by P wave-triggered signal-averaged electrocardiogram.
 To determine whether patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm, the signal-averaged electrocardiogram triggered by P waves was recorded in 42 patients with paroxysmal atrial fibrillation (Paf group) and in 50 control patients.
 The root mean square voltages (LP10, LP20, and LP30) for the last 10, 20, and 30 msec and the duration (Ad) of filtered (40-300 Hz) P wave of the spatial magnitude were measured.
 LP10 and LP20 were significantly lower in the Paf than in the control group (LP10, 1.92 +/- 0.58 versus 2.49 +/- 0.78 microV, p less than 0.001; LP20, 2.47 +/- 0.78 versus 3.46 +/- 1.20 microV, p less than 0.0001), although no significant difference in LP30 was found between groups.
 Ad was also significantly longer in the Paf than in the control group (137.0 +/- 14.3 versus 118.6 +/- 11.3 msec, p less than 0.001).
 These differences between the Paf and control groups remained significant even after dividing by the presence or absence of organic heart diseases.
 The criteria of ""LP20 = 3.5 microV or less"" and ""Ad greater than 120 msec"" as defining ""atrial late potential"" gave a sensitivity of 91% and a specificity of 76%.
 These findings suggest that patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm by using the P wave-triggered signal-averaged electrocardiogram.
",13
2064,"In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty.
 To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding.
 Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7).
 Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls).
 S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3).
 Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA.
 Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets.
 Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.
",13
2065,"Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period.
 Adenosine influences the function of several cell types thought to be involved in the pathogenesis of myocardial reperfusion injury.
 We have previously demonstrated that intracoronary administration of adenosine enhances myocardial salvage 24 hours after reperfusion.
 To determine if these beneficial effects could be obtained during a prolonged period of reperfusion using an intravenous route of administration, 22 closed-chest dogs were subjected to 90 minutes of proximal left anterior descending coronary artery occlusion and 72 hours of reperfusion.
 Animals randomly received either intravenous adenosine (0.15 mg/kg/min) or an equal volume of Ringer's lactate during the first 150 minutes of reperfusion.
 The area at risk was defined in vivo with Monastral blue, and infarct size was measured histologically with Mallory's trichrome stain.
 Serial global and regional ventricular function were determined with contrast ventriculography and analyzed using a computerized radial shortening method.
 Biopsies were obtained from the central ischemic zone to assess endothelial ultrastructure and capillary obstruction.
 No significant effects in heart rate or blood pressure were noted during adenosine infusion.
 Transmural collateral blood flow during ischemia was similar in the groups.
 Infarct size expressed as a percentage of the anatomical area at risk was significantly less in the adenosine-treated group (35.3 +/- 4.3% in controls versus 17.1 +/- 4.3% in treated animals, p less than 0.01).
 A progressive decrease in transmural blood flow was noted in control animals during reperfusion, resulting in a significant reduction at 3 hours compared with the preocclusion value (0.69 +/- 0.11 ml/min/g [at baseline versus 0.45 +/- 0.10 ml/min/g at 3 hours, p less than 0.05]).
 In contrast, flow in adenosine animals at 3 hours was similar to baseline values (0.91 +/- 0.15 ml/min/g at baseline versus 0.98 +/- 0.14 ml/min/g at 3 hours, p = NS) and was significantly higher (p less than 0.05) than the control group.
 Radial shortening in the ischemic zone was significantly improved at 3 (-2.6 +/- 2.8% in controls versus 11.6 +/- 3.3% in treated animals, p less than 0.01) and 72 hours (5.5 +/- 2.0% in controls versus 17.3 +/- 3.5% in treated animals, p less than 0.01) after reperfusion in treated animals.
 Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cell structure in the adenosine group.(ABSTRACT TRUNCATED AT 400 WORDS).
",13
2066,"Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Comparison of thallium scintigraphy with reinjection and PET imaging with 18F-fluorodeoxyglucose 
 In patients with chronic coronary artery disease and left ventricular dysfunction, the distinction between ventricular dysfunction arising from myocardial fibrosis and ischemic, but viable, myocardium has important clinical implications.
 By positron emission tomography (PET), enhanced fluorine-18-labeled fluorodeoxyglucose (FDG) uptake in myocardial segments with impaired function and reduced blood flow is evidence of myocardial viability.
 Reinjection of thallium-201 at rest immediately after stress-redistribution imaging may also provide evidence of myocardial viability by demonstrating thallium uptake in regions with apparently ""irreversible"" defects.
 To compare these two methods, we studied 16 patients with chronic coronary artery disease and left ventricular dysfunction (ejection fraction, 27 +/- 9%), all of whom had irreversible defects on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT) imaging.
 Thallium was reinjected immediately after the redistribution study, and SPECT images were reacquired.
 The patients also underwent PET imaging with FDG and oxygen-15-labeled water.
 A total of 432 myocardial segments were analyzed from comparable transaxial tomograms, of which 166 (38%) had irreversible thallium defects on redistribution images before reinjection.
 FDG uptake was demonstrated in 121 (73%) of these irreversible defects.
 Irreversible defects were then subgrouped according to the degree of thallium activity, relative to peak activity in normal regions.
 Irreversible defects with only mild (60-85% of peak activity) or moderate (50-59% of peak) reduction in thallium activity were considered viable on the basis of FDG uptake in 91% and 84% of these segments, respectively.
 In contrast, in irreversible defects with severe reduction in thallium activity (less than 50% of peak), FDG uptake was present in 51% of segments.
 In such severe defects, an identical number of segments (51%) demonstrated enhanced uptake of thallium after reinjection.
 In these severe ""irreversible"" defects, data on myocardial viability were concordant by the two techniques in 88% of segments, with 45% identified as viable and 43% identified as scar on both PET and thallium reinjection studies.
 These observations suggest that thallium imaging can be used to identify viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction.
 Most irreversible defects with only mild or moderate reduction in thallium activity represent viable myocardium as confirmed by FDG uptake.(ABSTRACT TRUNCATED AT 400 WORDS).
",13
2067,"Analysis of baroreflex control of heart rate in conscious dogs with pacing-induced heart failure.
 The autonomic components of the baroreflex control of heart rate were evaluated in conscious mongrel dogs before and after 4-6 weeks of ventricular pacing (250 beats/min).
 Arterial baroreflex sensitivity (BRS) was determined by the slopes of linear regression of pulse interval versus the preceding systolic arterial pressure in response to bolus injections of either phenylephrine or nitroglycerin.
 BRS was significantly depressed in the heart failure state [nitroglycerin slope, 5.0 +/- 2.7 (mean +/- SD) versus 16.6 +/- 5.1 msec/mm Hg, p less than 0.005; phenylephrine slope, 15.0 +/- 14.8 versus 32.0 +/- 26.7 msec/mm Hg, p less than 0.005].
 There was no depression in BRS in dogs that were used as time controls or were acutely paced for 30 minutes.
 After beta 1-adrenergic blockade with metoprolol, the resting heart rate in the heart failure state was depressed more than in the normal state (-17.0 +/- 5.0% versus -3.2 +/- 3.4%, p less than 0.001).
 Atropine significantly increased resting heart rate more in the normal state than in the heart failure state (115.8 +/- 36.7% versus 25.4 +/- 14.5%, p less than 0.005).
 Thus, dogs in the heart failure state appear to have high resting cardiac sympathetic tone and low resting vagal tone.
 For nitroglycerin administration, metoprolol depressed BRS by 47.6 +/- 26.3% in the normal state and by 63.6 +/- 58.5% in the heart failure state.
 Atropine decreased the BRS by 86.7 +/- 7.8% in the normal state and by 39.5 +/- 30.2% in the heart failure state.
",13
2068,"Reentrant ventricular arrhythmias in the late myocardial infarction period: mechanism by which a short-long-short cardiac sequence facilitates the induction of reentry.
 The electrophysiological mechanism by which a short-long-short stimulated cardiac sequence facilitates the induction of ventricular tachyarrhythmia was investigated in dogs 4 days after ligation of the left anterior descending coronary artery.
 In these dogs, reentry develops in the surviving electrophysiologically abnormal epicardial layer that overlies the infarct zone when premature stimulation results in a critically long arc of functional conduction block.
 The activation wavefront circulates around both ends of the arc, coalesces, and conducts slowly distal to the arc before reactivating sites proximal to the arc to initiate a figure-eight reentrant circuit.
 Epicardial isochronal activation maps and effective refractory periods (ERPs) were determined during three different stimulation protocols: A, a basic train of eight beats at a cycle length of 300 msec followed by a single premature stimulus (S2); B, a basic train of eight beats at a cycle length of 300 msec with abrupt lengthening of the last cycle of the train before S2 to 600 msec; C, a basic train of eight beats at a cycle length of 600 msec followed by S2.
 Protocol B was found to result in a differential lengthening of ERP at adjacent sites within the border of the epicardial ischemic zone, whereas protocols A and C induced, respectively, comparable shortening and lengthening of ERPs at the same sites.
 The differential lengthening of ERPs at adjacent sites resulted in an increased dispersion of refractoriness so that a premature stimulus induced functional conduction block between those sites.
 The development of a longer arc of conduction block and, hence, a longer reentrant pathway as well as slower conduction of the circulating wavefront during protocol B allowed more time for refractoriness to expire proximal to the arc and for the circulating wavefront to reexcite those sites to initiate reentry.
 The lengthening of ERP, associated with a single long cycle (protocol B), ranged from 44% to 79% of the total increase in ERP after a series of eight long cycles (protocol C).
 Epicardial sites with longer ERPs located close to the center of the ischemic zone showed more lengthening of refractoriness during protocol B compared with more normal sites near the border of the ischemic zone.
 This strongly suggests that the increased dispersion of refractoriness during protocol B is caused by the shorter memory of ischemic myocardium to the cumulative effects of preceding cycle lengths.
",13
2069,"Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study.
 The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men (2,398) aged 49-66 years at the time of study.
 Platelet aggregation induced by collagen, thrombin, and ADP was measured in fasting blood samples and was related to prevalent angina, past myocardial infarction, and electrocardiographic evidence of ischemic heart disease.
 A number of subjects had taken aspirin, other nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet aggregation 7 days before blood sample collection; after the exclusion of these subjects, data were available for 1,811 men.
 No relations were demonstrated with angina, but significant relations were shown between past myocardial infarctions and electrocardiographic evidence of ischemia and ADP-induced aggregation (both primary and secondary) and between electrocardiographic evidence of ischemia and thrombin-induced aggregation.
 The strongest relation indicated more than a twofold increase in the odds of a past myocardial infarction in subjects of the highest fifth of ADP-induced primary platelet aggregation compared with the lowest fifth.
 No significant relations were detected with collagen-induced aggregation.
 Accounting for a number of possible confounding factors had a relatively small impact on the relations between platelet aggregation and ischemic heart disease.
 Other evidence, including the well-established effect of aspirin on reducing the incidence of ischemic heart disease, indicates that the relations we describe are unlikely to be simply an effect of IHD on platelets.
",13
2070,"Myocardial infarction in Mexican-Americans and non-Hispanic whites. The San Antonio Heart Study.
 Mexican-American men experience reduced cardiovascular mortality compared with non-Hispanic white men.
 There is no corresponding ethnic difference in cardiovascular mortality in women.
 The difference in men could result either from a lower incidence of cardiovascular disease or a lower case fatality rate among Mexican-Americans.
 Although the incidence of cardiovascular disease in Mexican-Americans is unknown, we have collected data on prevalence of myocardial infarction in 5,148 individuals examined in the San Antonio Heart Study, a population-based survey of cardiovascular disease conducted between 1979 and 1988 in Mexican-Americans and non-Hispanic whites aged 25-64 years.
 Myocardial infarction was assessed by Minnesota-coded electrocardiograms and by a self-reported history of a physician-diagnosed heart attack.
 For both end points, the age-adjusted prevalence of myocardial infarction was lower in Mexican-American men than in non-Hispanic white men.
 After adjustment for age and diabetes status (present/absent), the odds of a myocardial infarction, as defined by either criterion, was approximately one third lower in Mexican-American men than in non-Hispanic white men (p = 0.06).
 In women, the prevalence of both myocardial infarction end points was slightly higher in Mexican-Americans than in non-Hispanic whites, although neither of these differences was significant.
 Although the ethnic differences in prevalence in this study were not statistically significant, their pattern parallels the pattern in the mortality due to cardiovascular diseases.
 Therefore, the results support the hypothesis that the reduced cardiovascular mortality rate observed in Mexican-American men reflects a lower incidence of myocardial infarction rather than a reduced case fatality rate because the latter would result in a higher prevalence.
",13
2071,"Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group 
 The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52 months' follow-up after acute myocardial infarction.
 This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac mortality or recurrent nonfatal infarction) than such patients on placebo.
 We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events, but only in patients predisposed by LVD.
 Using the same characterizing variables as the primary MDPIT analysis, we found that patients with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection fraction (EF) at baseline were more likely to have CHF during follow-up than those without these markers of LVD.
 CHF was particularly frequent in the patients with LVD who were randomized to diltiazem.
 Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004).
 Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p = 0.0017).
 In addition, the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF.
 This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more, suggesting a unique association between diltiazem-related late CHF and systolic LVD.
",13
2072,"Transesophageal Doppler echocardiography evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation 
 Transesophageal echocardiography allows the evaluation of proximal coronary artery anatomy and coronary blood flow velocity (CBFV).
 To assess the potential of transesophageal echocardiography in evaluating CBFV and its variations induced by coronary-active drugs, we studied 15 patients by high-quality pulsed wave Doppler recordings of CBFV.
 In these patients, transesophageal Doppler evaluation of CBFV was performed before, 2 minutes after cessation of dipyridamole infusion (0.56 mg/kg in 4 minutes), and 2 minutes after aminophylline infusion (240 mg injected 4 minutes after cessation of dipyridamole infusion).
 The following CBFV parameters were evaluated at each of the three steps of the study protocol: maximal and mean diastolic velocities and maximal and mean systolic velocities.
 Furthermore, the following indexes of coronary flow reserve were evaluated: the ratio between maximal diastolic velocity recorded after and before dipyridamole administration and the ratio between mean diastolic velocity recorded after and before dipyridamole administration.
 Nine of the 15 patients had a normal left anterior descending coronary artery (group A), whereas the remaining six had significant (less than or equal to 75%) stenosis (group B).
 In group A patients, all CBFV parameters increased significantly during dipyridamole infusion and returned to near baseline values after aminophylline infusion.
 In group B patients, on the other hand, none of the CBFV parameters increased after dipyridamole infusion.
 Dipyridamole/baseline maximal diastolic velocity and mean diastolic velocity ratios were, respectively, 3.22 +/- 0.96 and 3.04 +/- 0.88 in group A and 1.46 +/- 0.45 (p less than 0.01 versus group A) and 1.48 +/- 0.49 (p less than 0.01 versus group A) in group B patients.
",13
2073,"Regurgitant jet size by transesophageal compared with transthoracic Doppler color flow imaging.
 Combined echocardiography and Doppler color flow mapping from transthoracic imaging windows has become the standard method for the noninvasive assessment of valvular regurgitation.
 This study compared regurgitant jet areas by Doppler color flow imaging derived from the newer transesophageal approach with measurements obtained from conventional transthoracic apical views.
 Maximal regurgitant jet area determinations and an overall visual estimate of lesion severity were obtained from 42 patients who underwent color flow examination by both techniques.
 Seventy-three regurgitant lesions were visualized by transesophageal flow imaging: 34 mitral, 22 aortic, and 17 tricuspid jets.
 Transthoracic studies in the same patients revealed fewer regurgitant lesions for each valve; 20 mitral, 16 aortic, and 12 tricuspid (p = 0.0009).
 A comparison of maximal jet areas determined by transesophageal and transthoracic studies showed a good overall correlation (r = 0.85, SEE = 2.8 cm2) and a systematic overestimation by the transesophageal technique (TEE = 0.96 TTX + 2.7).
 For the subgroup with mitral insufficiency, valve lesions visualized by both techniques were larger by the transesophageal approach (n = 18, 6.0 versus 3.6 cm2, p = 0.008).
 Semiquantitative visual grading of individual valve lesions by two independent observers revealed a higher grade of regurgitation with more jets classified as mild (38 versus 25), moderate (18 versus 13), and severe (17 versus 10) by esophageal imaging than by transthoracic imaging.
 Thus, transesophageal color flow mapping techniques yield a higher prevalence of valvular regurgitation than do transthoracic techniques in the same patients.
 Jet area and the overall estimate of regurgitant lesion severity were also greater by transesophageal color Doppler imaging compared with standard transthoracic imaging.
",13
2074,"Elevated pulmonary artery pressure. An independent predictor of mortality.
 Analyses in this study were based on hemodynamic and angiographic data obtained in a cohort of 1,371 predominantly black patients during right and left heart catheterization.
 All patients were followed up prospectively for a mean of 117 weeks, and 103 fatal events were recorded.
 In Cox survival analysis, three variables were found to be independently related to survival: pulmonary artery mean pressure (PAMP), number of stenosed vessels, and left ventricular (LV) ejection fraction (p less than 0.01); in multivariate stepwise analysis, PAMP entered the model first with the largest chi 2 value of the three prognostic variables (chi 2 = 33.4; p less than 0.0001).
 The PAMP was 32 percent higher in decedents compared with survivors (25 + 11 mm Hg vs 19 + 8 mm Hg, p less than 0.01 [mean, SD]) and a 10 mm Hg increase in PAMP was associated with a more than fourfold increase in the relative risk of dying; this finding was independent of pulmonary vascular resistance and therefore could not be attributed to primary pulmonary vascular or parenchymal disease.
 In both the subgroup of 1,118 patients with a normal LV ejection fraction (greater than 50 percent) and the 253 patients with a reduced ejection fraction (less than 50 percent), PAMP emerged as an independent predictor of mortality (p less than 0.0001 and 0.01, respectively), and is therefore a marker of cardiac disease beyond impairment of systolic contractile function.
 Among patients without obstructive coronary artery disease, PAMP alone provided prognostic information in the multivariate survival analysis.
",13
2075,"Renal vein thrombosis. Initial manifestation of Goodpasture's syndrome.
 We report a patient who presented with renal vein thrombosis and nephrosis that progressed to alveolar hemorrhage and renal failure.
 Renal biopsy immunofluorescence and serum antiglomerular basement membrane antibody titer studies confirmed the diagnosis of Goodpasture's syndrome.
 To our knowledge, this is the first report of renal vein thrombosis as the initial presentation of Goodpasture's syndrome.
",13
2076,"Safety and efficacy of thrombolytic therapy for superior vena cava syndrome 
 The experience at the Cleveland Clinic from 1982 to 1990 using thrombolytic therapy for superior vena cava (SVC) syndrome was retrospectively reviewed.
 Sixteen patients, 11 of whom had indwelling central venous catheters, were treated with either urokinase (n = 11) or streptokinase (n = 5).
 Either urokinase (4,400 U/kg bolus followed by 4,400 U/kg/h) or streptokinase (250,000 U bolus followed by 100,000 U/h) was used, and venograms were performed before and after.
 Overall, 56 percent of patients had complete clot lysis and relief of symptoms.
 Thrombolytic therapy was effective in eight (73 percent) of 11 patients receiving urokinase and one (20 percent) of five patients receiving streptokinase.
 Of those with a central venous catheter, eight (73 percent) of 11 patients were successfully lysed, whereas only one (20 percent) of five patients was successfully lysed if no catheter was present.
 If thrombolytic therapy was performed less than or equal to five days of symptom onset, seven (88 percent) of eight patients were successful, if thrombolytic therapy was performed greater than five days after symptom onset, two (25 percent) of eight patients were successful.
 Symptoms were relieved and the catheter was preserved in patients in whom thrombolytic therapy was effective.
 Factors predicting success were as follows: (1) the use of urokinase compared with streptokinase; (2) the presence of a central venous catheter; and (3) a duration of symptoms less than or equal to five days.
",13
2077,"Risk factors for gestational diabetes in black population.
 In a long-term longitudinal study of gestational diabetes mellitus in Black women, risk factors that were identified were age, obesity, a family history of diabetes, and the presence of hypertension.
 Poor predictors were a history of a previous large-for-date infant, parity, and age at first pregnancy.
 The prevalence of smooth muscle and nuclear autoantibodies was higher in gestational diabetic subjects.
 Gestational diabetic subjects who required insulin for glycemic control were more obese, had a lower frequency of the Bf-F phenotype and a higher frequency of the Bf-F1 phenotype, and had a lower frequency of the type 2 allele at the polymorphic locus adjacent to the insulin gene.
 Restriction-fragment-length polymorphisms flanking the insulin and apolipoprotein A-I and C-III genes, although not associated with gestational diabetes mellitus, may be associated with hyperlipidemia and subsequent atherosclerosis.
",13
2078,"Calcium channel blockers in geriatric hypertension.
 Though the calcium channel blockers have been used to treat angina pectoris for almost a decade, the long-acting forms of these agents that have become available in the last few years have made them practical for use as antihypertensive agents as well.
 They are becoming increasingly popular in this role, especially to treat elderly hypertensive patients.
 Because they are vasodilators with a mild diuretic action, they are logical treatment choices for the majority of hypertensive patients who have increased peripheral vascular resistance.
 They offer the advantage of a dual benefit for hypertensive patients with angina, and they have no effect on carbohydrate or lipid metabolism.
 Disadvantages include cost and a side effect profile that includes headaches, palpitations, ankle edema, and constipation.
",13
2079,"Congestive heart failure: a current overview.
 Congestive heart failure (CHF), a disease seen primarily in the older patient, can be due to either systolic or diastolic dysfunction.
 Management is quite different if the heart failure is due to a filling abnormality as compared to poor ventricular systole.
 The disorder also poses many diagnostic pitfalls in the elderly.
 Current understanding of CHF and its influence on diagnosis and management is the focus of this review.
",13
2080,"Training increases muscle blood flow in rats with peripheral arterial insufficiency.
 This study investigated the effect of physical training on muscle blood flow (BF) in rats with peripheral arterial insufficiency during treadmill running.
 Bilateral stenosis of the femoral artery of adult rats (300-350 g) was performed to reduce exercise hyperemia in the hindlimb but not limit resting muscle BF.
 Rats were divided into normal sedentary, acute stenosed (stenosed 3 days before the experiment), stenosed sedentary (limited to cage activity), and stenosed trained (run on a treadmill by a progressively intense program, up to 50-60 min/day, 5 days/wk for 6-8 wk).
 Hindlimb BF was determined with 85Sr- and 141Ce-labeled microspheres at a low (20 m/min) and high treadmill speed (30-40 m/min depending on ability).
 Maximal hindlimb BF was reduced to approximately 50% normal in the acute stenosed group.
 Total hindlimb BF (81 +/- 5 ml.min-1.100 g-1) did not change in stenosed sedentary animals with 6-8 wk of cage activity, but a redistribution of BF occurred within the hindlimb.
 Two factors contributed to a higher BF to the distal limb muscle of the trained animals.
 A redistribution BF within the hindlimb occurred in stenosed trained animals; distal limb BF increased to approximately 80% (P less than 0.001) of the proximal tissue.
 In addition, an increase in total hindlimb BF with training indicates that collateral BF has been enhanced (P less than 0.025).
 The associated increase in oxygen delivery to the relatively ischemic muscle probably contributed to the markedly improved exercise tolerance evident in the trained animals.
",13
2081,"Paradoxical embolism: an underestimated entity. A plea for comprehensive work-up.
 Forty-one cases of arterial embolism were reviewed.
 The work-up included M + 2D echocardiography in 29 patients (71%), arteriography in 22 (54%), both echocardiography and arteriography in 19 (46%), and abdominal aortic ultrasound in 18 (43%).
 The sources of emboli were probable cardiac (8 = 20%)--mural cardiac thrombus detected by echocardiogram; possible cardiac (12 = 29%)--arrhythmias or other cardiac pathology detected without mural thrombus; probable arterio-arterial (7 = 17%)--proximal arterial thrombus detected; probable paradoxical embolism (2 = 5%)--fulfills the Johnson criteria with cardiac defect and right-to-left shunt detected by contrast echo in one patient and cardiac catheterization in the other; possible paradoxical embolism (3 = 7%)--meets two of three Johnson criteria without evidence of other source; and unknown source (9 = 22%)--conventional work-up negative or incomplete.
 Five of nine patients (56%) less than 50 years old had probable or possible paradoxical embolism, while in two patients (22%), the origin was unknown.
 Conclusion: (1) A significant proportion of patients with an arterial embolus are discharged with the source of emboli unknown, (2) paradoxical embolism must be considered and contrast saline or transesophageal echocardiogram should be done in patients under 50 years old.
",13
2082,"Splenorenal arterial shunt in the treatment of renovascular hypertension. Approach by a lumbar-retroperitoneal incision.
 In a period of 16 years, 29 consecutive patients were operated on for a splenorenal arterial shunt through a lumbotomy incision and a retroperitoneal approach.
 There were 18 males and 11 females with a medium age of 42 years.
 All cases had uncontrollable and severe hypertension for an average medium time of 48 months, 11 patients had variable degrees of renal insufficiency.
 The diagnosis was made utilizing standard methods including in all cases angiography of the abdominal aorta, celiac axis and renal arteries.
 One patient died after the operation due to intestinal infarction, the remaining have been followed for a medium time of 50 months.
 All patients improved or cured their renal insufficiency.
 The hypertension was cured in 23, improved in 4 and failed in 1, this latter patient was successfully autotransplanted.
 A precise exposition of the surgical technique is presented with comments about their advantages and indications.
 A review of the literature in surgical experience with the technique of splenorenal arterial anastomosis has been done.
",13
2083,"Clinical results of femoropopliteal bypass using externally supported (EXS) Dacron grafts: with a comparison of above- and below-knee anastomosis.
 As of the end of September 1989, 52 EXS Dacron grafts had been implanted for femoropopliteal bypass operations.
 The distal ends of 27 grafts were anastomosed to above-knee popliteal arteries and those of 25 grafts to below-knee popliteal arteries.
 The cumulative patency rate of above-knee grafts was 71.3% at 54 months, and that of below-knee grafts was 78.8% at 48 months (n.s.).
 Kinking and stenosis of the arteriosclerotic proximal and/or mid popliteal artery when the knee was bent were angiographically remarkable.
 These changes may explain why some femoropopliteal grafts occlude with time and why the late results of above-knee grafts are not much better than those of below-knee grafts.
",13
2084,"Crural artery bypass with adjunctive arteriovenous fistula. A modification in distal anastomosis.
 We carried out crural artery bypass with an adjunctive arteriovenous fistula in 8 lower extremities of 7 patients with severe ischemic symptoms and poor distal run-off.
 Mean blood flow rates in the implanted grafts ranged from 43 to 340 ml/min and those of the reconstructed crural arteries from 20 to 100 ml/min.
 A stenotic lesion was noted on postoperative angiogram in one patient and stasis symptoms caused by downward blood flow into the distal veins in another.
 The other patients have remained well with good function of the grafts 1-5 years after surgery.
 We modified the distal corner of the anastomosis as follows: three additional interrupted simple sutures were made on the anterior wall of the concomitant arteriotomy and venotomy incisions after making the common posterior wall of the vessel incisions.
 A vascular pocket formed at the distal corner of the anastomosis prevents stricture at the anastomosis.
 The vein is finally ligated just distal to the fistula to intercept downward blood flow into the distal veins.
 This modification in technique is recommended to prevent stricture of the distal anastomosis and postoperative stasis symptoms.
",13
2085,"Preoperative evaluation and surgical treatment for tricuspid regurgitation associated with acquired valvular heart disease. The Kay-Boyd method vs the Carpentier-Edwards ring method.
 This study compared the results of annuloplastic repair of tricuspid regurgitation (TR) using Doppler echocardiography.
 Sixty-three patients who underwent tricuspid annuloplasty were studied.
 Thirty-four patients received Kay-Boyd annuloplasty and 29 Carpentier-Edwards ring annuloplasty.
 A new classification of TR based on the direction and area of regurgitation flow on Doppler echocardiogram was applied preoperatively.
 In the Kay-Boyd group, 10 cases showed massive TR and 24 cases showed localized TR preoperatively.
 Localized TR was well controlled in all cases, but 8 of 9 cases of massive TR showed grade III residual TR.
 In the C-E group, 21 cases showed massive TR and 8 cases showed localized TR.
 All cases were well controlled postoperatively.
 We conclude that (1) although the Kay-Boyd method is acceptable for localized TR, the C-E method should be employed for massive TR; (2) analyzing the regurgitant pattern of TR by Doppler echocardiogram is useful in selecting an appropriate surgical technique.
",13
2086,"New quantitative method for evaluating tricuspid regurgitation.
 A new quantitative method for evaluating regurgitation (TR) is proposed in order to select the most suitable treatment for functional TR associated with acquired valvular heart disease.
 The regurgitant volume per beat (VTR) is calculated using two-dimensional color Doppler and continuous-wave Doppler echocardiographies.
 In a study of 48 patients, preoperative VTR showed a significant correlation with tricuspid annular diameter at end-diastole, right atrial mean pressure and right ventricular end-diastolic pressure.
 Patients were classified into 3 groups according to preoperative VTR: Group I, VTR less than 10 cc (no.
 18); Group II, VTR = 10-20 cc (no.
 18); Group III, VTR greater than or equal to 20 cc (no.
 12).
 This classification correlated well with the intraoperative findings of TR.
 In all Group I patients, VTR decreased without any tricuspid valve repair.
 In Group II, 17 of 18 patients underwent tricuspid annuloplasty, and showed a decrease in VTR to below 10 cc after surgery.
 In Group III, 10 underwent tricuspid annuloplasty and 2 tricuspid valve replacement.
 Three of the 10 with tricuspid annuloplasty showed a significant degree of postoperative VTR (10-20 cc).
 These 3 patients as well as the 2 with tricuspid valve replacement showed a preoperative peak-to-peak pressure difference across the tricuspid valve during the ejection phase (RVsp-TAv) of less than or equal to 20 mmHg and tricuspid annular diameter at end-diastole of greater than or equal to 50 mm.
 In conclusion, no tricuspid valve repair was required in Group I (TR I).
 For group II (TR II) patients, tricuspid annuloplasty was necessary and adequate for TR correction.
 For Group II (TR III) patients, a more substantial procedure like tricuspid valve replacement should be performed, especially when the preoperative RVsp-RAv is less than or equal to 20 mmHg and tricuspid annular diameter at end-diastole is greater than or equal to 50 mm.
",13
2087,"Surgical indication for aortic arch hypoplasia in infants.
 To determine the surgical indications for aortic arch hypoplasia, the distal arch outer diameter, distal arch index (ratio of the distal arch diameter to the normal aortic ring diameter), and postoperative pressure gradient across the aortic arch were studied in 23 patients under 6 months of age who underwent surgery for coarctation and/or aortic arch hypoplasia.
 The ratio of the pressure gradient across the arch to the right radial artery was used to evaluate the postoperative level of stenosis.
 The maximum ratio of the pressure gradient that could be tolerated after surgery was considered to be 0.15 from the operative results.
 Negative correlations were found between the distal arch outer diameter and postoperative pressure gradient ratio (r = 0.80), and the distal arch index and postoperative pressure gradient ratio (r = 0.80).
 These correlations proved that in order to obtain a postoperative pressure gradient ratio of 0.15 or less, a distal arch outer diameter of 3.9 mm or more and a distal arch index of 0.63 or more were necessary.
 Consequently, a distal arch outer diameter of 3.9 mm or a distal arch index of 0.63 is considered to indicate that aortic arch hypoplasia is in need of repair.
",13
2088,"Annulo-aortic ectasia with DeBakey type II dissecting aneurysm in Gaucher's disease.
 Annulo-aortic ectasia is an extremely rare complication of Gaucher's disease.
 We report successful surgery in a patient with Gaucher's disease complicated by annulo-aortic ectasia and aortic dissection.
 Cabrol's operation was accomplished without bleeding or sternal adaptation problems.
",13
2089,"Repair of coarctation with persistent fifth arterial arch and atresia of the fourth aortic arch.
 Coarctation of the aorta with persistent fifth arterial arch and atresia of the fourth aortic arch between the left common carotid and left subclavian arteries was treated surgically in a two-month-old boy with transposition of the great arteries and double-outlet right ventricle.
 The aortic arch was repaired using side-to-side anastomosis of the left common carotid and left subclavian arteries, patch repair of the coarctated segment at the origin of the left subclavian artery, and ligation of the patent ductus arteriosus.
 Pulmonary arterial banding and balloon atrioseptostomy were performed for associated anomalies.
",13
2090,"The use of PTFE graft to correct anomalous drainage of persistent left superior vena cava.
 A new technique to correct persistent left superior vena cava (LSVC) drainage into the left atrium is described in a 14-year-old patient with situs inversus, left atrial isomerism common atrium, and mitral valve regurgitation.
 During surgery, occlusion of the LSVC markedly increased the venous pressure, precluding its ligation.
 Because of the malposition of the heart and the unusual atrial anatomy, correction with an intra-atrial baffle was not attempted.
 After correcting the intra-cardiac anomaly, the LSVC was divided and anastomosed to the ""right"" atrial appendage using a segment of PTFE graft.
 The postoperative course was uneventful and an angiogram demonstrated excellent performance of the graft.
",13
2091,"Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia.
 The effect of brief myocardial ischemia on the expression of heat shock protein (HSP 70) was examined in an in vivo rabbit model of myocardial ischemia using Northern blotting.
 Functional studies were carried out in the open-chested anesthetized rabbit.
 The large marginal branch of the left circumflex was occluded four times for 5 min.
 Using piezoelectric crystals implanted midwall in the ischemic zone, end-diastolic length, end-systolic length, and percent segmental shortening were assessed.
 Expression of HSP 70 was measured by Northern blotting.
 A single 5-min coronary occlusion doubled the expression of HSP 70 whereas four cycles of 5 min of ischemia/5 min of reperfusion resulted in a threefold increase in HSP 70 mRNA (P less than 0.001).
 Measurements with the piezoelectric crystals showed mild myocardial dysfunction concomitant with the increase in HSP 70.
 This increase in HSP 70 mRNA after repetitive brief ischemia was transient, occurring as early as 1 h and returning to baseline by 24 h after ischemia.
 Western blot analysis with a monoclonal antibody to HSP 70 was used to compare sham and postischemic myocardial HSP 70 levels.
 Changes in the amount of HSP 70 were evident as early as 2 h and were even more striking at 24 h.
",13
2092,"Payment mechanism and patterns of use of medical services: the example of hypertension.
 This study explores the relationship between the use of medical services by hypertensive patients and mechanisms for payment within a single primary care practice.
 Three payment mechanisms were explored: public assistance, a capitated health maintenance organization (HMO), and fee-for-service.
 Patterns were examined across reimbursement type for the following variables: age, sex, visit reason, number of visits, medications, tests ordered, referrals made, and recommendations for follow-up visits.
 Illness severity was controlled in two ways: (1) by the study being focused on one diagnosis--mild to moderate hypertension, and (2) by concurrent chronic illnesses being enumerated and included in the analysis.
 Medical visits to the physician were examined over a 2-year period for 25 to 30 patients randomly sampled from each of the three payment mechanisms.
 Statistically significant differences were found for patient behaviors (total number of patient visits) and physician behaviors (number of medications and recommendations for revisits).
 The highest visit frequency was found for those on public assistance, followed closely by those covered by an HMO, and more distantly by those choosing fee-for-service.
 In a climate of cost consciousness, further study is needed to explore the impact of reimbursement mechanisms on the use of health care services.
",13
2093,"Association between post-dexamethasone cortisol level and blood pressure in depressed inpatients.
 We examined the clinical data for 230 depressed inpatients who had completed a dexamethasone suppression test (DST) to determine whether those with an elevated post-DST serum cortisol level exhibited any of the classic physiological stigmata of Cushing's syndrome.
 Hypertension was significantly more frequent among DST nonsuppressors (21.2%) than among normal suppressors (11.3%).
 Percent blood lymphocyte count was significantly lower among nonsuppressors.
 Confounders such as gender, age, body weight, and use of antihypertensives did not account for the findings.
 Implications for morbidity and mortality rates among patients with affective disorder are discussed.
",13
2094,"Free and peptide-bound amino acids as indicators of ischemic damage of the rabbit spinal cord.
 The concentrations of free and peptide-bound amino acids aspartate (Asp), glutamate (Glu), glycine (Gly) and gamma-aminobutyric acid (GABA) were studied following ischemia and recirculation in the ventral and dorsal gray matter of the rabbit spinal cord.
 No changes in the concentration of amino acids following ten minutes (min) of ischemia and four days of recovery were found.
 The most significant change after 20 min, and especially 40 min, of ischemia was a decrease in free Asp and GABA levels in both parts of the gray matter.
 The relatively greater decrease in the concentration of free amino acids in the ventral horns corresponds with the greater morphological damage to this part of spinal cord following ischemia.
 Following 40 min of ischemia and recirculation decrease in peptide-bound Glu in the ventral horns and Asp and Glu in the dorsal horns was found.
",13
2095,"Selective vasopressin inhibition in rats with heart failure decreases afterload and results in venodilatation.
 The hemodynamic effects of selective inhibition of arginine vasopressin (AVP) with a V1 antagonist, (CH2)5yreAVPa CL-1-4A, were studied in normal rats (n = 17) and in rats 4 weeks after coronary artery ligation with large myocardial infarctions and elevated left ventricular end-diastolic pressures (n = 22).
 In normal rats AVP inhibition with a 35-micrograms/kg bolus of AVP V1 antagonist did not change heart rate, right atrial, left ventricular systolic, left ventricular end-diastolic or aortic pressures.
 There were also no changes in mean circulatory filling pressure, unstressed vascular volume, blood volume or venous compliance.
 In rats with infarction and elevated left ventricular end-diastolic pressures, AVP inhibition did not change heart rate, right atrial pressure, mean circulatory filling pressure or blood volume, but mean aortic pressure decreased from 103 +/- 3 to 88 +/- 2 mm Hg (P less than .001), venous compliance increased (P less than .001) from 2.17 +/- 0.07 to 3.04 +/- 0.11 ml/mm Hg/kg and unstressed vascular volume decreased from 42.3 +/- 3.1 to 34.7 +/- 2.6 ml/kg (P less than .05).
 We conclude that inhibition of AVP with a specific V1 antagonist had no effect on the venous or arterial circulations in normal rats, but in rats with left ventricular dysfunction and heart failure after chronic myocardial infarction, AVP inhibition decreased arterial pressure and caused venodilatation.
",13
2096,"Pharmacologic activity of bepafant (WEB 2170), a new and selective hetrazepinoic antagonist of platelet activating factor.
 The hetrazepine WEB 2170 (international nonproprietary name: bepafant), a thieno-triazolodiazepine that is structurally related to the recently described platelet activating factor (PAF) antagonist WEB 2086, is a potent and selective PAF antagonist both in vitro and in vivo.
 WEB 2170 inhibited PAF-induced human platelet and neutrophil aggregation in vitro (IC50 values: 0.3 and 0.83 microM, respectively) but had little or no inhibitory action against aggregation induced by other agonists.
 The potency in vitro was comparable to that described recently for WEB 2086 (Casals-Stenzel, J., Muacevic, G.
 and Weber, K.H.: J.
 Pharmacol.
 Exp.
 Ther.
 241: 974-981, 1987).
 When guinea pigs were given i.v.
 infusions of PAF at 30 ng x kg-1 x min-1, oral (0.005-0.5 mg/kg) as well as intravenous (0.005-0.05 mg/kg) treatment with WEB 2170 abrogated the intrathoracic accumulation of 111In-labeled platelets, the bronchoconstriction and the hypotension as well as the finally occurring death in a dose-dependent fashion.
 Oral (0.01-1 mg/kg) and intravenous (0.005-0.1 mg/kg) WEB 2170 shared with the beta 2 agonist fenoterol and the steroid dexamethasone the property of protecting elderly NMRI mice from the lethal effect of PAF.
 In anesthetized rats, intravenous (0.001-0.1 mg/kg) and oral (0.05-1 mg/kg) WEB 2170 inhibited PAF-induced hypotension in a dose-related manner.
 Coadministration of WEB 2170 inhibited PAF-induced increase of vascular permeability in rat skin very effectively.
 The half-time of duration of action in the rat was estimated to be about 5 to 6 h after oral administration and about 1.1 to 2.3 h after intravenous application.
 In conclusion, the hetrazepine WEB 2170 is a strong and selective PAF antagonist, which is in vitro more or less equipotent to WEB 2086.
 In contrast, in vivo oral WEB 2170 is--depending on the species and considered parameter--about 5 to 40 times more potent against exogenous PAF-induced alterations than the recently described hetrazepine WEB 2086.
 Particularly in mice and rats, oral WEB 2170 is by far superior to WEB 2086.
",13
2097,"Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene 
 The relation between risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene was examined in a population case-control study of 110 cases of angina, identified by the Chest Pain Questionnaire, and 394 controls selected from a sample of 6000 men aged 35-54.
 Plasma concentrations of vitamins C and E and carotene were significantly inversely related to the risk of angina.
 There was no significant relation with vitamin A.
 Smoking was a confounding factor.
 The inverse relation between angina and low plasma carotene disappeared and that with plasma vitamin C was substantially reduced after adjustment for smoking.
 Vitamin E remained independently and inversely related to the risk of angina after adjustment for age, smoking habit, blood pressure, lipids, and relative weight.
 The adjusted odds ratio for angina between the lowest and highest quintiles of vitamin E concentrations was 2.68 (95% confidence interval 1.07-6.70; p = 0.02).
 These findings suggest that some populations with a high incidence of coronary heart disease may benefit from eating diets rich in natural antioxidants, particularly vitamin E.
",13
2098,"Blood pressure measurements during dental checkups representative of 26-hour registration.
 The effect of dental checkups on blood pressure was investigated.
 In 27 normotensive patients (13 men and 14 women) aged 22 to 64 years (mean 39.75 +/- 10.5 years), a 26-hour continuous, noninvasive blood pressure registration was carried out.
 Of each patient at least 175 blood pressure measurements were registered during these 26 hours, giving a total amount of 4725 blood pressure measurements.
 A dental checkup appointment with the family dentist was included.
 Blood pressure values displayed the well-known diurnal variation, but the visit to the dental surgeon was not accompanied by a rise in blood pressure.
 There was no significant difference between the blood pressure values during the 26-hour period and those during the checkup period.
 During a rest period after the dental checkup, neither the systolic nor the diastolic pressure fell to any degree in relation to the 26-hour values or the visit to the surgeon.
",13
2099,"Assessment of stable ischemic heart disease. Which tests are best for which patients?
 An understanding of the importance of various risk factors, the pathogenesis of myocardial ischemia, and the appropriate use of various noninvasive and invasive tests is essential for management of patients with known or suspected coronary artery disease (CAD).
 Although coronary angiography remains the ""gold standard"" for diagnosis of CAD, much of the data obtained from risk factor assessment, medical history, and various noninvasive tests provides information that may be even more important than cardiac catheterization data alone for defining prognosis and directing management.
",13
2100,"Prevalence of hemodynamically significant stenosis of the carotid artery in an asymptomatic veteran population.
 The results of previous studies have suggested that significant stenosis of the carotid artery occurs in less than 6 per cent of asymptomatic patients.
 However, some populations studied were not representative of those seen by most vascular surgeons.
 Accordingly, we examined two cohorts of patients at the Veterans Administration Medical Center using Duplex scanning.
 There were 153 volunteers in group 1, all more than 50 years of age, who were being treated at our outpatient department for nonvascular problems.
 There were 116 patients of similar age in group 2 but who were known to have significant arterial occlusive disease of the lower extremity.
 The majority of patients were men with a mean age of 64.4 years.
 Risk factors in the total population included hypertension, diabetes mellitus, coronary arterial disease, peripheral vascular disease and smoking.
 Over-all, significant (greater than 50 per cent diameter) stenosis of the carotid artery was discovered in 25 of 269 patients.
 The prevalence for those in group 1 was 6.5 per cent versus 12.9 per cent for those in group 2 (p = 0.058).
 The prevalence in patients with cardiac disease was 15.2 per cent compared with 6.8 per cent in those without cardiac disease (p = 0.032).
 Smoking was associated with a 10.6 per cent rate of significant disease compared with a 2.3 per cent rate in nonsmokers (p = 0.065).
 Hypertension and diabetes were not significant risk factors.
 Significant stenosis of the carotid artery was found in seven of 40 patients in whom coronary arterial disease, peripheral vascular disease and smoking were all present.
",13
2101,"The syndrome of bilateral hemispheric border zone ischemia.
 Symptoms compatible with vertebrobasilar ischemia have been reported in patients with unilateral or bilateral carotid occlusive disease.
 Intracranial steal phenomena have been proposed to explain the symptoms.
 In a review of 54 patients with angiographically documented severe bilateral carotid stenosis (less than or equal to 2 mm residual lumen) or occlusion, eight had symptoms suggesting vertebrobasilar insufficiency.
 Five patients were identified retrospectively, and the other three were evaluated prospectively.
 Symptoms included various combinations of hemodynamically mediated, transient bilateral motor, sensory, or visual impairment.
 Dysarthria, dysphagia, and diplopia were generally absent.
 Each patient also described additional symptoms compatible with transient hemispheric or retinal ischemia.
 The anatomic regions subserving the bilateral vertebrobasilar-like symptoms could be correlated with angiographically estimated arterial border zones in both hemispheres and may thus represent bilateral hemispheric border zone ischemia rather than brain stem ischemia.
 An intracranial steal need not be invoked.
",13
2102,"Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion.
 Using in vivo brain microdialysis, we studied amino acid release in the striatum and cortex of eight rats following permanent middle cerebral artery occlusion.
 We then processed all brains for histopathologic assessment of the volume of ischemic damage 4 hours after occlusion.
 Ischemic damage was varied by occlusion of the middle cerebral artery at a point either proximal (n = 4) or distal (n = 4) to the lenticulostriate vessels.
 Proximal occlusion elevated the dialysate contents of all amino acids.
 The largest increases occurred for the potentially neurotoxic amino acids aspartate and glutamate and for taurine (800-2,800% of basal efflux).
 We observed smaller increases for the ""metabolic"" amino acids (280-580% of basal efflux).
 Distal occlusion did not affect amino acid efflux in the striatum, and release in the cortex was significantly lower than that following proximal occlusion.
 We compared release data with acute histopathologic outcome.
 Proximal occlusion resulted in a large volume of ischemic damage in the cortex and striatum (25-48% of hemispheric volume).
 A smaller volume of ischemic damage was noted following distal occlusion (0-21% of hemispheric volume).
 The volume of ischemic damage and the amount of amino acid release were significantly correlated (p less than 0.05).
",13
2103,"Angiographic contrast media interference with laser-induced fluorescence excitation and detection in atherosclerotic human coronary arteries.
 Laser-induced fluorescence has been used in conjunction with angiography for laser angioplasty guidance.
 The effect of radiopaque contrast media on the excitation and detection of arterial fluorescence has not been previously reported.
 Accordingly, fluorescence emission spectra from human coronary artery necropsy specimens (n = 7) during excitation with pulsed excimer laser excitation (308 nm) was examined before and after the addition of three different contrast media, sodium and meglumine diatrizoate, sodium and meglumine ioxaglate, and iopamidol.
 A decrease in overall fluorescence intensity was observed at all wavelengths for each contrast agent examined.
 The decrease in intensity of fluorescence emission was more marked at wavelengths less than 410 nm than at wavelengths above 425 nm.
 Similar effects were observed for contrast media diluted with whole blood.
 Absorption spectra for all three contrast media demonstrated absorption in the ultraviolet centered around 240 nm.
 We conclude that preferential absorption in the ultraviolet range by contrast media interferes with the excitation and detection of laser-induced fluorescence; use of visible light excitation may obviate interference with laser-induced fluorescence analysis of plaque.
",13
2104,"Normalization of Doppler indices of diastolic dysfunction during pacing is a sign of ischemic mitral regurgitation.
 Twenty-three patients with angina who were undergoing diagnostic cardiac catheterization underwent cardiac pacing with simultaneous hemodynamic and Doppler echocardiographic evaluation to assess the effects of pacing-induced ischemic on mitral valve velocity.
 Seventeen patients had significant coronary artery disease, and six patients had normal coronary arteries.
 Doppler and hemodynamic measurements were performed at rest and immediately after pacing was discontinued to 91% +/- 7% of maximal predicted heart rate.
 Seven patients experienced new or significant increases in severity of mitral regurgitation after pacing as revealed by Doppler examination.
 This group had a significant increase (p = 0.007) in early but not in late peak filling velocities immediately after pacing was discontinued, with a resultant decrease in late to early ratios, which decreased from 1.01% +/- 0.12 to 0.70% +/- 0.19 (p = 0.006).
 Left ventricular end-diastolic pressure increased significantly from 16.7% +/- 6.8 mm Hg to 29.4% +/- 5.3 mm Hg after cardiac pacing (p less than 0.001).
 Patients with coronary disease who did not develop mitral regurgitation also had significant increases in left ventricular end-diastolic pressure from 18.7% +/- 5.8 mm Hg to 24.3% +/- 8.6 mm Hg (p less than 0.05).
 There were no changes in late or early wave amplitude, late to early ratio, or other Doppler measurements in any of the other groups.
 We conclude that mitral regurgitation caused by pacing-induced myocardial ischemia normalizes Doppler indices of mitral inflow, which in turn, may mask persistent or worsened left ventricular diastolic dysfunction.
",13
2105,"Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study.
 To determine whether associations of elevated resting pulse rate with CHD incidence or death in white men are independent of other risk factors and whether such associations exist for women and blacks, data were examined from the NHANES I Epidemiologic Follow-up Study.
 Over a follow-up period of 6 to 13 years, elevated RR for CHD incidence were found for older white men with baseline pulse greater than 84 beats/min compared with less than 74 beats/min after controlling multiple risk factors (RR = 1.37, 95% CL 1.02, 1.84).
 Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases were also elevated for white men with elevated pulse rate independent of other risk factors.
 CHD incidence was increased in white women with elevated pulse rate.
 Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases, were also elevated for white men with elevated pulse rate independent of other risk factors.
 CHD incidence was increased in white women with elevated pulse rate.
 Risk of death from all causes and cardiovascular diseases was elevated in black men and women with elevated pulse rate.
 Risk of death from noncardiovascular disease was elevated in black men with elevated pulse rate.
 The association with cardiovascular death was particularly striking in black women, even after adjusting for baseline risk factors (RR 3.03, 95% CL 1.46, 6.28).
 Further studies are needed to assess associations of pulse rate with CHD in blacks and to elucidate mechanisms in all groups.
",13
2106,"The utility of echocardiography in the diagnostic strategy of postinfarction ventricular septal rupture: a comparison of two-dimensional echocardiography versus Doppler color flow imaging.
 The diagnostic accuracy of Doppler color flow imaging in the diagnosis of postinfarction ventricular septal defects has not been established.
 In this study, 43 patients with unexplained hypotension or a new murmur in the periinfarct period were evaluated with conventional two-dimensional echocardiography and Doppler color flow imaging.
 The presence of a ventricular septal defect was confirmed by oximetry, ventriculography, operative repair, or autopsy in each case.
 Both two-dimensional and Doppler color flow imaging were 100% specific in excluding a ventricular septal defect.
 Doppler color flow imaging correctly identified the 12 confirmed ventricular septal defects in this study (100% sensitivity), whereas any combination of two-dimensional criteria only correctly identified seven (58% sensitive) (p less than 0.05).
 Doppler color flow imaging is superior to conventional two-dimensional imaging in the diagnosis of a postinfarction ventricular septal defect.
 In addition, Doppler color flow imaging localized the septal defect, and thus guided therapy and technique for repair.
 Carefully performed Doppler color flow examination can exclude or result in the rapid diagnosis of a ventricular septal defect, which eliminates the need for further time-consuming confirmatory testing.
",13
2107,"Dipyridamole perfusion scintigraphy: the experience with its application in one hundred seventy patients with known or suspected unstable angina.
 We evaluated the safety, accuracy, and potential clinical utility of intravenous dipyridamole perfusion scintigraphy with thallium-201 in 170 patients, 78 with suspected and 92 with known unstable angina.
 All had coronary angiography.
 Noncardiac side effects (26%), induced chest discomfort (44%), and ST segment changes (12%) were similar in the two groups.
 No significant arrhythmias occurred.
 Two patients had prolonged chest pain, both with extensive reversible image abnormalities and associated creatinine kinase-MB release.
 Both had elective bypass surgery.
 Twenty-eight patients had normal coronary arteries, and 35 had single-vessel disease.
 Scintigraphic per patient sensitivity and specificity were 91% and 79% with a per vessel sensitivity of 74% and a per vessel specificity of 78% without between-group differences.
 During a brief follow-up period, 62 patients with image abnormalities had coronary revascularization, and there were seven deaths without intergroup differences.
 In a similar patient group that did not have angiography, scintigraphic defects were less frequent and less extensive, revascularization was not performed, and subsequent deaths occurred less often.
 Dipyridamole perfusion scintigraphy is an accurate alternative to exercise testing in the evaluation of patients with unstable angina pectoris.
 Although not without risk, the method appears relatively safe and should be considered as a guide to diagnosis, and probably to prognosis and management.
",13
2108,"Myocardial metabolic and hemodynamic effects of a sustained intravenous infusion of nifedipine with and without metoprolol in patients with unstable angina.
 We tested the usefulness of a sustained intravenous infusion of nifedipine and a combination of nifedipine and metoprolol in the early management of 14 patients with unstable angina pectoris.
 After a 24-hour run-in period, nifedipine was titrated in a stepwise fashion (mean dose 27 +/- 7 micrograms/min).
 After nifedipine treatment coronary blood flow increased from 150 +/- 66 to 183 +/- 74 ml/min (p less than 0.05), whereas double product, myocardial oxygen consumption, and both arterial and coronary sinus (nor)epinephrine levels were unchanged.
 Myocardial lactate uptake increased from 3.4 +/- 26.1 to 31.3 +/- 26.6 mumol/min (p less than 0.005) and free fatty acid uptake from 7.2 +/- 22.1 to 34.5 +/- 33.7 mumol/min (p less than 0.05).
 A small nonsignificant improvement in amino acid metabolism was observed.
 Metoprolol was added in seven patients and led to a decrease in double product (-2.2 +/- 1.6 x 10(3); p less than 0.01) and myocardial oxygen consumption (-3.2 +/- 3.8 ml/min; p less than 0.05).
 The lactate uptake/oxygen uptake ratio increased by 18% after metoprolol (p = NS).
 The number of episodes of chest pain decreased from 2.4 +/- 1.1/24 hours to 0.1 +/- 0.2 in the nifedipine group and from 2.9 +/- 1.1/24 hours to 0.3 +/- 0.5 in the nifedipine plus metoprolol group (both p less than 0.01).
 We conclude that in the acute phase of unstable angina, intravenous nifedipine can be carefully titrated to improve coronary blood flow and oxidative metabolism.
 The addition of metoprolol is also associated with a reduction in myocardial oxygen demand.
 This treatment results in significant hemodynamic stability.
",13
2109,"Fragmented atrial activity in patients with transient atrial fibrillation.
 Prediction of atrial fibrillation (AF) is very important in patients with Wolff-Parkinson-White syndrome or in the selection of pacemaker therapeutic modality.
 In 25 patients with transient AF, the response of the atrial activity width to extrastimuli was examined in comparison with 25 patients without AF to see if the results could be used as an index of subsequent occurrence of AF.
 Programmed electrical stimulation using eight basic stimuli followed by single or double extrastimuli (P1P2 or P1P2P3) were delivered to the high right atrium, and the atrial activities were examined.
 The prolongation of the atrial activity caused by extrastimuli was termed fragmentation (Frg), and it was defined as the prolongation of more than 150% of the basic stimuli.
 Frg zone was defined as the zone of coupling intervals of the extrastimuli (P1P2 or P2P3) that caused Frg, and delta max Frg was defined as the difference between the widest Frg and the atrial wave width during basic stimuli.
 Fragmentation was reproducibly induced by extrastimuli, and there was an inverse relationship between Frg duration and the coupling interval of the extrastimuli (P1P2 or P2P3).
 Frg zone and delta max Frg were wider and longer in patients with transient AF in comparison with the control group for both single and double extrastimuli (p less than 0.001).
 AF inducibility using double extrastimuli was significantly high in patients with AF.
",13
2110,"Management of multiple risk factors for coronary heart disease in patients with hypertension.
 Hypertension intervention trials, which have involved mainly the use of diuretics and beta-blockers, have demonstrated a disappointing benefit in terms of reduction of coronary heart disease (CHD).
 Rather than suggesting that elevated blood pressure and CHD are not causally related, these data suggest that the antihypertensive agents used were not optimal for the management of hypertension and a review of the currently recommended therapies is needed.
 Major risk factors for CHD, which include increased blood pressure, elevated serum cholesterol levels, and smoking, are highly prevalent in the general population and appear to cluster in patients with hypertension.
 Therefore the treatment of hypertension demands a multifactorial approach, one that takes into consideration all the risk factors for CHD.
 Diuretics and beta-blockers adversely affect the serum lipid profile, and this could negate some of the CHD benefit afforded by blood pressure reduction.
",13
2111,"Effects of doxazosin on serum lipids: a review of the clinical data and molecular basis for altered lipid metabolism.
 The goal of antihypertensive treatment must be not only the reduction of high blood pressure, but also the effective management of elevated cholesterol levels and other risk factors of coronary heart disease (CHD).
 In controlled clinical trials, doxazosin has been shown to have antihypertensive efficacy comparable with other classes of antihypertensive agents and to lower the levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides while increasing the levels of high-density lipoprotein cholesterol.
 Doxazosin appears to inhibit the development of CHD on two fronts.
 First, doxazosin binds to the alpha 1-adrenoreceptor and inhibits the receptor-mediated responses to epinephrine and norepinephrine.
 Second, doxazosin has direct and indirect effects on lipid metabolism by increasing LDL receptor activity, decreasing intracellular LDL synthesis, reducing the synthesis and secretion of very low-density lipoprotein cholesterol, and stimulating lipoprotein lipase activity.
 Doxazosin may also inhibit platelet aggregation.
 Long-term studies will determine how these actions translate into reductions in the morbidity and mortality rates of CHD.
 First-year results from the Treatment of Mild Hypertension Study (TOMHS) have demonstrated expected reductions in blood pressure for all antihypertensive agents studied.
 The lipid changes have varied with the type of antihypertensive treatment and have been favorable for doxazosin.
",13
2112,"Preliminary results of the Norwegian doxazosin postmarketing surveillance study: a twelve-week experience.
 The study was designed to investigate the safety and efficacy of doxazosin in the control of blood pressure in general medical practice; the results presented concern the first 748 patients evaluated over a 12-week period.
 Blood pressure was significantly reduced after treatment with doxazosin (-13/-9 mm Hg), and heart rate was not significantly altered.
 In addition, doxazosin significantly reduced total cholesterol levels (-6.7%), reduced triglyceride levels (-19.8%), increased high-density lipoprotein cholesterol levels (+2.5%), and the high-density lipoprotein:total cholesterol ratio (+9.7%).
 The calculated risk of coronary heart disease was reduced by 20.5% over a 12-week period.
 Thirty-five percent of patients reported at least one side effect, and the number of patients experiencing severe adverse reactions was small.
 Twenty patients (2.7%) discontinued treatment because of adverse events, and 2.7% had the dose of doxazosin reduced.
",13
2113,"Doxazosin: a study in a cohort of patients with hypertension in general practice--an interim report.
 The objective of this study was to assess the safety and efficacy of doxazosin in a substantial cohort of hypertensive patients drawn from general practice.
 A total of 4027 patients entered the study, 1472 of whom (36.6%) were untreated hypertensive patients.
 Patients were not advised to change diet, smoking habit, or life-style during the study.
 Twenty-one percent were cigarette smokers, and concurrent diabetes was present in 2.3%.
 Baseline blood cholesterol exceeded 200 mg/dl (5.2 mmol/L) in 90% and 250 mg/dl (6.5 mmol/L) in 56% of patients.
 The mean decrease in blood pressure produced by doxazosin was 22/15 mm Hg after 10 weeks of therapy; there was a mean decrease in heart rate of 1 beat/min.
 The mean maintenance dose for all patients was 3.1 mg/day.
 Side effects considered related or possibly related to treatment were reported in 705 patients.
 Treatment was discontinued in 233 patients (5.8%) because of adverse events related or possibly related to treatment with doxazosin.
 Doxazosin produced a significant (p less than 0.001) decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and a significant increase in high-density lipoprotein cholesterol and the ratio of high-density lipoprotein:total cholesterol.
 The potential reduction in 10-year coronary heart disease risk (according to the Framingham equation) was calculated to be 20.4%.
",13
2114,"An open, noncomparative study of doxazosin in essential hypertension: experience in general practice in The Netherlands.
 The antihypertensive efficacy, safety, and lipid effects of doxazosin, a selective alpha 1-inhibitor, were assessed in a general practice setting.
 Three hundred twenty-six patients were entered into the study, which involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received 1 to 8 mg of doxazosin once daily, and (3) a 4-week maintenance period.
 After 12 weeks, 78.8% of efficacy-evaluable patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline or greater than or equal to 10 mm Hg reduction from baseline).
 The mean daily dose in patients considered a therapy success was 2.8 mg.
 By the final visit, sitting systolic/diastolic blood pressures of these patients were reduced by 16.4/13.5 mm Hg from a mean baseline of 170/106 mm Hg.
 The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 70% of patients.
 Of the 326 patients, 30.7% reported a total of 160 side effects; 78% of the side effects were mild or moderate in severity, and 24 patients (7.4%) discontinued treatment because of adverse experiences.
 The investigators' global assessment of toleration was excellent or good for 87% of patients.
 Doxazosin produced a significant decrease in total cholesterol (p = 0.02) and triglyceride (p less than 0.001) levels.
 From baseline to final visit there was also a highly significant reduction of 17% (p less than 0.001) in calculated risk score for coronary heart disease on the basis of the Framingham Heart Study risk equation.
",13
2115,"Doxazosin and atenolol as monotherapy in mild and moderate hypertension: a randomized, parallel study with a three-year follow-up.
 The efficacy and safety of doxazosin (n = 83) and atenolol (n = 81) have been compared during a 3-year period.
 Doxazosin (mean dose at 3 years, 5.2 mg/day) and atenolol (mean dose, 66.4 mg/day) produced a sustained and overall similar reduction in blood pressure, with no evidence of tolerance.
 Doxazosin decreased mean blood pressure from 158/104 mm Hg to 146/90 mm Hg; with atenolol the decrease was from 160/103 mm Hg to 144/88 mm Hg.
 Whereas the reduction in blood pressure with atenolol was paralleled by a significant (p less than 0.05) decrease in heart rate (from a mean of 74 to 60 beats/min), doxazosin produced no clinically meaningful changes in heart rate.
 In contrast to atenolol, doxazosin reduced triglyceride levels by -5.9% (atenolol +22.5%), increased high-density lipoprotein cholesterol levels by +3.7% (atenolol, -11.2%), and increased the high-density lipoprotein/total cholesterol ratio by +5.9% (atenolol, -10.3%); all of these values were significantly (p less than 0.001) different from those of atenolol-treated patients.
 Doxazosin also reduced the calculated low-density lipoprotein cholesterol levels by -3.3% (atenolol, unchanged).
 The adverse effect of atenolol on lipid levels apparently negated any beneficial effect of blood pressure reduction, because the calculated coronary heart disease (CHD) risk actually increased significantly.
 In contrast, the reduction in calculated CHD risk in the doxazosin group was statistically significant at all points during the study.
 The safety profile of the drugs was similar.
 With the added potential of the reduction in the calculated risk of CHD among hypertensive patients,doxazosin represents an appropriate first-line drug for the treatment of essential hypertension.
",13
2116,"Cardiovascular disease risk profiles.
 This article presents prediction equations for several cardiovascular disease endpoints, which are based on measurements of several known risk factors.
 Subjects (n = 5573) were original and offspring subjects in the Framingham Heart Study, aged 30 to 74 years, and initially free of cardiovascular disease.
 Equations to predict risk for the following were developed: myocardial infarction, coronary heart disease (CHD), death from CHD, stroke, cardiovascular disease, and death from cardiovascular disease.
 The equations demonstrated the potential importance of controlling multiple risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, glucose intolerance, and left ventricular hypertrophy) as opposed to focusing on one single risk factor.
 The parametric model used was seen to have several advantages over existing standard regression models.
 Unlike logistic regression, it can provide predictions for different lengths of time, and probabilities can be expressed in a more straightforward way than the Cox proportional hazards model.
",13
2117,"Double-blind comparison of doxazosin and enalapril in patients with mild or moderate essential hypertension.
 The antihypertensive efficacy and safety of doxazosin and enalapril were compared in the general practice setting (n = 54).
 Both agents produced comparable, statistically significant (p less than 0.05) reductions in mean blood pressure with no clinically relevant changes in heart rate.
 Side effects in the two groups were mild or moderate and disappeared or were tolerated with continued treatment.
 Doxazosin, in contrast to enalapril, produced a significant (p less than 0.05) reduction in the total serum cholesterol concentration, a reduction in the level of triglycerides, and a favorable increase in the high-density lipoprotein/total cholesterol ratio.
 The reduction in calculated coronary heart disease risk produced by doxazosin (-27.58%) was highly significant (p less than 0.0002) and greater than that produced by enalapril (-18.49% p less than 0.02).
",13
2118,"A double-blind comparative study of doxazosin and prazosin when administered with beta-blockers or diuretics.
 The antihypertensive efficacy and safety of doxazosin (once daily) and prazosin (twice daily) were compared in patients with mild or moderate essential hypertension (diastolic blood pressure [DBP] 95 to 114 mm Hg) not adequately controlled by diuretics and beta-blockers.
 Doxazosin produced significantly greater mean reductions in standing (p = 0.01) and supine (p = 0.04) DBP than did prazosin; there were no significant between-group differences in either mean systolic blood pressure or heart rate.
 The overall mean daily doses for efficacy-evaluable patients were 4.7 mg of doxazosin and 6.7 mg of prazosin.
 Sixteen patients (84.2%) treated with doxazosin and 13 patients (56.5%) treated with prazosin were considered therapeutic successes (decrease in standing DBP greater than or equal to 10 mm Hg or to less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline).
 Of the 19 efficacy-evaluable patients treated with doxazosin, 15 (78.9%) showed improvement in the severity category of hypertension; an improvement in severity was reported in 14 patients (60.9%) treated with prazosin.
 Doxazosin produced a more favorable effect on serum lipid levels than did prazosin, although no statistically significant within- or between-group differences were observed.
 Most side effects experienced with either doxazosin or prazosin were mild or moderate and were tolerated or disappeared with continued treatment.
 The overall evaluation of toleration was excellent or good for 18 (90%) doxazosin- and 21 (91%) prazosin-treated patients.
 Clinical efficacy was rated as excellent or good for 16 patients (80%) treated with doxazosin and 15 patients (68%) treated with prazosin.
",13
2119,"The addition of doxazosin to the treatment regimen of patients with hypertension not adequately controlled by beta-blockers.
 When doxazosin was given to patients with hypertension not adequately controlled by beta-blockade, blood pressure was normalized in 94% of the 34 patients (blood pressure less than or equal to 140/85 mm Hg).
 This reduction in blood pressure was obtained with doxazosin in combination with metoprolol or oxprenolol at a mean final daily dose of 1.3 mg or pindolol or atenolol at 2.0 mg/day.
 Exercise-induced increase in systolic and diastolic blood pressure was also lower with combined beta-blocker and doxazosin therapy than with beta-blocker alone.
 After 12 weeks of treatment, the combination of doxazosin and beta-blocker significantly reduced total serum cholesterol and triglyceride levels.
 All side effects were mild and only one patient was withdrawn from therapy.
",13
2120,"A double-blind comparative study of doxazosin and prazosin in the treatment of essential hypertension.
 Two hundred sixty-six patients took part in a multicenter comparative study of doxazosin and prazosin.
 Both drugs produced a significant reduction (p less than 0.001) in blood pressure and no increase in heart rate.
 Blood pressure was considered ""markedly decreased"" or ""decreased"" in 70.8% of patients treated with doxazosin and 70.0% of patients treated with prazosin.
 No statistically significant between-group differences in antihypertensive efficacy were observed.
 Both doxazosin and prazosin were well tolerated; seven patients (5.6%) in each group had the therapy withdrawn.
",13
2121,"Clinical experience with doxazosin in general medical practice in New Zealand.
 This study investigated the safety and efficacy of doxazosin treatment in a large population of patients (n = 336) with essential hypertension and assessed the effect of doxazosin on the serum lipid profile and the calculated risk of developing coronary heart disease.
 Patients were assigned to two groups: those with a baseline diastolic blood pressure greater than or equal to 95 mm Hg (group 1) and those with a baseline diastolic blood pressure less than 95 mm Hg (group 2) that was controlled by previous antihypertensive therapy.
 Doxazosin treatment (monotherapy in 76.2% of patients) significantly (p less than 0.05) reduced the blood pressure of patients in group 1 (-23/-17 mm Hg) after 10 weeks and maintained the control of blood pressure for patients in group 2.
 Heart rate was essentially unchanged in both groups.
 Mean final daily doses of 3.6 and 3.2 mg were achieved in groups 1 and 2, respectively.
 Treatment with doxazosin improved the severity category of hypertension for 88.4% of patients in group 1; 87.3% of patients were considered a therapy success.
 Doxazosin had a favorable effect on the serum lipid profile in both groups of patients.
 The majority of lipid changes achieved statistical significance and resulted in a significant 27% decrease in the calculated risk of developing coronary heart disease.
 Doxazosin was well tolerated; only 24.1% of patients had side effects that were related or possibly related to treatment.
 In nine (2.7%) patients the dose of doxazosin was reduced and 26 (7.7%) patients withdrew from doxazosin therapy because of side effects.
",13
2122,"Doxazosin in the treatment of essential hypertension in general medical practice in Latin America.
 This Latin American study assessed in the general practice setting the efficacy and tolerance of once-daily doxazosin in the treatment of mild or moderate essential hypertension (sitting diastolic blood pressure, 95 to 115 mm Hg).
 Patients (n = 220) were treated with doxazosin for 12 weeks as monotherapy or in combination with other antihypertensive agents.
 At the final visit, doxazosin produced a mean change in sitting systolic/diastolic blood pressure of -18.4/-14.4 mm Hg, at a mean daily dose of 4.3 mg.
 One hundred sixty-three (77.6%) of the 210 evaluable patients were considered a therapeutic success.
 Lipid analyses identified a statistically significant (p = 0.02) reduction in total serum cholesterol (4.85%) and an overall decrease in triglyceride levels (5.12%).
 According to the Framingham Heart Study equation, doxazosin produced a highly significant (p less than 0.001) 20% reduction in the calculated probability of developing coronary heart disease in 10 years.
 Of the 220 patients evaluated, 54 (24.5%) reported side effects that were considered related to treatment.
 Ten (4.5%) patients reported side effects unrelated to treatment and 37 (16.8%) reported events of unknown relationship.
 Most side effects were mild or moderate and were tolerated or disappeared with continued treatment.
 Nine patients (4.1%) were discontinued from therapy and in 13 (5.9%) the dose was reduced.
 The most prevalent side effects were headache and dizziness.
 The investigator's overall assessment of antihypertensive efficacy was excellent or good for 176 patients (80.4%); tolerance was considered excellent or good in 193 patients (88.5%).
",13
2123,"A multicenter study of doxazosin in the treatment of essential hypertension in France.
 This study was designed to assess the efficacy and tolerance of doxazosin in patients with mild, moderate, or severe essential hypertension in a general practice setting.
 Ninety-six adults of a mean age of 55 1/2 years took part in the 14-week study, consisting of a placebo phase (2 weeks), a dose-adjustment phase with doxazosin (8 weeks), and a maintenance phase (4 weeks).
 Doxazosin, at a final mean daily dose of 3.4 mg, produced a significant (p less than 0.05) reduction in blood pressure at all points of measurement during the study.
 The mean change in sitting blood pressure at the end of treatment was -15.4/-15.8 mm Hg.
 Of the 85 patients who could be categorized as a success or failure, 78 (92%) were considered a therapeutic success; 78 (89%) of the 88 efficacy-evaluable patients demonstrated an improvement in the severity category of their hypertension.
 Treatment with doxazosin produced a reduction in serum cholesterol (-3.1%) and triglyceride (-3.8%) levels, although these changes did not attain statistical significance.
 The calculated probability of developing coronary heart disease in 10 years (according to the Framingham equation) was significantly (p less than 0.001) reduced by 22%, from 16.7 chances per 100 (baseline) to 14.3 chances per 100 (final visit).
 Twenty-six patients (27.1%) reported side effects that were possibly related to treatment, the most prevalent of which were vertigo (7.3%) and headache (6.3%).
 In four (4.2%) patients the dose of doxazosin was reduced and two (2.1%) were withdrawn prematurely.
 The investigator's assessments of tolerance was reduced and two (2.1%) were considered to be excellent or good in 85 (88%) patients.
",13
2124,"Clinical experience with doxazosin in general medical practice in The Netherlands.
 This study was designed to investigate the efficacy and toleration of once-daily doxazosin in the treatment of essential hypertension (sitting diastolic blood pressure 95 to 115 mm Hg) in a general medical practice.
 Fifty-three patients with mild or moderate essential hypertension entered a study of 14 weeks' duration.
 This consisted of a baseline run-in period of 2 weeks, a dose-adjustment phase with doxazosin (8 weeks), and a maintenance phase of 4 weeks.
 Doxazosin was initiated at 1 mg/day, and every 2 weeks the dose was doubled unless blood pressure was normalized (sitting diastolic blood pressure less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline) or significant side effects emerged.
 The maximum daily dose administered was 8 mg.
 Doxazosin produced a significant (p less than 0.05) final mean change in sitting blood pressure of -17.4/-12.2 mm Hg at a final mean daily dose of 4.1 mg.
 Heart rate was not significantly altered.
 A nonsignificant decrease in total cholesterol concentration (-2.66%, p = 0.06) and triglycerides (-8.80%, p = 0.09) was also observed.
 The effect of doxazosin on blood pressure and serum cholesterol resulted in a significant (p less than 0.001) reduction of 19% in calculated risk of coronary heart disease.
 The investigators' assessment of patient toleration of doxazosin was excellent or good in 86.8% of patients.
",13
2125,"A long-term study of doxazosin in the treatment of mild or moderate essential hypertension in general medical practice.
 This study assessed the long-term (54 weeks) antihypertensive efficacy and safety of doxazosin in the treatment of mild or moderate essential hypertension, defined as sitting and standing diastolic blood pressure of 95 to 114 mm Hg.
 Of the 153 patients who successfully completed an initial 14-week trial, 61 continued uninterrupted into a 40-week extension study.
 Optimal antihypertensive efficacy was achieved by week 12 and maintained in all patients for the duration of 1 year.
 The final mean sitting blood pressure was 148/84 mm Hg and was reduced from a mean baseline level of 173/102 mm Hg.
 Occasional decreases in heart rate were observed, but these were not considered to be clinically relevant (1 to 3 beats/min).
 The mean final dose of doxazosin for patients evaluable for efficacy was 2.4 mg/day; 91.7% of patients were taking less than or equal to 4 mg/day.
 No increase in daily maintenance dose was observed from the initial phase to the long-term extension study.
 After 1 year of treatment, 93.3% of patients were considered a therapeutic success (sitting diastolic blood pressure greater than or equal to 10 mm Hg reduction from baseline or less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction).
 In no patients was there a worsening in the severity category of the hypertension.
 Total serum cholesterol concentrations were reduced significantly (6.6% p = 0.03) at the end of week 14.
 Reductions in total serum cholesterol levels persisted throughout the extension study, with a final reduction of 5.4%.
",13
2126,"Doxazosin in the treatment of mild or moderate essential hypertension: an echocardiographic study.
 Sixteen patients with mild or moderate essential hypertension received 1 to 8 mg/day of doxazosin (mean daily dose, 2.7 mg).
 Blood pressure reduction (supine and standing) was highly significant (p less than 0.001), and no significant changes in heart rate were observed.
 A significant reduction (p less than 0.01) in left ventricular mass was seen without a change in left ventricular systolic function.
 All side effects were mild, and only one patient withdrew from the study.
",13
2127,"Echocardiographic assessment of doxazosin on left ventricular mass in patients with essential hypertension.
 A single daily dose of doxazosin taken during a 12-week period produced a significant reduction in blood pressure and left ventricular mass index in patients with mild or moderate hypertension.
 The systolic shortening coefficient was also increased and a trend in the improvement of ejection fraction, rate of circumferential fiber shortening, systolic contraction time, and preejective/ejective ratio was observed.
 No change in heart rate was recorded and no patients had side effects.
 The serum lipid profile was modified favorably, particularly with regard to the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio.
 By producing a reduction in blood pressure and left ventricular mass while favorably modifying the serum lipid profile, doxazosin produced a beneficial change in the overall coronary heart disease risk profile.
",13
2128,"Efficacy and safety of doxazosin in the treatment of patients with mild or moderate essential hypertension and elevated levels of cholesterol.
 In hypertensive patients, elevated serum cholesterol is a frequent and sinister additional coronary risk factor.
 Selective alpha 1-adrenoreceptor inhibitors appear to have the unique ability to control both risk factors.
 Forty-two patients, ages 42 to 65 years, including 21 men with sustained hypertension and elevated serum cholesterol levels, were included in a trial of monotherapy with doxazosin administered once daily (range, 1 to 16 mg).
 The influence of the drug on high blood pressure and elevated serum cholesterol was evaluated over a 28-week period, which consisted of a 4-week, single-blind placebo lead-in period, an open 10-week dose-adjustment period, and finally a 14-week maintenance period.
 Of the 39 efficacy-evaluable patients, 25 (64%) achieved adequate blood pressure control (diastolic blood pressure less than 90 mm Hg or a decrease in diastolic blood pressure greater than 10 mm Hg) at a mean daily dose of 2 mg of doxazosin.
 No persistent changes occurred in heart rate.
 In the 32 patients with evaluable lipid data, there were nonsignificant trends to an increase in high-density lipoprotein cholesterol and a reduction in total cholesterol, together with a significant reduction in serum triglyceride concentration.
 The combined changes in blood pressure and blood lipid levels resulted in a reduction of 36% in the calculated risk of coronary heart disease.
 Eleven patients reported side effects and four were withdrawn from therapy.
 These results confirm the antihypertensive and anticholesterolemic efficacy of once-daily treatment with doxazosin.
",13
2129,"A multicenter study of doxazosin in the treatment of patients with mild or moderate essential hypertension and concomitant intermittent claudication.
 This study assessed the efficacy and safety of once-daily doxazosin in the treatment of patients (n = 19) with mild or moderate essential hypertension (sitting diastolic blood pressure [DBP] 95 to 114 mm Hg) and concomitant intermittent claudication (Doppler ankle/arm ratio of less than 0.80 and walking tolerance of less than 700 m on the treadmill).
 After 14 weeks of treatment with doxazosin, a significant (p less than 0.05) reduction in systolic blood pressure and DBP was observed.
 Mean blood pressures were reduced from 170/100 mm Hg at baseline to 161/93 mm Hg at the end of treatment.
 Minor changes in heart rate occurred, which with continued treatment were not statistically significant from baseline.
 In 12 of 16 (75.0%) efficacy-evaluable patients blood pressure was normalized (DBP to less than or equal to 90 mm Hg with an greater than or equal to 5 mm Hg reduction from baseline) with a mean daily dose of 7.6 mg/day.
 Doxazosin improved the hypertension severity category in 13 of 16 (81.3%) patients.
 The blood pressure ratios between both the thighs and arms and ankles and arms showed no statistically significant changes after treatment with doxazosin.
 Thigh blood flow at rest and the reactive hyperemia after 3 minutes of arterial occlusion did not change statistically.
 There was a tendency for pain-free distance to improve.
 Laboratory data were not significantly changed after treatment with doxazosin.
 Of the 19 patients studied, 5 reported mild or moderate side effects that were either tolerated or disappeared with continued treatment.
 No patient had therapy withdrawn and no patient required a dose reduction.
",13
2130,"Doxazosin for the treatment of chronic congestive heart failure: results of a randomized double-blind and placebo-controlled study.
 In this study we evaluated the effects of once-daily administration of oral doxazosin in patients with chronic congestive heart failure (CHF).
 After a stabilization period of at least 2 weeks with digitalis and diuretics, 73 patients with chronic CHF were randomized to receive additionally either doxazosin or placebo in double-blind fashion.
 Patients underwent weekly dose adjustments with increasing doses of doxazosin (1, 2, 4, 8, and 16 mg daily) or placebo for 5 weeks, and 67 were evaluated for 12 additional weeks on maximally tolerated doses of blinded study drugs.
 Treatment groups were evaluated with respect to symptoms of heart failure, indexes of quality of life and left ventricular function, frequency and type of arrhythmia, adverse events, and mortality rates.
 Doxazosin (11.9 +/- 0.9 mg) given once daily produced a favorable trend in the investigators' and patients' assessments of symptomatic change.
 Doxazosin was associated with a significantly higher level of voluntary submaximal exercise and a favorable trend on left ventricular ejection fraction (increase of 9.8% of the baseline value vs 2.7% with placebo; p = NS).
 During the 3-month steady-dosing period, patients treated with doxazosin had a significant (p less than 0.004) reduction in ventricular arrhythmias and significantly fewer morbid and mortal cardiac events (including episodes of worsening heart failure severe enough to prompt discontinuation of the study, myocardial infarction, and death).
 Doxazosin was well tolerated, producing no major side effects and only a slightly higher frequency of minor treatment-related side effects compared with placebo (p = NS).
",13
2131,"The effect of doxazosin on platelet aggregation in normotensive subjects and patients with hypertension: an in vitro study.
 An in vitro assay was used to investigate the effects of doxazosin on the platelet aggregation induced by epinephrine, collagen, and adenosine diphosphate.
 Platelet-rich plasma from normotensive subjects and patients with hypertension was compared.
 Doxazosin produced a concentration-dependent inhibition of platelet aggregation in both groups, but significantly lower concentrations were required to inhibit platelet aggregation in plasma taken from patients with hypertension.
 The concentrations of doxazosin that inhibited platelet aggregation in vitro were similar to those that are used clinically to control blood pressure in patients with hypertension.
",13
2132,"Evidence of an antiplatelet aggregation action of doxazosin in patients with hypertension: an ex vivo study.
 Eighteen patients with a mean age of 54.7 years were included in the study.
 All patients had a diagnosis of mild or moderate essential hypertension (sitting diastolic blood pressure of 96 to 114 mm Hg).
 The study design was single blind and in two phases: phase I, placebo (4 weeks), and phase II, the active treatment (8 weeks) with increasing doses, if needed, of doxazosin every 2 weeks (1, 2, 4, and 8 mg/day).
 Results show that doxazosin has an antihypertensive effect that is dose dependent.
 Systolic, diastolic, and mean blood pressures were decreased significantly, and no effect on heart rate was observed.
 Doxazosin significantly inhibited the platelet aggregation induced by epinephrine, adenosine diphosphate, and collagen in a dose-dependent manner.
 In addition, treatment with doxazosin lowered total serum cholesterol and triglyceride levels, without changing other standard biochemical parameters.
 This indicates that doxazosin could offer a distinct therapeutic advantage in the modulation of atherogenic and thromboembolic factors associated with coronary heart disease.
",13
2133,"Role of oxygen free radicals in ischemic and reperfused myocardium.
 In recent years there has been considerable interest concerning the role of oxygen radicals in myocardial ischemia and reperfusion injury.
 The sequential univalent reduction of oxygen gives rise to very reactive intermediate products.
 Normally, the tissue concentration of these intermediate products of oxygen is limited and the aerobic myocardium survives because of the existence of a delicate balance between the generation of the various oxidants and the maintenance of the antioxidant defense mechanism.
 Several possible sources have been identified for the production of active oxygen species after ischemia and reperfusion and these sources may be mutually interactive.
 The ability of scavengers of oxygen free radicals, including vitamin E, to improve mechanical, mitochondrial, and sarcoplasmic reticulum function in animal models of ischemic-reperfusion injury also suggests that oxygen free radicals are partly responsible for myocardial damage in these models, although caution in the interpretation of these data is necessary.
",13
2134,"Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology.
 Essential antioxidants were determined in plasma of middle-aged men representing 16 European study populations, which differed sixfold in age-specific mortality from ischemic heart disease (IHD).
 In 12 populations with ""common"" plasma cholesterol (5.7-6.2 mmol/L) and blood pressure, both classical risk factors lacked significant correlations to IHD mortality, whereas absolute levels of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002).
 Evaluating all populations, cholesterol and diastolic blood pressure were moderately associated, but their correlation was inferior to that of vitamin E.
 In stepwise regression and multiple regression analysis, mortality was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol), and to 87% by all the above parameters plus blood pressure.
 Thus, in the present study the cross-cultural differences of IDH mortality are primarily attributable to plasma status of vitamin E, which might have protective functions.
",13
2135,"On the inheritance of abdominal aortic aneurysm.
 To determine the mode of inheritance of abdominal aortic aneurysm, data on first-degree relatives of 91 probands were collected.
 Results of segregation analysis performed on these data are reported.
 Many models, including nongenetic and genetic models, were compared using likelihood methods.
 The nongenetic model was rejected; statistically significant evidence in favor of a genetic model was found.
 Among the many genetic models compared, the most parsimonious genetic model was that susceptibility to abdominal aortic aneurysm is determined by a recessive gene at an autosomal diallelic major locus.
 A multifactorial component in addition to the major locus does not increase the likelihood of the data significantly.
",13
2136,"Chronic therapy for congestive heart failure with benazepril HCl, a new angiotensin converting enzyme inhibitor.
 Benazepril HCl is an orally effective angiotensin converting enzyme (ACE) inhibitor previously shown to have significant acute hemodynamic benefits in patients with congestive heart failure.
 In this study, 21 patients with New York Heart Association Class III or IV congestive heart failure were treated with 2 to 15 mg of benazepril HCl as a single daily oral dose for 28 days to determine the clinical and hemodynamic value of chronic therapy.
 Each patient underwent clinical evaluation during the 28-day period, as well as invasive hemodynamic studies on the first two and last two days of the trial.
 Plasma ACE activity and aldosterone levels fell significantly and renin levels rose after therapy.
 Benazepril HCl produced significant (p less than 0.01) reductions in arterial pressure and systemic vascular resistance, with corresponding increases in cardiac output and decreases in pulmonary artery wedge pressure.
 Responses after 28 days of therapy were equivalent to those after the initial doses.
 Clinical effects included reduced rest, exertional and paroxysmal nocturnal dyspnea, as well as reduced peripheral edema.
 Only one patient developed symptomatic orthostatic hypotension.
 Thus, benazepril HCl, given once daily, is an effective and well tolerated oral agent for the chronic treatment of advanced congestive heart failure.
",13
2137,"Cardiorespiratory effects of antagonism of diazepam sedation with flumazenil in patients with cardiac disease.
 The specific benzodiazepine antagonist flumazenil is currently under intense study.
 Despite much clinical experience, no detailed invasive hemodynamic studies of its use in cardiac patients have been published.
 In the present study, hemodynamic and respiratory variables were measured in 10 cardiac patients undergoing catheterization of the right and left sides of the heart, before and after sedation with intravenous diazepam, and after reversal of sedation with flumazenil.
 A sleep dose of diazepam (12.2 +/- 5.1 mg, mean +/- SD) caused only slight decreases in mean arterial pressure (103 +/- 12 to 98 +/- 14 mm Hg; P less than 0.05), pulmonary capillary wedge pressure (13.2 +/- 6.3 to 11.7 +/- 6.6 mm Hg; P less than 0.05), and left ventricular end-diastolic pressure (20.8 +/- 7.5 to 17.3 +/- 10.0 mm Hg; P less than 0.05), with no significant changes in respiratory gas homeostasis.
 Intravenous flumazenil (0.22 +/- 0.07 mg) resulted in spontaneous awakening and return to full orientation, yet caused no significant alteration in either hemodynamic or respiratory variables measured.
 Reversal of diazepam-induced sedation by flumazenil in cardiac patients appears safe and effective.
",13
2138,"Surgical repair of Wolff-Parkinson-White syndrome complicated with myocardial bridging.
 Myocardial bridging causes myocardial ischemia during supraventricular tachycardia.
 We present a case of Wolff-Parkinson-White syndrome combined with myocardial bridging.
 The patient complained of angina pectoris during paroxysmal supraventricular tachycardia because of severe constriction of the left anterior descending coronary artery during systole.
 A myocardial scintigram revealed myocardial ischemia in the anteroseptal wall during paroxysmal supraventricular tachycardia.
 Myotomy to prevent myocardial bridging and interruption of the accessory conduction pathway was successfully accomplished in a one-stage operation.
",13
2139,"Alternative technique for repair of sinus venosus atrial septal defect.
 A technique is described for closure of a sinus venosus atrial septal defect using a single patch held in place by sutures placed from outside the right atrium and underneath the superior vena cava.
 The superior vena cava does not require enlargement and potential damage to the artery to the sinoatrial node is avoided.
",13
2140,"Comparison of supraannular and subannular pledgeted sutures in mitral valve replacement 
 Ten fresh canine hearts were used to compare the peak left ventricular pressure required to disrupt prosthetic mitral valves sutured in place with horizontal mattress sutures with either subannular or supraannular pledgets.
 Each group consisted of 5 animals.
 A 29-mm Medtronic mitral valve was secured in the mitral position with ten pledgeted sutures.
 The aorta was cannulated and normal saline solution was infused into the left ventricle until valvar disruption occurred.
 The peak pressure and the location and mechanism of disruption were then noted.
 At the peak left ventricular pressure required for valvar disruption, no individual sutures were broken.
 Instead, in all specimens a subannular myocardial rupture occurred in the posterior portion of the mitral annulus along the extent of the atrioventricular groove.
 In addition, the posterior wall of the left atrium dissected upward subsequently.
 Significantly greater pressures were required in the group with subannular suture placement as compared with the supraannular group (354 +/- 37 versus 236 +/- 33 mm Hg; p less than 0.0007).
 These data suggest that placement of horizontal mattress sutures with pledgets in the subannular position is superior to the currently recommended method of supraannular suture placement in mechanical valves.
",13
2141,"Does cholesterol screening result in negative labeling effects? Results of the Massachusetts Model Systems for Blood Cholesterol Screening Project.
 Several previous studies that looked at the effects of labeling individuals as hypertensive found increases in psychosocial distress, diminished feelings of well-being, or absenteeism.
 Other studies found no such effects.
 Thus far, similar studies relating to labeling for high blood cholesterol levels have not been published.
 The Massachusetts Model Systems for Blood Cholesterol Screening Project investigated whether labeling effects occurred as a result of the community-based screening, education, and referral programs it conducted in Worcester and Lowell.
 Nine questions concerning perceptions of physical and psychological well-being were asked on a questionnaire given to screening participants.
 The same questions were asked as part of a follow-up questionnaire given to all individuals identified as having high blood cholesterol levels at one of the screenings.
 Comparison of the baseline and follow-up results did not demonstrate significant overall negative effects among any age, sex, racial, income, or educational groups.
 On the contrary, responses to many of the questions revealed small but statistically significant improvements in perceptions of physical and psychological well-being.
 The absence of negative labeling effects may be attributable to the positive, supportive approach to participant counseling taken by the project.
",13
2142,"Weight gain at the time of menopause.
 We studied prospectively the weight change and the effect of weight change on changes in coronary heart disease risk factors in a population-based sample of 485 middle-aged women.
 All women were studied first in 1983 to 1984, when they were premenopausal and aged 42 to 50 years, and then restudied in 1987.
 Women gained an average of 2.25 +/- 4.19 kg during this 3-year period; 20% of women gained 4.5 kg or more, and only 3% lost 4.5 kg or more.
 There were no significant differences in weight gain of women who remained premenopausal and those who had a natural menopause (+2.07 kg vs +1.35 kg).
 Weight gain was significantly associated with increases in blood pressure and levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and fasting insulin.
 Weight gain is thus a common occurrence for women at the time of menopause and is related to the changes in coronary heart disease risk factors observed during this period.
 Efforts to lose weight or to prevent weight gain may help to mitigate the worsening in coronary heart disease risk factors in middle-aged women.
",13
2143,"Lipoprotein-related coronary risk factors in patients with angiographically defined coronary artery disease: relation to number of stenosed arteries.
 To determine whether an index estimating antagonism between low density lipoprotein (LDL) and high density lipoprotein (HDL) would improve separation between groups with and without coronary artherosclerosis, patients undergoing coronary catheterization (35 women and 99 men) were analysed for total cholesterol (TC), HDL cholesterol (HDLc), apolipoprotein A (apo A) and apolipoprotein B (apo B).
 The subjects were categorized as groups 0, 1, 2 or 3 according to the number of stenosed arteries (greater than 75% areal stenosis).
 Thirty of the patients showed no significant coronary atherosclerosis (group 0).
 Serum apo B and TC concentrations were directly related to the number of stenosed vessels, whereas the concentrations of apo A and HDLc were negatively correlated with the number of stenosed arteries.
 An 'atherogenic Index' (ATH index) calculated as the product of serum concentrations of apo B, and TC minus HDLc divided by the product of apo A and HDLc, proved more satisfactory than individual lipoprotein components for discrimination between subjects with and without stenosis.
 Accordingly, identification of coronary groups may be improved by using the ATH index.
",13
2144,"Effects of long-term treatment with metoprolol and hydrochlorothiazide on plasma lipids and lipoproteins.
 In order to evaluate the effects of one-year antihypertensive treatment on plasma lipids and lipoproteins, 65 patients whose diastolic blood pressure was in the range 95-120 mmHg were randomly allocated to groups that received either hydrochlorothiazide or metoprolol, or both drugs when the response to one of them was insufficient to control blood pressure.
 Blood pressure was effectively reduced in all groups.
 Patients on hydrochlorothiazide showed a significant increase (P less than 0.01) in low-density lipoprotein cholesterol (LDL-C) after 3 months of treatment.
 A significant increase in triglycerides was observed after 6 and 12 months, together with a decrease in high-density lipoprotein cholesterol (HDL-C) after 12 months (P less than 0.05) of treatment in patients on metoprolol.
 In patients treated with both hydrochlorothiazide and metoprolol, total cholesterol increased after 3 (P less than 0.001) and 6 months (P less than 0.05), triglycerides increased after 6 (P less than 0.01) and 12 months (P less than 0.01), and LDL-C increased after 3 (P less than 0.05), 6 (P less than 0.001) and 12 months (P less than 0.01) of treatment, respectively.
 In 61% of the patients, three or more lipid parameters were affected during the study period.
 We conclude that long-term antihypertensive treatment with hydrochlorothiazide, metoprolol, and particularly with both drugs, can induce lipid effects that deserve recognition, because in some cases these might counteract the possible benefit of a reduction in blood pressure on the prevention of coronary heart disease.
",13
2145,"Wives of coronary high-risk men--are they also at higher risk? The Tromso Heart Study.
 Blood lipids, blood pressure, body mass index (BMI), smoking, dietary and exercise habits were studied in 911 wives of men with high risk for coronary heart disease (CHD).
 Following the 1979/80 Tromso Survey, 1373 men, aged 30-54 years, were identified as having high risk for CHD (HDL-cholesterol/total cholesterol less than or equal to 17.6% and/or total cholesterol greater than or equal to 7.86 mmol l-1).
 Of the 1373 men, 911 individuals had wives who also attended the screening.
 These wives were compared to age-matched, married women in the general population.
 A significantly higher total cholesterol level (5.98 mmol l-1 vs.
 5.78 mmol l-1), lower HDL-cholesterol/total cholesterol (30.01% vs.
 31.58%), higher BMI and higher coronary risk score (4.55 vs.
 3.82) was found among the wives of the high-risk men.
 Furthermore, a higher proportion of these individuals were daily cigarette smokers (47.3% vs.
 42.1%), and had received fewer years of education.
 They also had more dietary habits associated with increased risk of CHD than other married women in the general population.
 Our findings support the hypothesis that members of the same household as a person with increased risk for CHD also have increased risk.
 This is most probably due to shared lifestyle.
",13
2146,"Verapamil increases serum alkaline phosphatase in hypertensive patients.
 In rats, verapamil decreases intestinal absorption of calcium, increases serum parathyroid hormone (PTH), and induces osteopenia.
 In this prospective study, verapamil 80-120 mg three times daily was given for 2 months to 20 patients with hypertension, and the effects on calcium homeostasis were recorded.
 This dose of verapamil significantly reduced supine systolic and diastolic blood pressure (+/- SD) from 158/100 +/- 9/8 mmHg to 146/89 +/- 14/8 mmHg (P = 0.001).
 Serum alkaline phosphatase (ALP) increased significantly from 2.77 +/- 1.06 mu kat l-1 to 3.19 +/- 1.22 mu kat l-1 (P = 0.004), and isoenzymes of ALP of skeletal origin appeared after verapamil treatment.
 The excretion of sodium in the urine increased (Na/creatinine ratio 8.95 +/- 6.01 before and 13.16 +/- 8.26 after verapamil; P = 0.04), while the excretion of calcium, phosphate and potassium was not changed.
 PTH was slightly increased at the end of verapamil treatment (1.09 +/- 0.54 vs.
 0.98 +/- 0.74 microgram l-1; P = 0.07), and s-1,25(OH)2D3 was also somewhat increased (22.3 +/- 14.4 vs.
 17.6 +/- 4.9 ng l-1; P = 0.26).
 Serum Ca was not affected by verapamil (before verapamil 2.43 +/- 0.11 mmol l-1, after verapamil 2.40 +/- 0.12 mmol l-1; P = 0.28).
 The increase in serum ALP demonstrates that verapamil affects bone cell metabolism in man.
 This effect could be secondary to the enhancement of PTH secretion.
",13
2147,"Lower extremity arterial disease in elderly subjects with systolic hypertension.
 The ratio of ankle-to-arm systolic blood pressure (ankle/arm index or AAI) appears to be a non-invasive indicator of flow-significant atherosclerosis and may be a useful measure of burden of disease in a high risk population.
 The prevalence of lower extremity arterial disease (LEAD) was assessed by this method in the Systolic Hypertension in the Elderly Program (SHEP).
 Subjects were aged 60 and older with systolic blood pressure greater than 160 mmHg upon entry to the study.
 An AAI of 0.90 or less was considered indicative of flow-significant LEAD.
 The prevalence of LEAD by this method was 26.7% (50/187), while the prevalence of intermittent claudication (IC) was only 6.4% (12/187).
 Of those with IC, 66.7% (8/12) had confirmed LEAD.
 The prevalence of LEAD as measured by AAI increased with age in women and was associated with a history of current smoking and lower levels of high density lipoproteins.
 In this study population with systolic hypertension, LEAD, as measured by the AAI, is more prevalent than previously described in elderly populations and is associated with other risk factors for atherosclerosis.
",13
2148,"A prospective comparison of rubidium-82 PET and thallium-201 SPECT myocardial perfusion imaging utilizing a single dipyridamole stress in the diagnosis of coronary artery disease 
 The purpose of the present study is to prospectively compare myocardial perfusion imaging with rubidium-82 (82Rb) by positron emission tomography (PET) with thallium-201 (201Tl) imaging by single-photon emission tomography (SPECT) by recording both studies with a single dipyridamole handgrip stress, and reading both sets of images with the same display technique.
 In a series of 202 patients with previous coronary arteriography, the sensitivity, specificity, and accuracy of 82Rb PET were 93%, 78%, and 90% and for 201Tl SPECT 76%, 80%, and 77%, respectively.
 When 70 patients with previous therapeutic interventions were excluded, the remaining 132 patients showed a sensitivity, specificity, and accuracy of 95%, 82% and 92% for 82Rb PET and 79%, 76%, and 78% for 201Tl SPECT.
 The improved contrast resolution of PET resulted in markedly superior images and a more confident identification of defects.
",13
2149,"Reducing unnecessary coronary care unit admissions: a comparison of three decision aids 
 OBJECTIVE: To determine whether published decision rules for ischemic heart disease have practical value in reducing unnecessary admissions to coronary care units.
 DESIGN: Prospective cohort study.
 SETTING: A community hospital emergency room.
 PATIENTS: 235 consecutive patients presenting to an emergency room with a chief complaint of chest pain.
 MEASUREMENTS: Clinical information, including observations needed to use previously published decision aids, was collected on special forms at the time of the emergency room visit.
 Follow-up information was obtained from the medical records of patients who were admitted and by telephone interviews with patients who were discharged.
 The authors compared the residents' actual decisions with the predictions of the decision aids regarding their ability to predict complications (that is, to identify patients who needed admission or intensive care).
 MAIN RESULTS AND CONCLUSIONS: None of the decision aids could reduce unnecessary admissions without seriously increasing the rate of inappropriate discharges.
 However, within the clinically relevant subgroup of patients for whom the decision to admit or discharge was not obvious on clinical grounds (those without complications on presentation whom the residents chose not to discharge), the decision aids examined, used in combination to verify the need for admission, might have safely averted some unnecessary admissions.
",13
2150,"Arginine vasopressin gene expression in chronic cardiac failure in rats.
 Arginine vasopressin (AVP) is known to be increased in patients and experimental animals with chronic cardiac failure (CCF).
 The importance of an increase in biosynthesis of AVP in the hypothalamus has, however, not heretofore been investigated and is the purpose of the present study.
 CCF secondary to infarction of myocardial tissue was induced by ligation of the left anterior descending coronary artery and sham operated animals served as controls.
 Four weeks later hypothalamic AVP mRNA was determined by solution hybridization using sense and anti-sense strand RNA.
 The blood pressure was lower in CCF than sham animals (131.2 +/- 3.1 vs.
 112.8 +/- 4.0 mm Hg, P less than 0.05) and the total heart, and right and left ventricle weights were significantly higher in CCF rats.
 Plasma AVP was higher in CCF (sham 6.78 +/- 0.30; CCF 11.46 +/- 0.64 pg/ml, P less than 0.001) and plasma atrial natriuretic peptide was also higher in CCF than sham animals (205 +/- 36 vs.
 554 +/- 56 pg/ml, P less than 0.001).
 The AVP mRNA in hypothalamus was significantly higher in CCF than sham animals (55.5 +/- 3.7 vs.
 95.9 +/- 4.0 pg/micrograms total RNA, P less than 0.001).
 There was no difference in beta-actin mRNA in the hypothalamus of sham and CCF rats, indicating that the AVP-mRNA increase was specific in CCF.
 These results therefore demonstrate that increased AVP biosynthesis in the hypothalamus, in addition to release of the hormone from the posterior pituitary, may occur in CCF.
",13
2151,"Studies of myocardial protection in the immature heart. V. Safety of prolonged aortic clamping with hypocalcemic glutamate/aspartate blood cardioplegia.
 This study tests the hypothesis that multidose, hypocalcemic aspartate/glutamate-enriched blood cardioplegia provides safe and effective protection during prolonged aortic clamping of immature hearts.
 Of 17 puppies (6 to 8 weeks of age, 3 to 5 kg) placed on vented cardiopulmonary bypass, five were subjected to 60 minutes of 37 degrees C global ischemia without cardioplegic protection and seven underwent 120 minutes of aortic clamping with 4 degrees C multidose aspartate/glutamate-enriched blood cardioplegia ([Ca++] = 0.2 mmol/L), preceded and followed by 37 degrees C blood cardioplegic induction and reperfusion.
 Five puppies underwent blood cardioplegic perfusion for 10 minutes without intervening ischemia to assess the effect of the cardioplegic solution and the delivery techniques.
 Left ventricular performance was assessed 30 minutes after bypass was discontinued (Starling function curves).
 Hearts were studied for high-energy phosphates and tissue amino acids.
 One hour of normothermic ischemia resulted in profound functional depression, with peak stroke work index only 43% of control (0.7 +/- 0.1 versus 1.7 +/- 0.2 gm x m/kg, p less than 0.05).
 There was 70% depletion of adenosine triphosphate (7.6 +/- 1 versus control 20.3 +/- 1 mumol/gm dry weight, p less than 0.05) and 75% glutamate loss (6.6 +/- 1 versus control 26.4 +/- 3 mumol/gm, p less than 0.05).
 In contrast, after 2 hours of aortic clamping with multidose blood cardioplegia preceded and followed by 37 degrees C blood cardioplegia, there was complete recovery of left ventricular function (peak stroke work index 1.6 +/- 0.2 gm x m/kg) and maintenance of adenosine triphosphates, glutamate, and aspartate levels at or above control levels adenosine triphosphate 18 +/- 2 mumol/gm, aspartate 21 +/- 1 versus control 2 mumol/gm, and glutamate 25.4 +/- 2 mumol/gm).
 Puppy hearts receiving blood cardioplegic perfusion without ischemia had complete recovery of control stroke work index.
 We conclude that methods of myocardial protection used in adults, with amino acid-enriched, reduced-calcium blood cardioplegia, can be applied safely to the neonatal heart and allow for complete functional and metabolic recovery after prolonged aortic clamping.
",13
2152,"Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis [published erratum appears in Proc Natl Acad Sci U S A 1991 Apr 1;88(7):2967]
 The gene coding for plasminogen has been compared with several abnormal genes from Japanese patients by the polymerase chain reaction and DNA sequence analysis.
 Two types of abnormal genes coding for plasminogen were identified in these patients.
 In the type I mutation, a guanosine in GCT coding for Ala-601 near the active-site histidine was replaced by an adenosine resulting in ACT coding for threonine.
 This mutation was also shown by the loss of a cleavage site for Fnu4HI endonuclease, a restriction enzyme that recognizes GCTGC but not ACTGC.
 In the type II mutation, a guanosine in GTC coding for Val-355 was replaced by a thymidine resulting in TTC coding for phenylalanine.
 This change was readily shown by digestion with Ava II endonuclease, a restriction enzyme that recognizes GGTCC and not GTTCC.
 The type I mutation has been found to be identical to a plasminogen variant identified in Japanese patients by amino acid sequence analysis and also detected by isoelectric focusing, whereas the type II mutation is a unique amino acid substitution in the connecting region between the third and fourth kringles in plasminogen.
 DNA sequence analysis also revealed that the abnormal genes carry several silent nucleotide substitutions located primarily within introns and 5' and 3' flanking regions.
",13
2153,"A histopathologic study of spinal cord ischemia using an isohistogenic rat upper-half-body transplantation model.
 To study the histopathologic changes of spinal cords exposed to long-duration complete ischemia, the authors developed an upper-half-body transplantation model of inbred rat.
 In this model, an infant Lewis rat is transplanted to the inguinal region of another adult Lewis rat using microsurgical vascular anastomosis.
 Even when 2-week-old donor rats were exposed to complete ischemia for 90 minutes, functions of the spinal cord were comparatively preserved.
 In histopathologic observations, degeneration proportional to complete ischemia duration was noted.
 In the 60-minute ischemia group of 2-week-old donor rats, however, no substantial differences from normal spinal cord were observed.
 Under conditions of equal ischemia duration, it appeared the younger animal had the greater ischemic tolerance.
",13
2154,"Severity of single-vessel coronary arterial stenosis and duration of angina as determinants of recruitable collateral vessels during balloon angioplasty occlusion.
 To determine the factors that influence the presence of collateral vessels during coronary occlusion, we performed standardized contrast injection of the contralateral coronary artery in 58 consecutive patients, without previous myocardial infarction, undergoing percutaneous transluminal coronary angioplasty for 1-vessel disease (left anterior descending artery in 45, right coronary artery: in 10 and left circumflex artery in 3).
 The presence of collateral vessels during coronary occlusion, defined as partial or complete epicardial opacification by collateral vessels of the vessel dilated, was related to clinical, angiographic and electrocardiographic parameters.
 The angiographic appearance of collateral vessels during balloon inflation showed a weak, although statistically significant, correlation to the percent diameter stenosis before angioplasty (r = 0.28; p = 0.03) and the duration of angina (r = 0.37; p = 0.004).
 By combining lesion severity with the duration of angina, collateral vessels during coronary occlusion were particularly related to a lesion severity greater than or equal to 70% and duration of angina greater than or equal to 3 months (p less than 0.001).
 Furthermore, the presence of collateral vessels was associated with an absence of ST-segment shift (greater than or equal to 1 mm) during 1 minute of coronary occlusion (p less than 0.001).
",13
2155,"Characteristics of black patients admitted to coronary care units in metropolitan Seattle: results from the Myocardial Infarction Triage and Intervention Registry (MITI).
 Since 1988, 641 black and 11,892 white patients with chest pain of presumed cardiac origin have been admitted to coronary care units in 19 hospitals in metropolitan Seattle.
 Black men and women were younger (58 vs 66, p less than 0.0001), more often admitted to central city hospitals (p less than 0.0001), and developed evidence of acute myocardial infarction (AMI) less often (19 vs 23%, p = 0.01).
 In the subset of 2,870 AMI patients, blacks (n = 121) were younger (59 vs 67, p less than 0.0001) and had less prior coronary artery bypass graft surgery (2 vs 10%, p = 0.005) and more prior hypertension (67 vs 46%, p less than 0.0001).
 During hospitalization, whites (n = 2,749) had higher rates of coronary angioplasty (18 vs 10%, p = 0.03) and coronary artery bypass graft surgery (10 vs 4%, p = 0.04), although thrombolytic therapy and cardiac catheterization were used equally in the 2 groups.
 Hospital mortality was 7.4% for black and 13.1% for white patients (p = 0.07).
 However, after adjustment for key demographic and clinical variables by logistic regression, this difference was not as apparent (p = 0.38).
 Questions about the premature onset of coronary artery disease, excess systemic hypertension, and the differential use of interventions in black persons have been raised by other investigators.
 Despite differences in age, referral patterns and the use of coronary angioplasty and bypass surgery, black and white patients with AMI in metropolitan Seattle had similar outcomes.
",13
2156,"Late results of 200 repeat coronary artery bypass operations.
 To determine the clinical outcome and the long-term results of a second coronary artery bypass operation, we studied preoperative clinical status and catheterization data in 200 consecutive patients over a 9-year period (1979 to 1987) (mean follow up time 34 months, maximum 120).
 The study group included 169 men and 31 women (mean age 58.4 years [7% greater than 70 years]).
 Sixty-four percent of patients had severe angina (New York Heart Association class IV), 70% had 3-vessel coronary artery disease and 21% had poor left ventricular function.
 Reoperation was performed after a mean interval of 58 months after the first procedure.
 A mean of 3.3 distal anastomoses was placed.
 The operative mortality rate (30 days) was 7.5%, with additional cardiac morbidity (myocardial infarction, heart failure) in 11.5% of patients.
 Multivariate analysis showed an increased risk in women (risk ratio 3.6) and in patients with poor left ventricular function (risk ratio 3.1).
 The cumulative 5-year survival rate was estimated at 84%, with a rate of 77% for patients with poor left ventricular function (difference not significant).
 The probability of remaining free of a cardiac-related event (myocardial infarction, angioplasty, third operation, cardiac death) was 64% for 5 years.
 At the end of follow-up, 79% of the surviving patients were in New York Heart Association class I or II and nearly 50% of patients in the fifth year after the reoperation had good functional status.
 It is concluded that a reoperation is effective but carries an increased, immediate, operative risk.
",13
2157,"Cardiovascular risk factor clustering and ratio of total cholesterol to high-density lipoprotein cholesterol in angiographically documented coronary artery disease.
 High levels of cardiac risk factors tend to cluster together and act synergistically.
 To develop a suitable and practical marker for clustering, we evaluated 380 consecutive patients at the time of coronary angiography.
 Analyses of lipid, rheologic, clinical and arteriographic profiles indicated a variety of interwoven relations.
 Because the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (total/HDL cholesterol) was closely related to both the presence and extent of greater than or equal to 50% diameter reduction of greater than or equal to 1 coronary arteries, it was used to divide patients into quartiles.
 Clustering of high- and low-level risk factors was demonstrated in the highest and lowest quartiles of total/HDL cholesterol, respectively (p less than 0.001).
 The highest quartile may be characterized by an only moderately elevated total cholesterol level but patients in this quartile may have a very low HDL cholesterol level, high triglycerides, a tendency toward high hemoglobin and fibrinogen levels, a history of smoking, previous myocardial infarction and multivessel disease.
 These results suggest that total/HDL cholesterol serves as a marker not only for obstructive coronary disease but also for a cluster of potentially modifiable risk factors.
",13
2158,"Ventricular tachycardia and accelerated ventricular rhythm presenting in the first month of life.
 Fourteen infants aged less than 1 month presented to our institution during the last 22 years with ventricular tachycardia (VT) or accelerated ventricular rhythm and a structurally normal heart.
 In 2, VT was associated with long QT syndrome.
 Both are alive on beta-blocker therapy, 1 with an implanted pacemaker.
 Twelve infants had accelerated ventricular rhythm, and 2 of these died in the first 2 months of life of unrelated conditions.
 The other 10 are alive at a median age of 4 years (range 2 months to 11 years), and none were lost to follow-up.
 Hemodynamic compromise did not occur with accelerated ventricular rhythm.
 The ventricular rate was very close to the sinus rate in all 12, less than 12% above the sinus rate.
 The mean QRS duration during accelerated ventricular rhythm was 92.5 ms, and averaged twice the QRS duration during sinus rhythm.
 Fusion beats were seen in all 12, and there was atrioventricular dissociation with capture beats in 10.
 In 2, ventriculoatrial conduction was present.
 Treatment was attempted in 5 of the 10 survivors with accelerated ventricular rhythm, and was thought to be successful in 4.
 Treatment was later successfully withdrawn in all 5, so that all 10 survivors were free of accelerated ventricular rhythm and were not receiving antiarrhythmic medications at last follow-up.
 Because of the excellent long-term outcome and the lack of hemodynamic compromise during the rhythm, it seems reasonable to withhold antiarrhythmic therapy in infants with accelerated ventricular rhythm and await resolution of the rhythm.
",13
2159,"Characterization of spontaneous termination of sustained ventricular tachycardia associated with coronary artery disease.
 To characterize the change in cycle length and QRS morphology before spontaneous termination of sustained ventricular tachycardia (VT), electrocardiograms were recorded and VT cycle length measured for the periods 31 to 21 and 11 to 1 beats before termination in 55 episodes from 28 patients with coronary artery disease.
 Beats 31 to 21 were designated as a period of stable arrhythmia and served as a reference for changes occurring just before termination.
 Forty-four episodes of VT occurred in the setting of antiarrhythmic drug therapy; 11 episodes occurred in patients not treated with antiarrhythmic drugs.
 Variability in cycle length was indexed by the standard deviation of the mean cycle length and by the percentage of consecutive cycles varying by greater than or equal to 40 ms (% greater than or equal to 40 ms).
 There was greater variability just before termination (standard deviation of the mean cycle length, 25.8 ms; % greater than or equal to 40 ms, 16.7%) than during the stable period (standard deviation of the mean cycle length, 8.5 ms; % greater than or equal to 40 ms, 5.4%; p less than 0.001 for both).
 This was true irrespective of antiarrhythmic drug use, although the differences in the standard deviation of the mean cycle length for beats 11 to 1 and for beats 31 to 21 were greater for the antiarrhythmic drug group (29.6 vs 8.9 ms, p less than 0.001) than for the group not receiving antiarrhythmic drugs (11.0 vs 6.7 ms, difference not significant).
 No specific patterns of cycle length variability characteristic of VT termination were found.
",13
2160,"Comparison of lisinopril versus atenolol for mild to moderate essential hypertension.
 The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension.
 After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol.
 Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol.
 Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol.
 No important changes in hematologic and biochemical profiles were seen with either drug.
 Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group.
 Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension.
",13
2161,"Hemodynamic effects of renin inhibition by enalkiren in chronic congestive heart failure.
 Previous efforts to block the renin-angiotensin system in patients with chronic congestive heart failure (CHF) have focused on 2 distal sites in the system, the angiotensin-converting enzyme and the angiotensin II receptor.
 Recent work, however, has led to the development of agents that directly inhibit renin, the proximal step in the cascade.
 In this study, we investigated the hemodynamic effects of renin inhibition in 9 patients with chronic CHF by using enalkiren, a primate-selective, dipeptide renin inhibitor, which has been previously shown to suppress plasma renin activity and to lower blood pressure in hypertensive patients.
 The acute intravenous administration of enalkiren (1.0 mg/kg) produced increases in cardiac index (2.0 +/- 0.3 to 2.3 +/- 0.1 liter/min/m2) and stroke volume index (26 +/- 3 to 34 +/- 4 ml/m2) and decreases in left ventricular filling pressure (31 +/- 3 to 25 +/- 3 mm Hg), mean right atrial pressure (15 +/- 1 to 13 +/- 2 mm Hg), heart rate (78 +/- 5 to 72 +/- 6 beats/min) and systemic vascular resistance (2,199 +/- 594 to 1,339 +/- 230 dynes.s.cm-5) (all p less than 0.01 to 0.05).
 These observations indicate that renin inhibition produces hemodynamic benefits in patients with chronic CHF and could potentially provide a novel approach to interfering with the renin-angiotensin system in patients with this disorder.
",13
2162,"Effects of bucindolol on neurohormonal activation in congestive heart failure.
 To examine the effects of beta-adrenergic blockade on neurohormonal activation in patients with congestive heart failure, 15 men had assessments of hemodynamics and supine peripheral renin and norepinephrine levels before and after 3 months of oral therapy with bucindolol, a nonselective beta antagonist.
 At baseline, plasma renin activity did not correlate with any hemodynamic parameter.
 However, norepinephrine levels had a weak correlation with left ventricular end-diastolic pressure (r = 0.74, p less than 0.01), stroke volume index (r = 0.61, p less than 0.02) and pulmonary vascular resistance (r = 0.54, p less than 0.05).
 Plasma renin decreased with bucindolol therapy, from 11.6 +/- 13.4 to 4.3 +/- 4.1 ng/ml/hour (mean +/- standard deviation; p less than 0.05), whereas plasma norepinephrine was unchanged, from 403 +/- 231 to 408 +/- 217 pg/ml.
 A wide diversity of the norepinephrine response to bucindolol was observed with reduction of levels in some patients and elevation in others.
 Although plasma norepinephrine did not decrease, heart rate tended to decrease (from 82 +/- 20 vs 73 +/- 11 min-1, p = 0.059) with beta-adrenergic blockade, suggesting neurohormonal antagonism at the receptor level.
 No changes in I-123 metaiodobenzylguanidine uptake occurred after bucindolol therapy, suggesting unchanged adrenergic uptake of norepinephrine with beta-blocker therapy.
 Despite reductions in plasma renin activity and the presence of beta blockade, the response of renin or norepinephrine levels to long-term bucindolol therapy did not predict which patients had improved in hemodynamic status (chi-square = 0.37 for renin, 0.82 for norepinephrine).
",13
2163,"Outcomes of direct coronary angioplasty for acute myocardial infarction in candidates and non-candidates for thrombolytic therapy.
 Coronary angioplasty without prior thrombolytic therapy was performed in 383 patients with acute myocardial infarction (AMI).
 Patients were divided into 2 groups depending on whether they were candidates or non-candidates for thrombolytic therapy.
 Patients were not considered thrombolytic candidates if they: (1) presented in cardiogenic shock, (2) were greater than or equal to 75 years of age, (3) had had coronary artery bypass surgery or, (4) had a reperfusion time of greater than 6 hours.
 Thrombolytic and nonthrombolytic candidates had similar rates of reperfusion (92 vs 88%), nonfatal reinfarction (6.0 vs 5.9%) and recurrent myocardial ischemia (1.8 vs 0%).
 Thrombolytic candidates had a lower mortality rate (3.9 vs 24%, p less than 0.0001) and a lower incidence of bleeding (4.6 vs 10.9%, p less than 0.05).
 Improvement in left ventricular ejection fraction at follow-up angiography was 4.4% in thrombolytic and 10.5% in nonthrombolytic candidates (p less than 0.002).
 Ejection fraction improved most in patients with anterior wall AMI (7.7% in thrombolytic candidates, 15.1% in nonthrombolytic candidates) and in patients with reperfusion times greater than 6 hours (14.2%).
 These outcomes suggest that direct coronary angioplasty is a viable alternative method of reperfusion in patients with AMI who are candidates for thrombolytic therapy.
 Nonthrombolytic candidates are a high-risk group of patients.
 Direct coronary angioplasty may be beneficial in certain subgroups, especially for patients in cardiogenic shock and for patients presenting greater than 6 hours after the onset of chest pain with evidence of ongoing ischemia.
",13
2164,"Effect of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics in essential hypertension.
 The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics were studied in essential hypertension.
 A 4-week study was performed in eight patients with essential hypertension who were given a regular sodium diet in the first and third weeks, and a sodium-restricted diet in the second and fourth weeks.
 Nicardipine, 60 mg/d, was administered in the third and fourth weeks.
 The urinary sodium excretion rate (UNaV) was plotted on the y-axis against the mean arterial pressure (MAP) on the x-axis before and after the administration of nicardipine.
 Assuming the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure across the glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar resistance (RA) and efferent arteriolar resistances (RE), glomerular pressure (PG), and gross filtration coefficient (KFG) were calculated.
 Although the MAP on regular salt diet was lowered from 125 +/- 3 to 109 +/- 2 mm Hg by nicardipine, neither the renal blood flow rate (RBF) (670 +/- 40 mL/min) nor the glomerular filtration rate (GFR) (79 +/- 2 mL/min) was altered.
 The RA was estimated to be reduced from 9,300 +/- 900 to 7,400 +/- 700 dyne.s.cm-5 (P less than 0.01), while no changes were noted in RE (4,900 +/- 400 dyne.s.cm-5), PG (50 +/- 1 mm Hg), or KFG (0.180 +/- 0.041 [mL/s]/mm Hg).
 Essential hypertension has been characterized by a prominent increase in RA, resulting in maintenance of normal PG.
 This Ca-entry blocker worked to normalize intrarenal hemodynamics in essential hypertension by dilating afferent arterioles alone.
",13
2165,"Twelve-year incidence of coronary heart disease in middle-aged adults during the era of hypertensive therapy: the Framingham offspring study [published erratum appears in Am J Med 1991 Apr;90(4):537]
 PURPOSE: To provide information on the incidence of coronary heart disease (CHD) in the offspring of the original cohort from the Framingham Heart Study.
 PATIENTS AND METHODS: From 1972 to 1974, offspring of the original participants in the Framingham Heart Study underwent a baseline examination for standard cardiovascular risk factors.
 At entry into the study, these offspring were 30 to 59 years old and free of CHD.
 They were followed for 12 years, during which time 156 of 1,663 men and 55 of 1,714 women developed CHD.
 RESULTS: In a multivariate proportional hazards model, CHD was significantly associated with age, lower high-density lipoprotein cholesterol (HDL-C) levels, and number of cigarettes smoked.
 Fasting glucose levels and low-density lipoprotein cholesterol (LDL-C) were highly associated with CHD in men, but borderline in women, while triglycerides and very-low-density lipoprotein cholesterol were not significantly associated with CHD after adjustment for HDL-C and glucose.
 Blood pressure medication was used in half of the hypertensive individuals, and systolic pressure was associated with CHD in women only.
 CONCLUSIONS: This study confirms the importance of the common CHD risk factors of cigarette smoking and LDL-C, and extends the prognostic role of HDL-C in a middle-aged cohort.
 The impact of blood pressure, with or without use of hypertensive medications, was reduced in this study, and the data suggest that this attenuation was due to successful treatment.
",13
2166,"Furosemide-131I-hippuran renography after angiotensin-converting enzyme inhibition for the diagnosis of renovascular hypertension.
 PURPOSE: We have previously demonstrated the greater sensitivity of 131I-hippuran renography than 99mTC-DTPA scintigraphy to diagnose renovascular hypertension (RVH).
 This study assesses the predictive diagnostic value of furosemide-131I-hippuran renography after angiotensin-converting enzyme (ACE) inhibition in patients with and without RVH.
 PATIENTS AND METHODS: All patients were investigated at the University of Miami/Jackson Memorial Medical Center.
 Twenty-eight patients had RVH and 22 did not.
 Twenty-eight patients had normal or minimally decreased renal function (serum creatinine level 1.5 mg/dL or less) and 22 had renal insufficiency (serum creatinine level 1.8 mg/dL or more).
 Renography was performed 60 minutes after oral administration of 50 mg captopril or 10 minutes after intravenous injection of 40 micrograms/kg enalaprilat.
 Forty milligrams of furosemide were administered intravenously 2 minutes after injection of 131I-hippuran.
 The residual cortical activity (RCA) of 131I-hippuran was measured at 20 minutes.
 RESULTS: RVH was unlikely when RCA after ACE inhibition was less than 30% of peak cortical activity.
 Conversely, RVH was present when 131I-hippuran cortical activity steadily increased throughout the test to reach 100% at 20 minutes.
 In azotemic patients with RCA between 31% and 100%, RVH was differentiated from intrinsic renal disease by obtaining a baseline renogram without ACE inhibition and comparing RCA in that study and RCA after ACE inhibition.
 If RCA increased (indicating worsening renal function) after ACE inhibition, RVH was likely; whereas, intrinsic renal disease was more likely if RCA remained unchanged or decreased (indicating improved renal function) with ACE inhibition.
 The test had a specificity of 95% and a sensitivity of 96% in this population.
 There was a direct correlation between the results of angioplasty or surgery on high blood pressure and the changes in RCA before and after intervention (n = 20).
 CONCLUSION: Furosemide-131I-hippuran renography with ACE inhibition is highly predictive in identifying patients with RVH.
",13
2167,"Infusion of a stable prostacyclin analogue, iloprost, to patients with peripheral vascular disease: lack of antiplatelet effect but risk of thromboembolism.
 PURPOSE: Prostacyclin, a potent inhibitor of platelet function and vasodilator, has been used to treat peripheral vascular disease.
 The aim of this study was to monitor the thrombotic status of patients treated by infusion of a stable prostacyclin analogue, iloprost.
 PATIENTS AND METHODS: Thirteen patients with peripheral vascular disease underwent iloprost infusion for 3 days (8 hours each day) in a dose ranging from 0.5 to 2 ng/kg/minute.
 Variable parameters of thrombosis such as platelet reactivity (shear-induced hemostatic plug formation and thrombus formation on a collagen fiber), coagulation, and spontaneous thrombolysis (dislodgment of hemostatic plugs) were measured from non-anticoagulated blood samples by hemostatometry immediately before and 1 hour after the infusion and on the last day, 4 hours after initiation of the infusion.
 RESULTS: Analysis of data from all patients 1 hour after the infusion showed no changes in platelet reactivity and spontaneous thrombolysis, but coagulation was significantly enhanced.
 In four patients, significant platelet hyperreactivity was observed after the infusion.
 Four of the five patients tested while undergoing iloprost infusion showed an enhanced thrombotic reaction and markedly enhanced coagulation.
 Iloprost employed in vitro in a concentration that corresponds to the therapeutic peak blood level caused no inhibition of platelet function but significantly enhanced coagulation.
 The threshold in vitro iloprost concentration at which anti-platelet effect and increased spontaneous thrombolysis were observed was twice that of the therapeutic blood level.
 CONCLUSIONS: These findings challenge the view that antagonism of platelet function is an important factor of iloprost therapy.
 Furthermore, platelet hyperreactivity in some patients and markedly enhanced coagulation during and after infusion of iloprost in general, represent a risk of thromboembolism, especially as patients are already in a prethrombotic condition.
",13
2168,"Protamine-heparin-induced pulmonary hypertension in pigs: effects of treatment with a thromboxane receptor antagonist on hemodynamics and coagulation.
 Adverse hemodynamic reactions after protamine neutralization of heparin are an infrequent but important clinical problem.
 Pre-treatment of swine with a thromboxane A2 receptor antagonist has been reported to prevent the pulmonary hypertensive response occasionally seen after protamine reversal of heparin anticoagulation.
 In the current study, a control group of pigs (n = 9) received intravenous heparin (300 IU/kg), followed after 10 min by a neutralizing dose of protamine (3 mg/kg).
 A treatment group of pigs (n = 11) was treated identically, except that the thromboxane A2 receptor antagonist L-670596 (2 mg/kg) was infused intravenously 2 min after the protamine infusion.
 Hemodynamic and coagulation profiles were monitored during these procedures.
 Pulmonary hypertension developed and reached a peak within 2 min of protamine administration, often at the same time that L-670596 was administered in the treatment group.
 There was no statistical difference between control and treatment groups' peak pulmonary arterial pressure and peak pulmonary vascular resistance.
 However, the interval for return of mean pulmonary artery pressure from peak to baseline values was 11.6 +/- 3.1 versus 5.5 +/- 1.9 min (mean +/- SD) for control and treatment groups, respectively (P less than 0.01).
 Thromboxane B2 plasma concentrations increased in both groups and were correlated with the pulmonary hypertensive response (r = 0.86, P less than 0.01).
 Platelet aggregation to collagen was inhibited by the thromboxane A2 receptor antagonist (P less than 0.05).
 Bleeding time was prolonged beyond normal range in 50% of L-670596-treated pigs.
 All other coagulation tests in both groups returned to baseline after reversal of heparin with protamine and were unaffected by L-670596.
",13
2169,"Coronary and left ventricular hemodynamic responses following reversal of flunitrazepam-induced sedation with flumazenil in patients with coronary artery disease.
 The effects of reversal of flunitrazepam-induced sedation with flumazenil on coronary hemodynamics, myocardial oxygen consumption (MVO2), and left ventricular (LV) performance were investigated, in a double-blind trial, in 12 patients with stable coronary artery disease undergoing cardiac catheterization.
 Coronary sinus blood flow was measured by continuous thermodilution.
 Arterial and coronary sinus blood were analyzed for oxygen and lactate contents.
 The determinants of LV performance were obtained from the cardiac output measured by thermodilution and from left heart catheterization data.
 To reverse flunitrazepam-induced sedation, patients were randomly allocated to receive placebo or flumazenil (by increment, up to 1 mg) at the end of procedure.
 In the placebo group, no significant hemodynamic changes were observed.
 In the flumazenil group, heart rate, cardiac index, maximum velocity of shortening, and relaxation time constant were not significantly altered.
 By contrast, mean aortic pressure and LV end-diastolic pressure (baselines: 90 +/- 5 and 7.3 +/- 4.1 mmHg, respectively) increased (9%, P less than 0.05 and 67%, P less than 0.05, respectively) after flumazenil administration, but these changes represented mainly a return toward presedation values.
 MVO2 and coronary resistance were not significantly altered, whereas CSBF increased slightly (baseline: 119 +/- 20 ml/min; increase 10%, P less than 0.05).
 No electrocardiographic evidence of myocardial ischemia was observed during the study.
 These data show that reversal of benzodiazepine effects with flumazenil is not associated with a major alteration of LV systolic function, relaxation, or coronary hemodynamics in patients with coronary artery disease.
 Nevertheless, it should be cautiously used when LV end-diastolic pressure is increased at the time of its administration.
",13
2170,"Morphometry of the subepithelial circulation in sheep airways. Effect of vascular congestion.
 In order to quantitate the subepithelial microvascular volume and its relation to the airway lumen, we conducted a morphometric analysis of the vascular compartment in the wall of the trachea (within a 55-microns depth from the epithelial basement membrane) and of 1.0 and 0.5-mm bronchioles of sheep.
 The lungs were fixed by bronchial and pulmonary artery perfusion with glutaraldehyde under three experimental conditions: (1) bronchial artery pressure, 100 mm Hg pulmonary artery pressure, 20 mm Hg (control); (2) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pulmonary hypertension, PH); (3) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pharmacologic vasodilation with sodium nitroprusside, PH + V).
 Venous pressures were atmospheric.
 Under control conditions, the microvascular volume fraction comprised 12, 16, and 15% of the subepithelial tissue in the trachea and 1-mm and 0.5-mm bronchioles, respectively.
 PH increased the microvascular volume fraction in the bronchioles (p less than 0.05), but it had no effect on the microvasculature in the trachea.
 PH + V approximately doubled the microvascular volume fraction in the trachea and the bronchioles.
 PH increased the mean wall thickness, and PH and PH + V decreased the airway cross-sectional area in the 1-mm bronchioles.
 These observations demonstrate that the microvasculature constitutes a considerable volume fraction of the subepithelial airway tissue and that vascular congestion can narrow the bronchiolar lumen.
",13
2171,"Estimating left ventricular filling pressure during positive end-expiratory pressure in humans.
 In the critically ill, accurate measurements of left ventricular (LV) filling pressure using pulmonary artery occlusion pressure (Ppao) are important for diagnostic and therapeutic purposes.
 In patients receiving positive end-expiratory pressure (PEEP), Ppao may not reflect LV filling pressure because of elevated pericardial pressure (Ppc).
 It has been proposed that in humans, Ppc and right atrial pressure (PRA) are equal, so that referencing Ppao to PRA may improve the assessment of LV filling pressure when Ppc is elevated.
 Similarly, it has also been shown in the dog that nadir Ppao immediately after airway disconnection from PEEP (nadir Ppao), accurately reflects LV filling pressure when LV filling pressure is greater than or equal to 10 mm Hg.
 We examined methods of estimating LV filling pressure using Ppao measurements under conditions in which increases in Ppc were the primary determinants of differences in the two measurements.
 Using left atrial pressure (PLA) relative to Ppc, called transmural PLA (PLAtm), as LV filling pressure, we compared the accuracy of Ppao, nadir Ppao, and Ppao relative to PRA to reflect PLAtm in 15 postoperative cardiac surgery patients in whom an air-filled pericardial balloon catheter and a left atrial catheter were inserted during surgery.
 PEEP was sequentially increased from zero to 15 cm H2O.
 We found that PRA always exceeded Ppc (p less than 0.01) and increased less with PEEP than did Ppc (p less than 0.05).
 At less than or equal to 5 cm H2O PEEP, both Ppao and nadir Ppao were similar to each other and to PLAtm.
",13
2172,"Fibrin- and fibrinogen-related antigens in patients with venous disease and venous ulceration.
 Abnormalities in systemic fibrinolysis have been implicated in the pathogenesis of venous ulceration.
 Patients with venous disease have a prolonged euglobulin lysis time and elevated plasma fibrinogen levels, yet little is known about the metabolism of fibrinogen and fibrin in such patients.
 In this study, we have used a technique that involves electrophoresis and densitometric analysis of captured fibrin-related antigens to measure the concentration and proportions of the individual fibrin and fibrinogen degradation products in patients with venous disease of the lower extremity.
 As a group, patients with venous disease had markedly elevated levels of total fibrin-related antigen and D-dimer, the terminal degradation product of cross-linked fibrin.
 Levels of D-monomer, the breakdown product of fibrinogen and non-cross-linked fibrin monomer, and a measure of fibrinogenolysis were normal in all patients.
 In patients with ulcers, the levels of D-dimer were disproportionately higher than expected from fibrin monomer levels.
 On an individual basis, significant elevations of D-dimer were present in six (55%) of the 11 patients with venous disease with ulcers and in three (43%) of the seven patients with venous disease without ulcers.
 We conclude that patients with venous disease have uniform evidence for enhanced fibrin formation, as evidenced by elevated levels of total fibrin-related antigen and D-dimer.
 This is regardless of whether the venous disease is accompanied by ulceration.
",13
2173,"Deterioration following delay in performing femoral angioplasty.
 It is not uncommon for a delay to occur between assessment arteriography and angioplasty attempt.
 We reviewed retrospectively the arteriograms of 61 patients where such a delay occurred to assess progression of superficial femoral artery (SFA) disease in this interval.
 A mean delay of 14.6 days (range 2-60 days) occurred between arteriogram and angioplasty attempt.
 Arteriographic deterioration was found in six of 61 patients (9.8%) and in three this precluded angioplasty.
 Of the six patients four had initial arteriography via the same side as the SFA disease whilst two had arteriography via the contralateral femoral approach.
 We discuss the aetiology of this phenomenon and suggestions are made to reduce its incidence.
",13
2174,"Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and nifedipine in experimental porcine pulmonary hypertension.
 BACKGROUND AND METHODS: We compared the hemodynamic effects of four vasodilators in experimental embolic pulmonary hypertension in a randomized controlled trial, using nine pigs weighing 16 to 23 kg.
 After anesthesia induction and cannulation with arterial, central venous, and thermodilution output pulmonary artery catheters, animals were repetitively embolized with glass beads (60 to 160 mu) in order to establish pulmonary hypertension (pulmonary artery pressure [PAP] doubled from baseline).
 Prostaglandin E1 (PGE1), isoproterenol, prostacyclin (PGI2), and nifedipine were compared at doses producing equivalent reduction in systemic BP.
 RESULTS: Only PGE1 and PGI2 decreased both PAP and pulmonary vascular resistance (PVR).
 PGE1 decreased PAP from 39 +/- 1 to 33 +/- 1 mm Hg; prostacyclin decreased PAP from 38 +/- 1 to 31 +/- 1 mm Hg and produced the largest increase in cardiac output (Qt).
 Isoproterenol did not change PAP, markedly increased heart rate (162 +/- 8 to 216 +/- 11 beats/min), and resulted in significant arrhythmias.
 Nifedipine increased PVR from 1044 +/- 113 to 1125 +/- 100 dyne.sec.cm-5 and decreased Qt.
 CONCLUSIONS: Vasodilators demonstrate unique hemodynamic drug profiles.
 Isoproterenol infusion is characterized by tachycardia and arrhythmias.
 Both PGE1 and PGI2 effectively decrease PAP and PVR.
 Nifedipine depressed Qt significantly in this glass-bead embolization model of acute pulmonary hypertension.
",13
2175,"Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension.
 OBJECTIVE: To study the effects of milrinone on pulmonary vasculature.
 BACKGROUND: It has been suggested that bipyridines or their derivatives may have a selective pulmonary vasodilation effect.
 METHODS: Preliminary study: milrinone administration to 12 normal dogs (low dose [bolus 75 micrograms/kg for 5 min followed by a continuous infusion at 0.75 micrograms/kg.min, n = 6]; high dose [bolus 150 micrograms/kg for 5 min followed by continuous infusion at 1.5 micrograms/kg.min, n = 6]).
 Main study: milrinone administration to 18 dogs with pulmonary hypertension due to pulmonary embolism induced by a massive injection of autologous muscle cubes.
 The pulmonary hypertension dogs were divided into three groups: a) group E (n = 6) received embolization only, as control; b) group L (n = 6) received low-dose milrinone; and c) group H (n = 6) received high-dose milrinone, equivalent to the preliminary study group.
 Hemodynamic measurements and blood samplings were obtained at baseline and at 15, 30, and 60 min after start of milrinone infusion.
 RESULTS: Milrinone did not change mean pulmonary artery pressure (MPAP) in normal dogs.
 Milrinone decreased MPAP significantly in dogs with pulmonary hypertension.
 Pulmonary vascular resistance index remained at an almost constant level in normal dogs, but decreased significantly in dogs with pulmonary hypertension.
 Mean arterial pressure was maintained at a constant level in all groups.
 High-dose milrinone administration decreased systemic vascular resistance index (SVRI) significantly; low-dose milrinone administration decreased SVRI slightly.
 CONCLUSIONS: Milrinone may have a selective pulmonary vasodilatory effect only in dogs with pulmonary hypertension.
 The mechanism that produced a selectivity on pulmonary vasculature in dogs with pulmonary hypertension is unknown.
 However, an inhibition of platelet aggregation may decrease the MPAP resulting from an increase in cAMP caused by milrinone.
 Further studies are needed to resolve the pulmonary vasodilatory effect of milrinone in dogs with pulmonary hypertension.
",13
2176,"A prospective study of sodium-lithium countertransport and hypertension in Utah.
 A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah pedigrees, screened from 1980 to 1985, was done to determine whether baseline levels of sodium-lithium countertransport were associated with an increased risk of future hypertension.
 Subsequent new hypertension (n = 39) was ascertained in 1989 from detailed follow-up medical questionnaires (67% response).
 Previous segregation analyses on a subset of these pedigree members who responded (n = 342) using family relationships in addition to countertransport levels have shown statistically inferred major gene segregation of sodium-lithium countertransport levels.
 In the normotensive adults inferred by segregation analysis to carry the recessive major gene for high sodium-lithium countertransport, new-onset hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6, 13.9]; p = 0.03).
 However, an elevated baseline sodium-lithium countertransport level without genotype information from segregation analysis did not increase the risk of future hypertension in the complete cohort of adult pedigree members (relative risk, 1.02 [0.85, 1.22]).
 Adjustment for other risk factors reduced the relative risk to 0.90 (0.72, 1.11).
 We conclude that the presence of a major gene for sodium-lithium countertransport or another closely linked gene, rather than the actual level of sodium-lithium countertransport, may increase the risk of hypertension onset.
 High sodium-lithium countertransport levels do not increase the risk of future hypertension for individuals in whom only polygenic and environmental effects determine sodium-lithium countertransport level.
",13
2177,"High-normal blood pressure progression to hypertension in the Framingham Heart Study.
 This study sought to determine if individuals with high-normal blood pressure (diastolic blood pressure of 85-89 mm Hg) progress to hypertension more frequently than those with normal blood pressure (diastolic blood pressure less than 85 mm Hg), thus advancing to a higher cardiovascular risk category.
 Individuals from the Framingham Heart Study were placed in normal and high-normal blood pressure categories and followed for 26 years for the development of hypertension.
 With hypertension defined as a diastolic blood pressure of 95 mm Hg or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2% of women with normal blood pressure developed hypertension compared with 54.2% of men and 60.6% of women with high-normal blood pressure.
 The relative risk for the development of hypertension associated with high-normal blood pressure was 2.25 for men (95% confidence interval [CI], 1.8-2.8; p less than 0.0001) and 1.89 for women (95% CI, 1.5-2.3; p less than 0.0001).
 The age-adjusted relative risks estimated by the proportional hazards model were 3.36 for men and 3.37 for women (p less than 0.001).
 Among those risk factors examined, baseline systolic and diastolic blood pressure, Metropolitan relative weight, and change in weight over time were significant predictors of future hypertension in men and women whose initial blood pressure was normal.
 For men with high-normal blood pressure, systolic blood pressure and change in weight were identified as risk factors for future hypertension.
 These results indicate that the probability of individuals with blood pressure in the high-normal range developing hypertension is twofold to threefold higher than in those with normal blood pressure.
",13
2178,"Renal manifestations of NaCl sensitivity in borderline hypertensive rats.
 Compared with the normotensive Wistar-Kyoto rat, the spontaneously hypertensive rat exhibits exaggerated alterations in renal sympathetic nerve activity and excretory function during volume expansion (exaggerated natriuresis) and environmental stress (antinatriuresis).
 The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat and develops hypertension with increased dietary NaCl intake.
 The present investigation sought to determine whether the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress.
 Borderline hypertensive rats fed a 1% NaCl diet remained normotensive and exhibited renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress that were similar to those of their Wistar-Kyoto parent.
 Borderline hypertensive rats fed an 8% NaCl diet developed hypertension and exhibited responses that were similar to those of their spontaneously hypertensive parent.
 Thus, the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress.
 The results suggest that increased dietary NaCl intake is able to induce or unmask the capabilities for these responses, which are genetically conveyed to the borderline hypertensive rat by the spontaneously hypertensive rat parent in latent forms.
",13
2179,"Exclusion of the Na(+)-H+ antiporter as a candidate gene in human essential hypertension.
 The primary abnormalities that contribute to the pathogenesis of human essential hypertension are unknown.
 The known genetic contribution to this disorder suggests the possible use of genetic linkage analysis to test whether specific candidate genes contribute to the pathogenesis of either essential hypertension or intermediate phenotypes.
 Among such phenotypes, elevated erythrocyte Na(+)-Li+ countertransport (SLC) is the best known, supporting major gene inheritance by pedigree analysis.
 Striking similarities between SLC and Na(+)-H+ exchange suggest that mutations at the Na(+)-H+ antiporter gene locus (APNH) might result in elevated SLC and contribute to the subsequent pathogenesis of hypertension.
 We have tested these hypotheses by genetic linkage analysis, with APNH as a candidate gene.
 By determining genotypes at APNH and flanking loci in pedigrees that support major gene segregation of elevated SLC, we have excluded linkage of APNH and the major SLC locus with a LOD score of -5.91, an odds ratio of almost 1,000,000:1 against linkage.
 In the analysis of 93 hypertensive sibling pairs, we have further demonstrated that APNH explains none of the variance in SLC in hypertensive individuals (r2 = 6 x 10(-7), p greater than 0.99).
 Finally, we have directly tested for linkage of APNH to genes predisposing toward hypertension by linkage in hypertensive sibling pairs.
 Mean allele sharing at APNH is not greater than expected from random assortment in hypertensive siblings (0.92 versus 1.0, p greater than 0.80), and the upper 95% confidence limit of this value (1.04) indicates that mutations at APNH rarely if ever contribute to the pathogenesis of hypertension in this population.
",13
2180,"Methodology of sodium sensitivity assessment. The example of age and sex.
 This article addresses the methodology of sodium sensitivity assessment.
 There have been reports to suggest that a high sodium intake is a cause of elevated blood pressure and trials to indicate that a reduction in sodium intake may reduce blood pressure that is already high; the implications of these findings are discussed.
 Many studies on sodium sensitivity suffer from what could be called the ""normal probability fallacy""; without appropriate control conditions, an intervention such as sodium restriction may incorrectly be assigned to a more pronounced response in a subgroup of the study population.
 As an example, findings are reviewed of age and sex as determinants of a response of blood pressure to variations in sodium intake.
 The limited data available suggest that subjects that are older and have higher blood pressure levels seem to benefit more from a reduction in sodium intake.
 In addition, elderly subjects at a high dietary sodium intake may have a higher risk of developing hypertension.
 Findings in both nonexperimental and experimental studies tend to support this view.
 Findings on sex differences are less consistent.
 A systematic approach to the assessment of factors and mechanisms responsible for sodium sensitivity in some subjects is needed to determine who might benefit most.
 Until more data are available, there is little basis to discriminate sodium-sensitive from sodium-resistant hypertensive subjects.
",13
2181,"Racial and ethnic modifiers of the salt-blood pressure response.
 The relation between sodium and blood pressure is a centuries-old question.
 A substantial body of epidemiological and experimental data has accumulated that strongly implicates NaCl as having a causal role in the genesis of arterial hypertension.
 Prospective studies that have been performed in diverse populations that have manipulated NaCl exposure by diet or infusion have repeatedly documented an NaCl pressor effect.
 Further, similar studies in biracial populations have also demonstrated a greater prevalence of ""salt sensitivity"" in blacks compared with whites.
 The reasons for this observation are not entirely clear; however, intrinsic or hypertension-induced renal abnormalities that limit natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion transport disturbances, differential exposure to psychological stressors, greater insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been suggested as possibly playing a role.
 Salt sensitivity appears to be a widespread phenomenon.
 However, it is critically important to determine what factors account for racial differences in salt sensitivity.
 Moreover, the prevalence of salt sensitivity in the general population is unknown.
 Current definitions of salt sensitivity are varied and unidirectional.
 In comparison with bidirectional criteria (blood pressure increase with salt loading and blood pressure decrease with salt restriction), they are probably inadequate to identify salt-sensitive individuals who manifest less extreme blood pressure change after dietary sodium or plasma volume manipulations.
 More sensitive criteria for diagnosing salt sensitivity will facilitate a better understanding of racial and ethnic differences in the prevalence of salt sensitivity.
",13
2182,"Biohistory of slavery and blood pressure differences in blacks today. A hypothesis.
 Genetic factors are known to play an important role in the variations in blood pressure levels.
 However, genetic factors that explain the higher average blood pressure levels of western hemisphere blacks when compared with African blacks have not been seriously considered.
 Because the genetic makeup of a population is largely determined by biological and ecological forces in the past, an examination of the biohistory of blacks, specifically the slavery era, was conducted.
 An overview of the salient findings of that investigation is included in this article.
 The published historical evidence on the transatlantic slave trade and New World slavery (from the 16th century to the 19th century) reveals that conditions existed for ""natural selection,"" and therefore, genetic changes were virtually inevitable in the slave populations.
 During this period of history, mortality was extremely high, and fertility (or reproductive success) was so low among the survivors that most plantation societies in the western hemisphere depended on a constant importation of captives (over 12 million) from Africa for the viability of the plantation communities.
 Because the major causes of death were salt-depletive diseases such as diarrhea, fevers, and vomiting, it is argued that individuals with an enhanced genetic-based ability to conserve salt had a distinct survival advantage over others and were, therefore, more likely to bequeath their genotype to subsequent generations of Western hemisphere blacks.
 Thus, it is predicted that blacks in the Americas have a greater frequency of individuals with an enhanced genetic-based ability to conserve salt than African blacks.
",13
2183,"Sodium-potassium interaction in hypertension and hypertensive cardiovascular disease.
 Epidemiological evidence suggests that low potassium intake is associated with the probability of occurrence of hypertension and stroke.
 The short-term response to increased potassium intake is increased sodium excretion as well as increased potassium excretion; the short-term response to increased sodium intake is increased potassium excretion as well as increased sodium excretion.
 In some experimental studies, increased amounts of potassium have been able to block the noxious influences of sodium.
 Sodium and potassium must be concomitantly considered in the investigation of the association of either of these cations with hypertension and cardiovascular disease.
 The chloride ion is also important for sodium's effects; its importance in potassium's effects has not been extensively explored.
",13
2184,"A consensus approach to electrolytes and blood pressure. Could we all be right?
 This commentary sets forth the hypothesis that the putative beneficial or detrimental effects of specific electrolytes on blood pressure regulation in fact reflect highly integrated responses to interactions among these cationic and anionic species.
 In this paradigm, the impact of any given intake of an electrolyte on arterial pressure will be influenced by the concurrent consumption of other electrolytes.
 Thus, the heterogeneous blood pressure response in humans to isolated manipulations of nutrients such as sodium, calcium, and potassium may be determined, in part, by the adequacy of the dietary intake of other mineral elements.
 If this hypothesis is validated by continued research in this area, we would have new strategies available to improve blood pressure control in humans.
 For example, treatment of ""NaCl sensitivity"" in some humans might be more effectively approached by correcting dietary deficiencies of either potassium or calcium than by restricting dietary NaCl.
",13
2185,"Dietary sodium reduction for hypertension prevention and treatment.
 Nutritional-nonpharmacological approaches for the treatment and prevention of hypertension are of great interest.
 Sodium reduction is one of the primary methods recommended for these purposes.
 The general public is interested in the reduction of dietary sodium intake and has responded with a decrease in table salt use, the purchase of lowered sodium food products, and the use of food labels to help guide food purchases.
 Countervailing trends in the use of convenience foods and dining out increase the difficulty for individuals to lower sodium intake.
 Clinical trials that have used sodium reduction alone or in combination with other lifestyle therapies have demonstrated the feasibility of reducing dietary sodium intake from 30% to 50% for up to 4 years, in a variety of populations.
 Trials that used lifestyle and weight loss interventions have also achieved significant reductions in body weight and alcohol consumption and increases in physical activity.
 A variety of studies indicate that long-term sodium reduction is feasible and that it is acceptable to patients.
 No negative consequences of these interventions have been observed, and in some cases improvement in the intake of other nutrients has occurred.
 Nonpharmacological interventions have resulted in hypertension control in significant proportions of the trial populations.
 These studies demonstrate that the foregoing types of interventions can significantly contribute to hypertension treatment and prevention.
",13
2186,"A perspective on reducing salt intake.
 Epidemiological, clinical, and experimental evidence links excessive salt consumption to hypertension; there appears to be no evidence that it is beneficial.
 I conclude that it should be public policy to advise and help Americans to reduce their salt intake.
 Because even mild hypertension increases risk, the overall problem does not appear to be amenable to treatment, although treatment for those with clinical hypertension will always be needed.
 There appears to be little likelihood that identification of those ""at risk"" will be successful, nor does it appear that we have the capacity at this time to conduct successful preventive field trials.
 It is difficult for the individual to modify his diet alone.
 The successful strategy is to modify the food supply by changing public demand.
 The public responds to dietary advice if acceptable and identifiable products are available.
 Because most of the salt is in commercially prepared foods and because their consumption will increase in the future, the major responsibility for lowering salt consumption will fall on the food manufacturers.
 They are beginning to respond, and there appears to be ample opportunity for them to reduce the salt content of foods markedly.
 Our temporary objectives, however, should be modest, because unrealistic objectives only discourage those who attempt to follow them.
",13
2187,"An overview of randomized trials of sodium reduction and blood pressure 
 To test for effects on systolic and diastolic blood pressure and to provide precise estimates of their magnitude, we conducted an overview of randomized clinical trials that aimed to reduce the intake of sodium in human subjects.
 We excluded from pooled analyses trials with confounded designs, those that compared intake levels beyond the usual range in the population, and those without published reports.
 Two reviewers abstracted information in duplicate and differences were reconciled.
 Twenty-three trials with outcome data from an aggregate of 1,536 subjects were included.
 Data were pooled both separately for hypertensive and normotensive subjects and for all trials combined.
 With the use of sample size weighting, blood pressure reductions (net of controls) were 4.9 +/- 1.3/2.6 +/- 0.8 mm Hg (systolic and diastolic, respectively, with 95% confidence limits) in hypertensive subjects and 1.7 +/- 1.0/1.0 +/- 0.7 mm Hg in normotensive subjects.
 The combined blood pressure reductions were 2.9 +/- 0.8/1.6 +/- 0.5 mm Hg.
 These changes were associated with mean reduction of urinary sodium excretion ranging from 16 to 171 mmol/24 hr for individual trials.
 A dose-response relation across trials was found, both in normotensive and in hypertensive subjects.
 These results indicate that sodium reduction lowers mean blood pressure in both hypertensive and normotensive individuals for periods of at least several months.
 The findings are highly consistent with results of observational epidemiological studies and have implications for preventive strategies of blood pressure control.
",13
2188,"Neurovascular mechanisms and sodium balance in the pathogenesis of hypertension.
 Physiological studies have clarified the role that the brain has in the interplay between salt balance and hypertension.
 Neural mechanisms and endocrine secretions play a pivotal role in the adaptation of mammals to changes in the intake and excretion of sodium.
 Maneuvers that alter the concentration of sodium in the plasma modify the sensitivity of baroreceptor reflexes and alter vascular reactivity.
 These changes may be mediated in part by the release of vasopressin.
 The research also suggests that the brain indirectly modulates the ability of the vascular endothelium to release vasoactive factors.
 Collectively, these studies illustrate the multiple effects of the sodium ion on the peripheral neural and central endocrine mechanisms that participate in the regulation of arterial pressure.
",13
2189,"Genetic traits related to hypertension and electrolyte metabolism.
 The genetic and cultural heritability and intercorrelation of traits related to hypertension have been carried out in 98 Utah pedigrees (2,500 person) and 58 sibships with two or more hypertensive persons (131 hypertensive persons).
 Although none of these traits has been established as a marker for ""sodium-sensitive hypertension,"" many of them are related at least indirectly to both electrolyte metabolism and risk of hypertension.
 Significant recessive monogenic effects and high total heritability (52-84%) were found for urinary kallikrein, high fat pattern index, intraerythrocytic sodium, Na-Li countertransport, and ouabain binding sites.
 Familial correlations more strongly attributable to shared environment than to genetic effects were found for Na,K-ATPase pump activity, intraerythrocytic magnesium, plasma digoxin-like factor, plasma renin activity, and plasma sodium concentration.
 All anthropometric variables tested showed highly significant genetic heritability with low and insignificant shared family environmental effects.
 Several of the genetically determined cellular cation tests also correlated with other genetic traits including plasma lipids, anthropometric measurements, and other cellular cation tests.
 Among hypertensive individuals with familial dyslipidemic hypertension, plasma insulin levels correlated with obesity and lipid abnormalities and with several cellular cation flux tests associated with hypertension.
",13
2190,"Sympathetic neural contribution to salt-induced hypertension in Dahl rats.
 The Dahl strain provides a model for examining mechanisms involved in the genetic sensitivity or resistance to salt-induced hypertension.
 Dahl salt-sensitive rats develop hypertension when fed a high salt diet; Dahl salt-resistant rats remain normotensive.
 Based on early experiments, it was thought that hypertension in Dahl salt-sensitive rats epitomized the overriding importance of renal and humoral mechanisms in salt-induced hypertension, but studies in the past 15 years have demonstrated that alterations in sympathetic neural mechanisms also participate critically in the genetic predisposition to salt-induced hypertension in Dahl salt-sensitive rats.
 This article briefly reviews sympathetic neural mechanisms in Dahl rats, including evidence for a role of afferent baroreceptor as well as central neural and peripheral adrenergic mechanisms in salt-induced hypertension in Dahl salt-sensitive rats.
",13
2191,"Relation between sodium intake, renal function, and the regulation of arterial pressure.
 The long-term regulation of arterial pressure requires the maintenance of a balance between sodium and water intake and sodium and water excretion.
 Normal salt and water balance leads to stable body fluid volumes and the maintenance of normal renal function is critical to establishing extracellular fluid volume homeostasis.
 This review focuses on the role of the kidney in the long-term control of salt and water balance with particular emphasis on the relations between sodium intake, the renin-angiotensin-aldosterone system, renal sympathetic nerve activity, and the regulation of arterial pressure via renal sodium and water excretion.
 The accumulation of evidence in recent years demonstrates that low level elevation of renin release, circulating angiotensin II or aldosterone, or activation of renal sympathetic outflow may alter renal function such that normal natriuretic and diuretic responses to arterial pressure are significantly impeded.
 Under these circumstances, the maintenance of normal sodium and water excretion requires a significant elevation of arterial pressure.
 Thus, compromised renal function leads to elevation of arterial pressure to maintain adequate sodium and water balance during periods of increased sodium intake.
 The resultant chronic elevation of arterial pressure then becomes a compromise that is used by the kidneys to maintain normal extracellular body fluid volumes.
",13
2192,"Dietary salt and blood pressure. A perspective.
 Although dietary salt restriction is often valuable as sole or adjunctive therapy of hypertensive disorders, it is abundantly clear that hypertensive patients comprise a heterogeneous group with regard to salt sensitivity of blood pressure.
 This is apparent despite the many methodological obstacles to defining salt sensitivity in an individual patient.
 Currently, dietary trial is the only sure means of defining a given patient as responsive to salt restriction.
 Easily definable markers of salt sensitivity would allow appropriate targeting of this rather ponderous therapy.
 Promising leads include the assessment of membrane ion transporters such as sodium-lithium exchange and of the activity of the renin-angiotensin system, including the phenomenon of ""non-modulating"" hypertension and other volume regulatory hormones such as atrial natriuretic factor.
 Although less intensively studied than in hypertensive patients, the blood pressure response of normal subjects to salt restriction is also marked by great variability.
 Given the possibility of deleterious consequences of population-wide salt restriction for at least some people in a setting such as the United States, it seems imprudent to recommend such a policy before its proven worth has been demonstrated by clinical trial.
 Pending such evidence and the development of markers, salt restriction should be reserved for those in whom it is of demonstrated efficacy.
",13
2193,"Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS) 
 The Cardiac Arrhythmia Pilot Study (CAPS) was a 1 year trial that analyzed the safety and effectiveness of arrhythmia suppression in 502 patients surviving acute myocardial infarction who had greater than or equal to 10 ventricular premature depolarizations/h or greater than or equal to 5 runs of ventricular tachycardia on a Holter recording obtained 6 to 60 days after the acute infarction.
 Because 100 of these patients received placebo in a double-blind fashion for 1 year, a comprehensive objective analysis was performed of spontaneous arrhythmia changes based on real data rather than statistical estimates.
 In the CAPS placebo group, 19% developed some serious clinical event in 1 year (death, heart failure, proarrhythmia) that could likely be attributable to antiarrhythmic drug toxicity.
 A significant reduction in the frequency of ventricular premature depolarizations (p = 0.004) occurred in the first few weeks of ""therapy"" with a further significant (p less than 0.04) decrease between 3 to 12 months.
 After initiation of placebo antiarrhythmic therapy, 27% had ""apparent ventricular premature depolarization suppression"" (greater than or equal to 70% reduction) after one Holter recording evaluation and nearly half (48%) after six Holter recordings to assess suppression were performed.
",13
2194,"Evaluation of preload reserve during isometric exercise testing in patients with old myocardial infarction: Doppler echocardiographic study.
 To estimate the preload reserve in response to an increase in afterload in patients with old myocardial infarction, the relation between the Doppler echocardiographic inflow velocity pattern and left ventricular end-diastolic pressure was investigated during isometric handgrip exercise testing.
 The study population consisted of 16 normal subjects and 40 patients with old myocardial infarction.
 The 40 patients were subdivided into two groups according to left ventricular end-diastolic pressure at rest: group I (22 patients), less than 18 mm Hg; group II (18 patients), 18 mm Hg or more.
 At rest, the ratio of peak velocity in atrial contraction phase to peak velocity in early diastolic filling phase (A/E) was significantly higher in the patients with old myocardial infarction than in normal subjects; values in the two subgroups of myocardial infarction did not differ significantly.
 The A/E ratio and left ventricular end-diastolic pressure increased significantly during exercise in group I.
 Conversely, the change in left ventricular end-diastolic pressure during exercise in group II was significantly greater than that in group I, and was associated with a decrease in the A/E ratio.
 Thus, an atrial compensatory mechanism operated effectively in response to the increase in afterload in patients with a normal left ventricular filling pressure, whereas this compensatory mechanism deteriorated in patients with elevated left ventricular filling pressure due to a limited preload reserve.
",13
2195,"Noninvasive assessment of intrinsic ventricular load dynamics in dilated cardiomyopathy 
 On the basis of hemodynamic theory, a new noninvasive method is developed to provide improved insights into the significance of depressed Doppler left ventricular ejection variables in patients with dilated cardiomyopathy.
 The net force (F) associated with intraventricular flow throughout ejection can be written as: F = A.dv/dt + B.v2, where v is the ejection velocity and A and B are variables related to the geometry of the ventricle and its outflow tract.
 Instantaneous levels of this force were calculated in 9 normal subjects and 10 patients with dilated cardiomyopathy using Doppler, M-mode and two-dimensional echocardiography.
 The maximal ejection force (Fmax) was 47.5 +/- 8.5 kdyn in normal subjects and 25.5 +/- 6.2 kdyn in those with dilated cardiomyopathy (p = 0.0001).
 Peak local acceleration and outflow velocity were severely depressed in those with cardiomyopathy compared with normal subjects (1,260 +/- 129 versus 2,671 +/- 430 cm/s2 and 71 +/- 14 versus 109 +/- 7 cm/s, respectively; p = 0.0001).
 Maximal ejection force was attained very early in ejection.
 A significant linear correlation was found between peak outflow acceleration and maximal ejection force (n = 19; r = 0.91, p = 0.0001).
 At the time of peak ejection velocity, the net force had decreased to 64% of its peak value in those with cardiomyopathy, whereas in normal subjects, it had decreased to only 84% of its peak value (p = 0.008).
 In normal subjects, the ejection force was positive during the first 75% of ejection, but in those with cardiomyopathy, it was positive only during the first 54% (p = 0.0003).
 Once its peak value was attained, total left ventricular systolic wall stress declined rapidly during ejection in normal subjects (to 33% of its peak value by end-ejection), whereas it remained elevated throughout ejection in patients with cardiomyopathy (at 60% of its peak value by end-ejection, p = 0.0001 versus normal).
 The maximal ejection force corresponded to a calculated intraventricular peak pressure gradient of 9.8 +/- 1.6 mm Hg in normal subjects and 6 +/- 1.2 mm Hg in those with cardiomyopathy (p = 0.0001).
 The average contribution of the intrinsic component of the left ventricular systolic load (that is, wall stress associated with the ventricular to aortic pressure gradient) to the total myocardial load was 9.1% (range 7.3% to 11.2%) in normal subjects and 6.2% (range 3.9% to 7.5%) in those with cardiomyopathy (p = 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS).
",13
2196,"Immediate reproducibility of electrically induced sustained monomorphic ventricular tachycardia before and during antiarrhythmic therapy 
 The immediate reproducibility of sustained ventricular tachycardia induction was evaluated prospectively during 106 studies performed in 53 patients with clinical sustained monomorphic ventricular tachycardia.
 Programmed electrical stimulation was performed twice, using the same protocol during 53 drug-free studies and 53 subsequent studies on antiarrhythmic therapy.
 Sustained monomorphic ventricular tachycardia was reproduced in 104 (98%) of the 106 studies.
 There was no significant difference in the incidence of reproducible tachycardia in the drug-free state compared with that observed during treatment with different classes of antiarrhythmic drugs.
 An increase in the number of extrastimuli was required to reinitiate the tachycardia in 9 (11%) of 83 studies in which single or double extrastimuli were initially required to induce the tachycardia.
 In 39 (37%) of 104 studies with reproducible tachycardia induction, the two tachycardias significantly differed in electrocardiographic (ECG) configuration and cycle length.
 These observations suggest that the overall reproducibility of ventricular tachycardia induction is sufficiently high to provide a reliable marker for evaluating the efficacy of therapeutic interventions.
 However, specific tachycardia characteristics such as cycle length and ECG configuration are more variable even within the same study and may be less useful in assessing the effects of subsequent interventions.
",13
2197,"Differences in QRS configuration during unipolar pacing from adjacent sites: implications for the spatial resolution of pace-mapping.
 To examine the spatial resolution of unipolar pace-mapping, 12 lead electrocardiograms (ECGs) recorded during pacing from each of the poles of a quadripolar catheter (5 mm interelectrode distance) were examined.
 Unipolar pacing was performed from each of the poles at late diastolic threshold, twice threshold and 10 mA at a cycle length of 500 ms.
 In 15 patients, pacing was performed at the right ventricular apex and in 14 at various left ventricular sites.
 Pacing from the distal catheter pole at threshold (index ECG) was used to simulate the site of origin of ventricular tachycardia, and all other ECGs were compared with the index ECG.
 Electrocardiograms were evaluated by two independent observers for 1) minor configuration differences (notch, new small component, change in the amplitude of individual components or change in QRS shape); 2) major differences in configuration (new large component, marked change in the amplitude of an existing component or two minor changes); and 3) peak to peak changes in amplitude.
 Minor differences in configuration were seen in a mean 2.4 +/- 1.9, 4.6 +/- 2.4 and 4.4 +/- 2.9 leads during pacing at 5, 10 and 15 mm from the distal electrode (index site).
 Major differences in configuration were seen in a mean of 0.3 +/- 0.5, 2.1 +/- 2.1 and 3.7 +/- 2.3 leads during pacing at 5, 10 and 15 mm from the index site.
 Differences in amplitude were seen in a mean of 3.1 +/- 2.2, 5.6 +/- 2.5 and 6.8 +/- 3.0 leads per ECG during pacing at 5, 10 and 15 mm from the index ECG pacing site, respectively.
",13
2198,"Longitudinal dissociation of atrioventricular accessory pathways.
 Unusual properties of atrioventricular (AV) accessory pathways were found during electrophysiologic investigations in four patients (three men and one woman).
 Anterograde longitudinal dissociation of the accessory pathway was observed in two patients and retrograde longitudinal dissociation in two others.
 Two patients had an accessory pathway with a slow conduction time, one in anterograde direction and one in retrograde direction.
 These observations further expand our knowledge of the spectrum of electrophysiologic properties of accessory AV pathways.
",13
2199,"Late noninvasive evaluation of cardiac performance in mildly symptomatic older patients with Ebstein's anomaly of tricuspid valve: role of radionuclide imaging.
 Ten patients 8 to 54 years of age with isolated Ebstein's anomaly of the tricuspid valve were evaluated by electrocardiography, maximal exercise treadmill testing, 24 h electrocardiographic (ECG) monitoring, echocardiography and rest radionuclide imaging of the left ventricle.
 The patients presented after the 1st year of life and had not undergone surgical intervention.
 All except one were in functional class II.
 No patient had preexcitation on the surface ECG, but abnormal tachyarrhythmias or bradyarrhythmias were seen in five patients on 24 h ECG monitoring.
 Subnormal exercise performance was observed in five patients.
 Echocardiography demonstrated typical variable tricuspid valve displacement and paradoxic interventricular septal motion.
 Left ventricular end-diastolic dimensions were normal in all patients, but posterior wall motion was reduced in two.
 Moderate to severe tricuspid regurgitation with a Doppler jet velocity less than 2.5 m/s was demonstrated in eight patients.
 Left ventricular radionuclide scintigraphy revealed a subnormal ejection fraction (less than 50%) in 5 of 10 patients; these 5 had previously shown suboptimal exercise performance.
 The two youngest patients (less than 15 years) had no arrhythmia, normal exercise performance and normal left ventricular ejection fraction.
 There was no correlation between the degree of tricuspid valve displacement or regurgitation and the presence of rhythm disturbance, exercise performance or radionuclide left ventricular function.
 Late evaluation of patients with Ebstein's anomaly may demonstrate significant unsuspected abnormalities in cardiac rhythm, exercise performance and left ventricular function.
 Radionuclide scintigraphy is a useful noninvasive technique for assessing left ventricular dysfunction in these patients.
",13
2200,"In-hospital mortality after balloon aortic valvuloplasty: frequency and associated factors.
 Percutaneous balloon aortic valvuloplasty has been accompanied by significant early periprocedural morbidity and mortality.
 Identification of factors associated with increased mortality might allow for improved selection of patients.
 The Mansfield Scientific Balloon Aortic Valvuloplasty Registry was analyzed to identify the frequency of in-hospital death and the factors associated with it.
 Of 492 patients undergoing the procedure, 37 (7.5%) died during the hospital stay in which valvuloplasty was performed.
 Twenty-four of these patients died within the first 24 h and the remainder died within 7 days after the procedure.
 There were significant differences in baseline clinical and hemodynamic characteristics as well as procedural and postprocedural variables between patients dying and those surviving the in-hospital period.
 Multivariate analysis identified four factors associated with increased mortality: 1) the occurrence of a procedure-related complication, 2) a lower initial left ventricular systolic pressure, 3) a smaller final aortic valve area, and 4) a lower baseline cardiac output.
 Thus, baseline hemodynamic, procedural and postprocedural variables and complications can be identified that are associated with increased mortality.
",13
2201,"Predictors of long-term survival after percutaneous aortic valvuloplasty: report of the Mansfield Scientific Balloon Aortic Valvuloplasty Registry.
 Percutaneous balloon aortic valvuloplasty was used to prospectively treat 492 elderly, symptomatic, nonsurgical patients suffering from severe aortic stenosis in 27 centers in North America and Europe.
 At 1 year the overall survival rate was 64% and the event-free survival rate (survival free of valve replacement or repeat valvuloplasty) was 43%.
 Clinical, catheterization and procedural variables were assessed to define prognostic variables.
 Univariate analysis revealed that patients who survived had a lesser frequency of previous myocardial infarction (2% versus 6%, p less than 0.005), lower incidence of severe ventricular dysfunction (22% versus 48%, p less than 0.001) and lower incidence of symptoms of heart failure (60% versus 75%, p less than 0.02).
 History of angina (56% versus 45%, p = NS) and syncope (23% versus 16%, p = NS) were similar for both groups.
 Values obtained at cardiac catheterization that differed in survivors and nonsurvivors included lower pulmonary artery systolic pressure (43 +/- 1 versus 54 +/- 2 mm Hg, p less than 0.001), lower mean pulmonary artery pressure (28 +/- 1.0 versus 36 +/- 1.0 mm Hg, p less than 0.001) and larger initial valve area (0.52 +/- 0.01 versus 0.47 +/- 0.02 cm2, p = 0.006).
 Discriminate function analysis was performed to identify variables that independently predicted improved probability of survival.
 Eight variables were significantly and independently predictive.
 These included age, initial cardiac output, initial left ventricular systolic pressures, initial left ventricular end-diastolic pressures, presence of coronary artery disease, New York Heart Association dyspnea classification, number of balloon inflations and final valve area.
",13
2202,"Ventricular load optimization by unloading therapy in patients with heart failure.
 The effects of unloading a depressed heart were assessed in terms of optimal coupling between the ventricle and arterial system.
 To assess the effects of preload on ventricular load coupling, preload was reduced with a lower body negative pressure of -20 mm Hg.
 Nitroprusside was used to evaluate the effects of afterload on the coupling under the condition that preload reduction was comparable to that with lower body negative pressure.
 In 13 patients with heart failure (ejection fraction 32 +/- 3%, mean +/- SE), direct arterial pressure was simultaneously recorded with the left ventricular echocardiogram as the pressure was elevated by phenylephrine.
 Left ventricular contractile properties were defined by the slope (Ees) of the end-systolic pressure-volume relation.
 The effective arterial elastance (Ea) was expressed by the slope of the end-systolic pressure-stroke volume relation.
 Left ventricular external work, end-systolic potential energy and work efficiency, defined as external work per pressure volume area (external work + potential energy), were determined.
 Baseline ventricular load coupling in these patients was characterized by an increase in the ratio of arterial elastance to ventricular elastance (Ea/Ees) (1.96 +/- 0.31).
 This ratio decreased significantly, to 1.45 +/- 0.22, with nitroprusside, and increased to 2.37 +/- 0.34 with lower body negative pressure.
 Therefore, end-systolic potential energy was decreased by nitroprusside but was unaltered by lower body negative pressure while external work was comparably decreased by both manipulations, indicating that work efficiency was significantly augmented with nitroprusside but declined with lower body negative pressure.
",13
2203,"Cardiovascular and hormonal effects of calcitonin gene-related peptide in congestive heart failure.
 The effects of infusing human alpha-calcitonin gene-related peptide were studied in eight patients with congestive heart failure, five normal rabbits and five rabbits with adriamycin-induced cardiomyopathy.
 In patients with heart failure, calcitonin gene-related peptide caused a dose-dependent increase in cardiac output and decrease in pulmonary and systemic vascular resistance and pulmonary artery pressure.
 The systemic blood pressure and right atrial and pulmonary wedge pressures decreased only at the highest infusion rate (16 ng/kg per min).
 Heart rate remained unchanged.
 Plasma epinephrine increased (p less than 0.05), whereas aldosterone, atrial natriuretic peptide and prolactin concentrations decreased (p less than 0.05).
 Plasma norepinephrine, renin activity, cortisol and growth hormone concentrations remained unchanged.
 In both groups of rabbits, the drug decreased blood pressure and increased cardiac output and heart rate.
 There was a significant increase in renal blood flow (p less than 0.05).
 The peptide did not affect the contraction amplitude of human and rabbit ventricular myocytes.
 These findings suggest that calcitonin gene-related peptide is a vasodilator in the rabbit and humans with little direct effect on ventricular myocardium.
 This peptide may be useful in some forms of heart failure.
",13
2204,"Experimental pericardial effusion: relation of abnormal respiratory variation in mitral flow velocity to hemodynamics and diastolic right heart collapse 
 Pericardial effusion is associated with an abnormal increase in respiratory variation in mitral flow velocity.
 However, the relation of the changes in flow velocity to pericardial pressure, hemodynamics and two-dimensional echocardiographic findings is not established.
 Therefore, 11 sedated dogs with extensive hemodynamic instrumentation were studied with two-dimensional and Doppler echocardiography during four stages of progressively larger pericardial effusion.
 During all stages of effusion, respiratory variation in peak mitral flow velocity in early diastole and left ventricular isovolumetric relaxation time was increased compared with baseline (p less than 0.05).
 This increase was seen at the earliest stage of effusion (mean pericardial pressure 4.2 +/- 1.4 versus -0.8 +/- 0.9 mm Hg at baseline, p less than 0.05), and preceded the appearance of unequivocal diastolic right heart collapse in every dog.
 Maximal respiratory variation coincided with the appearance of right atrial collapse (mean pericardial pressure 7.1 +/- 2.4 mm Hg; mean inspiratory decrease in aortic pressure 9.5 +/- 2.6 mm Hg; mean aortic pressure 88.2 +/- 15.2 versus 102.2 +/- 11.2 mm Hg at baseline, p less than 0.05; and cardiac output 3.8 +/- 1.2 versus 5.5 +/- 1.3 liters/min at baseline, p less than 0.05), but did not increase at stages associated with more severe hemodynamic compromise.
 In addition, the respiratory changes in peak mitral flow velocity in early diastole were associated with simultaneous changes in the diastolic transmitral pressure gradient.
 It is concluded that in this model of acute pericardial effusion 1) increased respiratory variation in early diastolic mitral flow velocity, peak mitral flow velocity in early diastole and left ventricular isovolumetric relaxation time occurs almost immediately as pericardial pressure increases and persists at all stages of increasing pericardial effusion; 2) the abnormal respiratory variation occurs before equalization of intracardiac pressures and before the onset of unequivocal right heart collapse; 3) the respiratory variation occurs as a result of changes in the diastolic transmitral pressure gradient; and 4) the magnitude of the respiratory change is not necessarily predictive of pericardial pressure or severity of hemodynamic compromise, especially at the more severe stages of pericardial effusion.
",13
2205,"Spontaneous alterations in coronary blood flow velocity before and after coronary angioplasty in patients with severe angina.
 Cyclic coronary artery flow variations with a spontaneous decline in coronary blood flow to very low levels have been documented in stenosed canine coronary arteries with endothelial injury.
 These flow variations are associated with transient platelet aggregation and dislodgment and the release of selected mediators, including thromboxane A2 and serotonin.
 However, cyclic or spontaneous flow variations have not been demonstrated in stenosed coronary arteries in humans.
 In this study, the hypothesis was tested that spontaneous coronary blood flow velocity variations occur in some patients with stenosed coronary arteries before or after coronary artery angioplasty.
 Thus, 13 patients with severe and limiting angina underwent intracoronary pulsed Doppler velocimetry of their dilated artery immediately before and after percutaneous transluminal coronary angioplasty, whereas 9 control patients underwent velocimetry of an angiographically normal coronary artery.
 A 3F catheter with a 20 MHz Doppler crystal was positioned to achieve a maximal stable signal, and the flow velocity signal was recorded continuously for 20 min.
 Spontaneous flow velocity variations (greater than or equal to 38% change in Doppler frequency shift with wide morphologic changes) were present in 3 of the 13 patients tested.
 Spontaneous flow velocity variations occurred before angioplasty in one patient, after angioplasty in another and both before and after angioplasty in a third.
 In addition, 2 of the 13 patients, 1 with spontaneous coronary artery flow velocity variations before angioplasty, had frank vasospasm in an adjacent area just distal to the area of coronary dilation immediately after balloon inflation.
 These data establish that spontaneous coronary artery flow velocity variations occur in some patients with severe and limiting angina before and after coronary angioplasty.
 These variations may be related to platelet aggregation or coronary vasoconstriction, or both, at sites of endothelial injury resulting from plaque fissuring or ulceration and endothelial and medial injury occurring during coronary angioplasty.
",13
2206,"Elevated plasma beta-endorphin levels in patients with congestive heart failure 
 Recent experimental studies show that the opioid system is important to the pathophysiology of cardiovascular impairment in congestive heart failure.
 Plasma beta-endorphin levels were measured in 37 patients with congestive heart failure and compared with those of 21 age- and gender-matched normal subjects.
 The relation of plasma beta-endorphin levels and cardiac function at rest and exercise capacity was assessed in 17 of the patients with dilated cardiomyopathy.
 Exercise capacity was determined by symptom-limited maximal treadmill exercise with expired gas analysis.
 Plasma beta-endorphin levels were elevated and correlated with the patients' New York Heart Association functional cardiac status (control: 14.0 +/- 4.4 pg/ml; class II: 17.9 +/- 3.6 pg/ml; class III: 28.3 +/- 8.8 pg/ml; class IV: 46.7 +/- 14.6 pg/ml, mean +/- SD).
 No relation was found between plasma beta-endorphin levels and left ventricular systolic performance as assessed by M-mode and Doppler echocardiography.
 Plasma beta-endorphin levels were negatively correlated with cardiac output determined by Doppler echocardiography and positively correlated with systemic vascular resistance (r = -0.733, r = 0.747, respectively, both p less than 0.001), but not correlated with calf blood flow as measured by a plethysmography.
 A good correlation was found between plasma beta-endorphin levels at rest and exercise capacity.
 The correlations with peak oxygen consumption, anaerobic threshold, and peak rate-pressure product were r = -0.721, -0.672, and -0.674, respectively (p less than 0.01).
 The data show that plasma beta-endorphin levels are elevated in patients with congestive heart failure and reflect, to some degree, the severity of the disease.
",13
2207,"Implications of echocardiographically assisted diagnosis of pericardial tamponade in contemporary medical patients: detection before hemodynamic embarrassment.
 Identification of suspected pericardial tamponade and the decision to perform invasive drainage of the pericardial space have historically been based on classic bedside findings.
 Two-dimensional echocardiography has improved detection of pericardial effusion, but it may be excessively sensitive in evaluation of patients for hemodynamic embarrassment.
 Therefore, 50 consecutive medical patients were examined who were identified by echocardiography to have probable tamponade (defined as the presence of right heart chamber collapse in the presence of a pericardial effusion) and who underwent combined right-sided cardiac catheterization and percutaneous pericardiocentesis.
 All patients had elevated pericardial pressure.
 However, many had minimal evidence of hemodynamic compromise (94% had systolic blood pressure greater than or equal to 100 mm Hg and 58% had a cardiac index greater than or equal to 2.3 liters/min per m2).
 Pericardiocentesis resulted in hemodynamic improvement, but frequently did not alleviate dyspnea or correct tachycardia.
 Patients with malignancy as the cause of tamponade had a high mortality rate (the cumulative probability of survival in such patients was only 17% at 1 year).
 Echocardiographically assisted diagnosis of pericardial tamponade in medical patients results in the identification of a substantial subset of patients with only subtle evidence of hemodynamic compromise.
 This subset of patients differs sharply from medical patients described in previous reports with classic tamponade.
 Although the patients can be managed by invasive catheter pericardiocentesis with few complications, the natural history and the optimal management strategy for this group are not resolved.
",13
2208,"Recognition and embolic potential of intraaortic atherosclerotic debris.
 Atherosclerotic disease of the thoracic aorta is common in the elderly and patients with clinical coronary artery disease.
 Although embolization can occur from atherosclerotic debris within the thoracic aorta, it is not commonly considered in the differential diagnosis of the source of a systemic embolism.
 In the current study, the prevalence, clinical significance and embolic potential of intraaortic atherosclerotic debris as detected by transesophageal echocardiography was determined.
 Intraaortic atherosclerotic debris was identified in 38 (7%) of 556 patients undergoing transesophageal echocardiography.
 An embolic event occurred among 11 (31%) of the 36 study patients with intraaortic atherosclerotic debris.
 The incidence of an embolic event was higher when the debris was pedunculated and highly mobile (8 [73%] of 11 patients) than when it was layered and immobile (3 [12%] of 25 patients) (p less than 0.002).
 Among 15 patients undergoing an invasive procedure of the aorta, the incidence of embolism was 27%.
 In conclusion, in a patient with an embolic event, the thoracic aorta should be considered as a potential source.
 Transesophageal echocardiography can reliably detect intraaortic atherosclerotic debris, and when it is identified, an invasive aortic procedure should be avoided if possible.
",13
2209,"Coronary arterial remodeling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis.
 Coronary arterial remodeling is a compensatory mechanism that may limit the adverse effects of coronary obstructive lesions by expansion of the entire vascular segment.
 To determine if this compensatory anatomic change occurs in patients, high-frequency epicardial echocardiography using a 12 MHz transducer was performed during open heart surgery in 33 patients (10 with normal coronary arteries undergoing valvular surgery and 23 with coronary atherosclerosis).
 From stop-frame videotape high-frequency epicardial echocardiographic images, cross-sectional measurements of luminal area and total arterial area (lumen, intima, media and dense adventitia) were made in the patients with atherosclerosis at the site of arterial lesions and from the most proximal portion of the same artery.
 Remodeling was defined as enlargement of the total arterial area.
 In normal arteries measurements were made from proximal and midarterial locations.
 In the patients with normal coronary arteries, total arterial area, as determined by high-frequency echocardiography, decreased from the proximal site to the midportion of the artery (from 10.4 +/- 0.9 to 8.4 +/- 1.0 mm2, p less than 0.05); luminal area also decreased (from 6.0 +/- 0.6 to 4.5 +/- 0.7 mm2, p less than 0.05).
 In patients with coronary arterial lesions, luminal area also decreased from the proximal site to the arterial lesion site (from 5.3 +/- 0.6 to 2.3 +/- 0.3 mm2, p less than 0.05), but total arterial area increased (from 11.6 +/- 1.0 to 13.0 +/- 1.0 mm2, p less than 0.05).
 Of the 25 coronary arteries evaluated, only 4 had angiographic evidence of coronary collateral formation.
 These data indicate that coronary arterial remodeling is an important compensatory mechanism in obstructive coronary disease.
",13
2210,"Detection of coronary blood flow associated with left main coronary artery stenosis by transesophageal Doppler color flow echocardiography.
 Demonstration of disordered blood flow in a coronary artery may be helpful in anticipating the presence of stenosis.
 To examine the possibility of disordered coronary blood flow associated with left main coronary stenosis, left main coronary flow was visualized by transesophageal Doppler color flow echocardiography in 52 patients undergoing coronary angiography.
 Twenty patients had significant left main coronary stenosis (Group 1) and 32 patients did not (Group 2).
 Adequate two-dimensional echocardiographic images of the left main coronary artery were obtained in 17 patients in Group 1 and 30 patients in Group 2.
 Sixteen patients in Group 1, including five patients in whom the stenosis could not clearly be defined by two-dimensional echocardiography, exhibited the aliased reddish-yellowish elements producing the mosaic pattern at the stenotic or poststenotic segments, or both.
 In contrast, nonaliased bluish jets, suggesting laminar flow away from the transducer, were seen in echocardiograms from 27 patients in Group 2.
 This group included four patients with stenosis-like images on two-dimensional echocardiography.
 The aliased mosaic pattern was found in only three patients in Group 2 (p less than 0.01).
 Thus, sensitivity to detect the stenosis was improved when Doppler color flow imaging was applied.
 Flow velocity was significantly higher at the site of stenosis in patients in Group 1 (116 +/- 28 cm/s, n = 10, mean +/- SD) than in Group 2 (29 +/- 12 cm/s, n = 21, p less than 0.01), suggesting that the augmentation of flow velocity with or without turbulence due to the stenosis contributed to the appearance of the mosaic flow images.
",13
2211,"Forearm blood flow response to posture change in the very old: non-invasive measurement by venous occlusion plethysmography.
 Little is known about the peripheral vascular response to posture change in very elderly people who are vulnerable to the development of orthostatic hypotension.
 This is due, in part, to the risks of currently utilized invasive vascular monitoring techniques in the elderly population.
 We studied the forearm vascular response to active standing in 18 healthy young, 10 healthy old, and 19 impaired elderly subjects, using the non-invasive technique of venous occlusion plethysmography.
 In six subjects this technique was compared to duplex doppler ultrasonography for the measurement of postural changes in forearm blood flow.
 Forearm blood flow changes determined by venous occlusion plethysmography were 11% larger than doppler measurements, but the two methods strongly correlated (r = 0.90, P less than .001).
 Mean forearm vascular resistance increased to a significantly greater extent at 1 minute of standing in young subjects than in both groups of old, although the response was quite variable in all groups.
 Two healthy elderly (20%) and eight impaired elderly (40%) subjects had unexpected forearm vasodilatation at 1 minute of standing.
 By 3 minutes, forearm vascular resistance had increased by similar amounts in all three groups of subjects.
 Five impaired elderly and no healthy young or healthy old subjects had orthostatic hypotension, defined as greater than or equal to 10 mm Hg decline in mean arterial blood pressure at 1 or 3 minutes of standing.
 Forearm vascular resistance changes did not correlate with blood pressure response to standing.
 Thus, forearm vascular response to 1 minute of active standing is attenuated in many elderly subjects.
 This abnormality may impair adaptation to orthostatic stress in advanced age.
",13
2212,"Ostium secundum atrial septal defect in the elderly.
 Atrial septal defect (ASD) is one of the most common congenital cardiac anomalies in adults.
 Life expectancy is shortened, and almost 90% of patients die by the age of 60 years.
 The progression of this congenital disease to congestive heart failure has been related to several factors such as the onset of pulmonary hypertension, arrhythmias, bronchopulmonary infections, or the development of other cardiovascular disease.
 We describe three cases of very old patients with significant ASDs and late development of symptoms.
 Given the higher risks and poorer long-term results of surgical closure of the defect in advanced age, the indications for such an intervention in elderly patients should be carefully evaluated.
",13
2213,"Arterial aneurysms in children: clinicopathologic classification.
 Thirty-one arterial macroaneurysms in 23 pediatric-aged patients (16 boys and 7 girls) were treated at the University of Michigan.
 The average age at time of diagnosis was 10.2 years (range 6 months to 18 years).
 Vessels involved the aorta (4), as well as hepatic (1), splenic (2), gastroepiploic (1), renal (12), iliac (1), superficial femoral (4), popliteal (1), brachial (1), radial (2), and ulnar (2) arteries.
 Twelve children exhibited overt clinical manifestations including presence of a mass (7), local pain (3), hematemesis (1), and painless obstructive jaundice (1).
 Eleven children had asymptomatic lesions.
 Aneurysm existence was confirmed by arteriography or operation.
 All but one child underwent surgical therapy, with 20 long-term survivors (mean follow-up 3.5 years).
 One operative death occurred and one death occurred 6 years after surgery.
 This experience and a review of previously reported cases served as a basis for categorization of childhood aneurysmal disease as true aneurysms associated with (I) arterial infection, (II) giant-cell aortoarteritis, (III) autoimmune connective tissue disease, (IV) Kawasaki's disease, (V) Ehlers-Danlos syndrome or Marfan's syndrome, (VI) other forms of noninflammatory medial degeneration, (VII) arterial dysplasias, (VIII) congenital-idiopathic factors, as well as (IX) false aneurysms associated with extravascular events causing vessel wall injury or disruption.
 Knowledge of the varied clinicopathologic characteristics of arterial aneurysms in children is important in treating these patients.
",13
2214,"The role of duplex scanning in the selection of patients for transluminal angioplasty.
 As part of our initial evaluation to determine whether patients with lower extremity ischemia are candidates for intervention, arterial duplex examinations are performed in the noninvasive vascular laboratory.
 Patients with isolated short stenoses on the duplex examination are referred for transluminal angioplasty.
 One hundred thirty-four arteriograms were performed for ischemic peripheral vascular disease in 122 patients between July 1987 and March 1990.
 One hundred ten (82%) of the arteriograms were preceded by a lower extremity arterial duplex evaluation.
 Fifty cases (45%) were scheduled for transluminal angioplasty based on the findings of the duplex examination.
 Transluminal angioplasty was performed in 47 of 50 cases (94%).
 No significant differences in age, sex, or diabetes were found between the patients who were referred for transluminal angioplasty and those who were not.
 These data demonstrate that duplex scanning of the lower extremities allows the detection of lesions that will be amenable to transluminal angioplasty.
 We think that duplex scanning should become the standard screening tool for detection of treatable lower extremity lesions.
",13
2215,"Ultrasound screening of first-degree relatives of patients with an abdominal aortic aneurysm.
 The pedigrees were constructed of 43 patients (probands) who underwent resection of an abdominal aortic aneurysm.
 Seven probands (16.2%) had a first-degree relative (parent, sibling, child) known to have had an abdominal aortic aneurysm (multiplex family).
 To determine the prevalence of undiagnosed abdominal aortic aneurysm, ultrasound screening of first-degree relatives over age 40 years was undertaken.
 Of 202 eligible relatives, 103 (51.0%) were screened.
 An occult abdominal aortic aneurysm was defined as an infrarenal aortic diameter greater than 3.0 cm or an infrarenal/suprarenal aortic diameter ratio of greater than 1.5.
 An incipient abdominal aortic aneurysm was defined as a clear focal bulge of the infrarenal aorta, which was less than 3.0 cm in greatest diameter.
 Four of 103 relatives (3.9%) were found to have an occult abdominal aortic aneurysm (age/sex: 57M, 60M, 62F, 65M), and three (2.9%) were found with an incipient abdominal aortic aneurysm (age/sex: 56M, 60M, 67F).
 These smaller abdominal aortic aneurysms were in patients younger than the operated probands (average age men, 67 years; women, 69 years).
 Six of seven individuals were in families previously considered simplex, increasing the actual multiplex family frequency from 16.2% to 27.9%.
 All seven new abdominal aortic aneurysms were found in the 49 siblings age 55 years or older.
 There were no abdominal aortic aneurysms found in the 39 relatives under age 55 years, in 14 children ages 50 to 59 years or in one parent.
 Therefore of the siblings age 55 years or older, 5/20 men (25.0%) and 2/29 women (6.9%) were found to have a previously undiagnosed abdominal aortic aneurysm.
",13
2216,"The influence of elastic compression stockings on deep venous hemodynamics.
 To determine the effect of elastic compression stockings on deep venous hemodynamics we measured ambulatory venous pressure, venous refill time, maximum venous pressure with exercise, amplitude of venous pressure excursion, and duplex-derived common femoral and popliteal vein diameter and peak flow velocities with and without stockings in 10 healthy subjects and 16 patients with chronic deep venous insufficiency.
 The effects of below-knee and above-knee 30 to 40 torr and 40 to 50 torr gradient stockings were studied.
 Despite documentation of substantial stocking compressive effects by skin pressure measurements, neither below-knee or above-knee elastic compression stockings significantly improved ambulatory venous pressure, venous refill time, maximum venous pressure with exercise, or the amplitude of venous pressure excursion in healthy patients or in patients with deep venous insufficiency (p greater than 0.05).
 In patients with deep venous insufficiency stockings modestly increased popliteal vein diameter and flow velocity in the upright resting position (p less than 0.02).
 After tiptoe exercise without stockings deep venous peak flow velocity increased in healthy patients and in patients with deep venous insufficiency by a mean of 103% in the popliteal vein and 46% in the common femoral vein (p less than 0.01).
 With the application of elastic compression stockings only modest augmentation of deep venous flow velocity occurred in both groups above that seen in the bare leg after exercise.
 Thus elastic compression stockings did not improve deep venous hemodynamic measurements in patients with deep venous insufficiency.
 The beneficial effects of stockings in the treatment of deep venous insufficiency must relate to effects other than changes in deep venous hemodynamics.
",13
2217,"The association of skin color with blood pressure in US blacks with low socioeconomic status 
 To determine the association of skin color, measured by a reflectometer, with blood pressure in US blacks, we studied a community sample of 457 blacks from three US cities.
 Persons taking antihypertensive medications were excluded.
 Both systolic and diastolic blood pressure were higher in darker persons and increased by 2 mm Hg for every 1-SD increase in skin darkness.
 However, the association was dependent on socioeconomic status, whether measured by education or an index consisting of education, occupation, and ethnicity, being present only in person with lower levels of either indicator.
 Using multiple linear regression, both systolic and diastolic blood pressure remained significantly associated with darker skin color in the lower levels of socioeconomic status, independent of age, body mass index, and concentrations of blood glucose, serum urea nitrogen, serum uric acid, and urinary sodium and potassium.
 The association of skin color with blood pressure only in low socioeconomic strata may be due to the lesser ability of such groups to deal with the psychosocial stress associated with darker skin color.
 However, these findings also are consistent with an interaction between an environmental factor associated with low socioeconomic status and a susceptible gene that has a higher prevalence in persons with darker skin color.
",13
2218,"The erythrocyte sedimentation rate in congestive heart failure.
 BACKGROUND AND METHODS.
 Physicians have long believed that the erythrocyte sedimentation rate is low in patients with congestive heart failure, but this concept is based on a misinterpretation of the results in a single report published in 1936.
 To reevaluate this concept in the modern era, we measured the sedimentation rate in 242 patients who were referred for treatment of chronic heart failure.
 RESULTS.
 The sedimentation rate was low (less than 5 mm per hour) in only 24 patients (10 percent) but was increased (above 25 mm per hour) in 50 percent.
 Patients with low or normal sedimentation rates (less than or equal to 25 mm per hour) had more severe hemodynamic abnormalities than patients with elevated rates: lower cardiac index (mean +/- SEM, 1.7 +/- 0.1 vs.
 2.0 +/- 0.1 liters per minute per square meter of body-surface area) and higher mean right atrial pressure (mean +/- SEM, 12 +/- 1 vs.
 9 +/- 1 mm Hg) (both P less than 0.0001).
 New York Heart Association functional class IV symptoms were present in 66 percent of the patients with a low or normal sedimentation rate, as compared with 42 percent of those with elevated rates (P less than 0.0001).
 After one to three months of therapy, patients whose sedimentation rates decreased showed little hemodynamic or clinical response to treatment, whereas both cardiac performance and functional status improved in patients whose rates increased (P less than 0.02 for the comparison between groups).
 The sedimentation rate was correlated with the plasma fibrinogen level (r = 0.64, P = 0.0025), and changes in the sedimentation rate during treatment were correlated inversely with changes in mean right atrial pressure (r = -0.57, P = 0.0002).
 During long-term follow-up, patients with low or normal sedimentation rates had a worse one-year survival than patients with elevated rates (41 vs.
 66 percent, P = 0.01).
 CONCLUSIONS.
 These data indicate that the erythrocyte sedimentation rate is correlated with the severity of illness in patients with chronic heart failure.
 Because of its lack of discriminatory power, however, the test is of limited value in the clinical management of this disorder.
",13
2219,"Circadian rhythms in blood pressure in school-age children of normotensive and hypertensive parents.
 The purpose of this study was to describe the characteristics of blood pressure rhythms in school-age children and to compare the circadian mesors and amplitudes between children of normotensive parents and children of hypertensive parents.
 The sample consisted of 40 healthy children between 8 and 10 years old; 20 children had a parental history of hypertension and 20 did not.
 Blood pressure was measured every 2 hours during the day and every 90 minutes during the night for one 24-hour cycle using a Dinamap monitor equipped with an automatic printer.
 Cosinor analyses revealed statistically significant circadian rhythms for systolic and diastolic blood pressures in 12 of the 40 subjects.
 The acrophases for systolic and diastolic pressures occurred between 1200-1800 hours.
 The mean systolic mesor was 108.50 while the mean diastolic mesor was 61.41.
 The mean amplitudes were 8.85 for systolic pressure and 7.44 for diastolic pressure.
 No statistically significant differences in circadian mesors and amplitudes between children of normotensive parents and children of hypertensive parents were found.
",13
2220,"Cineangiography of the heart in a single breath hold with a segmented turboFLASH sequence.
 Six healthy volunteers and three patients with cardiac anomalies were studied in a comparison of segmented turboFLASH (fast low-angle shot) cine, a method of magnetic resonance imaging that permits an entire series of high-resolution cine images to be obtained in one breath hold, with standard cine.
 Segmented turboFLASH uses a gradient-echo sequence designed for short imaging times in combination with a segmented data acquisition method.
 Presaturation pulses were applied to eliminate the blood pool signal; the signal-to-noise ratio was assessed with a phantom.
 Standard hardware and image reconstruction methods were used.
 The breath-hold images consistently showed reduced ghosting and blurring from respiration.
 Because a very short echo time was used, segmented turboFLASH was relatively insensitive to dephasing caused by local field disturbances or flow.
 The authors conclude that, by reducing imaging times and eliminating respiratory artifact, segmented turboFLASH can be useful for performing cine studies of the heart and great vessels.
",13
2221,"Gynecologic vascular abnormalities: diagnosis with Doppler US.
 The authors describe the use of duplex and/or color Doppler ultrasonography of the pelvis in three women to demonstrate the presence of venous malformations.
 One patient with a pulsatile vaginal mass was shown to have an arteriovenous malformation of the vaginal wall.
 The second patient was shown to have an unsuspected venous angioma in the endometrial cavity.
 The third patient was shown to have adnexal varices that closely mimicked hydrosalpinx.
 In the latter two cases, the duplex and color flow capabilities of an endovaginal probe were especially important.
",13
2222,"Noninvasive assessment of cerebral collateral blood supply through the ophthalmic artery.
 We assessed the potential of 2-MHz pulsed-wave transorbital Doppler ultrasonography to delineate the role of the ophthalmic artery as a source of collateral cerebral blood supply by comparing oculopneumoplethysmography, transorbital Doppler ultrasonography, periorbital continuous-wave Doppler ultrasonography, and transcranial Doppler ultrasonography in 25 patients with unilateral internal carotid artery occlusion and five controls with 10 normal internal carotid arteries.
 Systolic ophthalmic artery blood velocity was reduced ipsilateral to an internal carotid artery occlusion (38.2 +/- 10.2 cm/sec) compared with the contralateral and control velocities (46.0 +/- 10.3 and 47.5 +/- 6.8 cm/sec, respectively; p less than 0.05).
 Ophthalmic systolic pressure measured by oculopneumoplethysmography was 94.7 +/- 13.2 mm Hg ipsilateral to an internal carotid artery occlusion compared with 108.4 +/- 15.3 mm Hg on the contralateral side (p less than 0.01).
 Transorbital and periorbital Doppler ultrasonography detected reversed ophthalmic artery blood flow ipsilateral to an internal carotid artery occlusion in 44.0% and 40.0% of the patients, respectively.
 Systolic middle cerebral artery blood velocity was 55.2 +/- 22.3 cm/sec ipsilateral to an internal carotid artery occlusion compared with 79.4 +/- 23.5 cm/sec on the contralateral side (p less than 0.05) and 101.2 +/- 18.9 cm/sec in the controls (p less than 0.05).
 Reversed ophthalmic artery blood flow was associated with a low middle cerebral artery blood velocity and lack of major intracerebral collaterals.
 Transorbital Doppler ultrasonography permits noninvasive evaluation of the ophthalmic artery.
",13
2223,"Interpreting results of exercise studies after acute myocardial infarction altered by thrombolytic therapy, coronary angioplasty or bypass.
 Numerous studies have assessed the ability of exercise modalities to predict patient outcome after acute myocardial infarction (AMI).
 Implicit in the use of these prior data to assess the prognosis of patients currently undergoing exercise studies is the assumption that patients selected for exercise assessment are similar over time and that the data generated in the past are therefore applicable to the current patient populations.
 This study retrospectively assessed the clinical, exercise, and rest and exercise radionuclide angiographic data in 791 consecutive patients referred for exercise radionuclide angiography within 1 month after AMI during a 5-year period to determine if the clinical and exercise characteristics of patients referred for exercise evaluation after infarction have changed significantly over time.
 Most parameters examined demonstrated significant increasing trends, including thrombolytic therapy at the time of AMI, revascularization procedure between AMI and exercise assessment, age, beta-blocker usage, Q-wave AMI, inferior infarction, exercise double product, exercise capacity, significant ST-segment depression with exercise, peak ejection fraction, and change in ejection fraction with exercise.
 These data indicate that the characteristics of patients selected to undergo exercise after AMI in a large referral center have changed significantly over time.
 If these data are applicable to other referral centers and to other exercise testing modalities, previously published results regarding exercise assessment after AMI will need to be reconfirmed in patients currently selected for testing, since these results may no longer be applicable in this current era of aggressive medical and interventional management.
",13
2224,"Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris.
 A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes.
 After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning.
 Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography.
 During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less than 0.05).
 Time to greater than or equal to 1 mm ST depression was significantly greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72 seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than 0.0005).
 During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p less than 0.02 for both).
 The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment.
 Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes.
",13
2225,"Ablation of the atrioventricular junction with radiofrequency energy using a new electrode catheter.
 Percutaneous catheter ablation using radiofrequency energy can be used to interrupt atrioventricular (AV) conduction in patients with supraventricular tachycardia refractory to drugs.
 Results of radiofrequency ablation of the AV junction using a custom-designed catheter with a large, 3-mm-long distal electrode, 2-mm interelectrode spacing, and a shaft with increased torsional rigidity were compared with those using a standard quadripolar electrode catheter (Bard EP).
 An electrocoagulator (Microvasive Bicap 4005) supplied unmodulated radiofrequency current at 550 kHz, which was applied between the distal electrode of the ablation catheter and a large skin electrode.
 With use of the modified catheter, 12 of 13 patients (92%) had persistent complete AV block induced with 7 +/- 5 applications of 18 +/- 6 W of radiofrequency power.
 In contrast, complete AV block was produced in only 9 of 18 (50%) historical control patients treated with the standard catheter, despite a similar number of applications (7 +/- 5) and power output (16 +/- 4 W).
 A rise in impedance, due to desiccation of tissue and coagulum formation, occurred earlier (28 +/- 18 vs 52 +/- 24 seconds, p less than 0.001) and more frequently (54 vs 40% of applications, p = 0.047) in patients treated with the standard catheter than in patients treated with the modified catheter.
 The use of a catheter designed to increase the surface area of electrode-tissue contact allows more radiofrequency energy to be delivered before a rise in impedance occurs and appears to increase the effectiveness of radiofrequency ablation of the AV junction.
",13
2226,"Relative importance of activation sequence compared to atrioventricular synchrony in left ventricular function.
 This study evaluated the relative hemodynamic importance of a normal left ventricular (LV) activation sequence compared to atrioventricular (AV) synchrony with respect to systolic and diastolic function.
 Twelve patients with intact AV conduction and AV sequential pacemakers underwent radionuclide studies at rest and Doppler echocardiographic studies at rest and during submaximal exercise, comparing atrial demand pacing (AAI) to sequential AV sensing pacing (DDD) and ventricular demand pacing (VVI).
 Studies at rest were performed at a constant heart rate between pacing modes, and the exercise study was performed at a constant heart rate and work load.
 Cardiac output was higher during AAI than during both DDD and VVI (6.2 +/- 1 vs 5.6 +/- 1 and 5.3 +/- 1 liters/min, p less than 0.05).
 LV ejection fraction was likewise higher during AAI (55 +/- 12 vs 49 +/- 11 vs 51 +/- 13, p less than 0.05).
 VVI with or without AV synchrony was associated with a paradoxical septal motion pattern, resulting in a 25% impairment of regional septal ejection fraction.
 In addition, LV contraction duration was more homogenous during AAI.
 Peak filling rate during AAI and VVI was higher than during DDD (2.86 +/- 1 and 2.95 +/- 1 vs 2.25 +/- 1 end-diastolic volume/s; p less than 0.05).
 During VVI, the time to peak filling was significantly shorter than during both AAI and DDD (165 +/- 34 vs 239 +/- 99 and 224 +/- 99 ms; p less than 0.05).
",13
2227,"Effects of doxazosin on blood pressure, renin-angiotensin-aldosterone and urinary kallikrein.
 Doxazosin, a new quinazoline-derivative postsynaptic alpha 1-adrenoceptor antagonist, was studied in this randomized, double-blind, placebo-controlled 12-week study.
 Its effects on blood pressure (BP), heart rate, metabolic functions and renal hormones were analyzed after administration of a single oral morning dose in a 3-phase fashion when administered to 17 patients (11 women, 6 men, 21 to 59 years) with mild to moderate uncomplicated essential hypertension.
 After titrating the antihypertensive effective dose biweekly from 1 to 8 mg/day and a mean end titration-point dose of 4.14 +/- 0.1 mg (mean +/- standard error of the mean) at week 8 of treatment, it was adjusted to maintain diastolic BP at levels less than or equal to 90 mm Hg for up to 12 weeks of treatment when, at a final mean dose of 4.35 +/- 0.2 mg/day, BP decreased in all patients by a mean 31 +/- 3/17 +/- 2 (supine) and 39 +/- 3/15 +/- 3 (standing) mm Hg (p less than 0.005) with no increase in heart rate and no ""first-dose phenomenon."" Neither the renin-aldosterone system nor electrolyte excretion was significantly affected.
 Renal function and metabolic parameters also remained unchanged.
 Urinary kallikrein excretion was augmented 2.47-fold (p less than 0.002).
 There was good tolerance; 1 patient discontinued the study because of dry nose.
 These results suggest that long-term monotherapy with doxazosin is an effective and safe antihypertensive agent for mild to moderate essential hypertension that stimulates urinary kallikrein excretion.
",13
2228,"Effect of mitral regurgitation and volume loading on pressure half-time before and after balloon valvotomy in mitral stenosis.
 Doppler pressure half-time (PHT) is frequently used to assess mitral valve area (MVA), but the reliability of PHT has recently been challenged, specifically in the setting of balloon mitral valvotomy when hemodynamics have been abruptly altered.
 The effect of volume loading both before and after balloon mitral valvotomy on computation of MVA by Gorlin and by PHT in 18 patients with high-fidelity micromanometer measurements of left atrial and left ventricular pressure was therefore examined.
 Echocardiographic MVA increased from 0.91 +/- 0.15 to 1.97 +/- 0.42 cm2 after valvotomy.
 Volume loading produced significant increases in left atrial pressure (16 to 23 before and 12 to 20 mm Hg after valvotomy), in cardiac output (3.7 to 4.1 before and 3.9 to 4.6 liters/min after valvotomy), and in mitral valve gradient (11 to 14 before and 5 to 7 mm Hg after valvotomy).
 These hemodynamic changes were associated with modest but significant decreases in PHT and increases in MVA estimated by 220/PHT (0.66 to 0.81 before and 1.64 to 1.96 cm2 after valvotomy), whereas the MVA by Gorlin was not affected in a consistent fashion by volume loading (0.85 to 0.89 before and 1.66 to 1.69 cm2 after valvotomy).
 The correlation between Gorlin MVA and 220/PHT was only fair (r = 0.73, p less than 0.001) and was significantly poorer among patients with greater than 1+ mitral regurgitation (r = 0.72) than among those with less or no regurgitation (r = 0.79) (p = 0.001 by analysis of covariance for mitral regurgitation effect).
",13
2229,"Rarity of preclinical alcoholic cardiomyopathy in chronic alcoholics less than 40 years of age.
 Preclinical alcoholic cardiomyopathy, myocardial damage in the absence of overt congestive heart failure in chronic alcoholics, is well characterized at necropsy, but attempts to identify such a clinical entity before death have produced conflicting results.
 Studying subjects only at rest, the inclusion of older alcoholics and limitations of noninvasive techniques may explain some of the disagreement.
 To determine if preclinical alcoholic cardiomyopathy could be identified independent of the aforementioned limitations, 25 asymptomatic chronic alcoholics aged less than 40 years (mean 34), each of whom had consumed a minimum of 1 pint of whiskey or one 6-pack of beer greater than or equal to 5 days per week for greater than or equal to 5 years, underwent radionuclide ventriculography for measurements of systolic and diastolic function at rest, peak supine exercise and during recovery, and echocardiography for assessment of chamber size, wall thickness and left ventricular mass.
 Red blood cell levels of selenium and thiamine were measured to determine whether abnormalities were present in these 2 potential mediators of alcoholic cardiomyopathy.
 For comparison, an age-matched group of healthy control subjects was also studied.
 For alcoholics and control subjects at rest, mean ejection fraction (67 +/- 7% vs 71 +/- 6%) and diastolic peak filling rate (3.4 +/- 0.6 vs 3.3 +/- 0.6 end-diastolic volumes per second [EDV/s]) were similar.
",13
2230,"Prognostic value of thallium-201 perfusion defects in idiopathic dilated cardiomyopathy.
 To assess the prognostic significance of thallium-201 perfusion defects in patients with idiopathic dilated cardiomyopathy (IDC), 43 patients underwent thallium scintigraphy in addition to clinical, echocardiographic, angiographic and hemodynamic evaluation.
 Eleven patients had no significant thallium perfusion abnormality, 19 had multiple small defects and 13 had a large defect.
 During 3.2 +/- 2.2 years, 14 patients had disease-related mortality.
 The patients who died had a higher incidence of ventricular tachycardia (71 vs 31%; p less than 0.02), increased cardiothoracic ratio (60 +/- 6 vs 54 +/- 6; p = 0.005), decreased fractional shortening (11 +/- 6 vs 15 +/- 5; p less than 0.05), increased pulmonary wedge pressure (15 +/- 7 vs 10 +/- 6 mm Hg; p = 0.05), increased left ventricular end-diastolic pressure (21 +/- 8 vs 14 +/- 6 mm Hg; p = 0.02) and abnormal thallium perfusion defects (13 of 14 vs 16 of 26; p less than 0.05) compared with survivors.
 Age, gender, left ventricular end-systolic and end-diastolic dimensions, cardiac index and ejection fraction were not statistically different in the survivors versus the patients who died.
 Kaplan-Meier survival estimates at 1, 3 and 5 years were 100% in patients without significant perfusion abnormality; 89, 77 and 64%, respectively, in patients with multiple small defects; and 84, 76 and 30%, respectively, in patients with a large defect (p less than 0.025 by log rank test).
",13
2231,"An unusual venous anomaly of the placenta.
 The authors present an unusual vascular anomaly of the placenta.
 The placenta was very large, weighing 1,490 g.
 On the fetal surface, numerous dilated and tortuous vessels were observed on and under the chorionic membrane, of which three branches arose from a vein that was connected to the umbilical vein.
 One of them had a 5 x 2.5 cm aneurysmal dilatation, where three secondary branches arose.
 These venous channels were dilated and tortuous.
 The longest secondary branch was 133 cm in length and 1.2 cm in mean diameter and led into the placenta.
 Multiple, severely coiled or straight small branches arising from these vessels were also observed as vascular tangles.
 Some of these smaller vessels also led into the placenta.
 All abnormal vessels were veins.
 The umbilical cord was also normal except for a membranous insertion, and the placenta was unremarkable except for its large size.
",13
2232,"A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction.
 The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction.
 Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms.
 A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state.
 Coronary angiography was performed 48 hours after thrombolytic treatment.
 The overall patency rate was 74% (43/58).
 Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)).
 The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis.
 Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state.
",13
2233,"Dipyridamole magnetic resonance imaging: a comparison with thallium-201 emission tomography.
 Limitation of space and motion artefact make magnetic resonance imaging during dynamic exercise difficult.
 Pharmacological stress with dipyridamole can be used as an alternative to exercise for thallium scanning.
 Forty patients with a history of angina and an abnormal exercise electrocardiogram were studied by dipyridamole thallium myocardial perfusion tomography and dipyridamole magnetic resonance wall motion imaging with a cine gradient refocused sequence.
 Images for both scans were obtained in the oblique horizontal and vertical long axis and short axis planes before and after pharmacological stress with dipyridamole.
 The myocardium was divided into nine segments for direct comparison of perfusion with wall motion.
 Segments were assessed visually into grades--normal, hypokinesis or reduced perfusion, and akinesis or very reduced perfusion.
 After dipyridamole there were reversible wall motion abnormalities in 24 (62%) of 39 patients with coronary artery disease and 24 (67%) of 36 patients with reversible thallium defects.
 The site of wall motion deterioration was always the site of a reversible thallium defect.
 Thallium defects affecting more than two segments were always associated with wall motion deterioration but most single segment thallium defects were undetected by magnetic resonance imaging.
 There was a significant correlation between detection of wall motion abnormality, the angiographic severity of coronary artery disease, and the induction of chest pain by dipyridamole.
 There were no significant differences in ventricular volume or ejection fraction changes after dipyridamole between the groups with and without detectable reversible wall motion changes but the normalised magnetic resonance signal intensity of the abnormally moving segments was significantly less than the signal intensity of the normal segments.
",13
2234,"A controlled trial of community based coronary rehabilitation.
 Two hundred patients who had suffered an acute myocardial infarction 4-6 weeks before entered a randomised controlled trial of exercise treatment at a community sports centre supervised by a general practitioner.
 Eighty one per cent of the treatment group continued to exercise until they returned to work and 73% completed three months' exercise.
 There were no serious complications of the exercise course.
 The prevalence of angina pectoris fell by 10% in the treatment group but rose by 60% in the control group.
 The perceived energy level rose by significantly more in the treatment group than in the controls.
 The rise in predicted maximum oxygen uptake was significantly greater in the treatment group than in the control group as was the reduction in the double product (a reflection of myocardial workload) at peak exercise.
 Coronary rehabilitation in the community can be both safe and effective.
",13
2235,"A new method of haemodynamic assessment of mitral stenosis in atrial fibrillation: construction of a nomogram.
 Accurate haemodynamic assessment of mitral stenosis by hydraulic formulas requires measurement of the mean valve gradient and the cardiac output.
 The calculation is laborious, particularly in the presence of atrial fibrillation when averaged values obtained from multiple beat-to-beat determinations must be used.
 The relations between valve area, end diastolic gradient, and heart rate in 20 patients with mitral stenosis and atrial fibrillation were examined.
 In each patient the end diastolic pressure gradient for each cardiac cycle was related linearly to the RR interval of that cycle, and this relation was unchanged on exercise.
 The slope (S) and intercept (I) of this relation correlated with the degree of mitral stenosis as measured by the Gorlin valve area.
 The regression equations describing these relations were then used to construct a nomogram relating end diastolic pressure gradient to mitral valve area at different heart rates.
 When the nomogram was applied to catheterisation data from a further 30 patients the results correlated well with direct calculation of valve area by the Gorlin formula.
 The nomogram is simple to use, does not require measurement of cardiac output, and is independent of heart rate so that it is unnecessary for the patient to exercise during catheterisation.
",13
2236,"Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men.
 OBJECTIVE--To examine the association between the serum lipoprotein (a) concentration and subsequent coronary heart disease.
 DESIGN--Prospective case-control study based on a six year follow up of a general population sample of men aged 50 at baseline in 1983-4.
 Serum samples were frozen at the time of the baseline examination and kept at -70 degrees C for six years, after which the lipoprotein (a) concentrations in the samples were measured in cases and controls.
 SETTING--City of Gothenburg, Sweden.
 SUBJECTS--26 Men, from a general population sample of 776 men, who had sustained a myocardial infarction or died of coronary heart disease during the six years and 109 randomly selected controls from the same sample who had remained free of myocardial infarction.
 In neither cases nor controls was there a history of myocardial infarction at baseline.
 MAIN OUTCOME MEASURES--Proportion of myocardial infarction or deaths from coronary heart disease, or both, in relation to the serum lipoprotein (a) concentration.
 RESULTS--Men who suffered coronary heart disease had significantly higher serum lipoprotein (a) concentrations than controls (mean difference 105 mg/l; 95% confidence interval 18 to 192 mg/l).
 Men with the highest fifth of serum lipoprotein (a) concentrations (cut off point 365 mg/l) suffered a coronary heart disease rate which was more than twice that of men with the lowest four fifths of concentrations.
 Logistic regression analysis showed the serum lipoprotein (a) concentration to be significantly associated with coronary heart disease independently of other risk factors.
 CONCLUSION--The serum lipoprotein (a) concentration in middle aged men is an independent risk factor for subsequent myocardial infarction or death from coronary heart disease.
",13
2237,"Primary defect in alpha-adrenergic responsiveness in patients with varicose veins.
 Responsiveness of superficial hand veins to local infusions of noradrenaline was compared in patients with primary varicose veins and in healthy volunteers by use of the dorsal hand vein technique.
 Patients with varicose veins required significantly higher doses of noradrenaline for half-maximal venoconstriction than the dose required by control subjects (geometric mean, 11.6 ng/min in patients compared with 4.8 ng/min in control subjects; p = 0.006).
 Noradrenaline responsiveness in varicose veins was not significantly different from hand vein responsiveness in the same patients.
 Our findings indicate a constitutional decrease in venous alpha-adrenergic receptor responsiveness in patients with varicosities.
 Dilation of varicose veins does not further affect noradrenaline-induced venoconstriction.
",13
2238,"Calcium entry blockade and adrenergic vascular reactivity in hypertensives: differences between nicardipine and diltiazem.
 The interference of nicardipine and diltiazem infused into the brachial artery at systemically ineffective rates, with the forearm vascular response to graded exogenous norepinephrine, was evaluated in hypertensive patients.
 Nicardipine (1 and 3 micrograms/dl forearm tissue/min in both absence and presence of propranolol) increased forearm blood flow (venous plethysmography) and antagonized dose dependently the vasoconstrictor effect of norepinephrine, suggesting that functional alpha-antagonism may participate in the vasodilating and possibly the antihypertensive effect of the drug.
 On the contrary, no antagonism but rather potentiation of the responses to norepinephrine occurred after diltiazem (0.5 and 1 microgram/dl forearm tissue/min).
 Because intra-arterial propranolol abolished that potentiating action of the drug, whereas the local vasodilation to isoproterenol was clearly reduced, diltiazem probably interfered with beta-adrenergic receptor-mediated vasorelaxing mechanisms in human forearm arterioles.
 The data further stress the heterogeneity of calcium entry blockers in humans.
",13
2239,"Skeletal muscle metabolism in heart failure: a 31P nuclear magnetic resonance spectroscopy study of leg muscle.
 1.
 The gastrocnemius muscle of seven patients with mild to moderate chronic heart failure and of five healthy control subjects was studied using 31P nuclear magnetic resonance spectroscopy.
 Spectra were collected at rest and during an incremental, symptom-limited, exercise protocol.
 Blood flow was measured in the same study during brief interruptions to exercise.
 2.
 The phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio was lower in patients with heart failure than in control subjects at an exercise rate of 1.5 W, although intracellular pH and blood flow were similar.
 3.
 The cytosolic free adenosine 5'-diphosphate concentration was markedly increased in patients with heart failure exercising at 1.5 W compared with control subjects exercising at the same workload.
 4.
 Although the maximum workload achieved by patients with heart failure was less than half of that reached by control subjects, the pH and the phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio were lower in patients with heart failure at maximal load.
 Blood flow was less at maximal exercise in patients with heart failure than in control subjects in keeping with the reduced work load.
 5.
 The phosphocreatine depletion induced in the gastrocnemius muscle by exercise was more severe than previously described in the forearm of patients with heart failure.
 6.
 Metabolic abnormalities in skeletal muscle may contribute to exercise intolerance in heart failure, particularly during submaximal exercise.
",13
2240,"Dynamic association between artery shear flow condition and platelet cytosolic free Ca2+ concentration in human hypertension.
 1.
 Blood cells and vascular endothelial cells are subjected to a wide range of haemodynamically generated shear stress forces.
 In vitro, membrane stretching or shear stress have been observed to activate ion channels and cell metabolism and to facilitate erythrocyte and platelet aggregation.
 2.
 The present study was designed to evaluate the participation of shear stresses in the control of apparent platelet cytosolic free Ca2+ concentration in hypertensive patients.
 3.
 Shear conditions and platelet cytosolic free Ca2+ concentration in vitro were studied after a dynamic perturbation induced by 3 months of double-blind treatment with one of two beta-antagonists, carteolol and atenolol.
 Brachial artery wall shear rate and stress were estimated by means of a pulsed Doppler velocimeter, and blood viscosity was measured by a co-axial viscometer at a shear rate of 96 s-1.
 Platelet cytosolic free Ca2+ concentration was simultaneously measured by using the Quin-2 fluorescent chelator.
 The direct effect of atenolol and carteolol on platelet cytosolic free Ca2+ concentration in vitro was also measured after addition of the beta-blockers to platelet-rich plasma.
 4.
 Atenolol and carteolol decreased blood pressure similarly but their effects on shear rate (P less than 0.02), shear stress (P less than 0.01) and platelet cytosolic free Ca2+ concentration (P less than 0.05) differed after 3 months of therapy.
 In contrast, neither of the drugs significantly altered platelet cytosolic free Ca2+ concentration, in vitro per se.
 5.
 In the overall population, strong positive correlations existed not only between changes in platelet cytosolic free Ca2+ concentration and those in shear rate (r = 0.81, P less than 0.001) and shear stress (r = 0.83, P less than 0.001), but also between their absolute values, suggesting a possible haemodynamic shear-dependent modulation of transmembrane Ca2+ transport.
",13
2241,"Myocardial infarction prognostic scoring system.
 A myocardial infarction prognostic scoring system for patients treated in a coronary care unit is described.
 The prognostic significance of 22 variables, all which were available on admission, were analyzed.
 A prognostic index was then constructed by a modified stepwise logistic regressional analysis technique.
 The variables that were used in the scoring system were Killip hemodynamic class, infarct location, and the maximal ST segment elevation in a single lead.
 The scoring system was validated in an independent group of patients, including a group of patients treated with intravenous streptokinase.
 The scoring system may prove to be useful for individual patient prognostication and management strategies, and for the quantification of infarct severity for use in clinical studies.
",13
2242,"Wellness motivation in cardiac rehabilitation.
 Lack of patient adherence to prescribed regimens is a fundamental problem in cardiac rehabilitation programs.
 A causative factor in lack of patient adherence may be related to failure to address differences in individual health behavior motivation in cardiac rehabilitation.
 A group of 52 patients who had had myocardial infarction were sampled to test the relationship between social support systems, health locus of control, health value orientations, and wellness motivation.
 Pearson correlation coefficients indicated significant positive correlations between health locus of control variables, health value orientation variations, and wellness motivation.
 Health locus of control and health value orientation variables entered into a multiple regression equation to explain 32% of the variation in wellness motivation.
 Awareness of individual motivational responses that influence health behaviors in cardiac rehabilitation may enable nurses to develop intervention strategies for patients with cardiovascular disease who would benefit from modifying their risk-producing life-styles.
",13
2243,"Is phase 2 cardiac rehabilitation necessary for early recovery of patients with cardiac disease? A randomized, controlled study.
 In this study the effects of rehabilitation teaching plus exercise testing on perceived self-efficacy for and performance of daily activities were compared with and without exercise training.
 Subjects were patients who had had myocardial infarction or cardiac surgery (mean age 57.7 +/- 11.3 years) and who had already received inpatient rehabilitation services.
 Subjects were randomly assigned to one of three groups.
 Treatment group 1 (n = 11) received teaching, treadmill exercise testing, and exercise training (three times weekly for 5 weeks).
 Treatment group 2 (n = 15) received only teaching and exercise testing.
 The control group (n = 14) received only routine care without supervised exercise or teaching.
 Measurements of self-efficacy and activity performance were made at hospital discharge and at 4 and 9 weeks after the cardiac event.
 Repeated-measures analysis of variance showed an increase in self-efficacy scores (p less than 0.001) and performance of physical activity (p less than 0.001) for all groups.
 Both treatment groups, especially the training group, obtained the highest scores, but differences between groups were nonsignificant (p greater than 0.05).
 These results indicate that in a sample of uncomplicated, motivated patients who had participated in a phase 1 inpatient rehabilitation program, substantial improvements in self-efficacy and performance of daily activities were made early in recovery, before the onset of phase 2, formalized outpatient therapy.
",13
2244,"Myocardial infarction in the young adult.
 CAD in young male adults below the age of 40 years has generally been found to be associated with the usual risk factors associated with CAD.
 In a lesser number of young adults, MIs may be related to cocaine use.
 Sympathomimetic effects and increase in myocardial oxygen demand are factors considered responsible for acute MI in cocaine-abusing patients.
 In young adults who are asymptomatic following an acute MI and who are able to pass treadmill exercise stress tests at levels of Bruce stage 4 have been shown to have normal coronary arteriograms.
 Thus this subset should not require routine coronary angiograms following an acute MI.
",13
2245,"Proton magnetic resonance of exercise-induced water changes in gastrocnemius muscle.
 Exercise-induced water concentration changes have been determined in the medial gastrocnemius muscle noninvasively with image-guided in vivo proton magnetic resonance spectroscopy (MRS).
 These measurements were performed on seven normal male volunteers during and after isometric and ischemic-isometric exercise at 5, 10, and 20% maximum voluntary contraction (MVC).
 The observed water flux changes during different phases of exercise have been interpreted in terms of fluid transfer between the vasculature and exercising muscle.
 Good correlation between individual MVC and changes in water fluxes and the decay of water content was observed after 20% MVC exercise level.
 MRS results have been found to be consistent with those reported in the literature based on invasive biopsy techniques.
",13
2246,"The effects of etomidate on cerebral metabolism and blood flow in a canine model for hypoperfusion.
 The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on cerebral metabolism and blood flow were studied in 29 dogs during cerebral hypoperfusion.
 Three groups of animals were studied during a 45-minute normotensive and a 30-minute hypotensive period: 10 control animals without etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals receiving doses of etomidate sufficient to suppress electroencephalographic bursts (high-dose group).
 The mean arterial pressure fell to similar levels (p less than 0.05) during hypotension in all three groups (40 +/- 5, 38 +/- 3, and 27 +/- 6 mm Hg, respectively).
 The mean cerebral oxygen extraction fraction rose (p less than 0.05) from 0.23 +/- 0.02 to 0.55 +/- 0.08 in the five control animals tested and from 0.33 +/- 0.02 to 0.53 +/- 0.02 in the seven animals tested in the low-dose group, but did not increase (p greater than 0.05) in the four animals tested in the high-dose group (0.24 +/- 0.03 to 0.23 +/- 0.05).
 Mean cerebral blood flow levels decreased in all groups during hypotension (p less than 0.05): 42 +/- 3 to 21 +/- 4 ml/100 gm/min (52% +/- 12% decrease) in the five animals tested in the control group, 60 +/- 8 to 24 +/- 6 ml/100 gm/min (56% +/- 13% decrease) in the four animals tested in the low-dose group, and 55 +/- 8 to 22 +/- 3 ml/100 gm/min (60% +/- 4% decrease) in the four animals tested in the high-dose group.
 In summary, the cerebral oxygen extraction fraction increased in the control animals and low-dose recipients during hypotension, suggesting the presence of threatened cerebral tissue.
 In contrast, the cerebral oxygen extraction did not change during hypotension when high-dose etomidate was administered.
 It is concluded that high-dose etomidate may preserve the cerebral metabolic state during hypotension in the present model.
",13
2247,"Myocardial metabolism of fluorodeoxyglucose compared to cell membrane integrity for the potassium analogue rubidium-82 for assessing infarct size in man by PET 
 Potassium loss from damaged myocardial cells is linearly related to CPK enzyme loss reflecting extent of necrosis.
 The potassium analog, rubidium-82 (82Rb), is extracted after i.v.
 injection and retained in viable myocardium but is not trapped or washed out of necrotic regions.
 To compare myocardial cell metabolism with membrane dysfunction as indicators of necrosis/viability, 43 patients with evolving myocardial infarction and coronary arteriography had positron emission tomography using fluorodeoxyglucose (FDG) and the potassium analog 82Rb.
 Percent of heart showing FDG defects and 82Rb washout on sequential images indicating failure to retain the potassium analogue were visually assessed and quantified by automated software.
 Infarct size based on rubidium kinetics correlated closely with size and location on FDG images (visual r = 0.93, automated r = 0.82), suggesting that loss of cell membrane integrity for trapping the potassium analog 82Rb parallels loss of intracellular glucose metabolism, both comparable quantitative markers of myocardial necrosis/viability.
",13
2248,"Clinical validation of a miniature nuclear probe system for continuous on-line monitoring of cardiac function and ST-segment 
 A new, miniature cesium iodide/photodiode nuclear probe (the ""Cardioscint"") has been developed for continuous on-line measurement of left ventricular function and the ST-segment.
 Ejection fraction (EF) measurements in 77 patients were compared with gated equilibrium radionuclide ventriculograms.
 The probe was positioned over the left ventricle by first using a blind positioning algorithm and then by using the gamma camera.
 Background was measured both manually and automatically.
 There was good correlation between probe (positioned blind) and gamma camera EF with both manual (r = 0.80, n = 65) and automatic (r = 0.78, n = 66) backgrounds.
 Use of the gamma camera did not significantly alter the results.
 Correlation between the probe stroke counts and thermodilution-derived stroke index during atrial pacing in six subjects was also satisfactory (r = 0.69, n = 102).
 Thus, the Cardioscint is able to provide a reliable estimate of EF and can track rapid changes in cardiac volumes.
",13
2249,"UK-68,798: a novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells.
 UK-68,798 increased the duration and effective refractory period of cardiac action potentials recorded in vitro from canine ventricular muscle and Purkinje fibers in a concentration dependent manner from 5 nM to 1 microM.
 The resting membrane potential, amplitude and maximum upstroke velocity of action potentials were unaffected by UK-68,798, indicating the selective class III antiarrhythmic properties of this agent.
 UK-68,798 (5 nM-1 microM) increased the effective refractory period of isolated guinea pig papillary muscles at stimulation frequencies of 1 Hz and 5 Hz without influencing the conduction velocity, further confirming that UK-68,798 is devoid of class I antiarrhythmic activity including block of the sodium channel.
 Studies using single voltage clamped guinea pig ventricular myocytes indicated that UK-68,798 at concentrations of 50 nM and 2 microM blocks a time-dependent K+ current, with no appreciable effects on the time-independent K+ current or the inward calcium current.
 UK-68,798 is therefore a highly selective K+ channel blocking agent with class III antiarrhythmic properties, a profile that holds considerable promise for the therapy of life-threatening cardiac arrhythmias.
",13
2250,"Characterization of LY233569 on 5-lipoxygenase and reperfusion injury of ischemic myocardium.
 LY233569 produced concentration-dependent inhibition of isolated guinea pig 5-lipoxygenase (5-LPO) and 5-LPO activity of human polymorphonuclear leukocytes in vitro; IC50 values were 0.4 and 0.1 microM, respectively.
 LY233569 also inhibited (IC50 approximately 1.8 microM) zymosan-stimulated production of leukotriene B4 in canine whole blood but had little or no concomitant effect on the production of thromboxane B2.
 Concentrations of LY233569 as high as 10 microM did not inhibit production or scavenge superoxide from activated human neutrophils.
 In normal anesthetized dogs, infusion of LY233569 (0.11 mg/kg/min, i.v.) for 6 hr produced persistent inhibition (approximately 80%) of leukotriene B4 production in blood challenged ex vivo with zymosan; the plasma concentration (approximately 4 microM) of LY233569 was consistent with in vitro data illustrating selective and maximal inhibition of 5-LPO.
 In subsequent experiments, myocardial infarct size was measured after 1 hr of occlusion of the circumflex coronary artery and 5 hr of reperfusion.
 Continuous infusion of LY233569 (0.11 mg/kg/min, i.v.) had little or no effect on base-line systolic arterial pressure, cardiac rate and the pressure rate product when compared with time-related changes observed in control dogs.
 LY233569 infusion also did not alter the degree of ST-segment deviation or the intensity and duration of cardiac arrhythmias associated with coronary artery occlusion and reperfusion.
 Resultant myocardial infarct sizes were 45 +/- 5% of the left ventricle placed at risk in control dogs and 43 +/- 4% in dogs given LY233569.
 Myeloperoxidase activity of infarcted myocardium did not differ between groups.
",13
2251,"Interaction of citrus juices with felodipine and nifedipine 
 Six men with borderline hypertension took felodipine 5 mg with water, grapefruit juice, or orange juice.
 The mean felodipine bioavailability with grapefruit juice was 284 (range 164-469)% of that with water.
 The dehydrofelodipine/felodipine AUC ratio was lower, diastolic blood pressure lower, and heart rate higher with grapefruit juice than with water.
 Vasodilatation-related side-effects were more frequent.
 Orange juice had no such effects.
 Six healthy men took nifedipine 10 mg with water or grapefruit juice; the bioavailability with grapefruit juice was 134 (108-169)% of that with water.
",13
2252,"The effect of lateral tilt on maternal and fetal hemodynamic variables.
 We measured maternal blood pressure and heart rate, fetal heart rate, and umbilical artery velocity waveforms in 25 healthy women placed in the supine and in both right and left 5 degrees and 10 degrees lateral tilt positions.
 Although we found no significant difference among these variables in the various maternal positions, two of 25 women became hypotensive and symptomatic in the supine and 5 degrees tilt positions.
 Because we could not predict which women would become symptomatic, we recommend lateral tilt of all pregnant women during operative procedures beyond 20 weeks' gestation, including those in the lithotomy position for vaginal delivery.
",13
2253,"Fluosol: an oxygen-delivery fluid for use in percutaneous transluminal coronary angioplasty.
 Fluosol (20% intravascular perfluorochemical emulsion) is an oxygen-carrying emulsion used to deliver oxygen to ischemic myocardium during percutaneous transluminal coronary angioplasty (PTCA).
 Fluosol is composed of two perfluorochemicals, perfluorodecalin and perfluorotripropylamine.
 It has a high capacity for oxygen solubility, a low viscosity, and a small particle size.
 Following administration, the perfluorochemicals in fluosol are not metabolized.
 Rather, most are expired as gaseous particles through the lungs; the remainder are taken up by the organs of the reticuloendothelial system and later expired.
 When administered during balloon inflation in PTCA, fluosol preserves ventricular wall motion and global left ventricular ejection fraction.
 In addition, it minimizes ST segment changes and preserves cardiac output.
 Fluosol may be especially useful in patients who have poor contractile reserve, multivessel disease, or serious underlying illness.
 Other uses under investigation include limitation of myocardial infarct size and chemosensitization or radiosensitization of malignant tumors.
 Adverse effects secondary to the use of fluosol include ventricular arrhythmias, pruritus, bradycardia, chest pain, dyspnea, and increased respiratory rate.
 Fluosol must be thawed, admixed, warmed to body temperature, and oxygenated prior to intracoronary administration.
 The usual administration rate is 60 mL/min during each balloon inflation.
",13
2254,"Improving compliance and increasing control of hypertension: needs of special hypertensive populations.
 Approximately 60 million people in the United States have hypertension.
 More than half are either untreated or treated without blood pressure control, despite the well-known risks of hypertension and the established benefits of treatment.
 The major reason for inadequate control of hypertension is poor adherence to treatment.
 Approximately 50% of patients with hypertension fail to keep follow-up appointments, and only 60% take their medications as prescribed.
 Barriers to effective therapeutic adherence include poor doctor-patient communication, cost of antihypertensive therapy, and side effects of the drugs.
 To increase control of hypertension, compliance with therapy must be improved.
 Physicians and patients must be mutually committed to achieving control of blood pressure.
 Physicians should communicate instructions clearly and prescribe therapies that are effective, affordable, and have minimal or no adverse effects on patient quality of life or overall cardiac risk profile.
 The needs of special hypertensive populations (i.e., elderly, black, and young patients) must also be recognized and addressed.
 Patients must follow recommendations and alert their physicians to any problems with their medications--particularly those relating to side effects and cost.
 When selecting drug therapy it should be noted that older patients are sensitive to volume depletion and sympathetic inhibition.
 In this group of patients, initial drug doses should be low and increments smaller and more gradual than in younger patients.
 Black patients with hypertension show an accentuated response to diuretics and blunted responses to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors as monotherapy.
 However, when used with a diuretic, there are no racial differences in the blood pressure lowering effects of beta-blockers and ACE inhibitors.
",13
2255,"Preclinical pharmacology of celiprolol: a cardioselective beta-adrenergic antagonist and mild vasodilator.
 Celiprolol is a new antihypertensive agent that represents a new generation of beta-blockers.
 It combines cardioselective beta-adrenergic antagonism (beta 1) with a mild vasodilation via vasoselective beta-adrenergic agonism (beta 2).
 Results of animal studies show that celiprolol has beta 1-antagonist potency similar to that of propranolol and atenolol, and cardioselectivity slightly greater than that of atenolol.
 Celiprolol does not produce bronchoconstriction but has mild propranolol-resistant bronchodilatory properties in cats.
 The compound also relaxes vascular smooth muscle in a propranolol-sensitive fashion, suggesting a mechanism of beta 2-agonism.
 The beta 2-agonism results in a selective downregulation in beta 2-receptor number and response in tissue culture, as well as in peripheral tissue from celiprolol-treated volunteers.
 The decreases in beta 2-receptors are blocked by concomitant treatment with propranolol.
 Celiprolol is devoid of cardiac depressant activity and in fact has mild cardiostimulatory actions.
 The cardiostimulation is not via beta 1-stimulation, since it is not abolished by beta-blocking doses of propranolol.
 In a model of severe myocardial ischemia, celiprolol attenuates the ischemia-induced myocardial acidosis and improves the regional segment function.
 These results are suggestive of myocardial protection.
 In summary, celiprolol distinguishes itself from other beta-blockers by virtue of its cardioselectivity, vasorelaxation via beta 2-agonism, and the lack of bronchoconstriction and cardiodepression.
 These properties observed in animal studies have also been documented in clinical trials.
",13
2256,"Clinical safety and efficacy of celiprolol.
 The management of essential hypertension requires therapeutic selections that are not only effective in reducing diastolic blood pressure but are also tailored to the individual patient, with minimal effect on patient demographics, concurrent illnesses, and cardiovascular risk factors.
 Celiprolol hydrochloride is a new highly cardioselective vasodilating beta-adrenoceptor antagonist that has been proven effective and safe for the treatment of essential hypertension.
 It is comparable to other therapies in blood pressure control while demonstrating an excellent safety profile, favorable hemodynamic activity, and minimal effects on other cardiovascular risk factors.
 Celiprolol may offer the physician a unique therapeutic alternative.
",13
2257,"Metabolic considerations in the choice of therapy for the patient with hypertension.
 The objective of treating patients with hypertension is not simply to reduce blood pressure but rather to prevent the associated morbidity and mortality.
 Recent assessments of clinical trials have shown that while the risk of stroke is consistently lower with antihypertensive therapy, the same degree of success has not been demonstrated for coronary artery disease (CAD).
 Although there are many explanations of why we have not done as well in preventing CAD, one possibility is that the therapy used in clinical trials, primarily thiazide diuretics and beta-adrenoreceptor blockers, has increased the patient's risk of developing coronary atherosclerosis or lethal arrhythmias.
 Four classes of antihypertensive agents are recommended for initial therapy--thiazide diuretics, beta-adrenoreceptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium entry blockers.
 The metabolic effects of thiazide diuretics include electrolyte disturbances (hypokalemia, hypomagnesemia, and hyponatremia), dyslipidemia (increased triglycerides), abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance), and hyperuricemia.
 beta-Adrenoreceptor blockers have many of the same metabolic adverse reactions.
 beta-Adrenoreceptor blockers without intrinsic sympathomimetic activity (ISA) also cause dyslipidemias (lowered high-density lipoprotein cholesterol and increased triglycerides) and abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance).
 beta-Adrenoreceptor blockers with ISA and third-generation beta-blockers with selective partial agonist activity (celiprolol and dilevalol) do not cause dyslipidemia and to date do not appear to induce abnormalities in glucose metabolism.
 ACE inhibitors may decrease triglycerides and increase high-density lipoprotein cholesterol, and captopril may improve insulin sensitivity.
 Calcium entry blockers are metabolically neutral.
",13
2258,"Correlation of isomeric fatty acids in human adipose tissue with clinical risk factors for cardiovascular disease.
 The relationships between the adipose tissue concentrations of 19 geometric and positional fatty acid isomers and 10 cardiovascular disease risk factors were determined in 76 free-living adult males.
 The percentages for trans isomers (total mean +/- SD 4.14 +/- 0.97%) and cis isomers (total mean +/- SD 2.91 +/- 0.34%) in adipose tissue generally agreed with dietary estimates based on the consumption of hydrogenated oils.
 A major exception was the percentage of 11c-18:1, which was twofold higher in adipose tissue.
 The total level of fatty acid isomers in adipose tissue or a factor (derived by factor analysis) that was representative of isomers of dietary origin was not significantly correlated with the cardiovascular risk factors.
 Only three trans isomers (11t-18:1, 12t-18:1, and 5t-14:1) and three cis isomers (11c-18:1, 13c-18:1, and 7c-16:1) were weakly correlated either positively or negatively with age, body mass index, plasma and lipoprotein cholesterol, and/or blood pressure (P less than 0.05, r greater than 0.231).
",13
2259,"Blood pressure lowering in elderly subjects: a double-blind crossover study of omega-3 and omega-6 fatty acids.
 In 46 elderly (aged greater than or equal to 60 y) hypertensive subjects with entry systolic blood pressure (SBP) greater than or equal to 160 or diastolic blood pressure (DBP) greater than or equal to 90 mm Hg, our specific aim in a randomized, double-blind, crossover study (two 8-wk treatment periods separated by a 3-wk washout) was to compare blood pressure-lowering effects of 9 g fish oil/d [omega-3 (n-3) fatty acid] vs 9 g corn oil/d [omega-6 (n-6) fatty acid].
 After a 4-wk baseline period, 22 subjects were randomly assigned to receive fish oil and 24 to receive corn oil.
 For both 8-wk treatments there were no between-group differences in the change in blood pressure.
 There was a treatment difference for standing DBP when baseline values were compared with those after treatment 2; DBP decreased by 5.1 mm Hg in the fish-oil group vs 0.72 mm Hg in the corn-oil group (P = 0.024).
 Within groups during the first treatment, both fish oil and corn oil lowered all four blood pressure measures (P less than 0.05); blood pressures were not further lowered during the second treatment compared with the washout period.
 There were no significant between-group differences in laboratory safety tests or categorical side effects.
 Fish oil lowered triglycerides by 0.47 mmol/L (P less than 0.001).
 In elderly subjects, diet plus both omega-3 and omega-6 supplements (9 g/d) safely and effectively lower SBP and DBP.
",13
2260,"When do cerebral emboli appear during open heart operations? A transcranial Doppler study.
 The transcranial Doppler technique enabled the detection of cerebral air emboli in 10 of 10 patients during open-heart valve operations despite standard deairing procedures.
 With this technique, the occurrence of emboli in the right middle cerebral artery was followed continuously in patients undergoing aortic or mitral valve replacement.
 Membrane oxygenators were used.
 Scattered emboli were observed during the insertion of the aortic cannula, at the start of cardiopulmonary bypass, and after the declamping of the aorta with the heart beating while empty.
 During the period of aortic cross-clamping, no emboli were detected.
 Despite careful deairing procedures, the recordings indicated a large amount of emboli during filling of the empty beating heart in all 10 patients.
 Thus, this study indicates that cerebral emboli in open heart procedures are most likely to occur during the redistribution of blood from the heart-lung machine to the patient when the heart is beginning to eject actively, despite careful standard deairing procedures.
 Meticulous deairing before declamping the aorta is strongly advocated.
 In addition, a short period of filling of the beating heart before final closure of the aortic incision or vent may decrease the incidence of cerebral emboli.
 A concomitant reduction in cerebral blood flow by hyperventilation or anesthetics or both during filling of the empty beating heart may also be beneficial.
",13
2261,"Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection 
 This report presents the results in our first clinical series of patients receiving continuous warm blood cardioplegia through the coronary sinus.
 Warm oxygenated blood cardioplegia has certain theoretical advantages, such as continuously supplying oxygen and substrates to the arrested heart while avoiding the side effects of hypothermia.
 Retrograde infusion of cardioplegia also offers certain advantages (eg, in valve operations and in patients with severe coronary artery disease) that are complementary to warm blood cardioplegia.
 Retrograde warm blood cardioplegia was used in 113 consecutive patients (85 men and 28 women with a mean age of 61 years) undergoing various procedures.
 Three percent of the patients died, 7% needed transient intraaortic balloon pump support, 6% had evidence of perioperative myocardial infarction, and 96% had spontaneous return of rhythm.
 There were no coronary sinus injuries.
 This new technique of retrograde continuous warm blood cardioplegia is a simple, safe, and reliable method of myocardial protection that may change the way we currently protect the heart intraoperatively.
",13
2262,"Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a cardiac operation: effects on myocardial metabolism.
 Myocardial insulin resistance, in association with surgical stress, restricts the availability of carbohydrates and increases the load of free fatty acids (FFAs) on the heart.
 On theoretical grounds adrenergic drugs may be expected to aggravate this situation, whereas the opposite is expected from insulin.
 The influence of dopamine and a combination of dopamine (7 micrograms/kg body weight/min) and high-dose insulin (7 IU/kg) on myocardial energy metabolism was studied in 19 patients 4 to 6 hours after a coronary operation.
 Infusion of dopamine (7 micrograms/kg body weight/min) induced metabolic changes that may be unfavorable to the strained myocardium.
 There was an increase of the myocardial FFA load and a rise in myocardial oxygen expenditure by 60% to 70%.
 There changes were, however, not matched by an increase in myocardial substrate uptake.
 ""Oxygen wastage"" of FFA metabolism at high circulating catecholamine levels is suggested.
 There were also signs suggesting an amplified systemic trauma response: systemic oxygen consumption increased by 15%, and an increase in the arterial levels of FFAs, glucose, and ketones was observed.
 Divergent metabolic effects of dopamine and insulin were demonstrated.
 The most prominent metabolic effects of adding high-dose insulin to dopamine were a marked reduction of arterial FFA levels and a shift toward myocardial carbohydrate utilization at the expense of FFAs.
 Myocardial uptake of FFAs ceased.
 Myocardial insulin resistance may thus to a significant extent be overcome by supraphysiological doses of insulin, even during infusion of adrenergic drugs.
",13
2263,"Transesophageal echocardiography in acute aortic transection.
 Confirming the diagnosis of acute transection of the descending aorta can be problematic.
 Unnecessary patient movement and time delay are often associated with conventional investigations.
 We describe a patient in whom such an injury was clearly and quickly defined at the bedside by transesophageal echocardiography.
",13
2264,"Apical aortic cannulation: application of an old method with new paraphernalia.
 An instrument assembly consisting of a special aortic cross-clamp and double-lumen perfusion cannula is presented.
 The application of these instruments allows occlusion of the ascending aorta traversed by the perfusion cannula inserted directly or through the apex of the heart as well as simultaneous left ventricular venting.
",13
2265,"Popliteal aneurysms identified by intra-arterial streptokinase: a changing pattern of presentation.
 Five patients presenting with chronic or subacute leg ischaemia due to thrombosed popliteal artery aneurysm are described.
 Only one of these aneurysms was diagnosed before intra-arterial streptokinase infusion, which successfully lysed the thrombus in all cases.
 One aneurysm had been symptomatic for 5 years and another for 2 years.
 Popliteal aneurysm may well be underdiagnosed as a cause of chronic leg ischaemia.
",13
2266,"Influence of low osmolality contrast media on electrophysiology and hemodynamics in coronary angiography: differences between an ionic (ioxaglate) and a nonionic (iohexol) agent.
 It has recently been suggested that the addition of sodium to low osmolality contrast media may reduce the incidence of ventricular fibrillation and conduction disturbances during coronary angiography.
 In a randomized, double blind study of 30 patients undergoing coronary angiography we therefore examined the electrophysiological and hemodynamic effects of the two low osmolality contrast media-ioxaglate (with sodium) and iohexol (without sodium).
 Standard ECG, aortic blood pressure, and His bundle electrocardiogram were recorded.
 The contrast media were well tolerated and no serious arrhythmias were observed.
 Both induced a transient decrement in systolic blood pressure and reduction in heart rate 10 s following contrast injection (all P less than 0.01).
 Ioxaglate prolonged the QT interval at 10 s (P less than 0.01) and also when analysed for the whole observation period (120 s) (P less than 0.05), whereas iohexol did not cause any significant changes in the QT-interval.
 The AH-interval was prolonged by ioxaglate at 10 s (P less than 0.01), but not altered by iohexol.
 Thus, other factors than osmolality and sodium content might contribute to QT prolongation, since only the contrast agents with sodium (ioxaglate) induced QT prolongation in this study.
",13
2267,"Precertification for percutaneous transluminal coronary angioplasty in Medicare beneficiaries: a melting pot or a need for better national standards?
 The Health Care Financing Administration has contracted with state peer review organizations (PROs) in its effort to assure the quality of services and eliminate unreasonable and inappropriate care provided Medicare beneficiaries.
 By law, each state PRO must select 10 procedures for precertification.
 Coronary angioplasty has been chosen by 45 PROs for precertification and criteria in each state were developed with the advice of local physicians.
 This report describes the findings of a survey of these precertification criteria in an effort to determine their variability and to compare the PRO criteria to published national criteria created by expert panels.
 Current precertification criteria of Medicare beneficiaries show significant variability in the priorities and the clinical practice of cardiologists in performing coronary angioplasty, despite established and published guidelines for its safe and efficacious use.
 It is likely that the establishment of locally based criteria for coronary angioplasty will be geographically uneven and probably have a less than expected impact on the care provided to Medicare beneficiaries.
",13
2268,"Rib compression of the coronary arteries.
 This report describes the finding of coronary artery narrowing caused by compression by an overlying rib in two patients with cardiomegaly.
 There is probably no clinical significance to this finding.
 The primary differential diagnostic entity is myocardial bridging.
",13
2269,"Coronary stent implantation in acute vessel closure 48 hours after an unsatisfactory coronary angioplasty.
 We report the implantation of a balloon-expandable stent in a patient with acute vessel closure in the state of evolving myocardial infarction following 48 hr after unsatisfactory coronary angioplasty.
 The stent was implanted after successful recanalization of an occluded left anterior descending artery, with repeated unsatisfactory results of balloon angioplasty.
 Adjunct thrombolytic therapy was contraindicated.
 No residual stenosis was documented in immediate control angiograms, or after 24 hr, 3 weeks, and 4 months.
",13
2270,"Implantation of an endoluminal prosthesis at the distal anastomosis of a bypass graft for abrupt closure following balloon angioplasty.
 A coronary Wallstent was implanted in a 10-year-old saphenous vein bypass graft following a PTCA that was complicated by abrupt closure.
 Anterograde flow was restored and no myocardial necrosis resulted.
 One week later, bypass surgery was performed due to a bleeding complication associated with the anticoagulation regimen.
",13
2271,"Alfentanil pharmacokinetics in patients undergoing abdominal aortic surgery.
 The pharmacokinetics of alfentanil, 300 micrograms.kg-1 IV, were determined in patients undergoing elective abdominal aortic reconstruction.
 The mean age (+/- SD) of the patients was 64.3 +/- 7.4 yr; their mean weight was 74.7 +/- 13.8 kg.
 Five patients underwent aneurysm repair and six had aortobifemoral grafting.
 Serum alfentanil concentrations were measured by gas-liquid chromatography in samples drawn at increasing intervals over a 24-hr period.
 A three-compartment model was fitted to the concentration versus time data.
 The volume of the central compartment and the volume of distribution at steady state (Vdss) were 0.44 +/- 0.022 and 0.63 +/- 0.32 L.kg-1, respectively.
 Total drug clearance was 6.4 = 1.9 ml.min-1.kg-1.
 The elimination half-time was 3.7 +/- 2.6 hr.
 Patient age was positively correlated with both Vdss and elimination half-time.
 There were no significant correlations between the pharmacokinetic variables and the duration of aortic cross-clamping, the duration of surgery, or the rate or total volume of IV fluids infused intraoperatively.
 In general surgical patients, the elimination half-time of alfentanil has been reported to be 1.2-2.0 hr.
 Although the elimination half-time of alfentanil was longer in patients undergoing abdominal aortic surgery, alfentanil was eliminated much faster than either fentanyl or sufentanil in this patient population.
",13
2272,"Transoesophageal echocardiogram may fail to diagnose perioperative myocardial infarction.
 We report a case in which a 55-yr-old man undergoing aortocoronary bypass was monitored with electrocardiogram and transoesophageal echocardiogram.
 Intraoperative electrocardiogram and simultaneous ECG recordings using the Holter monitor showed an ST elevation of greater than 2 mm and new Q wave formation in leads AVF and V5 during skin closure.
 However, the transoesophageal echocardiogram showed no wall motion abnormalities.
 No significant haemodynamic abnormalities were observed during the period of intraoperative ECG changes.
 He was treated with nitroglycerin infusion.
 Confirmation of a perioperative myocardial infarct was documented by postoperative 12-lead ECG and CPK-MB.
 A post-operative transthoracic echocardiogram showed a hypokinetic left ventricle with an anteroapical infarct.
 Thus transoesophageal echocardiography failed to detect an apical wall motion abnormality when the probe was placed at the midpapillary level.
 This limitation can be overcome by periodically obtaining apical views or by using probes with more than one imaging plane.
",13
2273,"Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion.
 BACKGROUND AND METHODS: The purpose of this study was to determine the effects of nitric oxide (NO), believed to be endothelium-derived relaxing factor on reperfusion injury after myocardial ischemia (MI).
 The effects of NO were investigated in a 6-hr model of MI with reperfusion in open-chest, anesthetized cats.
 A solution containing NO was infused iv starting 30 min after occlusion of the left anterior descending coronary artery, continuing through reperfusion 1 hr later, and lasting for 5.5 hr.
 Estimated NO concentration in the circulation was 1 to 2 x 10(-9) M.
 RESULTS: The areas-at-risk expressed as a percentage of the total left ventricular weights were not significantly different among either of the MI groups.
 However, the necrotic area (expressed as a percentage of the myocardial area-at-risk) was significantly (p less than .01) lower in the NO-treated MI cats compared with the MI + vehicle group.
 Cardiac myeloperoxidase activities indicated that significantly (p less than .05) fewer neutrophils were attracted to the necrotic zone of the NO-treated MI cats when compared with MI cats receiving only the vehicle.
 Sodium nitrate (NaNO2) (pH 7.4), a major breakdown product of NO, failed to exert any protective effect in this same model of MI and reperfusion.
 CONCLUSIONS: NO appears to provide significant myocardial protection after ischemia and reperfusion.
 NO may afford cardioprotection by incorporation into circulating blood cells (i.e., neutrophils, platelets), thereby inhibiting their accumulation and adherence in the ischemic region, or by a direct cardiac cytoprotective effect.
 Further studies using NO donors rather than NO would be an appropriate clinically relevant mode of treatment in MI.
",13
2274,"Pulmonary function and cardiovascular risk factor relationships in black and in white young men and women. The CARDIA Study 
 Pulmonary function is known to be related inversely to incidence of coronary heart disease, congestive heart failure, chronic obstructive lung disease, lung cancer, and death from all causes.
 Reasons for some of these associations are poorly understood.
 Relationships between cardiovascular disease risk factors and pulmonary function were examined in 5,115 18- to 30-year-old black and white male and female participants in the study of Coronary Artery Risk Development in Young Adults (CARDIA).
 Forced expiratory volume in 1 s adjusted for height (FEV1/Ht2) was significantly lower in smokers than nonsmokers and in persons who reported shortness of breath; FEV1/Ht2 was correlated positively with a history of strenuous physical activity, duration of exercise on the treadmill, and high-density lipoprotein cholesterol.
 It was associated negatively with skinfold thicknesses, serum triglycerides, fasting serum insulin, and the Cook Medley scale of hostility.
 The association between pulmonary function and heart disease risk may reflect associations with physical fitness, vigor, fatness, and lipid profiles, as well as with cigarette smoking.
",13
2275,"Ischemia and reperfusion during intermittent coronary occlusion in man. Studies of electrocardiographic changes and CPK release.
 The course of 357 balloon inflations performed during 38 angioplasties for single-vessel coronary artery disease was prospectively studied using continuous ECG recording.
 Ischemic ECG changes appeared during 91 percent of the inflations at a mean of 20 +/- 8 seconds after inflation and resolved in 97 percent of those at a mean of 11 +/- 5 seconds after deflation.
 Elevation of the plasma CPK level was found in six patients who had ischemic ECG changes for at least 7.8 minutes.
 The duration of ischemia did not exceed 5.4 minutes in any of the patients without CPK elevation.
 Resolution of the ischemic changes was delayed in patients with CPK elevation and in last vs initial inflations.
 We conclude that in patients with noninfarcted myocardium, ECG changes follow coronary occlusion and reflow very rapidly, detecting these coronary events with a high sensitivity.
 Lack of rapid regression predicts lack of reperfusion, and persistence of ischemia for more than 7.8 minutes is sufficient to cause myocardial necrosis.
",13
2276,"Regression of the left main trunk lesion by steroid administration in Takayasu's aortitis.
 A 62-year-old man with unstable angina due to severe narrowing of the left main trunk (LMT) was examined.
 Emergency bypass surgery was performed with an internal mammary artery graft, instead of a saphenous vein graft, because of the thickened, edematous ascending aorta.
 Postoperative coronary angiography showed the lesion of the LMT markedly regressing.
 Presumably, this stenotic lesion of the LMT was caused by active aortitis and was partially reversible by steroid administration both during and after surgery.
 Steroid therapy can be added to the list of treatments for cases of LMT disease associated with Takayasu's aortitis, if signs of active inflammation are present.
",13
2277,"Monitoring the effect of CPAP on left ventricular function using continuous mixed-blood saturation.
 The hypothetic benefit of CPAP on cardiac performance and on a reduction in VO2 was tested in a patient before heart transplantation after acute myocardial infarction using continuous SvO2 monitoring.
 The CPAP added to inotropic support (enoximone plus dobutamine) and intraaortic balloon pumping dramatically increased SvO2 in relation to both an increase in cardiac output and a decrease in VO2 secondary to respiratory work reduction, validating the initial hypotheses.
",13
2278,"Pseudo pre-excitation with concertina effect in idioventricular tachycardia.
 The concertina effect is a phenomenon where the QRS complexes reflect alternating phases of gradual widening and narrowing.
 This is most commonly due to ventricular pre-excitation, and the changes in QRS morphology are due to variability of the ventricular zone that undergoes pre-excitation.
 This presentation reflects a case where the concertina effect is due to an idioventricular tachycardia at a rate nearly identical to the sinus rate.
 Variable degrees of ventricular fusion therefore occur, and the concertina effect ensues, in relation to slight variations of the sinus cycle.
",13
2279,"Traumatic and spontaneous extracranial internal carotid artery dissections.
 Seventy patients with spontaneous and 21 with traumatic extracranial internal carotid artery dissections were studied clinically and angiographically with mean follow-ups of 64 (spontaneous group) and 40 months (traumatic group).
 Sixty percent of the patients in the spontaneous group and 71% in the traumatic group also had follow-up angiograms.
 In traumatic dissections aneurysms were common, significantly fewer aneurysms resolved or became smaller and fewer stenoses resolved or improved, whereas more stenoses progressed to occlusion.
 Traumatic dissections were more likely to leave the patients with neurological deficits.
 A significantly higher percentage of the patients with spontaneous dissections were asymptomatic at follow-up compared with the traumatic group.
 Although both spontaneous and traumatic dissections of extracranial internal carotid arteries mostly carry a good prognosis, the outcome may be somewhat less favorable for the traumatic group.
",13
2280,"Prospective randomized multicenter comparison of in situ and reversed vein infrapopliteal bypasses.
 We have performed a prospective, randomized, multicenter study to compare in situ and reversed vein grafts for long limb salvage bypasses from the proximal thigh to an infrapopliteal artery.
 Three hundred eighty-four patients required an infrapopliteal bypass for critical lower extremity ischemia.
 Of these, 259 were excluded because a short vein bypass was performed or because the vein was considered inadequate.
 The remaining 125 patients had a randomized vein bypass, 63 reversed, 62 in situ.
 The two groups were similar with regard to risk factors, indications, graft dimensions, and outflow.
 Secondary patency at 30 months was similar for both techniques: reversed 67% +/- 9% (+/- SE); in situ 69% +/- 8%.
 For veins less than or equal to 3.0 mm in minimum distended diameter 24-month patency rates were 61% +/- 22% for 12 in situ veins and 37% +/- 29% for 10 reversed veins (p greater than 0.05).
 Angiographic evaluation of failing grafts revealed lesions similar in type and frequency in both types of grafts.
 These included focal (in situ, n = 4; reversed, n = 7) and diffuse vein hyperplasia (in situ, n = 2; reversed, n = 1), and inflow and outflow stenoses (in situ, n = 4; reversed, n = 3).
 The incidence of wound complications and the mortality rate were similar for the two groups.
 These data show no significant difference in overall patency rates for the two types of vein grafts at 2 1/2 years.
",13
2281,"Ruptured abdominal aortic aneurysm: the Harborview experience.
 During the last decade (1980 to 1989) 186 patients with ruptured abdominal aortic aneurysm were admitted to a single urban hospital.
 Ninety-six percent of these patients had a prehospital systolic blood pressure less than 90 mm Hg.
 Management included paramedic field resuscitation and transport, an emergency department diagnostic protocol completed in an average of 12 minutes, rapid transport to a dedicated emergency operating room, aneurysmorrhaphy by general surgery chief residents under the supervision of specialist vascular surgeons, and skilled postoperative intensive care unit care.
 Nevertheless, 130 (70%) patients died in the first 30 postoperative days--3% in the emergency department, 13% in the operating room, 51% in the intensive care unit, and 3% on the ward or at home.
 Certain features--age greater than 80 years, female gender, persistent preoperative hypotension despite aggressive crystalloid and blood replacement, admission hematocrit less than 25, transfusion requirements exceeding 15 units--were associated with a greater than 90% likelihood of death.
 No patient with preoperative cardiac arrest survived more than 24 hours.
 From this experience we conclude that, although ""optimal"" prehospital, emergency department, operating room, and postoperative care can improve the outcome of patients with ruptured abdominal aortic aneurysms in shock, most such patients will die.
 Certain clinical features predict such excessive mortality rates after ruptured abdominal aortic aneurysms that withholding operation may be reasonable.
 Screening of patients at high risk for abdominal aortic aneurysm, followed by elective aneurysmorrhaphy, is clearly indicated.
",13
2282,"Probability of rupture of an abdominal aortic aneurysm after an unrelated operative procedure: a prospective study.
 It has been assumed by some authors that patients with abdominal aortic aneurysms may be at increased risk of rupture after unrelated operations.
 From July 1986 to December 1989, 33 patients (29 men, 4 women) with a known abdominal aortic aneurysm underwent 45 operations.
 Twenty-eight patients had an infrarenal abdominal aortic aneurysm, and five patients had a thoracoabdominal aneurysm.
 The abdominal aortic aneurysm ranged in transverse diameter from 3.0 to 8.5 cm (average 5.6 cm).
 Twenty-seven patients underwent a single operation, and six patients had two or more (range of 1 to 6).
 Operations performed were abdominal (13); cardiothoracic (9); head/neck (2); other vascular (11); urologic (7); amputation (2); breast (1).
 General anesthesia was used in 29 procedures, spinal/epidural in 6, and regional/local in 10.
 One postoperative death occurred from cardiopulmonary failure.
 One patient died of a ruptured abdominal aortic aneurysm at 20 days after coronary artery bypass (1/33 patients [3%]; 1/45 operations [2%]).
 Fourteen patients had repair of their abdominal aortic aneurysm at a later date, an average of 18 weeks after operation.
 Four patients had abdominal aortic aneurysm considered too small to warrant resection (average 3.6 cm).
 Four patients were considered at excessive risk for elective repair.
 The five thoracoabdominal aneurysm were not repaired.
 Four patients are awaiting repair.
 During this same 40-month period, two other patients, not known to have an abdominal aortic aneurysm, died of a ruptured abdominal aortic aneurysm after another operative procedure, at 21 days and 77 days.
 All three ruptured abdominal aortic aneurysms were 5.0 cm or greater in transverse diameter.
",13
2283,"The accuracy of CT scanning in the diagnosis of abdominal and thoracoabdominal aortic aneurysms.
 As CT scanning has evolved as a reliable clinical tool, the use of angiography in the diagnosis of aortic aneurysmal disease has diminished.
 Fewer than 25% of patients with aortic aneurysmal disease undergo aortic angiographic evaluation at our institution.
 A prospective clinical study was undertaken to assess the validity of this policy.
 One hundred patients with clinical or ultrasonographic evidence of aortic aneurysms were evaluated prospectively during the period July 1987 to December 1989.
 All patients underwent CT scanning as an initial evaluation.
 Patients were selected for angiography if they fulfilled any of the following criteria: radiographic evidence of thoracoabdominal or juxtarenal aneurysms, or horseshoe kidney; or clinical suggestion of renal artery stenosis, mesenteric arterial insufficiency, aortoiliac occlusive disease, or lower extremity aneurysmal disease.
 During this period 19 patients (19%) underwent both CT scanning and angiography.
 The indications for angiography were thoracoabdominal aneurysms (7), juxtarenal aneurysms (2), clinical evidence of mesenteric insufficiency (1) or renal insufficiency (2), evidence of lower extremity aneurysmal disease (3), or severe aortoiliac occlusive disease (4).
 Eighty-one patients (81%) underwent CT scanning as the only radiographic evaluation.
 No patient was adversely affected by elimination of angiographic evaluation.
 CT scanning revealed inflammatory aneurysms (4), retroaortic renal veins (2), and horseshoe kidney (1).
 This study suggests that most (81%) patients with aortic aneurysmal disease can be adequately evaluated by CT scanning, and that a very selective policy of angiographic evaluation is indicated.
",13
2284,"Lacunar transient ischaemic attacks: a clinically useful concept?
 Lacunar ischaemic stroke syndromes are clinically, pathophysiologically, and prognostically distinguishable from cortical ischaemic stroke syndromes.
 Could cerebrovascular transient ischaemic attacks (TIAs) share similar heterogeneity? 130 patients with TIAs were prospectively studied, 71 of whom underwent carotid angiography.
 Symptoms were associated with a 50% or greater stenosis of the ipsilateral internal carotid artery in 36 (67%) of 54 patients with presumed cortical TIAs, but in only 1 (6%) of 17 patients with presumed lacunar TIAs (p less than 0.0001).
 These findings support the view that cortical TIAs are associated with ipsilateral extracranial internal carotid artery atheromatous disease, whereas patients with lacunar TIAs may have absent or insignificant large-vessel disease, and probable intracranial small-vessel disease.
 Accurate distinction between lacunar and cortical events may have implications for investigation and treatment of patients with TIAs.
",13
2285,"Degenerative aortic stenosis. One effect of the graying of America.
 Degenerative calcific aortic stenosis is evolving as a common geriatric problem.
 Once symptoms develop, it is a highly lethal disease that does not respond well to medical therapy.
 Aortic balloon valvuloplasty may offer palliation but is unlikely to alter the overall course of the disease.
 Aortic valve replacement is the therapy of choice, but high perioperative morbidity and mortality rates can be expected in the very elderly.
 The presence of other appreciable cardiac disorders may contribute to the occurrence of postoperative complications.
 Patients with asymptomatic aortic stenosis and normal left ventricular function can be treated medically and followed with serial aortic valve area determinations using Doppler echocardiography.
",13
2286,"When is pulmonary artery catheterization worth the risks?
 Bedside pulmonary artery catheterization has proven to be an important addition to the clinical assessment of critically ill patients.
 Properly used, the procedure may provide hemodynamic information that is not apparent from physical examination or radiography.
 It may be safely accomplished through various venous routes, but care must be taken to avoid potential complications.
",13
2287,"Relationship between blood groups and behavior patterns in men who have had myocardial infarction.
 Consistent correlations have been found between physical dysfunctional states and blood factors.
 Some of these disorders have possible psychosomatic components (eg, duodenal ulcer, myocardial infarction).
 This study focused on the relationship between blood types and various indices of behavior patterns (eg, type A behavior scores, anger ratings) in young patients who had had an initial myocardial infarction.
 Patients with blood type O scored significantly higher on type A behavior scales and related indices than those having blood type A.
 Those with blood group B responded on several scales between those with types A and O.
 We discuss the utility of blood groupings in future research in the prediction of myocardial infarction, methodologic limitations, the relationship of these results to temperament studies, Jenkins Activity Survey subtest patterns, anti-H reactivity pattern, and hypotheses relating blood factors and behavioral traits in patients with psychosomatic disorders.
",13
2288,"Comparative clinical pharmacology of calcium channel blockers.
 Calcium channel blockers are effective antihypertensive agents, both as initial monotherapy and in combination with other antihypertensive agents.
 These drugs are also effective in the treatment of chronic, stable angina, variant angina and supraventricular arrhythmias.
 Drugs in this class have different affinities for calcium channels in vascular smooth muscle, cardiac muscle, cardiac sinus and atrioventricular node.
 They are all useful in hypertension and angina, but only verapamil and diltiazem are also useful in the control of heart rate and supraventricular arrhythmias.
 Nimodipine may control vascular spasm following subarachnoid hemorrhage.
 Calcium channel blockers have also been used in the treatment of migraine headache and Raynaud's phenomenon.
",13
2289,"Complete left main coronary artery occlusion: angiographic evaluation of collateral vessel patterns and assessment of hemodynamic correlates.
 An angiographic study of eight patients with total occlusion of the left main coronary artery identified six patients with chronic occlusion and two with acute complete occlusion.
 In each of six patients, there were two to six different intercoronary collateral pathways.
 Altogether, a total of 13 specific collateral channels were recognized.
 One patient had evidence of unique homocollaterals represented by enlarged vasa vasorum, which created a vascular cuff that surrounded a totally obstructed left main artery.
 The ventricular function and hemodynamic parameters in these patients not only depend on the collateral vessels but may also be affected by the severity of coronary artery disease in the artery that supplies collaterals.
",13
2290,"Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging: a new marker of triple-vessel disease.
 To investigate the significance and mechanism of dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging, we performed both dipyridamole thallium-201 imaging and dipyridamole radionuclide angiography on 83 patients with known angiograms.
 The dipyridamole/delayed ratio of the left ventricular dimension from the thallium-201 image was defined as the left ventricular dilatation ratio (LVDR).
 An LVDR greater than the mean + two standard deviations in patients without coronary artery disease was defined as abnormal.
 Twenty-two of 83 patients showed an abnormal LVDR, and 18 of the 22 patients (82%) had triple-vessel disease.
 By defect and washout analysis, the sensitivity and specificity for correctly identifying the patients as having triple-vessel disease was 72% and 76%, respectively, whereas LVDR had a sensitivity of 72% and a specificity of 93%.
 When LVDR was used in combination with the defect and washout criteria, sensitivity increased to 84% without a loss of specificity.
 In those 22 patients with abnormal LVDRs, end-diastolic volume measured by radionuclide angiography did not change after dipyridamole infusion.
 Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging reflected relative subendocardial hypoperfusion induced by dipyridamole rather than actual chamber enlargement.
 The LVDR was moderately sensitive and highly specific for triple-vessel disease and provided complementary information to dipyridamole thallium-201 imaging.
",13
2291,"Percutaneous balloon valvotomy for patients with mitral stenosis: initial and follow-up results.
 Percutaneous double balloon mitral valvotomy (PMV) was performed in 25 patients with severe mitral stenosis who were followed for at least 6 months after the procedure.
 There were 22 women and 3 men, with a mean age of 51 +/- 14 years (range, 27 to 74).
 Hemodynamic and angiographic findings were evaluated before and after PMV and clinical status was assessed at follow-up.
 There was a significant decrease in mitral gradient following PMV, from 15.4 +/- 5.1 to 5.0 +/- 2.6 mm Hg (p less than .0001); an increase in cardiac output, from 4.6 +/- 1.1 to 5.2 +/- 1.1 L/min (p less than .01); and an increase in calculated mitral valve area, from 0.9 +/- 0.2 to 2.2 +/- 0.6 cm2 (p less than 0.0001).
 Mitral regurgitation developed or increased in severity in six patients (24%).
 At the time of follow-up (mean, 12 +/- 5 months), three patients required elective mitral valve replacement for symptomatic mitral regurgitation and 91% (20 of 22) of the remaining patients had continued improvement in functional class.
 PMV can safely be performed in properly selected patients with symptomatic mitral stenosis with good immediate and follow-up results.
",13
2292,"Value and limitations of Doppler pressure half-time in quantifying mitral stenosis: a comparison with micromanometer catheter recordings.
 The purpose of this study was to compare the Doppler and catheterization pressure half-time methods of estimating mitral valve area with valve areas obtained by the Gorlin equation in a group of patients with clinically significant mitral stenosis.
 Data were analyzed from 67 consecutive patients who were undergoing continuous-wave Doppler examination and catheterization with micromanometer catheters.
 Doppler pressure half-time was calculated as the interval between peak transmitral velocity and velocity divided by the square root of 2, as measured from the outer border of the spectral envelope.
 Doppler mitral valve area (MVA) was obtained with the equation: MVA = 220 divided by pressure half-time.
 For catheterization data, the pressure half-time was measured directly from simultaneously recorded left ventricular and left atrial pressure (18 patients) or pulmonary capillary wedge pressure (49 patients).
 The catheterization half-time was taken as the time required for the peak pressure gradient to fall to one half of the initial value.
 Calculations of the mitral valve area at catheterization were obtained by the Gorlin equation with pressure gradient and cardiac output determinations.
 Mitral valve area as determined by the Gorlin equation for all cases ranged from 0.4 to 2.0 (mean = 1.03 +/- 0.37) cm2.
 Linear regression analysis that compared cardiac catheterization and Doppler half-times yielded r = 0.68.
 For the subgroup of patients with sinus rhythm, the correlation improved to r = 0.76.
",13
2293,"Flosequinan: a vasodilator with positive inotropic activity.
 Flosequinan is an oral arterial and venous vasodilator that is currently under investigation for the treatment of congestive heart failure.
 The effects of flosequinan on ventricular performance and myocardial contractility were studied in 10 patients with severe congestive heart failure during right and left cardiac catheterization.
 Sixty minutes after a 100 mg oral dose of flosequinan, the peak rate of rise in left ventricular pressure (dP/dt) increased from 940 +/- 180 to 1050 +/- 240 mm Hg/sec (p less than 0.05), while left ventricular end-diastolic pressure decreased from 32 +/- 5 to 26 +/- 8 mm Hg (p less than 0.05), and cardiac index increased (2.1 +/- 0.4 to 2.3 +/- 0.5 L/min/m2, (p less than 0.05).
 The mean pulmonary artery pressure and vascular resistance decreased from 40 +/- 8 to 33 +/- 12 mm Hg (p less than 0.05) and from 330 +/- 240 to 290 +/- 170 dyne-sec/cm5 (p less than 0.05), respectively.
 Heart rate, mean aortic pressure, right atrial pressure, systemic vascular resistance, and serum norepinephrine levels did not change significantly.
 The increase in left ventricular peak dP/dt that was concomitant with a decrease in left ventricular end-diastolic pressure, and no change in systemic arterial pressure or sympathetic tone, argue for a direct positive inotropic effect of flosequinan.
",13
2294,"Dietary taurine deficiency and dilated cardiomyopathy in the fox.
 Taurine deficiency has been implicated as a potential cause of dilated cardiomyopathy.
 However, the relationship between taurine and myocardial function is presently unclear.
 The purpose of this study was to determine whether dilated cardiomyopathy in the fox is associated with dietary taurine deficiency.
 A total of 68 foxes from farms with a history of death caused by dilated cardiomyopathy and 14 foxes from a farm with no history of dilated cardiomyopathy were studied.
 Dilated cardiomyopathy was diagnosed by echocardiography in 48% of the foxes from one farm with a positive history and in none of the foxes from the control farm.
 Foxes less than 9 months of age were more commonly affected than older foxes (p = 0.03).
 Plasma taurine concentrations were significantly less (p less than 0.01) in foxes that had dilated cardiomyopathy (26.8 +/- 16.4 nmol/ml) than in the control foxes (99.3 +/- 60.2 nmol/ml).
 A significantly higher (p less than 0.01) incidence of dilated cardiomyopathy was present in foxes with a history of a sibling or offspring that died of dilated cardiomyopathy than in foxes without a family history of cardiac death.
 In one fox with dilated cardiomyopathy that was tested, the myocardial taurine concentration was lower (1.7 mumol/gm wet weight) than that of control foxes (7.3 +/- 1.6 mumol/gm wet weight).
 Hepatic cysteinesulfinic acid decarboxylase activity was significantly less (p less than 0.001) in foxes with dilated cardiomyopathy (0.97 +/- 0.2 nmol/mm.mg protein) than in control foxes (2.11 +/- 0.07 nmol CO2/mm.mg protein).
",13
2295,"Beat-to-beat detection of ventricular late potentials with high-resolution electrocardiography.
 To detect dynamic changes of VLPs we developed a low-noise, HR-ECG with a gain of 10(5)-10(6)X.
 This system allows the beat-to-beat detection of low-amplitude signals at the bedside in a nonshielded room without any averaging process.
 Analysis was performed in 39 normal subjects (group A: 27 men, 12 women, mean age, 28 +/- 8 years), in 98 patients with coronary artery disease without documented sustained ventricular tachycardia (group B: 86 men, 12 women, mean age, 59 +/- 10 years) and in 41 patients coronary artery disease with sustained monomorphic ventricular tachycardia (group C: 36 men, 5 women; mean age 63 +/- 9 years).
 Comparison was made with time-domain signal-averaging (SA-ECG) in all cases at the same electrode position and with identical band-pass filtering.
 In group A no VLPs were detected; the total filtered QRS duration was 84 +/- 8 msec (mean +/- SD), and the time interval during which the terminal QRS did not exceed 40 microV (I-40) was less than 30 msec in all cases (mean, 17 +/- 6 msec).
 In group B, VLPs were detected by HR-ECG in 34 of 98 patients (35%); the total QRS duration was 102 +/- 16 msec (mean +/- SD, p less than 0.01 vs group A), and the I-40 was 29 +/- 13 msec (mean +/- SD, p less than 0.01 vs (group A).
 In group C, VLPs were detected by HR-ECG in 38 of 41 patients (93%); the total QRS duration was 123 +/- 22 msec (mean +/- SD, p less than 0.01 vs group A and group B), and the I-40 was 40 +/- 14 msec (mean +/- SD, p less than 0.01 vs group A and group B).
 Concordant results between HR-ECG and SA-ECG were observed in 91% of the cases (59 positive and 103 negative results).
 Late potentials that exhibited dynamic variations were detected by HR-ECG alone in 13 cases, and very low amplitude VLPs were detected by SA-ECG alone in three cases.
 In conclusion, the present study demonstrates the feasibility of body-surface recording of VLPs on a beat-to-beat basis, without any averaging process, at the bedside in a nonshielded room.
 This new approach may allow the study of dynamic changes of VLPs during spontaneous ventricular arrhythmias or ischemia.
",13
2296,"Risk stratification in survivors of acute myocardial infarction: routine cardiac catheterization and angiography is a reasonable approach in most patients [editorial]
 Noninvasive risk assessment in survivors of AMI can effectively subdivide patients into groups with differing risk profiles after hospital discharge, but some patients at risk for late death or recurrent AMI may be incorrectly identified; data from cardiac catheterization and angiography provide complementary and generally more powerful prognostic information.
 Many patients may derive particular benefit from early cardiac catheterization and angiography, including: (1) patients with AMI complicated by recurrent myocardial ischemia, congestive heart failure, and/or complex ventricular arrhythmias; (2) patients with abnormal or inconclusive results of noninvasive testing or those patients unable to perform an exercise test; (3) patients with abnormal left ventricular global systolic function and those with increased left ventricular end-systolic volume; (4) ""young"" patients (younger than 50 years of age?); (5) older patients (older than 65 to 70 years of age?); (6) patients with non-Q wave AMI; and (7) patients who are receiving thrombolytic therapy.
 Performance of early cardiac catheterization and angiography in virtually all survivors of AMI, with selective use of appropriate noninvasive tests, may provide a more efficacious means of risk assessment after AMI; if all tests are performed judiciously, the cost of such an approach need not be excessive.
 A combination of invasive and selected noninvasive tests probably provides optimal information.
 The risks to the routine performance of diagnostic cardiac catheterization and angiography in all survivors of AMI are: (1) adequate care and attention may not be paid to proper performance of the procedure(s) and to detailed and proper analyses of the data; (2) the need for additional noninvasive testing in selected patients may be ignored; and most importantly, (3) premature or unnecessary revascularization procedures may be performed subsequently.
 For optimal patient care, the clinician must obtain all necessary data, avoid unnecessary and repetitive tests, know the accuracy of individual tests at his or her own facility, interpret all data in proper context, and then counsel patients objectively about available management strategies.
 With this approach, all patients who might appropriately benefit from coronary artery revascularization will be correctly identified, and patients who are truly at very low risk (minimal residual coronary artery disease and preserved left ventricular function particularly if associated with a patent infarct-related artery) may be similarly identified and managed appropriately with elimination of unnecessary additional testing and pharmacologic therapy.
 Finally, whatever approach to risk stratification one chooses for an individual patient, the importance of and the need to correct and/or ameliorate risk factors for coronary artery disease must be recognized and undertaken.
",13
2297,"Prognostic importance of delayed Q-wave evolution 3 to 24 hours after initiation of thrombolytic therapy for acute myocardial infarction.
 The timing of Q-wave evolution and its prognostic significance was studied in 201 patients who received thrombolytic therapy for a first acute myocardial infarction (AMI).
 One hundred forty-one patients (70%) had evidence of a Q-wave AMI within 3 hours of the initiation of thrombolytic therapy, 31 (16%) developed Q waves after 3 hours but before hospital discharge, and 29 (14%) were discharged with a non-Q-wave AMI.
 Laboratory indicators of myocardial damage and in-hospital morbidity and mortality were greater among patients with Q-wave AMIs than with non-Q-wave AMIs.
 When these indexes were examined with respect to the timing of Q-wave evolution, the prognosis of patients with delayed Q-wave development was similar to that of patients with non-Q-wave AMIs.
 Thus, compared to patients with early (less than or equal to 3 hours) Q-wave evolution, patients with delayed Q-wave evolution or with a non-Q-wave AMI had a smaller creatine kinase peak (mean 661 to 1,081 vs 1,251 to 1,541 IU; p = 0.005), better preservation of left ventricular function as measured by radionuclide ventriculography before discharge (mean +/- standard deviation 54 +/- 11% vs 47 +/- 13%; p less than 0.01), and a lower incidence of congestive heart failure at discharge (3 vs 15%; p = 0.02).
 In-hospital mortality was lower among patients with delayed Q-wave evolution or with a non-Q-wave AMI (5 of 141 vs 0 of 60; difference not significant).
",13
2298,"Immediate and short-term results of a 1988-1989 coronary angioplasty registry.
 To determine the relevance of recent refinements in angioplasty technology to our particular practice, the records of 507 consecutive patients undergoing a first percutaneous transluminal coronary angioplasty (PTCA) at our center between October 1988 and May 1989 were reviewed.
 At the time of PTCA, 41% of these patients had class IV angina and 44% were identified as having multivessel disease.
 Dilatation was attempted in 734 lesions (mean 1.5 per patient), of which 95 (13%) were chronic total occlusions.
 Overall, 69% of the 734 lesions were judged anatomically complex, and, in dilating these lesions, a rail-type device was used almost exclusively.
 Successful dilatation was achieved in 659 of the 734 (90%) attempted lesions.
 There were low incidences of the major complications of death (0.4%), myocardial infarction (1.8%) and emergency bypass surgery (1.8%).
 Acute rethrombosis occurred in 54 patients (11%).
 In these patients, initial strategy of repeat dilatation was successful in 38 of 47 patients (81%).
 Overall, primary clinical success at PTCA was achieved in 480 patients (95%).
 At a mean follow-up of 7.5 +/- 1.5 months in 497 of the study patients, the event-free rate (freedom from cardiac death, myocardial infarction, repeat PTCA or coronary bypass surgery or recurrence of severe [class III to IV] angina) was 71%.
 In conclusion, despite the often complex coronary disease in patients currently presenting to our center, a high initial success rate and acceptable short-term outcome of PTCA was achieved.
",13
2299,"Sustained reduction in valvular regurgitation and atrial volumes with tailored vasodilator therapy in advanced congestive heart failure secondary to dilated (ischemic or idiopathic) cardiomyopathy.
 Afterload reduction therapy can acutely improve hemodynamic function in patients with advanced heart failure; however, it is unknown if initial reductions in mitral and tricuspid regurgitation and atrial volumes can be sustained with oral therapy.
 Atrial volumes and atrioventricular valve regurgitation were measured using 2-dimensional and Doppler echocardiography with color-flow imaging in 14 patients with dilated heart failure (ejection fraction 17 +/- 4%) before and after 3 +/- 1 days of intensive vasodilator and diuretic therapy tailored to hemodynamic goals.
 Echocardiography was repeated again after 6 +/- 2 months on oral vasodilators and a flexible diuretic regimen.
 Acute therapy reduced systemic vascular resistance from 1,760 +/- 460 to 1,010 +/- 310 dynes.s.cm-5, pulmonary artery wedge pressure from 30 +/- 5 to 17 +/- 4 mm Hg, and right atrial pressure from 13 +/- 5 to 7 +/- 3 mm Hg, and led to a 61% increase in stroke volume (from 36 +/- 10 to 58 +/- 14 ml) (p less than 0.01).
 Mitral and tricuspid regurgitation, determined by color-flow fraction, initially decreased from 0.34 +/- 0.17 to 0.20 +/- 0.20 and from 0.33 +/- 0.15 to 0.13 +/- 0.13, respectively (p less than 0.001).
 This reduction was sustained at 6 months.
 Significant decreases occurred with acute therapy, with further reductions at 6 months in both mean left atrial volume (from 100 +/- 25 to 80 +/- 19 to 65 +/- 15 cm3) and right atrial volume (from 85 +/- 23 to 64 +/- 23 to 52 +/- 14 cm3) (p less than 0.001).
",13
2300,"Frequency and severity of mitral regurgitation one year after balloon mitral valvuloplasty.
 Mitral regurgitation (MR) was evaluated by Doppler echocardiography in 59 patients with mitral stenosis before, immediately after and 1 year after balloon mitral valvuloplasty (BMV).
 The severity of MR was graded on a scale from 1+ to 4+.
 Echocardiographic and hemodynamic variables were analyzed to study the potential factor(s) that might predict the long-term persistence of MR.
 Echocardiographic variables were mitral valve thickness and motion, subvalvular change, left atrial dimension, commissural calcification and effective balloon/mitral anular diameters.
 Hemodynamic variables were mitral pressure gradient, pulmonary arterial pressure, ejection fraction, mitral valve area index, age, gender and cardiac rhythm.
 Mitral valve area index increased from 0.9 +/- 0.5 to 1.5 +/- 0.8 cm2/m2 immediately after BMW, and to 1.4 +/- 0.3 cm2/m2 at 1 year follow-up (p less than 0.01).
 Immediately after BMV, MR grading did not change in 30 patients (51%), increased by 1+ in 23 patients (39%), by 2+ in 2 patients (3.3%) and by 3+ in 2 patients (3.3%), and decreased by 1+ in 2 others.
 At 1-year follow-up, only 1 patient with severe MR required valve replacement.
 Fifty-one patients (88%) had no change in the extent of MR (less than or equal to 1+) and 6 patients (10%) had a 1-grade decrease in their MR; only 1 patient had a 1-grade increase in MR.
 No clinical or hemodynamic variables or morphologic characteristics of the mitral valve could predict the development of significant MR after BMV.
 It is concluded that an increment in MR severity less than or equal to 2+ is frequently seen after BMV.
",13
2301,"Uses and limitations of transthoracic echocardiography in the assessment of atrial septal defect in the adult.
 Two-dimensional and color Doppler echocardiography accurately detected the presence of an atrial septal defect (ASD) in 47 of 50 adults (mean age 40 years) confirmed by surgery or cardiac catheterization, or both.
 It correctly categorized all patients with ostium secundum and ostium primum ASD but misdiagnosed 3 of 5 patients with surgically proven sinus venosus ASD.
 The shunt flow volume across the ASD was calculated with the standard Doppler equation, and assuming the ASD to be circular correlated with shunt flow volume obtained by cardiac catheterization (r = 0.74).
 The maximum width of the color flow signals moving across the ASD was taken as its diameter.
 Mean flow velocity was determined either by placing a pulsed Doppler sample volume parallel to the flow across the ASD as visualized by color Doppler or by color M-mode examination, which allowed determination of flow velocities using a previously validated method that incorporates a computer analysis of pixel color intensity.
 The pulmonary to systemic blood flow ratio obtained by color-guided conventional Doppler interrogation of the left and right ventricular outflow tracts correlated poorly with cardiac catheterization results (r = 0.38).
 In patients with associated tricuspid regurgitation, the peak systolic pulmonary artery pressure obtained by color Doppler-guided continuous-wave Doppler correlated well with that obtained at cardiac catheterization (r = 0.89).
 The maximum color Doppler jet width of the flow across the ASD poorly correlated with ASD size estimated at surgery (r = 0.50).
",13
2302,"Congestive heart failure, coronary events and atherothrombotic brain infarction in elderly blacks and whites with systemic hypertension and with and without echocardiographic and electrocardiographic evidence of left ventricular hypertrophy.
 Hypertension was present in 50% of 196 blacks and in 36% of 382 whites (p less than 0.001).
 A prospective study of 84 elderly blacks (70% women) and 326 elderly whites (73% women) with hypertension correlated echocardiographic and electrocardiographic left ventricular (LV) hypertrophy with incidences of congestive heart failure (CHF), coronary events and atherothrombotic brain infarction (ABI).
 Echocardiographic LV hypertrophy (p less than 0.02) and concentric LV hypertrophy (p less than 0.001) were more prevalent in hypertensive blacks than in hypertensive whites.
 Hypertensive blacks were younger (78 +/- 9 years) than hypertensive whites (82 +/- 7 years) (p less than 0.001).
 Other coronary risk factors were similar, except for higher serum triglycerides in whites than in blacks (p less than 0.02).
 Follow-up was 37 +/- 18 months in blacks and 43 +/- 18 months in whites (p less than 0.01).
 Incidences of CHF and coronary events were not significantly different in blacks and whites.
 ABI incidence was 38% in blacks and 21% in whites (p less than 0.005).
 Multiple logistic regression analysis showed that prior CHF (p = 0.000), concentric LV hypertrophy (p = 0.018) and echocardiographic LV hypertrophy (p = 0.022) were independent risk factors for CHF.
 Echocardiographic LV hypertrophy (p = 0.001), serum total cholesterol (p = 0.002), concentric LV hypertrophy (p = 0.005) and prior coronary artery disease (p = 0.042) were independent risk factors for coronary events.
 Prior ABI (p = 0.001), echocardiographic LV hypertrophy (p = 0.001) and electrocardiographic LV hypertrophy (p = 0.034) were independent risk factors for ABI.
",13
2303,"Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects.
 To evaluate the effects of calcium pretreatment on the disposition and electrocardiographic effects of verapamil, 8 healthy male volunteers received treatment in each of 3 phases in a randomized, double-blind, crossover manner.
 Phase I denoted 10 ml of 0.9% intravenous sodium chloride followed by 10 mg of intravenous verapamil; phase II denoted 10 ml of 10% intravenous calcium chloride followed by 4 ml of 0.9% intravenous sodium chloride; and phase III denoted 10 ml of 10% intravenous calcium chloride followed by 10 mg of intravenous verapamil.
 Blood samples for the determination of verapamil concentrations were drawn at 5, 10, 15, 20, 30, 45, 60 and 90 minutes, and at 2, 4, 6, 10 and 24 hours.
 Blood pressure, heart rate and PR intervals were also measured at these times.
 Pretreatment of verapamil with intravenous calcium did not alter the disposition of intravenous verapamil.
 Blood pressure was not significantly altered in any treatment phase, although calcium tended to increase mean arterial pressure and verapamil abolished this effect.
 Calcium had no significant affect on verapamil-induced PR prolongation (maximum percent change in PR interval: phase I = 19 +/- 11%, phase III = 18 +/- 7%; time to maximal prolongation: phase I = 0.38 +/- 0.21 hours, phase III = 0.37 +/- 0.26 hours; and area under the percent change in PR vs time curve: phase I = 15.5 +/- 10, phase III = 21 +/- 9).
 Verapamil caused a reflex increase in heart rate of similar magnitude in both phases I and III (24 +/- 10% and 21 +/- 7%, respectively).
",13
2304,"Are people more health conscious? A longitudinal study of one community.
 Secular changes in cardiovascular health awareness, knowledge and behavior were observed in four biennial cross-sectional surveys and a cohort survey in a New England community.
 These changes are not related to more health promotion activities in the social milieu of respondents, but are more likely due to national mass media health campaigns, the effects of which may influence outcomes of community-based cardiovascular disease prevention studies.
",13
2305,"Intraoperative detection of patent foramen ovale by transesophageal echocardiography.
 This study reports the intraoperative use of contrast and Doppler echocardiography techniques to diagnose patent foramen ovale (PFO).
 Fifty patients without known atrial septal defects undergoing elective cardiovascular surgery were studied.
 A 5-MHz esophageal echocardiographic probe was used to image the fossa ovalis (FO) and 10 ml agitated saline was injected into the right atrium during apnea.
 Echocardiographic contrast was then injected during end-inspiration at 20-cmH2O airway pressure.
 When opacification of the right atrium was complete, the airway pressure was released.
 During these maneuvers, color and pulsed-wave Doppler interrogation of the atrial septum were also performed.
 Right-to-left passage of saline contrast across the interatrial septum was seen in 11 of 50 patients (22%).
 Doppler echocardiography demonstrated a PFO in 2 patients without contrast evidence of shunting.
 Thus, the combination of contrast and Doppler echocardiography identified a 26% (13 of 50) prevalence of PFO, approximating the previously reported autopsy rate of 25%.
 These contrast and Doppler techniques may be useful in detecting patients at risk for paradoxical emboli and in identifying candidates for closure of the PFO.
",13
2306,"Active drainage of cardiac lymph in relation to reduction in size of myocardial infarction: an experimental study.
 Active drainage of cardiac lymph using hyaluronidase was attempted in dogs.
 The results were satisfactory and the ischemic myocardium was salvaged.
 The infarct risk area (I/R) ratio decreased after drainage.
 Regional myocardial ischemia and infarction were provided by means of ligature of the left coronary artery for 120 and 240 minutes respectively.
 Cardiac lymph was collected by conventional procedures.
 Enzymes released from the myocardium increased significantly in the cardiac lymph.
 The volume of cardiac lymph gradually increased after ligature of the coronary artery.
 Administration of hyaluronidase further increased the cardiac lymph flow and significantly decreased the I/R ratio as determined by triphenyl tetrazolium chloride (TTC) and methylene blue staining.
 Drainage of the cardiac lymph salvaged the ischemic myocardium.
 Reduction of interstitial edema and augmentation of cardiac lymph flow with the hyaluronidase prevented the development of the infarction.
 This is the first documentation of the effect of active drainage of cardiac lymph on the development of infarction through observation of the I/R ratio.
",13
2307,"Therapy of ischemic cardiomyopathy with pentoxifylline.
 Abnormal blood rheology is a known characteristics of coronary artery disease.
 The authors evaluated the effects of pentoxifylline on the exercise capacity ejection fraction and symptoms of 9 patients with ischemic cardiomyopathy.
 All patients had signs and symptoms of left ventricular dysfunction.
 All had at least two major vessels obstructed as determined by coronary angiography.
 Pentoxifylline 400 mg three times daily was administered for twelve weeks.
 Seven of 9 patients responded with increases in ejection fraction and exercise tolerance.
 Exercise tolerance correlated with improvement or lack of improvement in ejection fraction.
 For all patients at twelve weeks post-therapy mean ejection fraction increased 9.8% over baseline (p = .07), total treadmill time increased 15% (p = .27), and mean double product increased 13% (p = .03).
 Anginal symptoms were significantly improved over baseline at twelve weeks of therapy (p greater than .001), as well as dyspnea on exertion (p = .03).
 Pentoxifylline was well tolerated.
 Pentoxifylline may benefit ischemic cardiomyopathy by improving coronary perfusion owing to favorable alterations in hemorheologic properties.
",13
2308,"The effect of dopexamine HCl upon collateral perfusion of the acutely ischemic myocardium in anesthetized dogs.
 The effects of low-dose (10(-9) and 3 x 10(-9) mole/kg/min) infusions of dopexamine HCl, a new synthetic catecholamine with beta 2-adrenergic and DA1-dopaminergic agonostic actions, was tested in anesthetized dogs, with and without acute ligation of the left anterior descending coronary artery.
 The infusions caused diastolic arterial blood pressure to fall by 12 +/- 4 and 23 +/- 5 mmHg, respectively.
 Microsphere-estimated collateral blood flow to the ischemic myocardium did not change significantly during the drug infusions.
 The findings suggest that low doses of dopexamine HCl do not cause coronary ""steal"" from acutely ischemic myocardium.
",13
2309,"Aortic dissection with a fistulous communication into the right atrium: a case report.
 A case of aortic dissection (type 1, De Bakey) with a rent into the right atrium (RA), diagnosed by echocardiography (echo) and confirmed by aortography, is reported.
 The patient presented with cardiac failure and a continuous murmur in the right second and third intercostal spaces.
 The patient has survived for two years with medial treatment.
",13
2310,"Relation between three-dimensional geometry of the inflow tract to the orifice and the area, shape, and velocity of regurgitant color Doppler jets: an in vitro study.
 The relation between three-dimensional geometry of the inflow tract to the orifice and the area, shape, and velocity of regurgitant jets was studied in a pulsatile in vitro color Doppler flow model.
 A 2.5 MHz transducer connected to a diagnostic ultrasound machine was placed in a water tank facing pulsatile jets (duration, 0.5 second) obtained by a calibrated injector.
 Flow rate from 6 to 52 ml/sec were tested through a 5 mm diameter circular orifice.
 Four different three-dimensional inflow tract geometries were compared: (A) sharp-edged, (B) Venturi (funnel), (C) converging conical, and (D) diverging conical.
 Mean velocities of jets were measured by continuous-wave Doppler echocardiography.
 Driving pressures were also measured by means of a fluid-filled catheter.
 Two observers independently digitized contours of maximal color jet areas by computer system from two separate sets of experiments.
 Results are given as the mean values of the four measurements for each parameter.
 Jet areas were correlated to flow rate, with no difference from A through D.
 The shape (eccentricity) of jets was different between A and B (p less than 0.05), between B and D (p less than 0.01), and between C and D (p less than 0.01).
 The shape of jets was correlated with flow rate, continuous-wave velocity, and pressure gradient in B, C, and D but not in A.
 Measured pressure gradients and estimated gradients by continuous-wave Doppler echocardiography were similarly correlated from A through D.
",13
2311,"The reproducibility of intravascular ultrasound imaging in vitro.
 To determine which factors may affect the image quality when an intravascular ultrasound catheter is used in vivo, the influence of blood, temperature change, and contrast media were evaluated.
 In addition, to confirm the reproducibility of intravascular ultrasound imaging to measure cross-sectional lumen area, intraobserver and interobserver variability were determined.
 The findings indicated that ultrasound images in blood are mildly attenuated, that changes from room temperature to body temperature do not have a significant impact on the image quality, that contrast media attenuates the image intensity in a dose-dependent manner, and that the intravascular ultrasound imaging catheter provides a reproducible method for measuring arterial lumen area with excellent intraobserver and interobserver correlation.
",13
2312,"The natural history of left ventricular spontaneous contrast.
 Spontaneous contrast in the left ventricle is an unusual entity.
 We retrospectively studied 16 patients who were found to have spontaneous contrast present on two-dimensional echocardiograms, specifically noting their clinical characteristics, the reproducibility of this phenomenon, the presence of thrombi and embolic events, and prognostic implications.
 Diagnoses included ischemic heart disease in nine patients, dilated cardiomyopathy in six patients, and hypertensive cardiomyopathy in one patient.
 The mean ejection fraction was 17.6%.
 There were six thromboembolic events in four patients.
 The spontaneous contrast was reproducible for periods of time up to 39 months.
 Patients who had improvement in their left ventricular dysfunction or who underwent aneurysmectomy had disappearance of the spontaneous contrast.
 Those patients who had spontaneous contrast reproduced on subsequent echocardiograms did not seem to have a worse prognosis than patients with similarly depressed ventricular function, but a larger study is necessary to verify this.
",13
2313,"Role of ultrasonic tissue characterization to distinguish reversible from irreversible myocardial injury.
 Tissue characterization reflects structural and functional integrity of tissues.
 Inasmuch as reversible ischemia causes no structural damage and irreversible ischemia results in persistent structural myocardial damage, we postulated that ultrasonic tissue characterization can distinguish the two types of injuries.
 Anesthetized open chest dogs underwent 15 minutes (group 1, n = 5) and 90 minutes (group 2, n = 8) of acute total occlusion of the left anterior descending coronary artery, followed by 3 hours of reperfusion.
 Myocardial ischemia-infarction was confirmed with segment shortening, electronmicroscopic examination, and triphenyl tetrazolium chloride staining.
 Integrated backscatter Rayleigh 5 (IBR5), a measure of ultrasonic backscatter, and Fourier coefficient of amplitude modulation (FAM), an index of cardiac cycle dependent variation in backscatter, were measured at baseline, during ischemia, and after reperfusion.
 Group 1 (reversible ischemia) showed an increase in IBR5 from -48 +/- 1.2 dB at control to -45 +/- 1.0 dB (p less than 0.01) during ischemia, which returned to baseline after reperfusion (-47 +/- 1.3 dB).
 FAM was blunted during ischemia (6.2 +/- 1.0 dB during control versus 1.2 +/- 1.0 dB during ischemia, p less than 0.01) and recovered completely during reperfusion.
 Segment shortening was abolished during ischemia (18% +/- 3% during control versus -12% +/- 5% during ischemia, p less than 0.01) and recovered partially during reperfusion (4% +/- 5%).
 The group 2 animals with irreversible myocardial injury showed an increase in IBR5, from -49 +/- 1.2 dB during control to -44 +/- 1.0 dB during ischemia (p less than 0.01) and paradoxical bulging of the ischemic region (17% +/- 3% to -7% +/- 3%, p less than 0.01) during ischemia.
",13
2314,"Quantitative echocardiographic analysis of global and regional left ventricular function: a problem revisited.
 We recorded two-dimensional echocardiograms simultaneously with the respiration measurements of 20 normal subjects and 20 patients with anterior myocardial infarction.
 The apical long-axis and four-chamber views were quantitatively analyzed.
 Measurement variability of global ejection fraction and regional ejection fraction of 100 regions was calculated during inspiration and at end-expiration for two observers.
 To minimize variability, the endocardial contour was redefined and traced with an improved computer-assisted tracing system.
 Variability (absolute mean difference) between two beats at end-expiration was significantly less than during inspiration (p less than 0.05): for ejection fraction the variability at end-expiration was 3.4% and the variability during inspiration was 6.4% (mean, 54%; SD, 7%); for regional ejection fraction the variability at end-expiration was 11.8% and the variability during inspiration was 21.5% (mean, 56%; SD, 15%).
 Intraobserver and interobserver variability values of one beat at end-expiration for ejection fraction were 3.1% and 3.8%, respectively, and 9.5% and 12.8%, respectively, for regional ejection fraction.
 Variability in patients with myocardial infarction was comparable.
 This method of recording respiration and analyzing left ventricular function at end-expiration, with a new contour definition and tracing system, provides a measurement variability that is considerably less than that reported in previous echocardiographic studies and that is comparable to angiographic methods.
",13
2315,"Fenestrated atrial septal aneurysm: diagnosis by transesophageal echocardiography.
 The diagnosis of atrial septal defect by transthoracic echocardiography remains difficult in a small subset of patients because of either suboptimal acoustic windows or unusual anatomy, for example, fenestrated defects.
 We report the case of a 55-year-old woman with a fenestrated atrial septal aneurysm that was incompletely visualized by transthoracic echocardiography.
 Subsequent transesophageal echocardiography demonstrated three defects within the atrial septal aneurysm with left-to-right shunting across each defect.
 Normal pulmonary venous connections were also defined.
 All echocardiographic findings were confirmed at surgery.
 This case demonstrates the additional diagnostic accuracy of transesophageal echocardiography for detecting disease of the atrial septum.
",13
2316,"Sustained improvement in left ventricular function after successful coronary angioplasty.
 The short and long term effects of successful percutaneous transluminal coronary angioplasty on left ventricular function, at rest and on exercise were investigated in 49 patients.
 Thirty-four had had no previous infarction (group 1) and 15 had (group 2).
 Technetium-99m gated blood pool images were obtained at rest and during exercise before, six weeks after, and a mean of fifteen months after successful angioplasty.
 Before angioplasty the mean (SD) ejection fraction fell significantly on exercise in both groups from 58 (10)% to 53 (13)% in group 1 and from 48 (10)% to 40 (16)% in group 2.
 This change was paralleled by a worsening wall motion score (from 0.6 (0.4) to 1.6 (1.2) in group 1 and from 2.3 (1.9) to 3.3 (2.4) in group 2).
 Six weeks after the procedure there was little change in resting ejection fraction but it increased significantly on exercise (to 62 (11)% in group 1 and to 53 (13)% in group 2).
 There was a concomitant significant improvement in the exercise wall motion score (to 0.4 (0.6) in group 1 and to 1.8 (1.1) in group 2).
 This improvement in exercise ejection fraction and wall motion was maintained at later follow up with no significant deterioration in either variable and a clearly sustained improvement in ejection fraction (60 (10)% in group 1 and 51 (10)% in group 2) and wall motion score (0.2 (0.2) in group 1 and 1.3 (0.8) in group 2) compared with values before angioplasty.
",13
2317,"Post-extrasystolic potentiation without a compensatory pause in normal and diseased hearts.
 Variables derived from left ventricular volume were used to study post-extrasystolic potentiation.
 Left ventriculograms were obtained from 11 healthy individuals and 49 patients with coronary heart disease (30 with a previous myocardial infarction and 19 without any signs of myocardial damage).
 Post-extrasystolic potentiation was induced by a regularly driven right atrial rhythm that was interrupted by one atrial extrasystole in such a way that the post-extrasystolic RR interval was kept equal to the basic RR interval.
 The left ventricular end diastolic volumes of the pre-extrasystolic and post-extrasystolic beats were equal.
 In all groups there was evidence of post-extrasystolic potentiation in one or more of the indices of left ventricular function (ejection fraction, mean normalised systolic ejection rate, and systolic volume, and stroke volume).
 Potentiation was especially evident in patients with left ventricular damage; this suggests that a compensating mechanism is an intrinsic property of the myocardium.
 The Frank-Starling mechanism does not contribute to the increased performance of the post-extrasystolic beat in normal individuals or in patients with coronary artery disease.
",13
2318,"Streptokinase treatment for femoral artery thrombosis after arterial cardiac catheterisation in infants and children.
 Data on 205 children who underwent retrograde arterial catheterisation were studied to assess the frequency of femoral artery thrombosis and the safety and efficacy of systemic streptokinase treatment for this complication.
 In 29 (14%) a transarterial balloon dilatation was performed.
 In 15 (7.3%) patients impaired arterial perfusion due to vascular spasm with or without thrombus formation was seen in the cannulated leg after catheterisation.
 Despite heparinisation, signs of impaired arterial circulation persisted in nine patients (4.4% of the total).
 In these patients femoral artery thrombosis was strongly suspected.
 Six (53%) of these had undergone a balloon dilatation.
 Therefore in this study the risk of femoral artery thrombosis developing was 12 times greater after transarterial balloon dilatation than after arterial catheterisation without dilatation (20.6% v 1.7%).
 Systemic infusion of streptokinase was started in all patients with femoral artery thrombosis.
 Arterial perfusion became normal in all patients, though in one this was delayed.
 Haematological monitoring showed lengthening of the thrombin time and a decrease of the fibrinogen concentration during streptokinase treatment.
 There were no serious complications.
 Systemic infusion of streptokinase is a safe and useful treatment in children with persistent femoral artery thrombosis after arterial cardiac catheterisation.
",13
2319,"Preoperative measurement of pulmonary vascular resistance in complete transposition of the great arteries.
 Transposition of the great arteries is frequently complicated by the early onset of pulmonary vascular disease.
 It is difficult to measure pulmonary blood flow by the Fick principle because the pulmonary arteriovenous oxygen content difference is small and bronchial blood flow is increased in this condition.
 In eight patients (mean age 7.7 years, range 3 months to 29 years) with transposition of the great arteries mass spectrometry was used to measure oxygen uptake and predict pulmonary end capillary blood oxygen content.
 The effects of the bronchial circulation were studied by computer modelling.
 There was close agreement between pulmonary end capillary and pulmonary vein blood oxygen contents but the resultant percentage difference in arteriovenous content difference was significant (mean (SE of difference)) (14.5(3.8)%).
 The effect of the bronchial circulation was to give spuriously high estimates of pulmonary blood flow.
 The error was greatest when oxygen consumption was low and aortic blood was very desaturated.
",13
2320,"Transmural myocardial deformation in the ischemic canine left ventricle.
 The myocardium is a complex three-dimensional structure consisting of myocytes interconnected by a dense collagen weave that courses in different directions.
 Regional ischemia can be expected to produce complex changes in ventricular deformation.
 In the present study, we examined the effects of ischemia on two- and three-dimensional finite strains during acute transmural myocardial ischemia in 13 open-chest anesthetized dogs.
 In contrast to systolic deformation observed during the control period in which circumferential shortening exceeded longitudinal shortening, our results indicate that after 5 minutes of acute ischemia, end-systolic in-plane lengthening across the left ventricular wall occurs in approximately equal amounts in the circumferential and longitudinal directions.
 Along with these changes in extensional strains, there were significant negative transverse shearing deformations during ischemia.
 Myocardial ischemia also resulted in a loss of the normal end-systolic transmural gradients of shortening and thickening.
 Three-dimensional end-diastolic strains indicate that the left ventricular wall undergoes a significant passive reconfiguration that varies transmurally with lengthening in the epicardial tangent plane and wall thinning increasing from the epicardium toward the endocardium.
 The large systolic changes in shearing deformations with ischemia could potentially influence collateral blood flow and certainly indicate that uniaxial measurements of deformation in the ischemic myocardium, which do not account for shearing deformation, are incomplete and must be interpreted with caution.
 Moreover, normal transmural systolic gradients in deformation, which would be anticipated on geometric grounds, are lost during ischemia, implying that the material properties of ischemic tissue or the loading conditions imposed on the ischemic region by partially impaired adjacent myocardium vary transmurally.
",13
2321,"Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfusion and reperfusion in isolated rabbit hearts perfused with erythrocyte suspensions.
 Current therapy of myocardial infarction may include early reperfusion.
 We simulated myocardial perfusion conditions during evolving myocardial infarction in isolated, normothermic, isovolumic rabbit hearts perfused with buffer containing bovine red blood cells (hematocrit of 40%), and we assessed the effects of high levels of glucose and insulin as ""therapy"" during prolonged (150-minute) severe underperfusion and reperfusion.
 Protocol 1 consisted of underperfusion at a constant coronary perfusion pressure of 8 mm Hg.
 The control group (n = 8) received 5.5 mmol/l glucose and 15 microunits/ml insulin; the group treated with high levels of glucose and insulin (G + I) (n = 8) received 19.5 mmol/l glucose and 250 microunits/ml insulin during both underperfusion and reperfusion.
 Relative to the control group, the G + I group experienced 1) greater developed pressure during underperfusion and increased recovery during reperfusion, 2) preserved diastolic function during underperfusion and reperfusion, 3) lower coronary resistance and greater coronary flow during the underperfusion period, 4) increased glycolytic flux and preserved glycogen stores and high energy phosphate levels, and 5) less loss of myocyte enzymes (creatine kinase and alanine aminotransferase).
 In protocol 2, coronary flow was kept identical in control (n = 8) and G + I hearts (n = 8) during the underperfusion period, and left ventricular end-diastolic pressure was kept below 10 mm Hg in both groups to minimize subendocardial damage and vascular compression.
 In this protocol, the effect of the G + I intervention in the prevention of an increase in coronary resistance during the underperfusion period was distinguished from its myocellular metabolic effects; the high G + I substrate had protective effects on mechanical and metabolic function that were less marked than, but similar to, those in protocol 1, indicating that its mechanisms of protection during underperfusion affected both cardiac function and coronary resistance.
 We conclude that the G + I intervention, in clinically relevant concentrations, markedly protected severely underperfused myocardium for 150 minutes and may be a beneficial intervention in combination with reperfusion therapy in acute myocardial infarction.
",13
2322,"Effect of coronary hyperemia on Emax and oxygen consumption in blood-perfused rabbit hearts. Energetic consequences of Gregg's phenomenon.
 To assess the relation between increases in contractile function and oxygen consumption (VO2) during increased coronary flow (Gregg's phenomenon), we measured the end-systolic pressure-volume relation and the relation between VO2 and left ventricular systolic pressure-volume area (PVA, a measure of total mechanical energy output) in blood-perfused, isovolumically contracting rabbit hearts during control and intracoronary adenosine infusion.
 During adenosine infusion at a constant perfusion pressure (93 +/- 11 mm Hg), coronary flow increased by 99 +/- 76% (p less than 0.01), and the slope of the end-systolic pressure-volume relation, Emax (ventricular contractility index), increased by 18 +/- 15% (p less than 0.01).
 When compared at the same left ventricular volume, PVA increased by 20 +/- 14% (p less than 0.01) and VO2 by 19 +/- 15% (p less than 0.01) with adenosine.
 The VO2-PVA relation was linear under each condition (both median r = 0.98).
 With increased coronary flow, the VO2-intercept of the VO2-PVA relation (unloaded VO2) increased by 22 +/- 18% (p less than 0.01) without a change in the slope; that is, a parallel upward shift was observed, indicating that the contractile efficiency (energy conversion efficiency of the contractile machinery) remained constant.
 These increases in Emax and unloaded VO2 were not eliminated by beta-adrenergic blockade with propranolol.
 We conclude that increased coronary flow with adenosine at a constant perfusion pressure augments both Emax and the nonmechanical energetic cost for excitation-contraction coupling and basal metabolism via nonadrenergic mechanisms, without changing contractile efficiency.
",13
2323,"Spontaneous termination of reentry after one cycle or short nonsustained runs. Role of oscillations and excess dispersion of refractoriness.
 This study describes factors that contribute to spontaneous termination of reentry lasting one to 10 cycles after induction by a single premature stimulus.
 Reentry was studied in vitro in rings of canine atrial tissue from around the tricuspid valve orifice.
 Activation was recorded from a circular array of 10 extracellular bipolar electrodes equally spaced around the ring.
 In some experiments, transmembrane or monophasic action potential recordings were made near critical sites.
 Termination of reentry within one cycle after induction was recorded 110 times in 11 of 35 experiments.
 Important factors contributing to termination were 1) an obligatory reversal of the activation sequence that resulted in a long coupling interval in the critical region beyond the site of unidirectional block after the premature stimulus and 2) much longer refractory periods limited to this critical region, which facilitated unidirectional block but contributed to termination when this region was first activated with a short coupling interval at the end of the first reentrant cycle.
 Termination of nonsustained reentry lasting longer than one cycle resulted from oscillations of conduction and refractoriness initiated by the abrupt shortening of cycle length after initiation of reentry.
 Oscillations of conduction resulted from interval-dependent conduction of reentrant impulses that encountered partially refractory tissue.
 For reentry to become sustained, the oscillations after induction of reentry must dampen.
 Thus, damped cycle length oscillations after induction may identify clinical tachycardias caused by reentry with a partially excitable gap.
",13
2324,"Myocardial sulfhydryl pool alterations occur during reperfusion after brief and prolonged myocardial ischemia in vivo.
 Myocardial sulfhydryl (SH)-containing compounds, including reduced glutathione (GSH), are both defenses against and potential markers of reactive oxygen metabolite injury during ischemia and reperfusion.
 We examined the alterations in GSH and other myocardial SH pools during reperfusion in anesthetized dogs exposed to brief (15 minutes, n = 7) or prolonged (90 minutes, n = 6) regional ischemia caused by occlusion of the left anterior descending artery.
 Ninety minutes of ischemia followed by 5 hours of reperfusion, which resulted in myocardial necrosis of 43.9 +/- 4.0% of the area at risk, caused a 22% reduction in total myocardial SH groups (p less than 0.01), a 57% decrease in nonprotein myocardial SH groups (p less than 0.01), a 56% decrease in GSH (p less than 0.01), and a 62% decrease in non-GSH, nonprotein SH groups (p less than 0.02).
 However, protein SH groups were not significantly reduced (12% decrease, p = NS).
 Also, myocardial release of GSH and oxidized glutathione (GSSG) into the coronary venous effluent occurred during early reperfusion.
 In contrast, 15 minutes of ischemia, followed by 30 minutes of reperfusion, did not alter myocardial total SH groups, protein SH groups, or GSH (9% decrease, p = NS); nor was there reperfusion release of GSH or GSSG.
 However, even with brief ischemia, nonprotein SH groups decreased 23% (p less than 0.05), due mainly to a 59% decrease in the non-GSH, nonprotein SH pool (p less than 0.05).
 These changes after brief ischemia occurred without alterations in myocardial GSSG or the GSH/GSSG ratio.
",13
2325,"Accuracy of exercise electrocardiography in detecting physiologically significant coronary arterial lesions.
 The accuracy of exercise electrocardiography in detecting a physiologically significant coronary artery stenosis has been assessed previously by comparing the exercise test with a coronary arteriogram.
 The inherent inaccuracy of visually determined percent diameter stenosis measurements might have lead to the conclusion that the exercise electrocardiogram was less accurate than it truly was.
 To determine the accuracy of the exercise electrocardiography in detecting a physiologically significant coronary stenosis, we studied 40 patients with one-vessel, one-lesion coronary artery disease, a normal resting electrocardiogram, and no hypertrophy or prior infarction.
 Each patient underwent exercise electrocardiography (Bruce protocol) that was interpreted as abnormal if the ST segment developed 0.1-mV or greater depression 80 msec after the J point.
 The physiological significance of each coronary stenosis was assessed by measuring of coronary flow reserve (peak divided by resting blood flow velocity) in the stenotic artery using a Doppler catheter and intracoronary papaverine (normal, 3.5 or greater peak/resting velocity).
 The percent diameter and percent area stenosis produced by each lesion were determined using quantitative angiography (Brown/Dodge method).
 Of the 17 patients with reduced coronary flow reserve (3.5 or greater peak/resting blood flow velocity) in the stenotic artery, 14 had an abnormal exercise electrocardiogram (sensitivity, 0.82; 95% confidence interval, 0.70-0.94).
 Conversely, 20 of 23 patients with normal coronary flow reserves had normal exercise tests (specificity, 0.87; 95% confidence interval, 0.77-0.97).
 The exercise electrocardiogram was abnormal in each of 11 patients with markedly reduced coronary flow reserve (less than 2.5 peak/resting velocity) and in three of six patients with moderately reduced reserve (2.5-3.4 peak/resting velocity).
 The products of systolic blood pressure and heart rate at peak exercise were significantly correlated with coronary reserve in patients with truly abnormal exercise tests.
 In comparison, the sensitivity (0.61; 95% confidence interval, 0.46-0.76) and specificity (0.73; 95% confidence interval, 0.60-0.86) of exercise electrocardiography in detecting a 60% or greater diameter stenosis may be significantly lower (p less than 0.05).
 Exercise electrocardiography, therefore, was a good predictor of the physiological significance (assessed by coronary flow reserve) of a coronary stenosis in patients with a normal resting electrocardiogram and no hypertrophy or prior infarction.
 Its value in a broader and larger patient population will require further study.
 These results, however, underscore the importance of a physiological gold standard in assessing the accuracy of noninvasive studies for detecting coronary artery disease.
",13
2326,"Secular trends in Q wave and non-Q wave acute myocardial infarction. The Minnesota Heart Survey.
 The Minnesota Heart Survey examined trends of Q wave and non-Q wave acute myocardial infarction (AMI) using a 50% random sample of all hospital discharges of patients with AMI or another acute coronary disease from 35 of 36 hospitals in 1970 and 30 of 31 hospitals in 1980 in the Minneapolis-St.
 Paul metropolitan area.
 A total of 1,901 and 1,864 potential AMI cases were abstracted in 1970 and 1980, respectively.
 Electrocardiograms were coded according to the Minnesota code.
 AMIs were validated by computerized algorithm based on chest pain, enzymes, electrocardiograms, and autopsy.
 This study shows that with the use of a consistent, standard diagnostic algorithm, attack rates for Q wave AMI did not change significantly between 1970 and 1980 and that attack rates for non-Q wave AMI decreased significantly during the same decade.
 However, when the more sensitive cardiac enzymes creatine phosphokinase and creatine phosphokinase-MB were considered, attack rates of both Q wave and non-Q wave AMIs increased.
 This research documents four important trends for community AMI rates that are at variance with those reported by others.
 There was a decline in non-Q wave AMI attack rates from 1970 to 1980; women had outcomes equal to or worse than those for men for both case-fatality and 7-year survival rates; patients with non-Q wave AMIs had worse in-hospital prognoses than those with Q wave AMIs; and 7-year survival rates were worse for Q wave AMI in 1980.
 These findings demonstrate the need for standard diagnostic criteria for Q wave and non-Q wave AMI if trends are to be monitored.
 In the future, as new trials of operative and nonoperative therapies of AMI are undertaken, these considerations will increase in importance.
",13
2327,"Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy.
 This study was designed to determine the morphological correlate of chronic heart failure.
 Myocardial tissue from eight patients undergoing transplantation surgery because of end-stage dilated cardiomyopathy was investigated by electron microscopy and immunocytochemistry using monoclonal antibodies against elements of the cytoskeleton: desmin, tubulin, vinculin, and vimentin.
 The tissue showed hypertrophy, atrophy of myocytes, and an increased amount of fibrosis.
 Ultrastructural changes consisted of enlargement and varying shape of nuclei, numerous very small mitochondria, proliferation of T tubules, and accumulation of lipid droplets and glycogen.
 The most obvious ultrastructural alteration was the decrease of myofilaments, ranging from rarefication to complete absence of sarcomeres in cells filled with unspecified cytoplasm.
 Immunocytochemistry showed that desmin was localized at the Z lines.
 In diseased myocardium, the amount of desmin was increased, but it was disorderly arranged.
 Tubulin formed a fine network throughout the myocytes and was significantly increased in cardiomyopathic hearts.
 Vinculin, a protein closely associated with the cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but also within the myocardial cells.
 Ultrastructural changes and alterations of the cytoskeleton were severe in about one third of all cells.
 About one third of all cells showed moderately severe changes, and the remaining cells were normal.
 Vimentin was present in the interstitial cells and was increased in relation to the increase of fibrosis.
 We conclude that the increase of fibrosis, the degeneration of hypertrophied myocardial cells, and the alterations of the cytoskeleton are the morphological correlates of reduced myocardial function in chronic heart failure.
",13
2328,"HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies 
 We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study.
 To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles.
 Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005).
 A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls).
 HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22).
 We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p less than 0.007).
 A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination.
 For the combined studies, DR4 was elevated (51% versus 27% in controls, p less than 0.001), and DRw6 was decreased (9% versus 24% in controls, p less than 0.01).
 The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33.
",13
2329,"Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy 
 The acute hemodynamic effects of captopril were evaluated at cardiac catheterization in 16 children (age, 0.3-18 years) with cardiomyopathy.
 Twelve children had congestive cardiomyopathy, whereas four had restrictive cardiomyopathy.
 Hemodynamic measurements were obtained 30 and 60 minutes after the oral administration of captopril (0.5 mg/kg).
 Blood pressures were measured in the aorta, pulmonary artery, right atrium, and pulmonary capillary wedge position; cardiac outputs were measured by the thermodilution technique.
 Hemodynamic data could not be obtained after the administration of captopril in one child with congestive cardiomyopathy because of an immediate, severe hypotensive response.
 In 11 of 12 children with congestive cardiomyopathy, cardiac index increased by 22%, from 2.3 to 2.8 l/min/m2 (p less than 0.05), and stroke volume increased by 22%, from 23 to 28 ml/m2 (p less than 0.05).
 Systemic vascular resistance decreased from 32 to 21 units.m2 (p less than 0.01), but the mean aortic pressure did not change significantly.
 In contrast, four children with restrictive cardiomyopathy had no change in cardiac output after captopril, but there was a trend toward significant arterial hypotension (mean aortic pressure decreased from 78 to 59 mm Hg).
 Thus, captopril acutely reduced systemic vascular resistance and increased both cardiac output and stroke volume in children with congestive cardiomyopathy.
 In children with restrictive cardiomyopathy, however, captopril did not affect cardiac output, but it did decrease aortic pressure.
 These data indicate that captopril may benefit children with a congestive cardiomyopathy but that captopril probably should not be used in children with restrictive disease.
",13
2330,"What is the best method for assessing the long-term outcome of surgery for accessory pathways and atrioventricular junctional reentrant tachycardias?
 The success of surgery for supraventricular tachycardia (SVT) is evaluated by a variety of methods in different hospitals.
 Unfortunately, the predictive values of these methods are not known.
 We therefore compared the various methods in 261 patients undergoing surgery for SVT at Westmead Hospital since 1981.
 Surgical outcome was assessed by early tests during the first week after surgery (serial 12-lead electrocardiograms, telemetric monitoring of the electrocardiogram, and electrophysiological study performed using epicardial wires); later tests at 6 months after surgery (12-lead electrocardiograms and electrophysiological study); and symptomatic review done by telephone interview at a median of 34 months after surgery.
 Early tests were obtained in 97%, later tests were obtained in 76%, and symptomatic review was obtained in 98% of patients.
 All of the examined tests were inaccurate methods of surgical assessment compared with the late electrophysiological study.
 A large proportion of the patients proven to be surgical failures at the late electrophysiological study were not detected by early tests (83%), by later electrocardiograms (66%), or by symptomatic assessment (41%).
 Accurate assessment of surgical outcome requires a late electrophysiological study to permit comparison of surgical techniques.
 Late electrophysiological study also provides accurate information on the current risks and benefits of proposed surgery for communication to patients to enable them to make an informed decision on future treatment.
 Most patients are willing to have a late electrophysiological study and usually benefit from clarification of their true surgical outcome.
",13
2331,"Relation between leisure-time physical activity and blood pressure in older women.
 Although there is some evidence that physical activity may decrease blood pressure in young and middle-aged women, the physical activity-blood pressure association in older women has rarely been studied.
 As part of an ongoing community-based study of chronic disease, 641 Caucasian women between the ages of 50 and 89 years had blood pressure measured following the Hypertension Detection and Follow-up Program protocol.
 They also answered selected Health Interview Survey questions about their leisure-time activity and were classified into categories of light (58%), moderate (24%), heavy (6%), or no physical activity (12%) by the estimated metabolic rate required for each activity.
 Women who engaged in any physical activity were significantly younger and thinner than sedentary women and had lower fasting and 2-hour postchallenge insulin levels.
 They did not differ in alcohol consumption, cigarette use, or prevalence of coronary heart disease or diabetes.
 Rates of systolic and diastolic hypertension were significantly lower in women participating in light, moderate, or heavy physical activity compared with sedentary women.
 Blood pressure levels decreased with each increase in reported activity intensity (p less than 0.005 for trend), with systolic blood pressure approximately 20 mm Hg lower in the heaviest activity group compared with systolic blood pressure in sedentary women.
 Intergroup differences remained statistically significant after adjustment for age and body mass index.
 Although physical activity was associated with lower fasting and 2-hour postchallenge insulin levels (p less than 0.01 for trend), adjustment for insulin levels did not alter blood pressure differences among activity groups.
",13
2332,"Mechanisms of reoxygenation injury in cultured ventricular myocytes 
 To investigate factors contributing to reperfusion and reoxygenation myocardial injury, we exposed layers of cultured chick ventricular myocytes to severe hypoxia for up to 3 hours in the presence of 20 mM 2-deoxyglucose, zero glucose, and 5 mM pyruvate, and then exposed the myocytes to reoxygenation.
 Lactate dehydrogenase (LDH) release was moderately increased during 3 hours of hypoxia but was increased markedly during reoxygenation.
 Coincident changes in intracellular calcium concentration ([Ca2+]i) and cell motion were also measured during hypoxia and reoxygenation.
 During hypoxia, [Ca2+]i increased to more than 1 microM, and with reoxygenation, [Ca2+]i abruptly decreased slightly but remained elevated more than 1 microM.
 Cells developed a stable rigor after 30 minutes of hypoxia.
 Reoxygenation caused a marked hypercontracture within 5 minutes.
 Pretreatment of myocytes with either 2,3-butanedione monoxime, which inhibits Ca2(+)-dependent force development, or cyanide inhibited reoxygenation hypercontracture.
 LDH release after reoxygenation was also significantly reduced in the presence of 2,3-butanedione monoxime.
 Treatment of myocytes with superoxide dismutase and catalase during hypoxia also resulted in a decrease in LDH release during reoxygenation.
 We conclude that an abrupt increase in [Ca2+]i during reoxygenation does not account for reoxygenation injury.
 However, in the presence of elevated [Ca2+]i, reoxygenation and the resulting probable resynthesis of ATP causes [Ca2+]i-dependent myofilament crossbridge cycling, and the resulting hypercontracture contributes to myocyte damage.
 The generation of oxygen free radicals after reoxygenation also appears to contribute to cell injury in this system.
",13
2333,"A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice. An in vitro study.
 While color Doppler flow mapping has yielded a quick and relatively sensitive method for visualizing the turbulent jets generated in valvular insufficiency, quantification of the degree of valvular insufficiency has been limited by the dependence of visualization of turbulent jets on hemodynamic as well as instrument-related factors.
 Color Doppler flow imaging, however, does have the capability of reliably showing the spatial relations of laminar flows.
 An area where flow accelerates proximal to a regurgitant orifice is commonly visualized on the left ventricular side of a mitral regurgitant orifice, especially when imaging is performed with high gain and a low pulse repetition frequency.
 This area of flow convergence, where the flow stream narrows symmetrically, can be quantified because velocity and the flow cross-sectional area change in inverse proportion along streamlines centered at the orifice.
 In this study, a gravity-driven constant-flow system with five sharp-edged diaphragm orifices (ranging from 2.9 to 12 mm in diameter) was imaged both parallel and perpendicular to the direction of flow through the orifice.
 Color Doppler flow images were produced by zero shifting so that the abrupt change in display color occurred at different velocities.
 This ""aliasing boundary"" with a known velocity and a measurable radial distance from the center of the orifice was used to determine an isovelocity hemisphere such that flow rate through the orifice was calculated as 2 pi r2 x Vr, where r is the radial distance from the center of the orifice to the color change and Vr is the velocity at which the color change was noted.
 Using Vr values from 54 to 14 cm/sec obtained with a 3.75-MHz transducer and from 75 to 18 cm/sec obtained with a 2.5-MHz transducer, we calculated flow rates and found them to correlate with measured flow rates (r = 0.94-0.99).
 The slope of the regression line was closest to unity when the lowest Vr and the correspondingly largest r were used in the calculation.
 The flow rates estimated from color Doppler flow imaging could also be used in conjunction with continuous-wave Doppler measurements of the maximal velocity of flow through the orifice to calculate orifice areas (r = 0.75-0.96 correlation with measured areas).
",13
2334,"Effects of pressure and volume of the receiving chamber on the spatial distribution of regurgitant jets as imaged by color Doppler flow mapping. An in vitro study.
 Regurgitant jet dimensions imaged by color Doppler flow mapping have been used to evaluate the severity of valvular insufficiency in clinical studies.
 To study the effect of pressure and volume within the receiving chamber on the magnitude of spatial distribution of regurgitant jets assessed by color Doppler techniques, we designed a simple constant-flow model in which a jet was driven through a known orifice (1.5 mm2) into a compliant receiving chamber by a steady-flow pump.
 A distal tube at the outflow closed the system and maintained the volume of the chamber constant during pump operation.
 We varied flow rate from 60 to 270 ml/min into elastic balloons with different static compliances of 1, 2, 4.5, and 9 ml/mm Hg (pressures of 57, 28, 18, and 8 mm Hg, respectively); the balloons served as receiving chambers at the constant volume of 150 ml.
 We also evaluated the effect of different volumes of a receiving chamber (110, 130, and 150 ml and pressures of 5, 15, and 24 mm Hg) with a static compliance of 2 ml/mm Hg over the same range of flow rates.
 For each of the different balloons, jet area correlated linearly with the jet velocity across the orifice (r = 0.98, 0.99, 0.98, and 0.97) and also with flow rate (r = 0.97, 0.99, 0.98, and 0.99).
 At the same flow rate and volume of receiving chamber, however, the jet area imaged by color Doppler decreased as the pressure in the receiving chamber increased, although receiving-chamber volume was constant.
",13
2335,"Changes in left ventricular volume, mass, and function during the development and regression of supraventricular tachycardia-induced cardiomyopathy. Disparity between recovery of systolic versus diastolic function.
 Chronic supraventricular tachycardia causes a dilated cardiomyopathy in man.
 Terminating this tachycardia appears to result in symptomatic improvement; however, its effects on left ventricular (LV) volume, mass, and function have not been fully examined.
 Accordingly, hemodynamic studies using simultaneous echocardiography and catheterization were performed in three groups of pigs: 1) those subjected to rapid left atrial pacing (240 beats/min) for 3 weeks (SVT, n = 8), 2) those subjected to supraventricular tachycardia for 3 weeks followed by termination of pacing and a 4-week recovery period (PSVT, n = 9), and 3) sham-operated controls (CTR, n = 10).
 Systolic pump function was assessed using fractional shortening (FS), peak ejection rate [peak (-)dD/dt], and maximum rate of pressure development [peak (+)dP/dt].
 Diastolic function was assessed using the time constant of isovolumic pressure decline (tau), peak early diastolic filling rate [peak (+)dD/dt], the chamber stiffness constant (Kc), and the myocardial stiffness constant (Km).
 Supraventricular tachycardia caused LV dilation (end-diastolic dimension [EDD] increased from 3.5 +/- 0.4 cm in CTR to 4.9 +/- 0.5 cm in SVT, p less than 0.05) but no change in LV mass (LV weight-to-body weight ratio [LV/BW]) was 2.58 +/- 0.3 g/kg in CTR and 2.66 +/- 0.4 g/kg in SVT), all indexes of systolic function became abnormal (FS fell from 30 +/- 4% in CTR to 13 +/- 5% in SVT, p less than 0.05), and the indexes of relaxation and filling were slowed (tau increased from 36 +/- 3 msec in CTR to 51 +/- 13 msec in SVT, p less than 0.05).
 There were no significant changes in Kc or Km.
 After terminating the supraventricular tachycardia, LV volume fell but remained greater than that in CTR (EDD was 4.2 +/- 0.4 cm in PSVT, p less than 0.05 versus CTR) and substantial LV hypertrophy developed (LV/BW was 3.48 +/- 0.5 g/kg in PSVT, p less than 0.05 versus CTR).
 Systolic function returned to normal (FS was 31 +/- 5% in PSVT) but diastolic function remained abnormal.
 In PSVT, tau remained prolonged (49 +/- 12 msec, p less than 0.05 versus CTR), Kc increased from 3.7 +/- 1.0 in CTR to 7.4 +/- 1.2 (p less than 0.05), and Km increased from 4.4 +/- 1.5 in CTR to 13.9 +/- 9.7 (p less than 0.05).
 Thus, the improvement in systolic function that occurs after the termination of supraventricular tachycardia is associated with the development of LV hypertrophy and persistent diastolic dysfunction.
",13
2336,"Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion.
 We evaluated the effect of altered loading conditions on left ventricular (LV) diastolic pressure-volume relations during acute coronary artery occlusion that was produced by inflation of an intracoronary balloon.
 Open-chest anesthetized dogs (n = 18) were instrumented so that LV pressure (micromanometer) and LV volume (conductance) could be measured without disturbing the pericardium.
 The effects of brief periods of occlusion (1-2 minutes) were assessed under steady-state conditions before and after dextran infusion with the pericardium present and absent and during vena caval occlusion.
 Under steady-state conditions before dextran infusion with the pericardium removed, at an LV end-diastolic pressure (EDP) of 8.4 +/- 1.4 mm Hg, occlusion resulted in a rightward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 2.7 +/- 2.3 mm Hg; delta LVEDV, 6.3 +/- 4.7 ml, both p less than 0.05 versus control).
 After dextran infusion (LVEDP, 20.9 +/- 6.0 mm Hg), occlusion resulted in a rightward and upward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 5.8 +/- 4.4 mm Hg; delta LVEDV, 4.2 +/- 3.0 ml, both p less than 0.05 versus control).
 At low cardiac volumes before dextran infusion, the intact pericardium did not affect the response to occlusion.
 By contrast, after dextran infusion in the presence of an intact pericardium, LVEDP significantly increased (delta, 6.4 +/- 3.6 mm Hg, p less than 0.05) but LVDEV did not (delta, 0.7 +/- 1.5 ml, p = NS).
 There was a parallel upward shift in the diastolic portion of the LV pressure-volume loop that was eliminated by removal of the pericardium.
 Thus, the change in LV diastolic pressure and volume during occlusion varied and depended on the baseline cardiac volume and presence of the pericardium.
 Before dextran infusion with the pericardium present and absent, coronary artery occlusion did not alter the LV diastolic chamber stiffness parameter, which was calculated from the diastolic interval of an averaged steady-state beat (0.040 +/- 0.019 versus 0.036 +/- 0.015 mm Hg/ml, p = NS).
 After dextran infusion with the pericardium present and absent, coronary artery occlusion increased the LV diastolic chamber stiffness parameter (0.057 +/- 0.034 and 0.074 +/- 0.034 mm Hg/ml, both p less than 0.05 versus controls, respectively).
 Vena caval occlusion eliminated the shifts in the diastolic portion of the LV pressure-volume loop with the pericardium present and absent.(ABSTRACT TRUNCATED AT 400 WORDS).
",13
2337,"Left ventricular diastolic dysfunction limits use of maximum systolic elastance as an index of contractile function.
 We tested the hypothesis that maximum systolic elastance (Emax) fails to detect a decline in left ventricular (LV) contractile function when diastolic dysfunction is present.
 Canine hearts were studied in an isolated blood-perfused heart apparatus (isovolumic LV); contractile dysfunction was produced by 60 or 90 minutes of global ischemia, followed by 90 minutes of reperfusion.
 Nine normal hearts underwent 60 minutes of ischemia, and five underwent 90 minutes of ischemia.
 After the ischemia-reperfusion sequence, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 14 hearts.
 In the group undergoing 60 minutes of ischemia, LV diastolic pressure did not increase, whereas Emax decreased from 5.2 +/- 2.5 to 2.9 +/- 1.4 mm Hg/ml (p less than 0.05).
 In the group undergoing 90 minutes of ischemia, diastolic pressure increased (from 10 +/- 2 to 37 +/- 20 mm Hg, p less than 0.05), and Emax did not change significantly (from 5.1 +/- 4.3 to 4.3 +/- 2.5 mm Hg/ml).
 A second series of experiments was performed in 13 hearts with pressure-overload hypertrophy (aortic-band model with echocardiography and catheterization studies before the ischemia-reperfusion protocol).
 Five had evidence for pump failure, whereas eight remained compensated.
 After 60 minutes of ischemia and 90 minutes of reperfusion, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 13 hearts.
 In the group with compensated LV hypertrophy, LV diastolic pressure did not change, whereas Emax decreased from 6.9 +/- 3.0 to 3.1 +/- 2.3 mm Hg/ml (p less than 0.05).
",13
2338,"The natural history of peripheral vascular disease. Implications for its management.
 The durability and the eventual complication rate of endovascular therapy (percutaneous transluminal angioplasty, laser-assisted angioplasty, and atherectomy) are not yet entirely clear, especially with respect to the treatment of atherosclerotic lesions in the femoropopliteal or distal arterial segments.
 Therefore, the indications for its use have not been firmly established and must take into consideration the natural history of the occlusive disease itself.
 Although some type of procedural intervention clearly is warranted in the presence of ischemic rest pain or tissue necrosis, intermittent claudication is the only complaint in approximately 70% of patients who present with either aortoiliac or femoropopliteal involvement.
 Most nondiabetic patients experience substantial symptomatic improvement with a daily exercise program, and their long-term risks for either abrupt deterioration (20-25%) or amputation (less than 10%) are relatively low.
 In comparison, the 5-year mortality rate ranges from 20-40% even in claudicants, and as many as 40% of those with clinical indications of associated coronary artery disease have been shown angiographically to be candidates for myocardial revascularization.
 These observations suggest that traditional indications for surgical treatment (truly disabling claudication and/or limb salvage) also should be applied to endovascular therapy until its success is confirmed beyond speculation, and that incidental coronary disease deserves particular attention in patients with lower extremity ischemia.
",13
2339,"Impact of nonoperative therapy on the clinical management of peripheral arterial disease.
 Nonoperative therapy includes conservative noninterventional modalities and the endovascular interventional modalities of percutaneous transluminal angioplasty and a variety of laser systems and atherectomy devices.
 The role and impact of all nonoperative treatments are considered in the perspectives of the natural history of lower-extremity arteriosclerosis and its present surgical (operative) treatment.
 Nonoperative treatments may replace and/or facilitate surgical treatment in operative candidates.
 Nonoperative methods may also justify treatment in patients who cannot or should not be subjected to surgery.
 Facts and opinions relating to these uses of nonoperative treatments are presented, and the qualifications and credentialing of individuals who should be treating patients with lower-extremity ischemia resulting from peripheral arteriosclerosis are discussed.
",13
2340,"Diagnosis and evaluation of renovascular hypertension. Indications for therapy.
 Renovascular hypertension is caused by two distinct conditions with different causes, fibromuscular dysplasia and atheroma.
 Diagnosis of the former is both simpler and more rewarding, whereas atheromatous lesions of the renal artery may be secondary to essential hypertension.
 It is therefore important to establish existence of functional renal ischemia as well as an anatomical lesion.
 Universal screening of all hypertensive patients is not recommended because of the relatively low prevalence of the disease and insufficient accuracy of available screening tests.
 When renovascular hypertension is clinically suspected, an oral captopril test is the most reliable office screening test.
 After this, digital subtraction angiography with renal vein renins or captopril renography are appropriate steps.
 However, the latter procedure, while promising, requires further evaluation.
 Duplex scanning of the renal arteries also comes into this category.
 Arteriography is done last, so that if renal ischemia is indicated, angioplasty can be attempted at the same time as arteriography.
",13
2341,"Clinical and anatomical considerations for surgery in aortoiliac disease and results of surgical treatment.
 A variety of surgical procedures are available for the treatment of occlusive disease involving the aorta and iliac arteries.
 Use of the most appropriate operation in each patient, determined principally by disease location and patient risk, can provide highly effective relief of disabling claudication or limb-threatening ischemia with low morbidity and mortality rates.
 The excellent, durable results of current surgical practice should serve as the standard with which newer treatment modalities must be compared.
",13
2342,"Results and complications of angioplasty in aortoiliac disease 
 Percutaneous transluminal angioplasty was used to treat 340 aortoiliac lesions in 200 patients who were followed for as long as 90 months (mean, 28.7 months; median, 23 months).
 The initial success rate was 94.7% for lesions and 93.0% for patients.
 The indications for percutaneous transluminal angioplasty included claudication in 117 patients (58.5%), rest pain or ischemic night pain in 47 (23.5%), limb salvage in 33 (16.5%), and aiding in wound healing in three (1.5%).
 In the series, 70% of the patients had two or more cardiovascular risk factors.
 Angioplasty was initially unsuccessful in 14 patients, and 10 patients were lost to follow-up.
 Follow-up was obtained in 176 patients.
 The long-term results were analyzed using the life table method to determine cumulative patency.
 Fourteen patients were considered failures because of recurrent disease or symptoms.
 The projected 7.5-year cumulative patency rate was 85%.
 When the response to redilatation was considered, the projected 7.5-year cumulative patency rate was 92%.
 The results indicate that percutaneous transluminal angioplasty can successfully correct aortoiliac lesions and provide a long-term benefit for as long as 7.5 years.
",13
2343,"Standards for evaluating results of interventional therapy for peripheral vascular disease.
 Uniform standards for evaluating and reporting the results of therapeutic interventions for peripheral vascular disease are clearly needed.
 They are already established for vascular surgery, as represented by several reports by SVS/ISCVS committees, but they are not always followed by vascular surgeons and have been largely ignored by other vascular interventionists.
 In this article, the major problematic reporting practices are discussed and illustrated, and 14 recommendations are advanced to deal with them.
 They are intended to provide precise definitions, objective criteria of success or failure, standardized severity gradation schemes for peripheral vascular disease and its risk factors, and proper procedures for reporting the outcome of all forms of therapeutic intervention.
 Until these or some other agreed upon reporting standards are accepted and followed, the literature on peripheral vascular disease and its management will continue to be a source of confusion rather than enlightenment.
",13
2344,"Clinical and anatomic considerations for surgery in femoropopliteal disease and the results of surgery.
 From 1980 to 1988 we performed 288 femoropopliteal bypass operations in 231 patients at the Oregon Health Sciences University.
 The indication for the procedure was claudication in 31% and the relief of limb-threatening ischemia in 64%.
 Operative mortality occurred after four of these operations (1.4%), including three deaths from myocardial infarction and one death from stroke.
 The femoropopliteal bypass patients were divided into groups for patency analysis, including those undergoing bypass surgery with a good quality greater saphenous vein versus alternate bypass conduits and patients undergoing primary limb bypass versus those undergoing repeat bypass after prior bypass failure.
 Our overall primary graft patency for all femoropopliteal grafts was 79% at 5 years.
 Patients undergoing bypass with a good quality greater saphenous vein had primary graft patency of 85% at 5 years.
 Patients undergoing bypass using a conduit other than greater saphenous vein had a 5-year patency of 73%.
 Patients undergoing repeat bypass after a prior failed bypass had a 5-year patency of 57%.
",13
2345,"Femoropopliteal angioplasty. Factors influencing long-term success.
 Prospective data was recorded on 217 percutaneous transluminal angioplasty (PTA) procedures performed in the superficial femoral and popliteal arteries over an 8-year period.
 After the initial procedure, patients were followed with serial noninvasive studies and, in 71 patients, repeat angiography.
 The mean follow-up period was 7 years (range, 2-11 years).
 Standard life-table survival analysis was used to assess the factors potentially affecting long-term outcome.
 Excluding an initial technical failure rate of 10%, overall patencies at 1, 3, and 5 years were 81%, 61%, and 58%, respectively.
 After the first year, the prognosis (i.e., failure rate) appears to be linear over the long term (i.e., up to 10 years).
 Factors negatively influencing long-term patency include the presence of diabetes mellitus, diffuse atherosclerotic cardiovascular disease, or threatened limb loss.
 Technical factors correlated with failure include lesion length, moderate eccentricity, and a poor post-PTA appearance.
",13
2346,"Clinical and anatomic considerations for surgery in tibial disease and the results of surgery.
 Bypass vein grafts to the infrapopliteal arteries now achieve a 5-year cumulative patency equivalent to that of vein grafts to the popliteal arteries.
 The technique of in situ vein grafting to the tibial arteries is described and the results are presented.
 The 5-year cumulative patency for such bypasses and the 5-year limb salvage in the same patients have both been approximately 80%.
 These results coupled with those reported from other centers that have sizable experience in tibial artery reconstruction suggest that there has been real progress over the past decade in the salvage of lower extremities in patients with far advanced peripheral vascular disease through the use of autogenous venous bypass grafts.
",13
2347,"Hot-tip laser. Results and complications.
 The hot tip laser system for atheroablation has been used since mid-1984 as a device for broadening the indications for and extending the applicability of angioplasty in the management of lower-extremity atherosclerosis.
 It has been a controversial device.
 Although the system demonstrates that it can occasionally be useful for the management of occlusive as opposed to stenotic disease of the infrainguinal arteries, a close examination of the published data fails to demonstrate a consistent improvement in either the primary success or long-term patency rates for thermal energy applied to atheroma for recanalization of the lower extremity arteries.
",13
2348,"Prevention of hypertension and vascular changes by captopril treatment.
 Treatment of female spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats with captopril was carried out by the addition of the drug in the drinking water throughout pregnancy and lactation and after weaning.
 At 28 weeks of age, average systolic blood pressure of treated SHR was 113 +/- 3 mm Hg, which was below that of control SHR (188 +/- 3 mm Hg) and WKY rats (124 +/- 3 mm Hg).
 Body weight and heart rate of the SHR were not affected by the treatment.
 Tissue level of catecholamines was increased by captopril treatment in the superior cervical ganglia but remained unchanged in the plasma, heart, mesenteric arteries, and the adrenal glands of both SHR and WKY rats.
 Left ventricular weight, wall thickness, and internal diameter of the left ventricle in the SHR were reduced by the treatment.
 Morphometric measurements of the mesenteric arteries showed that vascular alterations present in the control SHR were prevented by the treatment.
 In the superior mesenteric artery and large mesenteric artery, smaller lumen size at maximal relaxation found in the control SHR was normalized to the level of the WKY rats.
 Hypertrophy of the medial wall in the superior mesenteric, large and small mesenteric arteries, and an increase in the number of smooth muscle cell layers in the large mesenteric artery of the SHR were prevented by the treatment.
 Perfusion study of the mesenteric vascular bed showed that reactivity of these vessels to norepinephrine was reduced, and sensitivity to norepinephrine (as determined by the effective dose that causes 50% of maximal response) was increased in the SHR by captopril treatment.
 Sensitivity of the tail artery in response to norepinephrine was not altered by the treatment.
 We conclude that long-term treatment with captopril of SHR before and after birth prevented the development of hypertension, structural and functional alterations of the mesenteric arteries, and cardiac hypertrophy.
",13
2349,"Isolation of preferentially expressed genes in the kidneys of hypertensive rats.
 By differential hybridization, three complementary DNAs designated as S3, S2, and SA were isolated, and the corresponding messenger RNAs (mRNAs) were differentially expressed between the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats.
 S3 is identical to cytochrome P450 IV A2.
 SA encoded a protein of 546 amino acid residues, and its carboxyl terminal region had a slight homology to luciferase.
 No homologous sequence has been reported in S2 sequences.
 S3 mRNA was about four times more abundantly expressed in the kidneys of 28-day-old SHR than in those of age-matched WKY rats, but there was no difference at age 16 weeks.
 A low NaCl diet positively modulated the expression of the S3 gene.
 S2 mRNA was almost undetectable in the kidneys of 28-day-old WKY rats but was clearly detected in those of age-matched SHR.
 The expression level of S2 mRNA in the livers of 16-week-old SHR was about five times higher than that of age-matched WKY rats.
 The expression of S2 mRNA in the livers was modulated by dietary NaCl and captopril.
 SA mRNA was more than 10 times more abundantly expressed in the kidneys of SHR than in those of WKY rats from age 4 weeks.
 With the administration of captopril, the expressions of SA mRNA in the livers of SHR were positively modulated.
 Because these three genes are not only differentially expressed between SHR and WKY rats but also related to sodium metabolism or blood pressure control, the identification of these genes may provide important probes to examine the mechanisms of hypertension.
",13
2350,"Impaired insulin action on skeletal muscle metabolism in essential hypertension.
 Previous studies have shown that essential hypertension is frequently associated with insulin resistance.
 The tissues responsible for this metabolic alteration have not been defined.
 We tested the hypothesis that skeletal muscle is the site of insulin resistance of essential hypertension with the use of the perfused forearm technique.
 Eight hypertensive (age 42 +/- 3 years, body mass index 27 +/- 1 kg/m2, intra-arterial mean blood pressure 126 +/- 4 mm Hg) and seven normotensive (age 48 +/- 3 years, body mass index 26 +/- 1 kg/m2, mean blood pressure 95 +/- 4 mm Hg) male volunteers were studied.
 After glucose ingestion (40 g/m2), normal glucose tolerance in the patients was maintained at the expense of a heightened plasma insulin response, suggesting the presence of insulin resistance.
 During graded, local (intra-arterial) hyperinsulinemia encompassing the physiological range (12-120 milliunits/l), glucose uptake by forearm tissues was significantly (p less than 0.03) reduced in the hypertensive subjects as compared with the controls at each of five insulin steps, by 43% on the average.
 In addition, forearm lactate and pyruvate release were significantly less stimulated in the hypertensive than in the normotensive group (p less than 0.01 for both), presumably as a consequence of the decreased glucose influx.
 Forearm exchange of oxygen, carbon dioxide, lipid substrates (free fatty acids, glycerol, and beta-hydroxybutyrate), and potassium were similar in the hypertensive and normotensive groups in the basal state.
 Insulin had no effect on oxygen consumption, carbon dioxide production, and respiratory quotient in either study group, whereas it stimulated free fatty acids, glycerol, and potassium uptake to the same extent in the hypertensive and normotensive groups.
",13
2351,"Nicotine impairs reflex renal nerve and respiratory activity in deoxycorticosterone acetate-salt rats.
 Smoking exacerbates the increase in arterial pressure in hypertension.
 The effect of nicotine on the baroreceptor-mediated reflex responses of renal nerve activity (RNA), heart rate, and respiratory activity (minute diaphragmatic activity [MDA]) after bolus injections of phenylephrine was compared in deoxycorticosterone acetate (DOCA)-salt sensitive and normotensive rats.
 Osmotic minipumps that dispensed either nicotine (2.4 mg/kg/day) or saline were implanted in DOCA and normotensive rats for 18 days.
 Anesthetized DOCA-nicotine, DOCA-saline, control-nicotine, and control-saline rats had mean arterial pressures (MAP) of 117 +/- 3, 110 +/- 9, 90 +/- 3, and 89 +/- 5 mm Hg, respectively.
 Nicotine decreased the sensitivity (p less than 0.05) of baroreceptor reflex control of RNA (% delta RNA/delta MAP) in the DOCA-nicotine rats (-0.92 +/- 0.08) compared with the DOCA-saline (-1.44 +/- 0.16), control-nicotine (-1.45 +/- 0.08), or control-saline (-1.45 +/- 0.21) rats.
 The reflex decrease in respiratory activity (% delta MDA/delta MAP x 100) was impaired (p less than 0.01) in both control-nicotine (-24.5 +/- 3.3) and DOCA-nicotine (-18.2 +/- 4.6) rats compared with control-saline (-59.2 +/- 9.1) and DOCA-saline (-52.5 +/- 9.9) rats.
 The reflex decrease in heart rate (absolute delta HR/delta MAP) in both DOCA-nicotine (1.56 +/- 0.17) and control-nicotine (1.54 +/- 0.24) rats was augmented compared with DOCA-saline and control-saline rats (0.91 +/- 0.12 and 0.97 +/- 0.14).
",13
2352,"Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. The TAIM Research Group.
 The Trial of Antihypertensive Interventions and Management is a multicenter randomized trial designed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension (diastolic blood pressure 90-100 mm Hg).
 Eight hundred and seventy-eight participants at 110-160% of ideal weight were randomly allocated to nine drug/diet treatment groups receiving either a placebo, chlorthalidone (25 mg), or atenolol (50 mg), combined with a usual, a weight loss, or a low sodium/high potassium diet.
 The primary outcome was diastolic blood pressure change from baseline to 6 months.
 Seven hundred and eighty-seven participants had follow-up data.
 The mean baseline diastolic blood pressure was 93.8 mm Hg; 55.9% of the participants were male, and the weight loss diet group lost an average of 4.7 kg.
 Multiple comparisons were accounted for in the analysis.
 A significantly greater lowering of diastolic blood pressure (12.4 mm Hg) was achieved in the atenolol group compared with either the low sodium/high potassium diet group (7.9 mm Hg, p = 0.001) or weight loss group (8.8 mm Hg, p = 0.006).
 Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering (15.1 mm Hg) when compared with the diuretic alone (10.8 mm Hg, p = 0.002), but adding a low sodium/high potassium diet (12.2 mm Hg, p = 0.029) did not.
 In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration, drugs outperform diet, and weight loss is beneficial, especially with diuretics.
",13
2353,"Characterization of auscultatory gaps with wideband external pulse recording.
 Three types of auscultatory gaps, called G1, G2, and G3, that occur during blood pressure measurement have been identified by using wideband external pulse recording.
 We have previously shown that the wideband external pulse recorded during cuff deflation can be separated into three components (K1, K2, and K3), one of which (K2) is closely related to the Korotkoff sound.
 G1 occurs with cuff pressure just below systolic and is characterized by the presence of K1 and K2 with intermittent disappearance of K2.
 G1 gaps are related to a phasic decrease of arterial (systolic) pressure and were exhibited by 13 of 60 hypertensive patients.
 G2 gaps are related to a phasic increase of arterial (diastolic) pressure, occur when cuff pressure is just above diastolic, and are characterized by the presence of K1, K2, and K3 with intermittent disappearance of K2.
 Seven of 60 hypertensive patients exhibited a G2 gap.
 G3 gaps occur with cuff pressure between systolic and diastolic and are characterized by an underdeveloped or blunted K2 signal.
 Three of 60 hypertensive patients exhibited a G3 gap.
 The identification of auscultatory gaps in relation to the wideband external pulse provides a qualitative measure of their existence, can be of significant value in better understanding aspects of the auscultatory blood pressure measurement technique, and provides an objective basis with which to better understand the mechanisms that cause them.
",13
2354,"Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.
 The regulation of protein metabolism in the human heart has not previously been studied.
 In 10 postabsorptive patients with coronary artery disease, heart protein synthesis and degradation were estimated simultaneously from the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the dilution of its specific activity across the heart at isotopic steady state.
 We subsequently examined the effect of branched chain amino acid (BCAA) infusion on heart protein turnover and on the myocardial balance of amino acids and branched chain ketoacids (BCKA) in these patients.
 In the postabsorptive state, there was a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32 nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than 0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism.
 During BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/- 24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07 +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min).
 BCAA infusion stimulated the myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates (P less than 0.001) in proportion to their circulating concentrations.
 Net uptake of the BCAA greatly exceeded that of other essential amino acids suggesting a role for BCAA and BCKA as metabolic fuels.
 Plasma insulin levels, cardiac double product, coronary blood flow, and myocardial oxygen consumption were unchanged.
 These results demonstrate that the myocardium of postabsorptive humans is in negative protein balance and indicate a primary anabolic effect of BCAA on the human heart.
",13
2355,"Sclerotherapy of varicose and telangiectatic leg veins. Minimal sclerosant concentration of hypertonic saline and its relationship to vessel diameter 
 The author reports the results of a double-blind, paired-comparison study using saline sclerosant plus or minus heparin additive.
 The study was designed to elucidate the effects of increasing concentrations of hypertonic saline with regard to vessel diameter, clinical efficacy, complications, and discomfort.
 Six hundred women with bilaterally symmetrical starburst telangiectasias or varicose veins were entered into the study.
 Sodium chloride 11.7% appeared to be the minimal sclerosant concentration of saline that produced the most effective vein sclerosis of vessels of less than 8 mm in diameter, while producing the least morbidity.
 The optimal concentration of the sclerosant may vary with the diameter of the vessels under therapeutic consideration.
",13
2356,"Natural history of moderate aortic stenosis.
 The natural history of severe, symptomatic aortic stenosis has been well documented.
 However, the natural history of moderate aortic stenosis remains poorly understood.
 Therefore, a group of 66 patients was identified who had a diagnosis of moderate aortic stenosis at the time of cardiac catheterization (aortic valve area 0.7 to 1.2 cm2) and who did not have surgical therapy during the 1st 180 days after cardiac catheterization.
 During a mean follow-up period of 35 months, 14 patients died of causes attributed to aortic stenosis and 21 underwent aortic valve replacement.
 The estimated probability for remaining free of any complication of aortic stenosis at the end of the first 4 years was 59%.
 Symptomatic patients with decreased ejection fraction or hemodynamic evidence of left ventricular decompensation were at greater risk for these complications.
 It is concluded that patients with moderate aortic stenosis are at significant risk for the development of complications.
",13
2357,"Effect of H1 receptor stimulation on coronary artery diameter in patients with variant angina: comparison with effect of acetylcholine 
 It has been suggested that histamine is involved in the pathogenesis of coronary spasm but its exact role remains unclear.
 H1 receptor stimulation of the coronary artery was performed with a selective intracoronary infusion of histamine (2 micrograms/min) in 21 patients with variant angina after blockade of the H2 receptor with cimetidine (25 mg/kg) and its effect on the coronary artery diameter was examined.
 Intracoronary injection of acetylcholine was also performed in 19 of the 21 patients.
 Ergonovine (0.2 mg) was intravenously administered in one patient.
 The coronary artery diameter was measured with cinevideodensitometric analysis.
 A mean plasma histamine concentration in the coronary sinus increased from 4 x 10(-9) to 7 x 10(-8) M 5 min after histamine infusion into the left coronary artery (n = 18).
 Coronary spasm was induced in 6 patients (29%) with histamine, in 18 (95%) with acetylcholine and in 1 with ergonovine.
 The effect of histamine on the luminal diameter was analyzed at the site of spasm in the 26 coronary arteries in which spasm was induced by acetylcholine or ergonovine.
 Of the 20 coronary arteries with a normal arteriogram or a fixed stenosis less than or equal to 50% of luminal diameter, histamine decreased the diameter in 4, increased it in 14 (70%) and caused no change in 2; of the 6 coronary arteries with a fixed stenosis greater than or equal to 75%, histamine decreased the diameter in 5 and increased it in 1.
 In the coronary arteries in which spasm was not induced by either acetylcholine or ergonovine, histamine increased the diameter, especially in those without advanced atherosclerosis.
",13
2358,"Percutaneous mitral valvuloplasty in surgical high risk patients.
 Among 126 consecutive patients undergoing percutaneous mitral valvuloplasty, 34 were judged to be at high risk for surgery on the basis of age greater than 70 years (n = 13), New York Heart Association functional class IV (n = 11), ejection fraction less than or equal to 35% (n = 3), severe pulmonary hypertension (n = 7), need for associated coronary bypass (n = 4) or additional valve surgery (n = 20) or severe pulmonary disease (n = 3).
 Baseline features of the high risk group were substantially worse than those of the other patients: age (65 +/- 11 versus 49 +/- 12 years; p = 0.0001) and echocardiographic score (9.4 +/- 1.8 versus 8.2 +/- 1.5; p = 0.005) were higher, whereas cardiac output (2.9 +/- 0.9 versus 4.1 +/- 1.2 liters/min; p = 0.0001) and mitral valve area (0.9 +/- 0.4 versus 1.1 +/- 0.3 mm2; p = 0.002) were lower.
 Three high risk patients experienced technical failures and three others had major complications.
 Among the remaining 28 patients, 18 (65%) had a complete hemodynamic success, 4 (14%) an incomplete success and 6 (21%) hemodynamic failure.
 Stepwise logistic regression analysis retained echocardiographic score as the only factor independently predictive of success.
 The percent increase in mitral valve area also correlated with echocardiographic score (r = 0.51, p less than 0.01).
",13
2359,"The variable extent of jeopardized myocardium in patients with single vessel coronary artery disease: quantification by thallium-201 single photon emission computed tomography 
 To assess the extent of jeopardized myocardium in patients with single vessel coronary artery disease of variable severity and location, quantitative exercise thallium-201 single photon emission computed tomography was performed in 158 consecutive patients with angiographically proved single vessel coronary artery disease.
 The extent of abnormal left ventricular perfusion was quantified from computer-generated polar maps of three-dimensional myocardial radioactivity.
 Patients with only a moderate (51% to 69%) stenosis tended to have a small perfusion defect irrespective of the coronary artery involved.
 Whereas a perfusion defect measuring greater than or equal to 10% of the left ventricle was found in 78% of patients with no prior infarction and severe (greater than or equal to 70%) stenosis, this was observed in only 24% of patients with moderate stenosis.
 Perfusion defect size increased with increasing severity of stenosis for the entire group without infarction and for those with left anterior descending, right and circumflex coronary artery stenosis.
 However, the correlation between stenosis severity and perfusion defect size was at best only modest (r = 0.38, p = 0.0001).
 The left anterior descending artery was shown to be the most important of the three coronary arteries for providing left ventricular perfusion.
 Proximal stenosis of this artery produced a perfusion defect approximately twice as large as that found in patients with a proximal right or circumflex artery stenosis.
 However, marked heterogeneity in perfusion defect size existed among all three vessels despite comparable stenosis severity.
 This was most apparent for the left anterior descending coronary artery, where mid vessel stenosis commonly produced a perfusion defect similar in size to that found in proximally stenosed vessels.
",13
2360,"Primary angioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99m isonitrile.
 Technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (technetium-99m isonitrile) is a new radiopharmaceutical compound that reflects myocardial perfusion.
 Its kinetics, especially its lack of redistribution after intravenous administration, permits the assessment of changes in myocardial perfusion without delay of therapy.
 Tomographic images at rest were obtained immediately and 6 to 10 days later in 17 consecutive patients undergoing successful primary angioplasty during their first transmural myocardial infarction.
 Thirteen patients had anterior infarction.
 The initial (acute) defect size before angioplasty of 48 +/- 17% of the left ventricle decreased significantly (p less than 0.0001) to 29 +/- 19% on the late scans.
 There was no correlation between the time to therapy and the reduction in defect size.
 Twelve of the 17 patients, including 7 of the 11 patients treated after 4 h, demonstrated a definite reduction in the initial defect size.
 Eight patients with angiographically proved persistent coronary occlusion underwent a similar imaging sequence.
 The initial defect size in this group remained unchanged on the late scans (24 +/- 16% versus 26 +/- 18%, p = NS).
 Primary angioplasty is an effective approach toward salvaging myocardium; comparison with thrombolytic drug therapy must await the results of controlled clinical trials.
",13
2361,"Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography.
 To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism (using F-18 2-deoxyglucose) with positron emission tomography can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 21 patients with severe left ventricular dysfunction who were evaluated for cardiac transplantation were studied.
 The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (11 patients) or nonischemic (10 patients).
 Images were visually analyzed by three observers on a graded scale in seven left ventricular segments and revealed fewer defects in dilated cardiomyopathy compared with ischemic cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03) and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03).
 An index incorporating extent and severity of defects revealed more homogeneity with fewer and less severe defects in subjects with nonischemic than in those with ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/- 3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less than 0.005).
 Diagnostic accuracy for distinguishing the two subgroups by visual image analysis was 85%.
 Using previously published circumferential count profile criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4 +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients with cardiomyopathy of coronary artery disease.
 The sensitivity for differentiating the two clinical subgroups using circumferential profile analysis was 100% and the specificity 80%.
 An index incorporating both number and severity of defects derived from circumferential profile analysis was significantly lower in subjects with dilated cardiomyopathy than in ischemic cardiomyopathy (0.3 +/- 0.8 versus 2.7 +/- 2.4; p less than 0.005).
 Thus, noninvasive positron emission tomographic imaging with N-13 ammonia and F-18 deoxyglucose is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy, and a semiquantitative index such as circumferential profile analysis is superior to that of visual analysis alone.
",13
2362,"Comparison of pre- and postoperative conduction patterns in patients surgically cured of atrioventricular node reentrant tachycardia.
 Patients with atrioventricular (AV) node reentrant tachycardia characteristically have short and constant retrograde His-atrium conduction times (H2A2 intervals) during the introduction of ventricular extrastimuli.
 It has therefore been suggested that the tachycardia circuit involves retrograde conduction up an accessory pathway located in perinodal tissue.
 If the mechanism of surgical cure of AV node reentrant tachycardia is interruption of this accessory pathway, postoperative changes in retrograde conduction would be expected.
 Thirteen patients with drug-refractory AV node reentrant tachycardia underwent surgery.
 Preoperatively, H2A2 intervals were short and constant.
 During AV node reentrant tachycardia, earliest atrial activation was seen near the His bundle and was 0 to 25 ms before ventricular activation in all patients except one.
 Surgery consisted of dissection of right atrial septal and anterior inputs to the AV node and central fibrous body.
 Postoperatively, the H2A2 interval remained short and constant compared with preoperative values although it was slightly prolonged (74 +/- 18 versus 61 +/- 21 ms, p less than 0.005).
 Twelve of the 13 patients are free of tachycardia after 28 +/- 13 months and no patient has had evidence of AV node block.
 Thus, surgical cure of AV node reentrant tachycardia is highly successful; however, there is no reason to postulate an accessory pathway or use of perinodal tissue as part of the tachycardia circuit and the mechanism of surgical success remains obscure.
",13
2363,"Prolonged and fractionated right atrial electrograms during sinus rhythm in patients with paroxysmal atrial fibrillation and sick sinus node syndrome.
 Intraatrial catheter mapping of the right atrium was performed during sinus rhythm in 92 patients: Group I = 43 control patients without paroxysmal atrial fibrillation or sick sinus node syndrome; Group II = 31 patients with paroxysmal atrial fibrillation but without sick sinus node syndrome; and Group III = 18 patients with both paroxysmal atrial fibrillation and sick sinus node syndrome.
 Atrial electrograms were recorded at 12 sites in the right atrium.
 The duration and number of fragmented deflections of the atrial electrograms were quantitatively measured.
 The mean duration and number of fragmented deflections of the 516 atrial electrograms in Group I were 74 +/- 11 ms and 3.9 +/- 1.3, respectively.
 The criteria for an abnormal atrial electrogram were defined as a duration of greater than or equal to 100 ms or eight or more fragmented deflections, or both.
 Abnormal atrial electrograms were observed in 10 patients (23.3%) in Group I, 21 patients (67.7%) in Group II and 15 patients (83.3%) in Group III (Group II versus Group I, p less than 0.001; Group III versus Group I, p less than 0.001).
 The mean number of abnormal electrograms per patient with an abnormal electrogram was 1.3 +/- 0.7 in Group I, 2.5 +/- 1.9 in Group II and 3.5 +/- 2.5 in Group III (Group I versus Group II, p less than 0.01; Group II versus Group III, p less than 0.05).
 A prolonged and fractionated atrial electrogram characteristic of paroxysmal atrial fibrillation can be closely related to the vulnerability of the atrial muscle.
",13
2364,"Spontaneous changes in ventricular tachycardia cycle length.
 Understanding spontaneous fluctuations in ventricular tachycardia cycle length is required to develop algorithms for ventricular tachycardia detection and termination.
 Variations in cycle length, time to stable cycle length and the range of RR intervals during ventricular tachycardia were analyzed in 74 episodes of sustained monomorphic ventricular tachycardia induced in patients not taking antiarrhythmic medication.
 Linear regression demonstrated cycle length variability to decrease over time (41 +/- 24 to 17 +/- 19 ms, p less than 0.001).
 Slower ventricular tachycardia had more cycle length variability than faster ventricular tachycardia (p less than 0.001).
 Ventricular tachycardia that was initially more variable tended to remain more variable (p less than 0.001).
 Fifty-four percent of episodes stabilized within the first 15 beats, 75% by 30 beats and 93% by 50 beats.
 The number of beats to stable cycle length was independent of ventricular tachycardia rate.
 The average range in cycle length per episode was 127 +/- 72 ms; 12% of ventricular tachycardia episodes varied by less than 50 ms and 45% by less than 150 ms.
 The maximal range in RR intervals from a single episode of ventricular tachycardia was 290 ms.
 Therefore, ventricular tachycardia demonstrates a wide range of cycle lengths and has time-dependent changes in variability and stability.
 These cycle length changes should be considered in the algorithms for ventricular tachycardia detection and termination by automatic antitachycardia devices.
",13
2365,"Echocardiographic evaluation of cardiac structure and function in elderly subjects with isolated systolic hypertension 
 One hundred four participants in the Systolic Hypertension in the Elderly Program (SHEP) trial (mean age 71 +/- 6 years) were examined by Doppler echocardiography to gain information on the cardiac structural and functional alterations in isolated systolic hypertension.
 Participants had a systolic blood pressure greater than 160 mm Hg with diastolic blood pressure less than 90 mm Hg and were compared with 55 age-matched normotensive control subjects.
 Left ventricular mass index was significantly higher in the participants than in the normotensive subjects (103 +/- 28 versus 87 +/- 23 g/m2, p = 0.0014) and 26% of the participants met echocardiographic criteria for left ventricular hypertrophy compared with 10% of normotensive subjects.
 Left atrial index was also greater in participants than in normotensive subjects (2.26 +/- 0.32 versus 2.11 +/- 0.24 cm/m2, p = 0.005) and 51% of participants had left atrial enlargement.
 Doppler measures of diastolic filling were significantly different between the two groups, with peak atrial velocity higher (76 +/- 17 versus 69 +/- 17 cm/s, p = 0.02) and ratio of peak early to atrial velocity lower (0.76 +/- 0.23 versus 0.86 +/- 0.22, p = 0.0124) in participants.
 There was no correlation between left ventricular mass index and Doppler measures of diastolic function, but relative wall thickness correlated significantly with peak atrial velocity (r = 0.22, p = 0.016) and peak early to peak atrial velocity ratio (r = 0.24, p = 0.007).
 There was no difference in M-mode ejection phase indexes of systolic performance (shortening fraction and peak velocity of circumferential fiber shortening) between the two groups.
",13
2366,"Immunosuppressive therapy in the management of acute myocarditis in children: a clinical trial.
 To assess whether steroid therapy influenced the clinical course of myocarditis in a pediatric population, findings in 13 consecutive infants and children (8 female, 5 male) with biopsy-proved myocarditis were reviewed.
 The mean age was 5.7 +/- 4.8 years (range 1.1 to 14.8).
 Congestive heart failure was present in all as were ST-T wave changes, cardiomegaly and pulmonary edema on chest roentgenogram.
 Echocardiography demonstrated pericardial effusion in five patients and mitral regurgitation in eight.
 Mean left ventricular ejection fraction was 34 +/- 12%.
 Prednisone was administered to all patients; one patient also received azathioprine.
 There was one death.
 All survivors showed clinical improvement with normalization of ECG changes, heart size and systolic function.
 No significant side effects occurred.
 Repeat myocardial biopsy in eight patients demonstrated improvement in all eight and elimination of the inflammatory infiltrate in six.
 Immunosuppressive therapy in this pediatric population appeared useful in improving the clinical course and cardiac function in acute myocarditis with no adverse side effects.
",13
2367,"Effect of atenolol and diltiazem on heart period variability in normal persons.
 Several time and frequency domain measures of heart period variability are reduced 1 to 2 weeks after myocardial infarction, and a reduced standard deviation of normal RR intervals over a 24 h period (SDNN) is associated with increased mortality.
 The predictive accuracy of heart period variability may be reduced by drugs used to treat patients after myocardial infarction.
 Accordingly, a randomized, three period, placebo-controlled, crossover (Latin square) design was used to determine the effect of atenolol and diltiazem on time and frequency measures of heart period variability calculated from 24 h continuous electrocardiographic recordings during treatment with atenolol, diltiazem and placebo in 18 normal volunteers.
 During atenolol treatment, the 24 h average normal RR (NN) interval increased 24% (p less than 0.001).
 The three measures of tonic vagal activity were significantly increased (p less than 0.001) during atenolol treatment: percent of successive normal RR intervals greater than 50 ms = 69%, root mean square successive difference of normal RR intervals = 61% and high frequency power in the heart period power spectrum = 84%.
 Low frequency power also increased 45% (p less than 0.01), indicating that this variable also is an indicator of tonic vagal activity over 24 h.
 Diltiazem had no significant effect on the 24 h average NN interval or on any measure of heart period variability.
 The decreased mortality rate after myocardial infarction associated with beta-adrenergic blocker but not calcium channel blocker therapy may be attributed in part to an increase in vagal tone caused by beta-blockers.
",13
2368,"Hypertrophy, fibrosis and diastolic dysfunction in early canine experimental hypertension.
 To examine the relations among hypertrophy, fibrosis and diastolic performance in early experimental hypertension, 18 control dogs and 12 dogs with experimental left ventricular hypertrophy were studied.
 Diastolic function was impaired in dogs with left ventricular hypertrophy, with decreased Doppler early to atrial inflow velocity ratio (E/A) (1.35 versus 1.72), increased atrial filling fraction (35% versus 29%), decreased sonomicrometric peak rates of wall thinning (-2.01 versus -3.37 liters/s) and filling (4.33 versus 6.64 liters/s) and prolonged time constant of isovolumetric relaxation (tau; 34.3 versus 28.1 ms).
 Neither chamber stiffness (k; P = AekV) nor passive elastic stiffness (E; E = k sigma, where sigma = stress) was increased.
 At postmortem examination, the hypertensive left ventricle weighed significantly more than normal (116 versus 80 g; p less than 0.01) and had greater muscle fiber diameter at endocardial and epicardial sampling sites in the apical free wall, basal free wall and septum (mean diameter 50 +/- 8 microns in hypertensive dogs, 37 +/- 8 microns in normal dogs; p less than 0.01).
 In contrast, neither percent fibrosis (1.2 +/- 0.8 versus 0.9 +/- 0.6 in normal dogs) nor fibrotic volume (1.21 +/- 0.63 versus 0.72 +/- 0.42%/g in normal dogs) was significantly increased.
 Peak volumetric filling rate was inversely related to fiber diameter (r = -0.74, p less than 0.001), although no variable of left ventricular function was significantly related to percent or volume fibrosis (all r less than 0.60, all p greater than 0.05).
 Thus, diastolic dysfunction may exist in the setting of hypertrophy without significant fibrosis.
 Increased myocyte size was associated with early diastolic filling abnormalities characteristic of the hypertensive left ventricle.
 Fibrosis appears to be a less important determinant of diastolic performance.
",13
2369,"Transesophageal echocardiography is superior to transthoracic echocardiography in the diagnosis of sinus venosus atrial septal defect.
 The purpose of this study was to compare transthoracic and transesophageal echocardiography in the diagnosis of various types of atrial septal defects.
 Forty-one adult patients with the clinical diagnosis of atrial septal defect were studied by transthoracic and transesophageal echocardiography (30 women, 11 men; 18 to 81 years of age).
 Transthoracic echocardiography demonstrated the atrial septal defect in 33 patients (secundum type in 28, primum type in 3 and sinus venosus type in 2).
 Transesophageal echocardiography demonstrated the defect in all 41 patients.
 Thus, in 8 (20%) of 41 patients the atrial septal defect was demonstrated by transesophageal and not by transthoracic echocardiography.
 Six of the eight had a sinus venosus type atrial septal defect; the other two patients had a secundum atrial septal defect (one of these two had a technically poor transthoracic echocardiogram and the other had a small atrial septal defect).
 Transthoracic echocardiography, therefore, failed to demonstrate the sinus venosus defect in six (75%) of eight patients.
 An anomalous venous connection associated with the sinus venosus defect was visualized by transesophageal echocardiography in seven of the eight patients but was not seen on transthoracic echocardiography in any patient.
 Sinus venosus type atrial septal defects are frequently not visualized in adults by conventional transthoracic echocardiography.
 Transesophageal echocardiography is recommended when an atrial septal defect is clinically suspected but cannot be visualized by transthoracic echocardiography.
",13
2370,"Physicians' perspectives on cholesterol and heart disease.
 In early spring of 1988, questionnaires were mailed to 4,000 Midwestern physicians to survey their attitudes and practices regarding elevated serum cholesterol and their use of referrals for nutrition counseling; 633 physicians responded.
 Sixty-eight percent of the physicians thought that reducing high serum cholesterol levels would substantially affect heart disease; however, physicians attributed considerably less preventive value to reducing the cholesterol level than to reducing blood pressure (80.3%) or ceasing smoking (90.0%).
 The range of serum cholesterol for which diet therapy was most frequently initiated was 5.70 to 6.20 mmol/L.
 The most frequent range for initiation of drug therapy was 7.80 to 8.25 mmol/L.
 The physicians reported that although their medical school training did not prepare them adequately for providing diet counseling, they did feel prepared to provide, and were successful in, counseling on diet modifications for reducing serum cholesterol.
 Few (10%) of the total sample reported having registered dietitians available for dietary counseling, and most (88.8%) believed that it is the physician's responsibility to provide such counseling.
 Although the low response rate limits the conclusions of the survey, it is likely that those physicians most interested in the topic responded.
 We conclude that registered dietitians should explore the need for their special services further.
 More aggressive marketing of dietetic services could benefit both physicians and patients in the campaign to reduce serum cholesterol.
",13
2371,"Influence of dietary cod liver oil on fatty acid composition of plasma lipids in human male subjects after myocardial infarction.
 A randomized crossover study was carried out to investigate the fatty acid profile and concentrations of plasma lipids in male patients with myocardial infarction (MI) who supplemented their diet with 20 ml cod liver oil daily for 6 weeks.
 Subjects were divided into two groups, A and B.
 Group A received cod liver oil daily for 6 weeks after hospital discharge, but none for the subsequent 6 weeks.
 Group B did not start taking cod liver oil until 6 weeks after hospital discharge, and they then took cod liver oil for 6 weeks.
 Diet, medication or smoking habits were kept as constant as possible during the study.
 During the period of cod liver oil intake, eicosapentaenoic acid (20:5 (n-3), EPA) and docosahexaenoic acid (22:6 (n-3), DHA) increased significantly in phospholipids (PL), triglycerides (TG) and cholesterol esters (CE), whereas linoleic acid (18:2 (n-6), LA), dihomo-gamma-linolenic acid (20:3 (n-6), DHGLA) and arachidonic acid (20:4 (n-6), AA) were significantly decreased in phospholipids.
 The plasma level of TG was significantly decreased during the cod liver oil intake.
 Total cholesterol, high density lipoprotein (HDL) cholesterol, and levels of apolipoproteins A1 and B were not affected by cod liver oil in these MI patients.
",13
2372,"Atrioventricular plane displacement in severe congestive heart failure following dilated cardiomyopathy or myocardial infarction.
 Echocardiographic recording of the atrioventricular (AV) plane displacement during the cardiac cycle was used to assess left ventricular (LV) global function in patients with congestive heart failure (CHF).
 The study population consisted of 70 patients with chronic CHF (NYHA functional groups III and IV) following dilated cardiomyopathy (DCM) or myocardial infarction (MI), and 35 age-matched healthy subjects.
 The AV plane displacement was recorded from the apical 4- and 2-chamber views at four LV sites located about 90 degrees apart and representing the septal, anterior, lateral and posterior parts of the LV wall.
 A mean value was calculated from the above sites (AV-mean).
 Patients with CHF showed a significant generalized reduction of AV plane displacement compared to healthy subjects (5.6 mm vs.
 14.5 mm, P less than 0.001).
 Thirty CHF patients also underwent radionuclide angiography in order to determine the ejection fraction (EF).
 The correlation between AV-mean and EF was good (r = 0.82, P less than 0.001).
 The selection of an AV-mean of less than 7 mm to define a severely depressed LV function (EF less than 30%) gave a sensitivity of 92% and a specificity of 67%.
 It is concluded that the AV plane displacement can be used to estimate LV systolic function in patients with CHF.
",13
2373,"Elevation of plasma neuropeptide Y-like immunoreactivity and noradrenaline during myocardial ischaemia in man.
 Plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline were studied for 25 h in 22 patients with acute ischaemic heart disease.
 On admission, NPY-LI levels were above normal in 16 patients, and 20 patients had increased noradrenaline levels.
 The initial plasma NPY-LI did not differ between patients with acute myocardial infarction (AMI) and angina pectoris.
 Initial plasma noradrenaline levels were higher in patients with AMI than in those with angina pectoris.
 Plasma levels of noradrenaline remained elevated in AMI patients, but decreased towards normal values in patients with angina pectoris.
 Levels of NPY-LI returned to normal within 25 h in all patients.
 Tachycardia and left ventricular failure were related to high NPY-LI and noradrenaline levels.
 A positive correlation was found between noradrenaline and NPY-LI in plasma.
 It is suggested that neuropeptide Y (NPY), an endogenous vasoconstrictor peptide, should be considered as one of the mediators involved in the cardiovascular response to sympathetic activation induced by myocardial ischaemia.
",13
2374,"Unnecessary deaths from valvular aortic stenosis.
 The annual mortality from aortic valvular stenosis was calculated among potential candidates for surgical replacement of the aortic valve.
 From the Swedish Central Register of Causes of Death, 70 patients below the age of 80 years who had died from aortic stenosis during a 1-year period in the County of Stockholm (population 1.5 million), were identified.
 A retrospective analysis of their medical records showed that 37 individuals were suitable candidates for surgery.
 The presence of aortic stenosis had been verified at autopsy in 31 (84%) patients.
 The remaining six patients (16%) had their aortic stenosis diagnosis established by a thorough non-invasive investigation performed before death.
 Although typical signs and symptoms of aortic stenosis were recorded in all 37 patients, only six (16%) of them had been considered by their physicians to be suitable candidates for surgery prior to death.
 The deceased patients were compared with a group of 68 patients who had undergone aortic valve replacement for aortic stenosis during the same period.
 There were no significant differences between the two groups with regard to symptoms and clinical findings, except for a higher incidence of syncope in the operated group.
 It is concluded that, of 105 (68 surgically treated and 37 deceased) eligible patients with aortic stenosis, 37 individuals did not receive surgical care in time.
 The reason for this was probably insufficient knowledge of the curability of the disease.
",13
2375,"High urinary cAMP in hypertensives despite careful drug treatment--an epidemiological study from the Dalby population.
 The correlation between serum calcium (S-Ca), plasma parathyroid hormone (P-PTH) and hypertension was determined in a population-based, cross-sectional study of carefully treated hypertensives (n = 391; diastolic blood pressure 90.2 mmHg; 57 years) compared with normotensive controls (n = 328; diastolic blood pressure 82.1 mmHg; 57 years).
 Levels of urinary cyclic-adenosinemonophosphate (U-cAMP), but not of plasma cAMP (P-cAMP), were higher (P less than 0.001) in hypertensives than in controls.
 This was the case regardless of the type of drug treatment and the blood pressure level that was reached.
 U-cAMP correlated with adrenaline in multivariate analyses.
 S-Ca levels were higher (P less than 0.001) and S-Mg levels were lower (P less than 0.001) in hypertensives than in controls.
 This was not explained by thiazide treatment.
 Thus, despite 'adequate' blood pressure reduction, substantial differences in S-Ca, S-Mg and U-cAMP still exist between hypertensives and normotensive controls.
",13
2376,"Increased whole blood viscosity combined with decreased erythrocyte fluidity in untreated patients with essential hypertension.
 Erythrocyte fluidity and other haemorheological variables were studied in 22 patients with essential hypertension and compared with age- and sex-matched healthy controls.
 Hypertensive patients displayed a significantly lower erythrocyte fluidity (P less than 0.001).
 Similarly, significantly elevated values for haematocrit, plasma and whole blood viscosity, as well as aggregation tendency were observed compared to controls.
 Although differing in these respects from controls, there were no obvious relationships between these rheological variables and either systolic or diastolic blood pressure.
 The significantly lower erythrocyte fluidity and other changes in haemorheological variables of red blood cells found in hypertensive patients may be explained by an enlarged metabolic pool of free calcium ions in these red blood cells.
 It is suggested that the molecular mechanisms underlying the evolution of essential hypertension are multifactorial rather than being based on a single molecular derangement.
 Primary events resulting in altered physicochemical properties of the red blood cells may work in concert in the development of essential hypertension, in addition to the increased availability of calcium ions and their potential role in smooth muscle contraction.
",13
2377,"Assessment of myocardial perfusion in patients after the arterial switch operation.
 In 21 patients who had undergone the arterial switch operation, the adequacy of myocardial perfusion was evaluated by thallium-201 computed scintigraphy 2.6 +/- 2 (0.3-7) yr after surgery.
 Fourteen patients had undergone the arterial switch procedure after pulmonary artery banding and seven as a primary repair.
 Isoproterenol stress increased the heart rate by at least 55%.
 Tomographic imaging was performed at peak stress and 3 hr later in the reperfusion phase.
 Nine patients had perfusion defects.
 The perfusion defects were located at the left ventricular apex in four (with extension to the inferolateral wall in one), left ventricular anterolateral wall in two, ventricular septum in one, left ventricular inferior wall in one, and right ventricular free wall in one.
 Some of these defects could be due to myocardial damage at the time of surgery, but these results also raise concern about long-term adequacy of myocardial perfusion following the arterial switch procedure.
",13
2378,"Myocardial uptake of carbon-11-acetate as an indirect estimate of regional myocardial blood flow.
 The rate of clearance of myocardial carbon-11 (11C) activity (after the administration of 11C-acetate) has been shown to correlate closely with myocardial oxygen consumption.
 In the present study, we hypothesized that regional net myocardial uptake of 11C-acetate, which reflects primarily delivery and extraction of tracer, would be markedly flow-dependent and potentially useful as an indirect index of regional myocardial blood flow.
 In 22 patients with stable coronary artery disease, the regional distribution of early net uptake of 11C-acetate was correlated with estimates of regional myocardial blood flow assessed with oxygen-15-water.
 The myocardial images of 11C-acetate uptake were of high quality.
 The correlation between the two approaches was close (r = 0.88) and not affected by the metabolic state of the tissue.
 Thus, in patients with stable coronary artery disease, under resting conditions, direct estimates of myocardial oxygen consumption in relation to the level of delivery of tracer to the tissue can now be obtained by PET with use of a single radiopharmaceutical, 11C-acetate.
 This approach may prove particularly useful in streamlining clinical protocols designed to assess myocardial oxygen consumption.
",13
2379,"Blood-pool radionuclide angiography in patients with a Novacor left ventricular assist device.
 Blood-pool radionuclide angiography was used to investigate the left ventricular function in eight patients who received a Novacor assist device as a bridge-to-cardiac transplantation.
 Studies were performed during maximal and minimal tolerated assist device flows.
 The left ventricular ejection fraction, volumes, cardiac output, and the pump ejection fraction were computer-assessed.
 All patients had severe left ventricular dilation and hypokinesis before insertion of the assist device, with a mean ejection fraction of 18% +/- 4% which improved to 44% +/- 18% (p less than 0.01) during maximal assist device flows, but fell to 25% +/- 15% (p less than 0.01) during minimal flows.
 The ventricular volumes became normal at maximal assist device flow but increased significantly (p less than 0.05) during minimal flow.
 The pump was well visualized and had an ejection fraction of 82% +/- 7%.
 These data indicate that this assist device effectively unloads the left ventricle.
 The deterioration in ejection fraction following decrease in assist device flow is in keeping with the dependency of these patients on the device to sustain adequate hemodynamics.
",13
2380,"Early scintigraphic detection of experimental myocardial infarction in dogs with technetium-99m-glucaric acid 
 Recent data have generated some interest in technetium-99m-(99mTc) glucaric acid as an in vivo viability marker.
 We studied 99mTc-glucaric acid retention in canine models of myocardial ischemia (20-min occlusion of the LAD/40-min reperfusion), acute myocardial infarction (MI) (90-min LAD occlusion/3-hr reperfusion), and chronic MI (90-min occlusion and either 48-hr or 10-day reperfusion).
 Regional myocardial blood flow was measured by radiolabeled microspheres.
 No preferential uptake of glucaric acid was observed in ischemic but viable myocardium.
 The compound showed high affinity for necrotic myocardial tissue for several days following injury.
 The preferential uptake in infarcted tissue disappeared by 10 days following injury.
 This study shows that 99mTc-glucaric acid acts exclusively as a marker of necrosis in canine models of MI.
 Technetium-99m-glucaric acid may have clinical utility in early cardiac imaging of myocardial infarction and in differentiating recent from old injuries.
",13
2381,"Effect of coronary occlusion and myocardial viability on myocardial activity of technetium-99m-sestamibi 
 The timing effect of sestamibi administration with respect to the onset of myocardial ischemia and reperfusion was studied in swine.
 In different groups of animals sestamibi was administered prior to coronary artery occlusion, during occlusion, or 1/2 hour following reperfusion.
 Sestamibi administered prior to coronary occlusion resulted in an insignificant decrease in 99mTc activity in the ischemic zone.
 However, infarct zone activity was reduced to 62 +/- 14% of the nonischemic zone.
 In contrast, administration during coronary occlusion resulted in similar significant reductions of both ischemic and infarct zone activity.
 Administration of sestamibi during reperfusion resulted in normal ischemic zone activity and markedly reduced activity in the infarct zone.
 Significantly reduced activity in the infarct zone was found to be independent of the timing of sestamibi administration with respect to the onset of myocardial ischemia and/or reperfusion.
 Thus, cell viability appears required for uptake and retention of isotope activity.
",13
2382,"The management of primary pulmonary hypertension.
 Primary pulmonary hypertension is a clinical syndrome characterized by pulmonary hypertension in the absence of sufficient underlying cardiac, parenchymal pulmonary, or systemic disease to account for it.
 The population of patients with primary pulmonary hypertension is a heterogeneous one, both clinically and histologically.
 As the etiologic mechanisms are unknown, therapy is directed toward the consequences of the pulmonary vascular process.
 Oxygen supplementation, the use of digoxin and diuretics for symptomatic heart failure, and anticoagulation all may have a role in treating primary pulmonary hypertension, although vasodilator therapy has been the main area of investigation.
 Screening for vasodilator responsiveness, defining a favorable vasodilator effect, predicting long-term effectiveness, and deciding who to treat have all been controversial.
 New approaches, such as use of high-dose calcium channel-blocking agents and continuous intravenous infusion of prostacyclin (an investigational agent), have recently been proposed.
 When medical therapies are exhausted, heart-lung or lung transplantation has increasingly become an option for selected patients.
",13
2383,"Thromboexclusion of the right ventricle in children with pulmonary atresia and intact ventricular septum.
 Twelve children with pulmonary atresia and intact ventricular septum underwent closure of the tricuspid valve as a part of a new surgical procedure.
 In two cases a concomitant Fontan operation was performed.
 In each patient the right ventricle was very small and right ventricular pressure was higher than systemic pressure.
 Ventricle-coronary connections provided flow of desaturated blood from the right ventricle into the coronary arteries in 11 of 12 cases.
 Five of the 12 children did not survive operation and postmortem examination of each revealed severe acute and chronic myocardial ischemic damage and high-grade obstruction or interruption of the proximal left anterior descending coronary artery.
 Preoperative angiography demonstrated occlusive changes in the coronary arteries, resulting in right ventricular dependent circulation, in all five children who died and in one child who survived operation.
 Seven children who survived operation are well 4 months to 3.5 years later.
 Two have undergone subsequent successful Fontan operation and two others are considered suitable candidates for this operation.
 Tricuspid valve closure is recommended for a carefully selected group of infants with pulmonary atresia and intact ventricular septum provided a right ventricular-dependent coronary circulation can be excluded on the basis of preoperative coronary cineangiography.
",13
2384,"Left ventricular mechanics of ejecting, postischemic hearts during left ventricular circulatory assistance.
 We measured the effects of left ventricular circulatory assistance on ventricular mechanics of ejecting sheep hearts before and after global ischemia.
 Flows from left atrium to femoral artery ranged between 20 and 100 ml/kg/min during circulatory assistance.
 In preischemic, ejecting hearts increasing flow through the left ventricular assist device progressively decreased stroke volume, end-diastolic volume, and circumferential systolic wall stress, but only slightly decreased end-systolic volume.
 In postischemic, ejecting hearts left ventricular assistance progressively and substantially decreased both end-diastolic volume and end-systolic volume; at high flows, end-systolic volume returned to the normal range of preischemic hearts.
 High flows through the assist device also shifted end-systolic points of pressure-volume loops leftward and increased the stroke work/end-diastolic volume ratio in ejecting postischemic hearts; these observations raise the possibility that left ventricular circulatory assistance acutely improves myocardial contractility of postischemic hearts.
",13
2385,"Evolution of human cardiac myocyte dimension during prolonged mechanical support.
 In animal models using left ventricular assist systems over long time periods, myocardial cellular atrophy has been reported, raising concern that prolonged clinical use of such systems might lead to deterioration in left ventricular function.
 At the University of Pittsburgh, long-term clinical use of the Novacor (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.) left ventricular support system for patients awaiting heart transplants has allowed study of the effects of long-term mechanical support on human subjects.
 This study determined that cardiac myocyte dimension is initially greater in patients with end-stage cardiac disease who require support rather than in patients with the same disease who do not require such support.
 Although myocyte dimension does decrease within a few days of the inception of support, this decrease merely brings cell size closer to the values usual in patients with chronic end-stage cardiac disease, and no further shrinkage is observed.
 Thus the Novacor left ventricular assist system does not appear associated with left ventricular atrophy, and its long-term use may not be detrimental to left ventricular function.
",13
2386,"Cerebral air embolism treated by pressure and hyperbaric oxygen.
 We used pressure and hyperbaric oxygen to treat 2 patients with cerebral air embolism, occurring as the result of invasive medical procedures, and neither suffered any permanent damage detectable by clinical examination and MRI.
 This outcome contrasts with reports of infarct and disability among untreated victims of air embolism.
",13
2387,"Abdominal aneurysms in childhood: report of a case and review of the literature.
 Abdominal aneurysms are rare in children and are usually found in association with congenital cardiac or aortic malformations, connective tissue disorders, trauma, or previous arterial catheter placement.
 A 4-year-old girl who had a common iliac artery aneurysm, who had no history of arterial catheter placement or trauma, and who had no evidence of Marfan's or Ehlers-Danlos syndrome, arteritis, coarctation of the aorta, or other diseases associated with childhood aneurysms is presented.
 Resection of the aneurysm and arterial reconstruction were performed without the use of prosthetic material or vein graft.
 Pathologic examination showed no evidence of inflammation or medial degeneration in any of the layers of the arterial wall.
 This is the fourth report found in the literature of documented idiopathic abdominal aneurysm in a child.
 The conditions associated with abdominal aneurysms in childhood are discussed, and the literature is reviewed.
",13
2388,"Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: evidence from a national cohort.
 A national sample of 1944 white menopausal women greater than or equal to 55 years old from the epidemiologic follow-up of participants in the National Health and Nutrition Examination Survey was reviewed to investigate the role of hormone therapy in altering the risk of death from cardiovascular disease.
 Women in the study were observed for up to 16 years after the baseline survey in 1971 to 1975.
 By 1987 631 women had died; 347 of these deaths were due to cardiovascular disease.
 History of diabetes (relative risk, 2.38; 95% confidence interval 1.73 to 3.26), previous myocardial infarction (relative risk, 2.12; 95% confidence interval 1.56 to 2.86), smoking (relative risk, 2.18; 95% confidence interval, 1.69 to 2.81), and elevated blood pressure (relative risk, 1.49; 95% confidence interval, 1.14 to 1.94) were strong predictors of cardiovascular disease-related death in this cohort.
 After adjusting for known cardiovascular disease risk factors (smoking, cholesterol, body mass index, blood pressure, previous myocardial infarction, history of diabetes, age) and education, the use of postmenopausal hormones was associated with a reduced risk of death from cardiovascular disease (relative risk, 0.66; 95% confidence interval, 0.48 to 0.90).
 The same protective effect provided by postmenopausal hormone therapy was seen in women who experienced natural menopause (relative risk, 0.69; 95% confidence interval, 0.45 to 1.06).
",13
2389,"The prevalence of retinal vascular abnormalities in children and adolescents with essential hypertension.
 We studied 97 children and adolescents with essential hypertension by evaluating photographs of the optic fundus and fluorescein angiography.
 Photographs were examined for the presence of arteriolar narrowing, tortuosity, and arteriovenous nicking.
 Intraobserver and interobserver variability in determination of abnormalities was low with agreement of 75% for narrowing, 90% for tortuosity, and 100% for arteriovenous nicking.
 The prevalence of abnormalities was 41% (95% confidence interval, 31% to 50%) for arteriolar narrowing, 14% (95% confidence interval, 19% to 21%) for tortuosity, and 8% (95% confidence interval, 5% to 11%) for arteriovenous nicking.
 Of 97 patients, 50 (51%) had one or more abnormality.
 Retinal abnormalities are relatively common in young patients with essential hypertension.
",13
2390,"Mucoid vasculopathy of unknown etiology.
 A new vascular disorder with generalized deposition of abnormal amounts of acid mucopolysaccharide (AMPS) material in arteries, veins, and vasanervorum has been observed in a large number of autopsies at the author's institution.
 It is unlike any of the known vascular diseases and has emerged as a distinct disorder of vascular connective tissue.
 This has been named ""mucoid vasculopathy of unknown etiology."" This hitherto unreported entity is described here.
",13
2391,"Giant left atrium--a case report.
 A seventy-seven-year old woman, with mitral stenosis, presented with cardiomegaly evident on her chest roentgenogram.
 The cardiac enlargement was due to a giant left atrium that distorted the cardiac structures.
 An echocardiogram and a first-pass nuclear angiogram were able to delineate the huge left atrium.
",13
2392,"Sudden appearance of coronary thrombus observed by angiography--a case report.
 A sudden coronary thrombus formation was documented by chance during cardiac catheterization in a patient with postinfarction angina.
 The thrombus was successfully treated with intravenous urokinase and heparin infusions, and thereafter, coronary angioplasty was performed without any complication.
",13
2393,"Spontaneous cerebral embolism from descending thoracic aortic aneurysm--a case report.
 A case in which an aneurysm of the proximal descending thoracic aorta was the likely source of retrograde cerebral embolism is described.
 Atherosclerotic disease of the descending thoracic aorta should be considered as an unusual source of cerebral emboli.
",13
2394,"Total occlusion of the left main coronary artery in a young woman with survival: a case report.
 The total occlusion of the left main coronary artery (LMCA) is rare, and the survival depends on the existence of collateral circulation.
 The author presents a case of total occlusion of the left main coronary artery with survival in a young woman because he thinks this is a very rare case, owing to the sex and age of the patient.
",13
2395,"Axillary subclavian vein thrombosis. Changing patterns of etiology, diagnostic, and therapeutic modalities.
 Fifty-two patients with axillary-subclavian vein thrombosis were treated in the last 10 years and were available for follow-up for at least 1 year.
 Eighteen of these were treated in the first 5 years, Group A, and 34 in the last 5 years, Group B.
 The causes in both Group A and Group B included respectively: effort or spontaneous 28 per cent and 29 per cent, catheter insertion related 17 per cent and 47 per cent, and malignancy or systemic disease 55 per cent and 24 per cent.
 None of the patients in Group A had noninvasive vascular testing (NIT).
 However, 27 patients in Group B had IPG/duplex imaging (NIT).
 All 18 cases in Group A and 27 cases in Group B were treated conventionally (anticoagulants).
 Seventy-three per cent of these had residual pain on exertion (venous claudication) and/or swelling.
 Fourteen of these cases had posttreatment NIT/venography.
 Four of these showed total resolution of the thrombus and all were symptom free.
 Ten had no resolution, and nine were symptomatic.
 Seven cases in Group B were treated with thrombolytic therapy.
 Five of these had total resolution of thrombus and were symptom free (71%).
 Two had no resolution with residual symptoms (29%) (statistically significant).
 In conclusion (1) More patients with axillary-subclavian vein thrombosis seen recently are catheter insertion related; 2) Diagnosis should be initiated with duplex imaging; and (3) Thrombolytic therapy significantly decreased residual symptoms and yielded better resolution than anticoagulants.
",13
2396,"Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension.
 OBJECTIVE: To assess the prognostic significance of left ventricular mass and geometry in initially healthy persons with essential hypertension.
 DESIGN: An observational study of a prospectively identified cohort.
 SETTING: University medical center.
 PATIENTS: Two hundred and eighty patients with essential hypertension and no pre-existing cardiac disease were evaluated using echocardiography between 1976 and 1981.
 Two hundred and fifty-three subjects or their family members (90%) were contacted for a follow-up interview an average of 10.2 years after the initial echocardiogram was obtained; the survival status of 27 patients lost to follow-up was ascertained using National Death Index data.
 MEASUREMENTS AND MAIN RESULTS: Left ventricular mass exceeded 125 g/m2 in 69 of 253 patients (27%).
 Cardiovascular events occurred in a higher proportion of patients with than without left ventricular hypertrophy (26% compared with 12%; P = 0.006).
 Patients with increased ventricular mass were also at higher risk for cardiovascular death (14% compared with 0.5%; P less than 0.001) and all-cause mortality (16% compared with 2%; P = 0.001).
 Electrocardiographic left ventricular hypertrophy did not predict risk.
 Patients with normal left ventricular geometry had the fewest adverse outcomes (no cardiac deaths; morbid events in 11%), and those with concentric hypertrophy had the most (death in 21%; morbid events in 31%).
 In a multivariate analysis, only age and left ventricular mass--but not gender, blood pressure, or serum cholesterol level--independently predicted all three outcome measures.
 CONCLUSIONS: Echocardiographically determined left ventricular mass and geometry stratify risk in patients with essential hypertension independently of and more strongly than blood pressure or other potentially reversible risk factors and may help to stratify the need for intensive treatment.
",13
2397,"The role of calcium channel blockers in the treatment of essential hypertension.
 Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients.
 Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties.
 These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives.
 Combination therapy with other agents usually results in an additive response.
 Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects.
 Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common.
 Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk.
",13
2398,"A standard heparin nomogram for the management of heparin therapy.
 A nomogram for the adjustment of heparin dosage was developed to standardize heparin therapy and to reduce delays in achieving and maintaining a therapeutic activated partial thromboplastin time (APTT) result.
 Fifty consecutive patients with acute venous thromboembolism had their continuous intravenous heparin therapy adjusted according to this heparin nomogram.
 The effect of the nomogram on heparin therapy in these patients was compared with data from 53 historical control patients.
 The proportion of patients in the nomogram group who reached a therapeutic APTT at 24 hours after the start of heparin therapy was 66%, which increased to 81% at 48 hours.
 In contrast, 37% and 58% of the control patients reached a therapeutic APTT at 24 and 48 hours, respectively.
 The percentage of therapeutic APTT results of the total number of APTT determinations was greater in the nomogram patients than controls.
 The use of this heparin nomogram resulted in (1) achieving a therapeutic APTT at 24 and 48 hours in a large proportion of patients and (2) reduced periods of inadequate anticoagulation and overanticoagulation during heparin therapy.
",13
2399,"Ventricular tachycardia during routine treadmill testing. Risk and prognosis.
 Exercise-induced ventricular tachycardia during exercise testing is considered to increase risk during testing.
 Moreover, exercise-induced ventricular tachycardia has been considered to confer a poor prognosis although this has not been specifically studied.
 On a retrospective review of 3351 patients who had undergone routine clinical exercise testing between September 1984 and June 1989, we identified 55 patients with exercise-induced ventricular tachycardia.
 The mean follow-up was 26 months (range, 2 to 58 months).
 Fifty patients had nonsustained ventricular tachycardia during exercise testing and one of these patients died due to congestive heart failure during the follow-up period.
 Five patients had sustained ventricular tachycardia during exercise testing and one died suddenly 7 months after the test.
 Ventricular tachycardia was reproduced in only two of the 29 patients who underwent repeated exercise testing.
 Ventricular tachycardia during routine clinical exercise testing occurred rarely (prevalence of 1.5%) and was not associated with complications during testing.
 The total mortality in the exercise-induced ventricular tachycardia group (3.6%) was not significantly different from the mortality in the entire population (5.1%).
 Nonsustained ventricular tachycardia occurring during clinical exercise testing is not an independent marker of a poor prognosis.
",13
2400,"An echocardiographic assessment of atrial mechanical behaviour.
 Relations between movement of the atrioventricular ring and changes in left atrial and ventricular dimensions were studied by echocardiography and compared with apexcardiography and Doppler mitral flow velocity traces in 20 healthy controls and in patients with left ventricular hypertrophy (n = 28) or dilatation (n = 16).
 During left ventricular systole the atrioventricular ring, a structure common to ventricle and atrium, moved towards the ventricular apex, thus increasing left atrial volume.
 This action matched pulmonary venous return because it was in phase with the transverse left atrial dimension measured from aortic root to posterior left atrial wall.
 During early diastole, the mitral ring moved rapidly towards the atrium as transmitral flow accelerated.
 This requires a force directed from ventricle to atrium, likely to be the result of elastic recoil arising from compression of the ventricular myocardium or stretching of the atrial myocardium during ventricular systole.
 Two additional mechanisms of ventricular filling with atrial systole were recognised: (a) an increase in ventricular volume as the atrioventricular ring moved upwards and (b) transverse left ventricular expansion by pressure driven transmitral flow.
 The former is undetectable by Doppler from the apex; it accounted for 10% of ventricular filling in the healthy controls, but for significantly less in those with ventricular dilatation.
 In left ventricular hypertrophy, left ventricular filling was maintained by both mechanisms compensating for the reduced increase in volume early in diastole.
 Interactions between the atrium and ventricle are functionally important during ventricular systole, early diastole, and in atrial systole.
 They are not included in the traditional separation of atrial function into reservoir, conduit, and pump functions.
",13
2401,"End diastolic flow velocity just beneath the aortic isthmus assessed by pulsed Doppler echocardiography: a new predictor of the aortic regurgitant fraction.
 End diastolic flow velocity just beneath the aortic isthmus was measured within 72 hours of cardiac catheterisation by pulsed Doppler echocardiography in 30 controls and 61 patients with aortic regurgitation.
 The end diastolic flow velocity was determined at the peak R wave on a simultaneously recorded electrocardiogram.
 In all controls there was no reverse flow at the end diastole beneath the aortic isthmus.
 In patients with aortic regurgitation the end diastolic flow velocity correlated well with the angiographic grade of regurgitation (r = 0.81) and regurgitant fraction (r = 0.82).
 The mean (SD) values were 6.3 (5.2), 12.2 (4.3), 22.1 (5.7), and 34.3 (9.3) cm/s for patients with regurgitant fraction of less than 20%, between 20% and 40%, between 41% and 60%, and greater than 60%, respectively.
 An end diastolic flow velocity of greater than 18 cm/s predicted a regurgitant fraction of greater than or equal to 40% with a sensitivity of 88.5% and a specificity of 96%.
 The study suggests that the pulsed Doppler derived end diastolic flow velocity is a useful index in the routine non-invasive assessment of the severity of aortic regurgitation.
",13
2402,"Interatrial shunt flow profiles in newborn infants: a colour flow and pulsed Doppler echocardiographic study.
 Interatrial shunt flow profiles in 36 normal term infants were examined serially by colour flow and pulsed Doppler echocardiographic techniques from within an hour of birth to four or five days after birth.
 Shunt flow across the foramen ovale was detected in 33 normal infants (92%) within an hour of birth (mean 40 minutes).
 The occurrence of interatrial shunting decreased with age, but a shunt signal was still detected in 17 infants (47%) on the fourth or fifth day of life, by then the ductus arteriosus had already closed in all the normal infants.
 The direction of interatrial shunt flow was predominantly left-to-right, but in 64% there was a coexistent small right-to-left shunt in diastole within an hour of birth; by four to five days it was found in 19%.
 In the six patients with persistent fetal circulation the direction of the interatrial shunt flow was predominantly right-to-left with biphasic peaks in diastole and systole at the early stage of the disease, and the period of right-to-left shunt flow during each cardiac cycle was significantly longer than that in normal infants examined within 1 hour of birth.
 In all patients the ductus closed before the foramen ovale.
 At the time of ductal closure in all patients with persistent fetal circulation right-to-left shunt flow was seen during diastole and its period was still prolonged.
 These findings suggest that interatrial shunting, predominantly left-to-right, is common in normal newborn infants.
",13
2403,"Extrahepatic portal vein aneurysm associated with a tortuous portal vein.
 Portal vein aneurysm is rare and its etiology is controversial.
 A case of extrahepatic portal vein aneurysm associated with an unusually tortuous portal vein is described.
 Real-time ultrasonography showed anechoic masslike lesions at the porta hepatis communicating with the superior mesenteric vein and intrahepatic portal branches.
 This suggested the presence of two saccular portal vein aneurysms, 27 x 21 mm and 21 x 13 mm in size.
 Magnetic resonance imaging and portal venography confirmed the portal vein aneurysms and an unusually tortuous portal vein curving caudally between them.
 The liver was histologically normal and there was no evidence of portal hypertension.
 It is speculated that these portal vein aneurysms may have been congenital and that the associated tortuous portal vein might have been secondary to hemodynamic changes in the portal venous system.
",13
2404,"Factors determining improvement in left ventricular function after reperfusion therapy for acute myocardial infarction: primacy of baseline ejection fraction.
 Improvement in left ventricular ejection fraction is a measure of salvage of ischemic myocardium after reperfusion therapy for acute myocardial infarction.
 The degree of improvement in left ventricular ejection fraction may be influenced by many factors.
 Therefore, 137 patients in whom paired radionuclide angiograms were obtained within 24 h of acute infarction and before hospital discharge were retrospectively evaluated to determine which factors most affect improvement in ejection fraction.
 Only baseline ejection fraction correlated significantly with improvement in ejection fraction by both univariate analysis (ejection fraction as a continuous variable; p less than 0.001; ejection fraction as a categorical variable, less than or equal to 45% versus greater than 45%, p less than 0.0001) and multivariate analysis (p less than 0.0001).
 Reperfusion status (patent versus occluded infarct artery) and extent of coronary artery disease (one, two or three vessel) were significant factors by multivariate but not by univariate analysis.
 Location of infarction, treatment modality and time to treatment did not correlate with change in ejection fraction by either statistical technique.
 Thus, of those factors tested, baseline left ventricular ejection fraction is the most potent predictor of improvement in ventricular function after acute infarction.
 Knowledge of baseline ejection fraction may be helpful in deciding whether to treat some patients with equivocal indications or contraindications for reperfusion therapy.
 Clinical trials of reperfusion strategies should stratify patients on the basis of baseline ejection fraction if ejection fraction is to be used as an end point for myocardial salvage.
",13
2405,"Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty.
 To assess the incidence and clinical significance of elevated total plasma creatine kinase (CK) and MB isoenzyme fraction after apparently successful coronary angioplasty, a prospective study of 272 consecutive elective procedures was undertaken.
 Total CK (normal less than 100 IU/liter) and CK MB isoenzyme (normal less than 4%) were measured immediately after successful completion of the procedure and every 6 h for 24 h.
 All nonelective procedures and results not fulfilling all American Heart Association/American College of Cardiology Task Force guideline criteria for a successful result were excluded from analysis.
 Of the 272 elective procedures, 249 (92%) were successfully; abnormally elevated CK or CK MB serum levels, or both, were found in 38 (15%) of the successful outcomes.
 Three patterns of abnormal enzymes were identified: 15 patients with CK greater than or equal to 200 IU/liter and CK MB greater than or equal to 5% (group 1), 4 patients with CK greater than or equal to 200 IU/litter and CK MB less than or equal to 4% (group 2) and 19 patients with CK less than 200 IU/liter and CK MB greater than or equal to 5% (group 3).
 The three groups were distinguishable by the nature of the complications causing the enzyme release (in particular, the etiology and clinical manifestations).
 There were significantly more clinically apparent events in group 1 than in the other groups (13 of 15 versus 11 of 23, p less than 0.01) and more events associated with persistent electrocardiographic changes (p = 0.05) and chest pain (p less than 0.05).
 However, no clinically important sequelae were recognizable in any group at hospital discharge.
 Thus, abnormal cardiac serum enzyme release after apparently successful coronary angioplasty is 1) relatively common; 2) has many possible causes, including both minor complications and early reversibility of impending major complications; and 3) results in no permanent clinical sequelae.
",13
2406,"Long-term follow-up of medical versus surgical therapy for hypertrophic cardiomyopathy: a retrospective study 
 In a retrospective analysis 139 patients with hypertrophic cardiomyopathy were followed up for 8.9 years (range 1 to 28 years).
 Patients were divided into two groups: Group 1 consisted of 60 patients with medical therapy and Group 2 of 79 patients with surgical therapy (septal myectomy).
 Groups 1 and 2 were subdivided according to the medical treatment.
 Group 1a received propranolol, 160 mg/day (n = 20); Group 1b verapamil, 360 mg/day (n = 18); and Group 1c, no therapy (n = 22).
 Group 2a received verapamil, 120 to 360 mg/day, after septal myectomy (n = 17) and Group 2b had no medical therapy after surgery (n = 62).
 In Group 1, 19 patients died (annual mortality rate 3.6%) and in Group 2, 17 patients died (mortality rate 2.4%, p = NS).
 Of the patients who died, approximately one half to two thirds in both Groups 1 and 2 died suddenly and the other one half to one third died because of congestive heart failure.
 The 10 year cumulative survival rate was 67% in Group 1, significantly smaller than that in Group 2 (84%, p less than 0.05).
 In the subgroups, the 10 year survival rate was 67% in Group 1a, 80% in 1b (p less than 0.05 versus 1a) and 65% in 1c (p less than 0.05 versus 1b).
 The 10 year survival rate was 100% in Group 2a (p less than 0.05 versus 1a, 1b, 1c) and 78% in Group 2b (p less than 0.05 versus 2a).
 It is concluded that cumulative survival rate is significantly better in surgically than in medically treated patients.
",13
2407,"Prediction of the frequency and duration of ambulatory myocardial ischemia in patients with stable coronary artery disease by determination of the ischemic threshold from exercise testing: importance of the exercise protocol 
 The relation between ambulatory myocardial ischemia and the results of exercise testing in patients with ischemic heart disease remains undefined, because of the dissimilar results of previous reports.
 To further investigate this issue and, in particular, to ascertain the importance of the exercise protocol in determining that relation, 70 patients with stable coronary artery disease underwent 48 h ambulatory electrocardiographic (ECG) monitoring and treadmill exercise tests after withdrawal of medications.
 Patients exercised using two different protocols with slow (National Institutes of Health [NIH] combined protocol) and brisk (Bruce protocol) work load increments.
 Exercise duration was longer with the NIH combined protocol (14.1 +/- 5 versus 6.8 +/- 2 min; p less than 0.0001), but the maximal work load and peak heart rate achieved were greater with the Bruce protocol (9.8 +/- 2 versus 6.5 +/- 2 METs, and 142 +/- 19 versus 133 +/- 22 beats/min, respectively; p less than 0.0001).
 A close inverse correlation between exercise testing and the results of ambulatory ECG monitoring was observed using the NIH combined protocol; the strongest correlation was observed between time of exercise at 1 mm of ST segment depression and number of ischemic episodes (r = -0.86; p less than 0.0001).
 With the Bruce protocol a significantly weaker inverse correlation was found (r = -0.35).
 The mean heart rate at the onset of ST segment depression was similar during monitoring and during exercise testing with the NIH combined protocol (97.2 +/- 13 versus 101.0 +/- 17 beats/min, respectively) but it was significantly higher (110.4 +/- 13) when using the Bruce protocol (p less than 0.001).
",13
2408,"Effects of standing on the induction of paroxysmal supraventricular tachycardia.
 To evaluate the effects of standing on induction of paroxysmal supraventricular tachycardia, electrophysiologic studies were performed in both the supine and standing positions in 22 patients with atrioventricular (AV) reciprocating tachycardia and in 11 with AV node reentrant tachycardia.
 AV reciprocating tachycardia was induced in 9 of the 22 patients with AV reciprocating tachycardia when they were in the supine position and in 17 when standing.
 The effective refractory period of the AV node markedly shortened, from 275 +/- 72 to 203 +/- 30 ms (n = 16, p less than 0.005) after standing.
 The effective refractory period of the accessory pathway shortened slightly, from 293 +/- 75 to 278 +/- 77 ms (n = 8, p less than 0.005), after standing.
 AV node reentrant tachycardia was induced in 3 of the 11 patients with AV node reentrant tachycardia when they were in the supine position and in 6 when standing.
 The effective refractory periods of the slow pathway and fast pathway shortened markedly, from 293 +/- 72 to 216 +/- 40 ms (n = 6, p less than 0.025) and from 416 +/- 85 to 277 +/- 50 ms (n = 10, p less than 0.005), respectively, after standing.
 Plasma norepinephrine levels increased during standing both in patients with AV reciprocating and in those with AV node reentrant tachycardia (n = 11, p less than 0.005, n = 8, p less than 0.005, respectively).
 In conclusion, standing, which is associated with increased sympathetic tone, changed the electrophysiologic properties of the reentrant circuits, facilitating induction of AV reciprocating tachycardia and AV node reentrant tachycardia.
",13
2409,"Surgery for Ebstein's anomaly: the clinical and echocardiographic evaluation of a new technique.
 Ten consecutive patients (age range 4 to 44 years, mean 22) underwent surgical repair of Ebstein's anomaly by vertical plication of the right ventricle and reimplantation of the tricuspid valve leaflets.
 No patient died during or after operation.
 Intraoperative postbypass echocardiography documented a good result in nine patients but severe tricuspid regurgitation in one patient, who then underwent prosthetic valve replacement during a second period of cardiopulmonary bypass.
 Two of four patients who had had right ventricular papillary muscle dysfunction in the early postoperative period showed improved papillary muscle function with concomitant reduction of tricuspid regurgitation 6 months later.
 All patients were evaluated clinically and by echocardiography 2 to 23 months later.
 All patients showed clinical improvement, seven by one functional class and three by two classes.
 All were in sinus rhythm.
 The mean cardiothoracic ratio decreased by 6% (p less than 0.05).
 On bicycle ergometry performed in six patients, peak oxygen consumption exceeded 20 ml/kg per min in five.
 Tricuspid regurgitation diminished in eight patients (by three grades in two patients, by two grades in five and by one grade in one patient); it remained unchanged in two.
 Comparison of preoperative and postoperative pulsed Doppler flow velocities across the pulmonary valve showed an increase in the peak velocity of flow across the valve (mean 83 +/- 14 versus 97 +/- 11 cm/s, p less than 0.005) and a decrease in the time to peak velocity (mean 130 +/- 16 versus 91 +/- 23 ms, p less than 0.05).
",13
2410,"The role of chronotropic impairment during exercise after the Mustard operation.
 To better understand the role of chronotropic impairment on exercise performance after the atrial switch (Mustard) operation, 20 patients who had undergone this operation for uncomplicated d-transposition of the great arteries exercised to maximal volition using a 1 min incremental treadmill protocol.
 Heart rate, oxygen consumption, carbon dioxide production and minute ventilation were monitored continuously.
 Two-dimensional echocardiograms were obtained before testing to calculate the right ventricular inflow volume indexed to body surface area.
 All patients achieved maximal aerobic capacity based on their ventilatory patterns and respiratory exchange ratio.
 Maximal heart rate was reduced (175 beats/min; 87% of predicted for age) and maximal oxygen consumption was decreased (31 ml/kg per min; 75% of predicted for age and gender).
 There was no correlation between maximal oxygen consumption and maximal heart rate.
 Right ventricular volume index, however, had a significant inverse correlation with maximal heart rate (r = -0.62, p less than 0.005).
 There was no correlation between right ventricular volume index and heart rate at rest.
 These results suggest that decreased maximal oxygen consumption in patients after the Mustard procedure is not a result of chronotropic impairment.
 Right ventricular dilation may be a compensatory response to chronotropic impairment.
",13
2411,"Effect of captopril, an angiotensin-converting enzyme inhibitor, in patients with angina pectoris and heart failure 
 The effects of captopril and placebo were compared in 18 patients with chronic heart failure and angina pectoris with use of a double-blind crossover trial design.
 Symptoms were assessed by patient treatment preference, visual analogue scores and nitroglycerin consumption.
 Exercise performance was assessed using two different treadmill protocols of different work intensity with simultaneous measurement of oxygen consumption and by supine bicycle exercise and simultaneous radionuclide ventriculography.
 Arrhythmias were assessed by 48 h ambulatory electrocardiographic monitoring.
 Patients generally preferred placebo to captopril, and this appeared to be due to an increase in symptoms of angina with captopril.
 Treadmill exercise time on a high intensity protocol was shorter with captopril than with placebo; on a low intensity protocol, angina became a more frequent limiting symptom even though overall exercise performance was not changed.
 The heart rate-blood pressure product was reduced, but largely because of a reduction in blood pressure rather than in heart rate.
 During supine bicycle exercise, no differences in symptoms, exercise performance, ejection fraction or changes in blood pressure were noted and ventricular arrhythmias were reduced.
 Captopril does not appear to be clinically useful in alleviating angina pectoris in patients with heart failure, and this effect may be related to a decrease in coronary perfusion pressure.
 Nonetheless, desirable metabolic effects, a reduction in arrhythmias and potential effects on survival require further study of captopril in patients with both angina and heart failure.
",13
2412,"Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia.
 The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries.
 The heart was paced at 1.7 times the heart rate at rest for 3 min.
 In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions.
 Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility.
 In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered.
 Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance.
 In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories.
 During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).
",13
2413,"Pressure-length loop area: its components analyzed during graded myocardial ischemia.
 The changes in total pressure-length loop area were compared with changes in effective shortening area, systolic lengthening area and postsystolic shortening area (defined with respect to end-diastolic and end-systolic lengths) of the pressure-length loop during myocardial ischemia in seven anesthetized dogs instrumented for measurement of left ventricular pressure and regional segmental wall motion (sonomicrometry) in the minor axis of the apical region of the left ventricle.
 Ischemia was induced by gradual tightening of a micrometer-controlled snare around the left anterior descending coronary artery, which supplied the apical myocardium.
 Data were obtained at normal flow, after critical constriction (loss of pulsatile coronary flow), mild ischemia (ischemia 1: onset of regional dysfunction, i.e., postsystolic shortening and mild hypokinesia) and moderate ischemia (ischemia 2: marked hypokinesia).
 At each stage, acute afterloading was performed by partially occluding the descending thoracic aorta.
 The pressure-length loops were analyzed in terms of four areas: total loop area, effective shortening area, postsystolic shortening area and systolic lengthening area.
 Total loop area decreased only when marked hypokinesia was present (176 +/- 18.3 mm Hg x mm at ischemia 2 versus 245.1 +/- 26.9 mm Hg x mm at ischemia 1, p less than 0.05).
 However, effective shortening area (98.2 +/- 0.8% of total loop area at baseline; 93.8 +/- 2.4% at critical constriction; 76.3 +/- 7.2% at ischemia 1; 51.9 +/- 12.2% at ischemia 2) and postsystolic shortening area (1.8 +/- 0.8% of total loop area at baseline; 5.2 +/- 1.9% at critical constriction; 14.3 +/- 3/4% at ischemia 1; 23.8 +/- 5.1% at ischemia 2) changed significantly with each progressive stage of ischemia.
",13
2414,"Follow-up of patients with low output, low gradient hemodynamics after percutaneous balloon aortic valvuloplasty: the Mansfield Scientific Aortic Valvuloplasty Registry.
 Symptomatic patients with a low cardiac output and low aortic valve gradient have a poor prognosis but are at high risk for aortic valve surgery.
 The outcome of percutaneous balloon aortic valvuloplasty in this subgroup of patients is unclear.
 Therefore, 67 patients (group 1) underwent percutaneous balloon aortic valvuloplasty between December 1, 1986 and November 1, 1987 who had a low cardiac index (less than 2.5 liters/min per m2) and a low aortic valve gradient (less than or equal to 40 mm Hg) before the procedure.
 The results were compared with 200 patients (group 2) who had a low cardiac index but not a low aortic valve gradient (greater than 40 mm Hg) before the procedure and who had similar baseline presenting symptoms.
 After balloon aortic valvuloplasty, there was a greater decrease in aortic valve gradient in patients in group 2 than in patients in group 1 (mean +/- SD -33.0 +/- 16.7 mm Hg and -14.6 +/- 6.9 mm Hg, respectively; p less than 0.001) although there was no significant difference in improvement in estimated aortic valve area (0.31 +/- 0.21 and 0.31 +/- 0.22 cm2, respectively; p = NS).
 In-hospital mortality was 11.9% for patients in group 1 which was not significantly different from the 7.5% mortality for patients in group 2.
 However, the actuarial probability of survival at 12 months for patients who survived the initial hospitalization was 46% in group 1 and 64% in group 2 (p less than 0.05).
 Moreover, at follow-up (mean 8.8 months) 64% of surviving group 1 patients displayed clinical improvement, compared with 70% of surviving group 2 patients.
",13
2415,"Platelet thromboxane release and delayed cerebral ischemia in patients with subarachnoid hemorrhage.
 Adenosine diphosphate-induced platelet aggregation and associated thromboxane B2 release were studied in 52 patients with subarachnoid hemorrhage (SAH) in order to detect a possible association between altered platelet function and development of cerebral ischemic complications after SAH.
 Compared to the values on admission, the patients showed significantly increased platelet aggregability (p less than 0.05) and thromboxane release (p less than 0.001) 1 to 2 weeks after SAH.
 The highest values of thromboxane release were seen in patients who deteriorated due to delayed cerebral ischemia with a permanent neurological deficit.
 Thromboxane release was significantly higher (p less than 0.05) before the onset of severe delayed ischemia in six patients with preoperative ischemia compared to the patients without delayed ischemia.
 In five others, both ischemic deterioration and elevated thromboxane release occurred after operation.
 These patients had preoperative values similar to the values in those without ischemic symptoms.
 The observations suggest that increased platelet aggregability and thromboxane release are associated with delayed cerebral ischemia both before and after surgery.
",13
2416,"Endovascular occlusion of vertebral arteries in the treatment of unclippable vertebrobasilar aneurysms.
 Twenty-one patients with aneurysms of the vertebrobasilar circulation underwent unilateral or bilateral endovascular occlusion of the vertebral artery.
 Six patients presented with subarachnoid hemorrhage (SAH), 10 with mass effect, four with mass effect and SAH, and one with ischemic symptoms.
 Thirteen patients had good outcomes with complete clinical and angiographic cure.
 Six patients had partial thrombosis of their aneurysms.
 There was one death and one treatment failure.
 One patient suffered transient stroke.
 It is concluded that endovascular occlusion of the vertebral artery following test occlusion is a safe and effective treatment for proximal aneurysms of the vertebrobasilar circulation.
",13
2417,"Effect of 21-aminosteroid U-74006F on lipid peroxidation in subarachnoid clot.
 The present study was undertaken to investigate the effect of U-74006F on malondialdehyde (a by-product of lipid peroxidation) in subarachnoid clot.
 Eighteen cynomolgus monkeys were divided into three groups of six each.
 There were two U-74006F-treated groups, receiving doses of 0.3 or 1.0 mg/kg, and a placebo-treated group.
 Each monkey underwent baseline cerebral angiography followed by right-sided craniectomy and placement of subarachnoid clot around the middle cerebral artery (MCA).
 Treatment was administered intravenously every 8 hours for 6 days.
 Seven days after the experimental subarachnoid hemorrhage (SAH), angiography was repeated and the animals were killed.
 In the placebo-treated group, significant vasospasm occurred in the MCA on the side of the clot (p less than 0.01).
 After U-74006F treatment at both dosages, significantly less vasospasm developed in the clot-side MCA (p less than 0.01).
 The content of malondialdehyde was measured by both the thiobarbituric acid test and high-performance liquid chromatography (HPLC).
 Comparing the two methods, HPLC proved to be more accurate than the thiobarbituric acid test, especially for measurement of low concentrations of malondialdehyde.
 In the placebo-treated group, the malondialdehyde content was significantly increased in the Day 7 clot (p less than 0.05).
 In contrast, malondialdehyde content in freshly prepared clot was very low.
 In the 0.3-mg/kg U-74006F group, the malondialdehyde content of clot was significantly less at Day 7 compared to clot from the placebo-treated group (p less than 0.05).
 Although the malondialdehyde content of clot from the 1.0 mg/kg U-74006F-treated group was less than that of placebo, it was not significantly so.
 Malondialdehyde was not detected in the actual vessel wall of the MCA of any group.
 These results suggest that lipid peroxidation in subarachnoid clot may play a role in the pathogenesis of vasospasm and that the salutary effects of U-74006F in vasospasm may be mediated by a reduction of lipid peroxidation in SAH.
",13
2418,"Superior hypophyseal artery aneurysm. Report of two cases.
 Two cases of saccular intracranial aneurysms arising from the superior hypophyseal artery take-off from the internal carotid artery are presented.
 The angiographic findings and technical details of the operative approach are discussed.
 Particular attention is focused on the use of fenestrated angled clips.
",13
2419,"Subarachnoid hemorrhage from a dissecting aneurysm of the middle cerebral artery. Case report.
 A case of subarachnoid hemorrhage (SAH) from a dissecting aneurysm of the inferior limb of the middle cerebral artery is reported.
 The patient's clinical status and the initial and follow-up angiographic appearance of the aneurysm are presented.
 Diagnosis and treatment are briefly discussed.
 It is suggested that, if angiography demonstrates luminal narrowing or vascular occlusion in a patient with unexplained SAH, a dissecting aneurysm of the carotid system should be considered as a cause of the hemorrhage.
",13
2420,"The role of alpha adrenoceptor subtypes in sympathetic control of the acral-cutaneous microcirculation.
 In pithed and anesthetized rats, laser-Doppler flowmetry was used to evaluate the role of alpha-1 and alpha-2 adrenoceptors in mediating sympathetic responses in acral regions of the cutaneous circulation.
 The intravenous administration of the selective alpha-1 agonist, phenylephrine, was a more potent vasopressor agent than BH-T 933 (a selective alpha-2 adrenoceptor agonist) in pithed rats.
 However, BH-T 933 was more potent and more efficacious than phenylephrine in reducing cutaneous microvascular perfusion (CP).
 BH-T 933 also caused a greater increase in cutaneous microvascular resistance.
 Neural and humoral sympathetic effects on CP were characterized with selective alpha-1 and alpha-2 adrenoceptor antagonists (prazosin and rauwolscine, respectively).
 It was found that frequency-related reductions in CP elicited by sciatic nerve stimulation were antagonized by prazosin, but not by rauwolscine.
 In fact, rauwolscine enhanced neurally evoked reductions in CP at the highest stimulation frequencies.
 However, both prazosin and rauwolscine antagonized reductions in CP elicited by electrical stimulation of the thoracolumbar outflow (sympathoadrenal activation).
 Ganglionic stimulation (intravenous 1,1-dimethyl-4-phenylpiperazinium) also caused a profound, transient reduction in CP that was abolished by rauwolscine, but was not significantly altered by prazosin.
 In contrast, 1,1-dimethyl-4-phenylpiperazinium-induced increases in mean arterial pressure were reduced by prazosin, but not by rauwolscine.
 In ketamine-anesthetized rats, rauwolscine caused a dose-related increase in CP without altering mean arterial pressure, whereas prazosin lowered mean arterial pressure but did not alter CP.
 We conclude that acral regions of the cutaneous vasculature are more sensitive to alpha-2 vis-a-vis alpha-1 adrenoceptor-mediated vasoconstriction.
",13
2421,"Peripheral alpha-1 and alpha-2 adrenergic receptors in three models of hypertension in rats: an in vitro autoradiography study.
 In vitro autoradiography was used to compare peripheral alpha-1 and alpha-2 adrenergic receptor binding in various tissues using [3H]prazosin and [3H]rauwolscine, respectively, in three models of experimental hypertension in rats.
 Models studied included two-kidney, one-clip hypertension, one-kidney, one-clip hypertension, desoxycorticosterone-salt hypertension, and three normotensive control groups: two-kidney control, one-kidney control and salt-loaded control.
 Blood pressures at death were significantly higher in all three hypertensive groups compared with normotensive controls, but there were no significant differences among the hypertensive or normotensive groups.
 Plasma norepinephrine levels were significantly elevated in all three hypertensive groups compared with respective controls, with no significant differences among hypertensive or control groups.
 In all three hypertensive groups, there were significant reductions in binding of aortic and mesenteric vascular alpha-1 receptors, renal tubular alpha-1 and alpha-2 receptors, and adrenal cortical alpha-2 receptors when compared with respective control groups.
 Reduced binding of cardiac ventricular alpha-1 and alpha-2 receptors was also found in all hypertensive groups, but not to statistically significant levels.
 No significant differences in intestinal alpha-1 and alpha-2 receptor binding were detected in either hypertensive or normotensive groups.
 The results suggest increased peripheral sympathetic activity in all three models of experimental hypertension, which is associated with down-regulation of alpha-1 and alpha-2 receptors in a number of peripheral tissues, especially those that control cardiovascular hemodynamics and fluid and salt balance.
 There is no evidence of an increase in peripheral alpha receptor binding as has often been found in some models of genetic or spontaneous hypertension.
",13
2422,"Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients 
 BACKGROUND.
 Studies in animals have shown that serotonin constricts coronary arteries if the endothelium is damaged, but in vitro studies have revealed a vasodilating effect on isolated coronary segments with an intact endothelium.
 To investigate the effect of serotonin in humans, we studied coronary-artery cross-sectional area and blood flow before and after the infusion of serotonin in seven patients with angiographically normal coronary arteries and in seven with coronary artery disease.
 METHODS.
 We measured the cross-sectional area of the coronary artery by quantitative angiography and coronary blood flow with an intracoronary Doppler catheter.
 Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10 micrograms per kilogram of body weight per minute, for two minutes).
 We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not in the endothelium.
 RESULTS.
 In patients with normal coronary arteries, the highest dose of serotonin increased cross-sectional area by 52 percent (P less than 0.001) and blood flow by 58 percent (P less than 0.01).
 The effect was significantly potentiated by administration of ketanserin.
 In patients with coronary-artery atherosclerosis, serotonin reduced cross-sectional area by 64 percent (P less than 0.001) and blood flow by 59 percent (P less than 0.001).
 Ketanserin prevented this effect.
 CONCLUSIONS.
 Serotonin has a vasodilating effect on normal human coronary arteries; when the endothelium is damaged, as in coronary artery disease, serotonin has a direct, unopposed vasoconstricting effect.
 When considered with other evidence, these data suggest that platelet-derived factors such as serotonin may have a role in certain acute coronary ischemic syndromes.
",13
2423,"Effect of intracoronary serotonin on coronary vessels in patients with stable angina and patients with variant angina 
 BACKGROUND.
 Serotonin, a major product of platelet activation, has potent vasoactive effects in animal models, but its role in human coronary artery disease remains largely speculative.
 METHODS.
 Using quantitative coronary angiography, we compared the effects of the intracoronary infusion of graded concentrations of serotonin (10(-7) to 10(-4) mol per liter) on coronary vessels in two groups of patients with different clinical presentations of coronary disease (nine with stable angina and five with variant angina), with the effects in a control group of eight subjects with normal vessels on angiography.
 RESULTS.
 Normal coronary vessels had a biphasic response to intracoronary serotonin: dilation at concentrations up to 10(-5) mol per liter, but constriction at 10(-4) mol per liter.
 Vessels in patients with stable angina constricted at all concentrations, with mean (+/- SEM) maximal decreases in diameter of 23.9 +/- 3.6, 33.1 +/- 3.9, and 41.7 +/- 3.1 percent from base line in proximal, middle, and distal segments at a serotonin concentration of 10(-4) mol per liter.
 Smooth segments constricted more than irregular segments (42.0 +/- 4.6 vs.
 21.1 +/- 1.6 percent).
 Four patients with stable angina had a marked reduction in collateral filling.
 All the patients with stable angina had angina during the intracoronary infusion of serotonin, and electrocardiographic changes were noted in six.
 All the patients with variant angina had angina, electrocardiographic changes, and localized occlusive epicardial coronary-artery spasm at concentrations of 10(-6) (n = 2) or 10(-5) (n = 3) mol per liter.
 CONCLUSIONS.
 Patients with stable coronary disease do not have the normal vasodilator response to intracoronary serotonin, but rather have progressive constriction, which is particularly intense in small distal and collateral vessels.
 Patients with variant angina have occlusive coronary-artery spasm at a dose that dilates normal vessels and causes only slight constriction in vessels from patients with stable angina.
 These findings suggest that serotonin, released after the intracoronary activation of platelets, may contribute to or cause myocardial ischemia in patients with coronary artery disease.
",13
2424,"Orbitozygomatic temporopolar approach for a high basilar tip aneurysm associated with a short intracranial internal carotid artery: a new surgical approach.
 For two cases of a high basilar tip aneurysm accompanied by a short intracranial internal carotid artery, the orbitozygomatic temporopolar approach consisting of an en bloc fronto-orbitozygomatic temporal craniotomy and temporopolar approach was carried out.
 On angiograms, the height of the bifurcation of an elongated basilar artery and the length of the intracranial internal carotid artery from the interclinoid line between the anterior and posterior clinoid process were 20 mm and 6 mm in Case 1, and 18 mm and 5 mm in Case 2, respectively.
 The skin flap was separated subfascially to preserve the frontotemporal branch of the facial nerve.
 The fronto-orbitozygomatic temporal bone flap was made, and a part of the basal bony structures of the orbital roof, the sphenoid ridge, and the temporal bone were removed.
 The basilar tip aneurysm could be seen and clipped easily by upward and oblique viewing from below through the wide operative space consisting of the less retracted internal carotid and middle cerebral arteries, the oculomotor nerve, the tentorial hiatus, and the emptied anterior temporal fossa obtained by partial division of the temporal bridging veins.
 The operative procedure is presented in detail and compared with other surgical approaches that have been described previously.
",13
2425,"Impairment of cerebral autoregulation during the development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates.
 We studied the impairment of autoregulation of cerebral blood flow (CBF) and its effect on the electrical activity of the brain during the development of chronic cerebral vasospasm after subarachnoid hemorrhage, using a vasospasm model in primates.
 Fourteen animals were divided into two groups: a clot group (8) and a sham-operated group (6).
 To induce subarachnoid hemorrhage, all the animals underwent craniectomy, and in the clot group, the autologous blood clot was located around the arteries dissected free from the arachnoid membrane.
 Cerebral angiography was performed before subarachnoid hemorrhage and 7 days after (Day 7).
 On Day 7, regional CBF in the parietal lobe--measured by the hydrogen clearance method--and central conduction time were studied during either graded hypertension or hypotension.
 In the clot group, the mean vessel caliber of the cerebral arteries on the right side (clot side) of the circle of Willis showed significant (P less than 0.01) reduction (more than 40%) as compared with the values on the contralateral, non-clot side.
 The values for the bilateral parietal CBF in the sham-operated group and the left parietal CBF in the clot group were fairly constant when the mean arterial blood pressure (MABP) was in the range of 60 to 160 mm Hg.
 In the clot group, right parietal CBF was significantly (P less than 0.05) smaller than that on the left side at an MABP level of 40 to 100 mm Hg, and increased at an MABP level of 180 mm Hg.
 The right parietal CBF increased as the arterial blood pressure increased, showing impairment of autoregulation.
",13
2426,"Cavernous malformations and capillary telangiectasia: a spectrum within a single pathological entity.
 Cerebral vascular malformations have traditionally been divided into four categories: arteriovenous, venous, cavernous, and capillary telangiectases.
 A controversy exists about separating the latter two lesions into separate entities.
 Critics claim the distinction is arbitrary but have been unable to present convincing evidence linking the two types of lesions.
 We have reviewed the histories of 20 patients with cavernous malformations and have analyzed the clinical, radiographic, and surgical-autopsy data associated with these lesions.
 In some patients, multiple lesions, including cavernous malformations, capillary telangiectases, and transitional forms between the two, were identified.
 Based on this analysis, we conclude that capillary telangiectasia and cavernous malformations represent two pathological extremes within the same vascular malformation category and propose grouping them as a single cerebral entity called cerebral capillary malformations.
",13
2427,"Depression after acute myocardial infarction. The role of primary care physicians in rehabilitation.
 Depression is a common problem after myocardial infarction.
 Diagnosis is facilitated by use of the criteria for depression in the Diagnostic and Statistical Manual of Mental Disorders and self-rating questionnaires.
 Treatment may involve both psychological and pharmacologic interventions.
 The patient's medical status must be carefully assessed before administration of antidepressant medication.
 All antidepressants are contraindicated immediately after myocardial infarction.
 When signs and symptoms of depression are exhibited early in the recovery phase, alprazolam (Xanax) may offer advantages over more traditional antidepressants.
 Further research is necessary to determine the safety of newer antidepressants.
",13
2428,"US-assisted aspiration thrombectomy: in vitro investigations.
 The authors describe the use of a new ultrasound (US)-aspiration thrombectomy technique.
 An oscillating US probe was inserted into a thin-walled, large-bore aspiration catheter.
 Experiments tested the ability of the new device and other catheter combinations to remove clot material from a Petri dish, as well as from small and large vessel models made of silicone and glass tubes, respectively.
 Results of the experiments demonstrated that an oscillating 1.0-mm US probe inserted into an aspiration catheter (7-9 F in diameter) promoted clot fragmentation and allowed continuous aspiration of thrombi of any size.
 When compared with simple large-bore catheter aspiration and with mechanical fragmentation by means of a US probe within a catheter that was flushed to cool the probe, US-assisted aspiration thrombectomy demonstrated significantly better results for percutaneous transcatheter removal of fresh thrombi.
",13
2429,"Renal vein renins: inability to predict response to revascularization in patients with hypertension.
 To determine whether the captopril-stimulated renal vein renin ratio (CSRVRR) could enable identification of patients with hemodynamically significant renovascular lesions who would respond to revascularization, the authors measured CSRVRRs in 143 consecutive patients with hypertension who had been selected because of clinical features suggestive of renovascular hypertension.
 All patients underwent conventional renal arteriography.
 Renovascular hypertension was the final diagnosis if revascularization resulted in cure or improvement in blood pressure.
 Complete data were available for 133 patients.
 Twenty patients had renovascular hypertension; CSRVRR was greater than 1.5 in 13 of these 20 patients (sensitivity, 65%).
 However, it was also greater than 1.5 in 54 of the 113 patients without renovascular hypertension (false-positive rate, 47.8%).
 The positive predictive value of CSRVRR was 18.6%; the negative predictive value, 89.3%.
 It is concluded that CSRVRR is not sufficiently sensitive to enable prediction of which patients will respond to revascularization and is not specific enough to exclude patients who do not have renovascular hypertension.
",13
2430,"Patient evaluation for cardiac transplantation.
 The aim for cardiac transplantation is to improve the quality of life and the survival in patients with end-stage heart failure.
 Given the scarcity of donor organ availability, the expense of the transplantation process and follow-up care, as well as the tremendous emotional burden the process places on a patient and his/her family, it is essential to carefully screen potential candidates for their symptomatic, functional, hemodynamic, and psychosocial eligibility, and to rule out coexisting hemodynamic or comorbid conditions that would jeopardize successful transplantation and immunosuppression.
 Comprehensive screening of potential transplant candidates, which is best accomplished by a multidisciplinary team approach working closely with patients and their families, is essential to insure that maximum benefit is derived from this scarce and valuable resource.
",13
2431,"Electrocardiographic subset analysis of diltiazem administration on long-term outcome after acute myocardial infarction. The Multicenter Diltiazem Post-Infarction Trial Research Group.
 The effect of diltiazem on long-term outcome after acute myocardial infarction (AMI) was assessed in 2,377 patients enrolled in the Multicenter Diltiazem Post-Infarction Trial and subsequently followed for 25 +/- 8 months.
 The study population included 855 patients (36%) with at least 1 prior AMI before the index infarction and 1,522 patients (64%) with a first AMI, of whom 409 (27%) had a first non-Q-wave AMI, 664 (44%) a first inferior Q-wave AMI, and 449 (30%) a first anterior Q-wave AMI.
 This post hoc analysis revealed that, among patients with first non-Q-wave and first inferior Q-wave AMI, there were fewer cardiac events during follow-up in the diltiazem than in the placebo group, and that the reverse was true for patients with first anterior Q-wave AMI or prior infarction.
 The diltiazem:placebo Cox hazard ratio (95% confidence limits) for the trial primary end point (cardiac death or nonfatal reinfarction, whichever occurred first) was: first non-Q-wave AMI-0.48 (0.26, 0.89); first inferior Q-wave AMI-0.66 (0.40, 1.09); first anterior Q-wave AMI-0.82 (0.51, 1.31); and prior AMI-1.11 (0.85, 1.44).
 Use of cardiac death alone as an end point gave an even more sharply focused treatment difference: first non-Q-wave AMI-0.46 (0.18, 1.21); first inferior Q-wave AMI-0.53 (0.27, 1.06); first anterior Q-wave AMI-1.28 (0.68, 2.40); prior infarction-1.26 (0.90, 1.77).
 Further analysis revealed that these differences in the effect of diltiazem in large part reflected the different status of the 4 electrocardiographically defined subsets in terms of left ventricular function.
",13
2432,"Exercise echocardiography and technetium-99m MIBI single-photon emission computed tomography in the detection of coronary artery disease.
 To compare the relative diagnostic value of exercise echocardiography with perfusion technetium-99m metoxyisobutylisonitrile single-photon emission computed tomography (SPECT) in detecting coronary artery disease (CAD), 75 patients with suspected CAD but a normal electrocardiogram (ECG) at rest were included in a prospective correlative study.
 Both the exercise echocardiograms and SPECT studies were performed in conjunction with the same symptom-limited bicycle exercise test.
 The development of either a new wall motion abnormality or a reversible perfusion defect after exercise, or both, were regarded as a positive test for the exercise echocardiographic and SPECT studies, respectively.
 The results of these 2 diagnostic tests were compared with coronary arteriography.
 Exercise echocardiography identified 35 (71%) and SPECT 41 (84%, p = 0.13) of the 49 patients with significant CAD (defined as greater than 50% diameter stenosis).
 Twenty-five of the 26 patients (96%) without significant coronary stenosis had negative exercise echocardiographic results and 23 of 26 (88%) had negative SPECT results.
 Exercise-induced new wall motion abnormalities showed a good correlation with reversible perfusion defects, and the results of the 2 methods were concordant in 65 of 75 patients (agreement = 88%, kappa = 0.75 +/- 0.14).
 Both the diagnostic accuracy of exercise echocardiography and SPECT were significantly higher than the exercise ECG (81 vs 64%, p less than 0.02 and 88 vs 64%, p less than 0.005).
 The sensitivity and specificity for detecting individual diseased vessels were 60 and 95% for exercise echocardiography and 67 and 94% for SPECT.
",13
2433,"Impaired left ventricular filling and regional diastolic asynchrony at rest in coronary artery disease and relation to exercise-induced myocardial ischemia.
 Impaired left ventricular (LV) diastolic filling at rest is frequently observed in patients with coronary artery disease (CAD) who have normal LV systolic function and no previous infarction.
 To test the hypothesis that abnormal diastolic function at rest might reflect the functional severity of CAD, as estimated by exercise-induced ischemia, the relation between regional and global LV diastolic function at rest and during exercise-induced ischemia was evaluated in 49 patients with radionuclide angiography.
 All patients had normal systolic function at rest.
 Group 1 (n = 26) patients manifested a normal ejection fraction response to exercise and group 2 (n = 23) patients an abnormal response.
 Data obtained from 22 age-comparable normal volunteers were used for comparison.
 Although regional and global diastolic function were not different between normal subjects and group 1 patients, peak filling rate was lower in group 2 patients than in normal subjects (2.5 +/- 0.8 vs 3.2 +/- 0.6 end-diastolic counts/s; p less than 0.01).
 Moreover, regional diastolic asynchrony, as assessed from the radionuclide data by using a regional sector analysis of the LV region of interest, was greater in group 2 patients (46 +/- 44 ms) than in both normal subjects (25 +/- 16 ms; p less than 0.05) and group 1 patients (23 +/- 16 ms; p less than 0.05).
 Thus, among patients with CAD and with normal LV systolic function at rest, impaired LV filling and regional asynchrony predict a greater degree of exercise-induced ischemia, suggesting a greater extent of jeopardized myocardium.
",13
2434,"Predictors of cardiac survival after percutaneous transluminal coronary angioplasty in patients with severe left ventricular dysfunction.
 To assess the outcome of percutaneous transluminal coronary angioplasty (PTCA) in patients with severe left ventricular (LV) dysfunction and to determine the predictors of mortality, 73 patients with LV ejection fraction less than or equal to 40% who underwent initial PTCA were analyzed.
 The majority of patients had prior (greater than 1 week) myocardial infarction (62 patients, 85%).
 Congestive heart failure and unstable angina were present in 24 (45%) and 49 (67%) patients, respectively.
 Multivessel coronary artery disease was present in 60 (83%).
 The LV ejection fraction ranged from 14 to 40% (mean 34%).
 Intraaortic balloon pump (15%) and percutaneous cardiopulmonary bypass support (4%) was used infrequently.
 Angiographic success was obtained in 109 of 128 lesions (85%) attempted.
 Complete revascularization was obtained in 16 of 60 patients with clinical success.
 Procedure-related mortality was 5% (4 patients).
 All patients were followed from greater than or equal to 6 to less than or equal to 71 months (average 26).
 The estimated survival was 79 +/- 5%, 74 +/- 6%, 66 +/- 7% and 57 +/- 8% at 1, 2, 3 and 4 years, respectively.
 A Cox regression analysis revealed that the presence of congestive heart failure, a lower LV ejection fraction and a higher myocardial jeopardy score for contractile myocardium were independent predictors of survival after PTCA in patients with LV dysfunction.
 In conclusion, a high-risk subset can be identified among patients with severe LV dysfunction who undergo PTCA.
",13
2435,"Comparison of left ventricular ejection fraction by magnetic resonance imaging and radionuclide ventriculography in idiopathic dilated cardiomyopathy.
 To assess the validity of gated magnetic resonance imaging (MRI) in determining left ventricular (LV) ejection fraction (EF), MRI (Spin Echo, multislice-multiphase technique on the short-axis plane) was compared with equilibrium radionuclide ventriculography in 32 patients with idiopathic dilated cardiomyopathy.
 All patients underwent MRI and radionuclide ventriculography, performed consecutively on the same day (mean time interval between the 2 examinations: 40 minutes).
 Comparison with LVEF showed a high correlation (y = 0.79 X +3.51, r = 0.91; p less than 0.001).
 Mean difference between radionuclide ventriculography and MRI data was 1.7, with the 95% confidence interval 0.71 to 2.68: MRI slightly underestimated LVEF.
 MRI interobserver and intrapatient variability (assessed in 15 of 32 patients) showed a high correlation (r = 0.91, r = 0.98).
 In conclusion, data suggest that MRI, using the short-axis approach and the multislice-multiphase technique, is an accurate, noninvasive, highly reproducible method of evaluating LVEF in patients with idiopathic dilated cardiomyopathy.
",13
2436,"Stroke volume during submaximal exercise in endurance-trained normotensive subjects and in untrained hypertensive subjects with beta blockade (propranolol and pindolol).
 The effect of beta-adrenergic blockade on stroke volume (SV) at increasing submaximal exercise intensities was studied in 12 endurance-trained normotensive and 12 untrained hypertensive (diastolic blood pressure greater than 95 mm Hg) men, aged 18 to 34 years.
 Subjects were assigned to each of 3 treatments in a double-blind, randomized order: placebo, propranolol (80 mg twice daily) and pindolol (10 mg twice daily) for 10 days, with a period of 48 to 60 hours from the initial dose to the first treadmill test and a 4-day washout period between drugs.
 Cardiac output was measured using the carbon dioxide rebreathing method and SV was calculated from cardiac output and heart rate as follows: SV = cardiac output/heart rate.
 Cardiac outputs were estimated at rest and while walking on a treadmill at 25, 45, 60 and 75% of the subject's previously determined maximal oxygen uptake (VO2max).
 No significant differences were found in cardiac output between either of the drugs and placebo at rest, or at any of the 4 rates of work.
 Propranolol significantly increased SV above placebo values (p less than 0.05) for both trained and untrained groups at the intensities of 45, 60 and 75%.
 Significant differences in SV were found between pindolol and placebo only at the intensities of 60 and 75% in the trained group.
 Contrary to expectations, SV showed no indication of a plateau with propranolol in the trained subjects throughout the 4 different exercise intensities, whereas a plateau was established under placebo conditions by 45% of VO2max in both trained and untrained subjects.
 These results suggest that both trained and untrained hypertensive persons can exercise with beta-adrenergic blockade at submaximal levels without compromised cardiac function.
",13
2437,"Hypertension, endothelium, and cardiovascular risk factors.
 The functions of the endothelium and the effects of hypertension, atherosclerosis, and diabetes on the endothelium are reviewed.
 The endothelium affects vascular tone by releasing vasodilators and modulating the effects of vasoactive substances such as catecholamines, bradykinin, serotonin, and angiotensin II.
 Relaxation of vascular smooth muscle depends upon a functionally intact endothelium and the release of the endothelium-derived relaxing factor nitric oxide.
 Endothelial cells also appear to release a hyperpolarizing factor that relaxes smooth muscle through activation of the sodium-potassium pump, and of the endothelium-dependent contracting factors.
 Similarities are found in the vascular injury resulting from hypertension, atherosclerosis, and diabetes.
 When these risk factors coexist, they can act synergistically and magnify the vascular injury.
 The endothelium appears to be one of the major targets for these forms of injury.
 Future therapeutic strategies will focus on ways to prevent, arrest, or reverse endothelial injury.
",13
2438,"Cardiovascular risk reduction: the role of antihypertensive treatment.
 The effects of antihypertensive drugs on mortality from stroke, coronary artery disease (CAD), and nonvascular causes have been studied in 14 trials involving more than 37,000 patients.
 In the treated patients, blood pressure was 5 to 6 mm Hg lower than that in placebo-treated patients, and whereas mortality from stroke was reduced by 42%, CAD mortality was reduced by only 14%.
 A major reason for this lack of effect on CAD mortality is apparently the adverse effects of the primary drugs used in these trials (diuretics and beta blockers) on glucose tolerance, lipid levels, and insulin resistance.
 The angiotensin-converting enzyme inhibitors favorably influence many CAD risk factors, and their use can be expected to reduce CAD mortality in patients treated for hypertension.
",13
2439,"The tangled web of coronary risk factors.
 Although epidemiologic, genetic, and pathophysiologic studies have shown that low-density lipoproteins (LDLs) are involved in the development of coronary artery disease, the standard measurement of LDL cholesterol comprises a number of separate components that may contribute in different ways to the disease process.
 Some of these components appear to be of particular pathologic importance.
 Intermediate-density lipoproteins (IDLs) and lipoprotein (a) are highly atherogenic species that each normally account for up to 10% to 15% total LDL cholesterol but may be disproportionately elevated in pathologic states and may therefore contribute disproportionately to coronary disease risk in certain patients.
 Recently, another subclass of LDL, characterized by relatively small particle size and increased density, also has been found to be associated with relatively increased risk of coronary disease.
 Furthermore, levels of this subclass, designated LDL-III, are linked to a number of interrelated hormonal and metabolic factors, each of which have also been associated with risk of coronary artery disease.
 These include male gender, postmenopause, abdominal adiposity, elevated triglyceride levels, increased levels of apolipoprotein B, and reductions in high-density lipoproteins (HDLs), particularly in the HDL2 subclass.
 Other studies have demonstrated that many of these factors are also commonly associated with relative insulin resistance and hyperinsulinemia.
 Thus, a lipoprotein profile characterized by a relative increase in LDL-III and a reduction in HDL2 is indicative of a constellation of metabolic features that defines a high-risk state and that makes it extremely difficult to single out one or more factors that are most directly involved in the disease process.
 Combinations of genetic and environmental factors acting on this ""tangled web"" of risk factors may account for much of the variation in coronary disease susceptibility found in the general population.
",13
2440,"Regression of atherosclerosis: what does it mean?
 Angiographic evidence of coronary artery atherosclerosis regression has been demonstrated in controlled clinical trials.
 The significance of this regression appears to depend in a complex way on the degree of atherosclerosis present when a regression regimen is initiated.
 Angiographic trials indicate that lesion change is a continuum, with a gradual transition from progression to stability and regression.
 Divergent lesion change can be seen in the same patient with a progression of some lesions and a regression of others.
 This makes it necessary to perform a comprehensive survey of all visible coronary segments when evaluating angiograms to determine the outcome of a clinical trial.
 An important finding in clinical trials is that new lesion formation can be reduced.
 This indicates that effective control of atherosclerosis may be possible with procedures now available, but noninvasive coronary artery imaging methods need to be refined.
",13
2441,"Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology and clinical course of hypertension.
 Patients with untreated hypertension have been shown to be resistant to insulin-stimulated glucose uptake and are more hyperinsulinemic and hypertriglyceridemic than matched groups of patients with normal blood pressure.
 In addition, insulin resistance, hyperinsulinemia, and hypertriglyceridemia have been demonstrated in spontaneous hypertensive rats and in Sprague-Dawley rats fed a fructose-enriched diet.
 The defect in insulin-stimulated glucose uptake in these experimental models can also be shown at the cellular level.
 Experimental interventions that prevent insulin resistance or hyperinsulinemia from developing in fructose-fed rats also greatly attenuate the increase in blood pressure.
 Since endogenous hyperinsulinemia and hypertriglyceridemia have been identified as factors that increase the risk of coronary artery disease (CAD), it is likely that they contribute to the increased prevalence of CAD in hypertensive patients.
 Antihypertensive treatment may have exacerbated these metabolic abnormalities, which could help explain why it has been difficult to show that lowering blood pressure decreases the risk of CAD.
 These observations raise the possibility that abnormalities of carbohydrate and lipoprotein metabolism may play a role in both the etiology and clinical course of hypertension.
",13
2442,"New horizons in the treatment of coronary artery thrombosis.
 The application of recombinant DNA methodology to clinical medicine offers the clinician a new generation of more potent and specific therapies.
 Recombinant methods offer great promise in the treatment of coronary artery thrombosis.
 This review focuses on the characterization of 1) molecules that activate plasminogen locally (in the vicinity of a thrombus) rather than systemically, and 2) molecules that offer new approaches to the inhibition of platelet activation and thrombin activity.
 We first describe the methods used to uncover these molecules and their characterization at the molecular level.
 The ways in which this knowledge can lead to the development of agents tailored to clinical needs are then explored.
",13
2443,"Influence of desflurane on regional distribution of coronary blood flow in a chronically instrumented canine model of multivessel coronary artery obstruction.
 The influence of desflurane on myocardial perfusion measured by a microsphere technique during a total occlusion of the left anterior descending coronary artery and concomitant moderate or severe stenosis of the left circumflex coronary artery was evaluated in chronically instrumented dogs.
 Hemodynamics, regional contractile function, and myocardial blood flow were measured during the conscious state and after anesthesia with desflurane (8.2%-9.2% and 12.5%-12.7%) with and without control of arterial pressure.
 Total left anterior descending occlusion produced in combination with a left circumflex coronary artery stenosis significantly (P less than 0.05) increased heart rate and left ventricular end diastolic pressure in the absence of desflurane anesthesia.
 Desflurane, administered only in the presence of left anterior descending occlusion and left circumflex stenosis, significantly (P less than 0.05) decreased mean arterial pressure, left ventricular systolic pressure, and left ventricular positive dP/dt50 without change in heart rate.
 Blood flow to the subendocardium of normal myocardium was reduced during the high concentration of desflurane (P less than 0.05), but perfusion of the subepicardium and midmyocardium was maintained at conscious levels.
 When the left circumflex stenosis was of moderate severity, only blood flow to the subendocardium distal to the stenosis was reduced by desflurane (P less than 0.05).
 In the presence of a severe stenosis, perfusion was decreased in the subepicardium, midmyocardium, and subendocardium of the stenotic zone (P less than 0.05).
 During the reduction in arterial pressure produced by desflurane, collateral blood flow in the left anterior descending region was reduced in dogs with either a moderate or severe left circumflex stenosis (P less than 0.05).
 When arterial pressure and heart rate conditions observed in the postocclusion conscious state were restored during the high concentration of desflurane, myocardial blood flow in all regions returned to those levels present in the conscious state (P less than 0.05).
 Ratios of flow between occluded and normal zones were decreased when hypotension produced by desflurane was uncontrolled, but when arterial pressure and heart rate were adjusted to conscious postocclusion levels using partial thoracic aorta occlusion and atrial pacing, the ratio remained at conscious control levels regardless of the degree of left circumflex stenosis severity (P less than 0.05).
 Results of this investigation indicate that desflurane does not redistribute blood flow away from collateral-dependent myocardium to other regions via a ""coronary steal"" mechanism in a chronically instrumented canine model of multivessel coronary artery disease.
",13
2444,"Narrow QRS ventricular tachycardia.
 OBJECTIVE: To determine the frequency and clinical characteristics of narrow QRS ventricular tachycardia (QRS duration less than or equal to 0.11 seconds).
 DESIGN: Consecutive survey of patients with ventricular tachycardia.
 SETTING: Tertiary, referral-based arrhythmia service at a university medical center.
 PATIENTS: Sequential sample of patients with inducible ventricular tachycardia who had a 12-lead electrocardiogram of the tachycardia available for review.
 MEASUREMENTS AND MAIN RESULTS: Of 106 patients with ventricular tachycardia, 5 (4.7%; 95% CI, 2.1% to 10.6%) had ventricular tachycardia with a QRS duration less than or equal to 0.11 seconds.
 Three of the five patients were previously incorrectly diagnosed as having supraventricular tachycardia.
 All five patients had at least two electrocardiographic findings other than QRS duration to suggest ventricular tachycardia.
 CONCLUSIONS: Narrow QRS ventricular tachycardia should be considered in the differential diagnosis of narrow QRS tachycardias.
 Electrocardiographic findings other than QRS duration are usually present to suggest the diagnosis.
",13
2445,"Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease?
 OBJECTIVE: To explore the role of endothelin-1, a potent endothelial-derived vasoconstrictor peptide, in pulmonary hypertension, by measuring its concentration in arterial and venous plasma.
 DESIGN: A survey, case series study.
 SETTING: University-affiliated hospitals and outpatient clinics.
 PATIENTS: Twenty-seven patients with pulmonary hypertension: 7 with primary, and 20 with secondary pulmonary hypertension of various causes.
 The control groups (n = 16) comprised 8 healthy volunteers and 8 patients with coronary artery disease but without evidence of pulmonary hypertension.
 MEASUREMENTS AND MAIN RESULTS: Pulmonary artery pressure was markedly increased (94/43 +/- 23/13 mm Hg) in the patients with pulmonary hypertension.
 Venous plasma immunoreactive endothelin-1, measured by a specific radioimmunoassay, was significantly higher in patients with pulmonary hypertension (3.5 +/- 2.5 pg/mL, P less than 0.001) than in normal subjects (1.45 +/- 0.45 pg/mL), or patients with coronary disease (0.75 +/- 0.64 pg/mL).
 The arterial-to-venous ratio of immunoreactive endothelin-1 was significantly greater than unity in primary pulmonary hypertension (2.21 +/- 0.72, P = 0.01), whereas the patients with secondary pulmonary hypertension had a mean ratio not different from 1 (0.97 +/- 0.42).
 In contrast, the mean arterial-to-venous ratios were significantly less than unity in both control groups (0.59 +/- 0.35, and 0.54 +/- 0.64; P less than 0.02, for normal subjects and coronary disease patients, respectively), indicating a possible clearance of endothelin-1 across the healthy lung.
 CONCLUSIONS: Patient with pulmonary hypertension have substantial alterations in plasma immunoreactive endothelin-1, which may reflect changes in net release or clearance of endothelin-1 by the lung.
 In patients with primary pulmonary hypertension, the high levels in arterial compared with venous plasma suggest pulmonary production of endothelin-1, which may contribute to elevated pulmonary vascular resistance.
",13
2446,"Evaluation of drug therapy for treatment of hypertensive urgencies in the emergency department.
 Oral nifedipine (N) and clonidine (C) are often used in the treatment of hypertensive urgencies; however, until recently, there were no comparative studies using the same patient population.
 The authors reviewed the records of hypertensive patients treated in the emergency department between October 1, 1987 and September 30, 1988.
 Selected patients had a diastolic blood pressure (DBP) of greater than 115 mm Hg without evidence of acute end organ damage.
 Patients were stratified into three treatment groups: N, C, and group 3 (G3).
 G3 received a variety of drug therapies but not exclusively N or C.
 Systolic blood pressure (SBP), DBP, mean arterial pressure (MAP), percent decrease in MAP (%MAP), time to lower blood pressure, admissions, and discharges were evaluated.
 Efficacy and safety were defined as reaching a DBP less than 110 mm Hg but %MAP of no greater than either 25% or 40%, respectively.
 Thirty-five N, 32 C, and 27 G3 patients were identified with no statistical difference between groups in race, gender, pretreatment SBP, DBP, or MAP.
 N, C, and G3 significantly reduced SBP, DBP, and MAP (P less than .01).
 Comparing N, C, and G3, no differences were observed in %MAP, admissions, discharges, efficacy, or safety.
 Time required to decrease blood pressure differed between all three groups (44 +/- 32 N v 77 +/- 57 C v 152 +/- 94 min G3) (p less than .05).
 These results indicate that N, C, and a variety of drug therapies are equally effective and safe in the treatment of hypertensive urgencies.
",13
2447,"Experience with esmolol for the treatment of cocaine-associated cardiovascular complications.
 The authors report their experience using esmolol, an ultra-short acting beta-adrenergic antagonist, for the treatment of seven patients with cocaine-associated cardiovascular complications.
 No consistent hemodynamic benefit was found with the use of this drug.
 Although there was a decline in mean heart rate of 23% (range 0% to 35%), they were unable to show a consistent antihypertensive response.
 Adverse effects occurred in three patients.
 This included one patient with a marked exacerbation of hypertension and one who became hypotensive.
 Another patient developed emesis and lethargy during esmolol therapy and required endotracheal intubation.
 They do not recommend the routine use of esmolol for cocaine cardiotoxicity.
",13
2448,"High resolution real-time ultrasound for the diagnosis of venous thrombosis in the rehabilitation setting.
 Accurate, noninvasive testing for deep venous thrombosis (DVT) by conventional methods is often not possible in the rehabilitation patient.
 Lower extremity amputation, a cast or bandage, or skin problems present obstacles to standard diagnostic methods.
 This report describes the use of duplex ultrasound (US) scanning for noninvasive diagnosis of DVT in a seventy-year-old man with a below-knee amputation, on whom Doppler and plethysmography examinations could not be performed.
 As experience is gained with this technique, the use of venography for diagnosis of DVT becomes more difficult to rationalize.
",13
2449,"Retinal arterial macroaneurysms: risk factors and natural history.
 A case control study was conducted to identify the systemic and ocular risk factors for retinal arterial macroaneurysms.
 Forty-three patients with 52 photographically confirmed macroaneurysms were located.
 Forty-three age-matched, race-matched concurrent control patients were also identified.
 The patients with macroaneurysms had decreased visual acuity (p less than 0.0001) and a higher prevalence of hypertension (p = 0.037), female sex (p = 0.099), and retinal vein occlusions (p = 0.055) than controls.
 In patients with both a macroaneurysm and venous occlusion there was a 12.0 times higher prevalence of macroaneurysms in the area of retina drained by the occluded vein (p less than 0.05).
 Common findings associated with macroaneurysms included retinal haemorrhage (81% of patients), retinal exudate (70%), vitreous haemorrhage (30%), macular involvement (30%), and distal arteriolar narrowing (26%).
 Arteriolar occlusion occurred spontaneously (8%) or after laser photocoagulation (16%).
",13
2450,"Hirudin interruption of heparin-resistant arterial thrombus formation in baboons.
 To determine the role of thrombin in high blood flow, platelet-dependent thrombotic and hemostatic processes we measured the relative antithrombotic and antihemostatic effects in baboons of hirudin, a highly potent and specific antithrombin, and compared the effects of heparin, an antithrombin III-dependent inhibitor of thrombin.
 Thrombus formation was determined in vivo using three relevant models (homologous endarterectomized aorta, collagen-coated tubing, and Dacron vascular graft) by measuring: (1) platelet deposition, using gamma camera imaging of 111In-platelets; (2) fibrin deposition, as assessed by the incorporation of circulating 125I-fibrinogen; and (3) occlusion.
 The continuous intravenous infusion of 1, 5, and 20 nmol/kg per minute of recombinant hirudin (desulfatohirudin) maintained constant plasma levels of 0.16 +/- 0.03, 0.79 +/- 0.44, and 3.3 +/- 0.77 mumol/mL, respectively.
 Hirudin interrupted platelet and fibrin deposition in a dose-dependent manner that was profound at the highest dose for all three thrombogenic surfaces and significant at the lowest dose for thrombus formation on endarterectomized aorta.
 Thrombotic occlusion was prevented by all doses studied.
 In contrast, heparin did not inhibit either platelet or fibrin deposition when administered at a dose that maximally prolonged clotting times (100 U/kg) (P greater than .1), and only intermediate effects were produced at 10-fold that dose (1,000 U/kg).
 Moreover, heparin did not prevent occlusion of the test segments.
 Hirudin inhibited platelet hemostatic function in concert with its antithrombotic effects (bleeding times were prolonged by the intermediate and higher doses).
 By comparison, intravenous heparin failed to affect the bleeding time at the 100 U/kg dose (P greater than .5), and only minimally prolonged the bleeding time at the 1,000 U/kg dose (P less than .05).
 We conclude that platelet-dependent thrombotic and hemostatic processes are thrombin-mediated and that the biologic antithrombin hirudin produces a potent, dose-dependent inhibition of arterial thrombus formation that greatly exceeds the minimal antithrombotic effects produced by heparin.
",13
2451,"Serum sialic acid concentration and cardiovascular mortality 
 OBJECTIVE--To determine whether serum sialic acid concentration may be used to predict short and long term cardiovascular mortality.
 DESIGN--Prospective study on all men and women who had their serum sialic acid concentration measured as part of a general health survey in 1964 or in 1965.
 All were followed up for an average of 20.5 years.
 SETTING--Geographical part of the county of Varmland, Sweden.
 SUBJECTS--Residents in the area participating in a health check up in 1964-5 (27,065 men and 28,037 women), of whom 372 men (169 with incomplete data and 203 lost to follow up) and 345 women (143 and 202 respectively) were excluded; thus 26,693 men and 27,692 women entered the study.
 The study sample was restricted to subjects aged 40-74 during any of the 20 years' follow up.
 MAIN OUTCOME MEASURES--Serum sialic acid concentration, serum cholesterol concentration, diastolic blood pressure, body mass index at the general health survey visit; cardiovascular and non-cardiovascular deaths during three periods of follow up (0-6 years, 7-13 years, and 14-20 years), according to the Swedish mortality register, in subjects aged 45-74.
 RESULTS--Mean serum sialic acid concentration (mg/100 ml) was 68.8 (SD 8.0) for men and 69.2 (8.0) for women; the average concentration increasing with age in both sexes.
 A total of 5639 (21%) men and 3307 (12%) women died during the follow up period, in whom death in 3052 (54%) men and 1368 (41%) women was from cardiovascular causes.
 During short (0-6 years), medium (7-13 years), and long (14-20 years) term follow up the relative risk of death from cardiovascular disease increased with increasing serum sialic acid concentration.
 The relative risk (95% confidence interval) associated with the highest quartile of sialic acid concentration compared with the lowest quartile was 2.38 (2.01 to 2.83) in men and 2.62 (1.93 to 3.57) in women.
 Similar results were found for deaths from non-cardiovascular disease with relative risks of 1.50 (1.34 to 2.68) in men and 1.89 (1.57 to 2.28) in women, but these relative risks were significantly lower than those for deaths from cardiovascular disease (p less than 0.001 and p less than 0.005 respectively).
 In multivariate analysis of total mortality and of cardiovascular mortality with sialic acid concentration, serum cholesterol concentration, diastolic blood pressure, and body mass index as independent variables the impact of sialic acid concentration was virtually the same as in univariate analysis.
 CONCLUSION--Serum sialic acid concentration is a strong predictor of cardiovascular mortality.
 A possible explanation of these findings is that the serum sialic acid concentration may reflect the existence or the activity of an atherosclerotic process, and this may warrant further investigation.
",13
2452,"Comparison of exercise performance in left main and three-vessel coronary artery disease.
 From a consecutive series of patients who underwent rest and exercise radionuclide angiography over several years, we retrospectively identified 34 patients with left main coronary artery disease and 103 patients with three-vessel coronary artery disease who did not have significant left main disease.
 The results of gated equilibrium radionuclide angiography were compared in these 2 groups.
 Multiple exercise hemodynamic, exercise electrocardiographic, and exercise radionuclide angiographic parameters were considered in an attempt to separate the 2 groups.
 The only parameter that was significantly different between the 2 groups was exercise heart rate.
 However, no value of the exercise heart rate could meaningfully separate the 2 groups.
 Despite their known difference in prognosis, patients with left main and three-vessel disease had very similar exercise performance and could not be distinguished from one another by exercise electrocardiography or exercise radionuclide angiography.
 The inability to distinguish these two groups is a clear limitation of noninvasive exercise modalities.
",13
2453,"Atrial septal occlusion improves the accuracy of mitral valve area determination following percutaneous mitral balloon valvotomy.
 We investigated the impact of the atrial communication on the mitral valve area calculation after percutaneous mitral balloon valvotomy in 17 patients (15 women, 2 men; mean age 56 +/- 4 years).
 The hemodynamic measurements and mitral valve area calculations were performed with and without balloon occlusion of the atrial septal puncture site.
 The mitral valve area determined with balloon occlusion was significantly smaller than the mitral valve area determined without occlusion (1.6 +/- 0.1 vs.
 1.9 +/- 0.1 cm2, P less than 0.01), and was similar to the echocardiographically determined valve area (1.6 +/- 0.1 cm2).
 This decrease in the calculated mitral valve area with occlusion was associated with a decrease in the measured cardiac output, without a change in the mitral valve gradient or the diastolic filling period.
 Occlusion of the atrial septal puncture site may permit more accurate determination of the mitral valve area and thus provide a better reference point for future comparison should the question or restenosis arise.
",13
2454,"Preservation of regional myocardial function during coronary angioplasty with an autoperfusion balloon catheter: a case report.
 Echocardiographic assessment of regional myocardial function was performed during standard balloon coronary angioplasty followed by autoperfusion balloon angioplasty of a proximal left anterior descending artery stenosis.
 Septal and apical akinesis occurred within 60 seconds of standard balloon inflation, but regional function was well preserved during prolonged autoperfusion balloon inflation.
",13
2455,"Successful mitral valvuloplasty using the Inoue balloon in a patient with mitral stenosis associated with subvalvular fibrosis and reduced left ventricular inflow cavity: a case report.
 Percutaneous transvenous mitral valvuloplasty (PTMV) was performed with two cylindric pigtail balloon catheters in a 52-year-old woman with symptomatic mitral stenosis.
 The subvalvular apparatus was fibrous with welded chordae and the subvalvular left ventricular space was markedly reduced.
 As a result of this distorted anatomy, during the inflations, the two balloons constantly slipped back into the left atrium before full inflation was obtained.
 After the procedure, the mitral valve area (MVA), as estimated by echo-doppler (ED), increased from 1.00 to 1.34 cm2.
 After 2 months of mild clinical improvement, the patient again became symptomatic and ED examination showed a MVA of 1.25 cm2.
 A second PTMV was performed with an Inoue balloon, the entire procedure taking less than 1 hour.
 A stable position of the Inoue balloon and complete dilatation were achieved.
 ED examination showed a mitral valve area of 2.30 cm2.
 There was no mitral regurgitation nor atrial septal defect.
 After 3 months, she has only N.Y.H.A.
 class I symptoms and MVA, as estimated by ED, was 2.40 cm2.
",13
2456,"Percutaneous right brachial artery approach with 5F catheters for studying coronary artery disease.
 We prospectively studied 60 ischemic patients with 5F catheters (Pigtail and Amplatz) using the percutaneous right brachial artery approach (group I), in order to compare this technique with two groups of 100 patients each randomly studied by the femoral route with either 5F (group II) or 8F (group III) catheters (Pigtail and Judkins).
 The following parameters were analyzed: need to change the initially elected catheter diameter or/and artery approach; technical difficulty for obtaining LV, LCA, and RCA angiograms; total time of X-ray exposure; quality image of LV, LCA, and RCA angiograms; incidence of arterial puncture related hematomas or total arterial occlusion; and duration of local compression after sheath removal.
 There were no differences between 5F brachial and femoral approaches except for the arterial compression time (p less than 0.01) and the X-ray exposure time (p = 0.03) which were longer with the brachial approach.
 Whatever the route used, 5F showed a mild increase difficulty (brachial p = 0.001; femoral p = 0.01) and a mild decreased quality image for LCA (branchial p = 0.006; femoral p less than 0.05).
 Mild hematomas were more frequent with 8F catheters (p less than 0.05).
 The procedure could be completed by the elected first artery and type of catheter (5F or 8F) in 57/60 patients in group I, in 95/100 in group II, and in 96/100 in group III (nonsignificant differences).
 Thus, the percutaneous right brachial artery approach using 5F catheters is similar to the femoral artery approach with the same catheters.
 Although both of them showed a mild increased technical difficulty and a mild decreased quality image compared to 8F, mainly for LCA angiograms, they allowed complete and reliable angiograms reading and analysis.
",13
2457,"Accuracy and reproducibility of quantitative coronary arteriography using 6 and 8 French catheters with cine angiographic acquisition.
 To determine the suitability of 6 French catheters for quantitative coronary arteriography, the relative accuracy and reproducibility of one type of these catheters was compared to that obtained with standard 8 French catheters in 20 stenoses.
 Duplicate injections with polyurethane 6 French catheters were obtained using hand and power injection technique with cineangiographic acquisition (four 6 French catheter injections total per stenosis).
 Measurements of both percent diameter stenosis and absolute dimensions were compared to those obtained with hand injection and cine acquisition using 8 French catheters as a ""gold standard."" While the reproducibility of dimension determination with the 6 French catheter was generally similar to that obtained with the 8 French catheter (0.27 +/- 0.23 mm for absolute diameter and 8.1 +/- 7.4% for percent diameter stenosis), accuracy was significantly less for the 6 French catheter for measurement of absolute dimensions.
 Thus, while apparently well suited for serial measurements of the same stenoses, 6 French catheters may not be as accurate in the determination of absolute artery dimensions as 8 French catheters.
",13
2458,"Coronary balloon angioplasty through diagnostic 6 French catheters.
 We investigated the use of ultralow profile balloon catheters (Scimed ACE, USCI Probe, Cordis, Orion) for coronary angioplasty through 6 French diagnostic catheters (Schneider, Cordis).
 Contrast injection was assisted with a Hercules pump (Cordis) in all cases.
 During 21 procedures, angioplasty of 27 lesions in 20 selected patients was attempted (1.3 lesion/procedure).
 Twelve lesions were in the right, 10 in the left anterior descending, and 5 in the left circumflex coronary artery.
 Balloon size varied between 2.5 and 3.5 mm.
 Twenty lesions could be successfully dilated (74%) through the 6 French catheter and 7 lesions required an exchange to a 7 French angioplasty guiding catheter.
 For 5 cases, another balloon was also necessary to complete the procedure.
 The final overall success rate was 100% per patient and per lesion and there were no major complications.
 Despite the small internal catheter lumen (1.22 mm) coronary visualization was adequate, and mechanical support was good.
 Failures of 6 French catheters were attributed to insufficient torque control and excessive friction when the balloon crossed the tapered end of the diagnostic catheter.
 Coronary angioplasty through a diagnostic 6 French catheter is feasible and may represent a reasonable alternative for simple cases that are done during the same session as the diagnostic angiography.
 Once available, 6 French high flow angioplasty guiding catheters without a tapered tip should improve success while retaining the advantage of a small femoral puncture site.
",13
2459,"Preliminary experience with 5 and 6 French diagnostic catheters as guiding catheters for coronary angioplasty.
 With the reduction in profile of balloon dilation catheters, until recently, it has been the internal dimensions and performance of the guiding catheter that has mandated the use of 7, 8 or 9 French (F) systems for the performance of percutaneous transluminal coronary angioplasty (PTCA).
 A new 5F catheter design (Sherwood Medical Co., St.
 Louis, MO) provided a large inner lumen (0.4"") permitting use of 0.20-0.22"" fixed-wire PTCA balloon catheters with good coronary visualization.
 Potential advantages include reduced coronary artery ostial trauma and catheter induced damping and enhanced patient comfort.
 We report our initial experience in 14 patients undergoing PTCA with a 5 and 6F guide/fixed-wire system.
 Mean age was 63 +/- 10 (43-78 years).
 PTCA indications: Cardiogenic shock (1), post-myocardial infarction angina pectoris (2), grade III angina (5) and unstable angina pectoris (6).
 Vessel attempted: Left anterior descending (3), circumflex (4), obtuse marginal (2), diagonal (1), right coronary artery (3), and internal thoracic artery (1).
 Twelve patients had femoral approach; two brachial approach.
 The USCI Probe (USCI Division, Billerica, MA) was used in 8 lesions and SCIMED ACE (SCIMED Life Systems, Maplegrove, MN) catheter in 7 lesions.
 Successful 5 or 6F guide/fixed-wire dilations reduced the stenosis (77 +/- 14 to 37 +/- 30%) and were successfully performed in 79% (11/14).
 One 5F patient required 8F guiding catheter and was dilated with 2.0 fixed-wire balloon.
 A second failed 5F PTCA could not be dilated with any larger conventional system.
 A third total occlusion could not be crossed with a guidewire or fixed wire balloon.
 No patient had a complication.
",13
2460,"Application of coronary angioplasty to the septal perforator arteries.
 Significant coronary artery disease affecting the septal perforator arteries can cause anginal pain, rhythm disturbances, or septal infarction.
 However, since these vessels are usually inaccessible to coronary bypass surgery, there is a tendency among angiographers and angioplasters to overlook lesions of the septal perforator arteries.
 Our experience suggests that if medical treatment is not sufficient to treat clinical manifestations resulting from septal perforator disease, then coronary angioplasty can be considered a therapeutic alternative for revascularization.
 We herein present 11 patients who underwent coronary angioplasty of a major septal artery and discuss angiographic and technical aspects of the procedure.
",13
2461,"Cardiotoxicity of interferon. A review of 44 cases.
 Cardiovascular complications have occurred in clinical trials of interferon.
 We review herein experience to date of cardiotoxicity with all types of interferons in cancer patients.
 The most common presentations of cardiotoxicity were cardiac arrhythmia, dilated cardiomyopathy, and symptoms of ischemic heart disease, including myocardial infarction and sudden death.
 The cardiac effects were not related to the daily dose, cumulative total dose, or period of therapy.
 Some of the patients in whom interferon has caused cardiovascular sequelae have had a history of coronary heart disease or have previously been given chemotherapy with drugs known to be cardiotoxic.
 In most of the patients, cardiac toxicity was reversible following the cessation of the drug therapy.
",13
2462,"Systemic to pulmonary bronchial blood flow in mitral stenosis.
 We measured systemic to pulmonary bronchial blood flow [Qbr(s-p)] during total cardiopulmonary bypass in 15 patients with mitral stenosis and elevated pulmonary venous pressure (group A, mean pulmonary wedge pressure = 22.2 +/- 5.4 mm Hg, mean +/- SD) and in 15 patients with coronary artery diseases and normal pulmonary venous pressure (group B).
 Qbr(s-p) is the volume of blood accumulating in the left side of the heart in the absence of pulmonary and coronary flows.
 This blood was vented through a cannula introduced into the left atrium and measured.
 Qbr(s-p) was 76.3 +/- 13.9 ml/min (2.18 +/- 0.37 percent of extracorporeal circulation pump flow) and 22.3 +/- 2.1 (0.63 +/- 0.15) in group A and B, respectively (p less than 0.01).
 During total cardiopulmonary bypass, pulmonary venous pressure is approximately atmospheric pressure, and no differences in systemic blood pressure, extracorporeal circulation pump flow, and airways pressure were observed between group A and B.
 Therefore, vascular resistance through the bronchial vessels draining into the pulmonary circulation is reduced in patients with mitral stenosis and elevated pulmonary venous pressure.
",13
2463,"Catheter-induced tricuspid regurgitation. Incidence and clinical significance.
 The incidence and severity of catheter-induced tricuspid regurgitation has not been studied extensively.
 Given the frequency with which right heart catheters are employed to measure cardiac output, it is important to know whether the severity of catheter-induced tricuspid regurgitation is sufficient to invalidate the measurement of thermodilution cardiac output.
 Accordingly, the purpose of the present prospective study was to determine the incidence and severity of catheter-induced tricuspid regurgitation in 25 men (mean age, 58.1 +/- 1.4 years) using Doppler ultrasound.
 The tricuspid valve was interrogated from two orthogonal views using pulsed-wave and color flow Doppler, either in the presence or absence of a 7-French catheter across the tricuspid valve.
 The severity of catheter-induced tricuspid regurgitation was graded semiquantitatively using a validated scoring system.
 Pulsed-wave Doppler studies showed that the incidence of catheter-induced tricuspid regurgitation was 48 percent, and that the average tricuspid regurgitation score increased from 0.41 +/- 0.16 to 0.61 +/- 0.17 (p less than 0.01).
 Color flow Doppler studies showed similar findings.
 Further, the incidence of catheter-induced tricuspid regurgitation was not related to the patient's underlying hemodynamic status or right ventricular geometry.
 In conclusion, this study shows for the first time that the quantitative extent of catheter-induced tricuspid regurgitation is small, and is therefore unlikely to be important clinically, particularly with regard to the assessment of thermodilution cardiac output.
",13
2464,"Venous air embolism. Diagnosis by spontaneous right-sided contrast echocardiography.
 This report describes the definitive diagnosis of venous air-embolism by documentation of spontaneous echo contrast in the right cardiac chambers following removal of a jugular venous catheter in a patient with hepatic failure.
 This complication was potentiated by the presence of concurrent hepatic coagulopathy which prejudiced effective hemostasis at the central venous puncture site.
",13
2465,"The effect of thromboxane synthetase inhibition on cardiopulmonary function during endotoxemia in sheep.
 The early pulmonary hypertension seen with endotoxin (lipopolysaccharide) has been reported as resulting from the release of thromboxane A2.
 We studied the cardiopulmonary response to endotoxin in sheep with and without treatment with a thromboxane synthetase inhibitor, OKY-046.
 The animals were implanted with instruments for crystallographic dimension analysis of the left ventricle and measurement of left ventricular, aortic, left atrial, and pulmonary arterial pressures and cardiac index.
 Thirteen sheep received 1.0 micrograms/kg of Escherichia coli endotoxin with (n = 6) and without (n = 7) OKY-046 (10 mg/kg bolus, then 10 micrograms/kg/min).
 OKY-046 prevented the increase in pulmonary arterial pressure and decrease in cardiac index usually seen during the early phase of endotoxemia.
 Between 8 and 12 hours after the administration of endotoxin, cardiac index increased from 6.4 +/- 0.8 to 8.4 +/- 0.8 L/min/m2.
 Concomitantly, the end-systolic pressure/diameter relationship (a sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7 mm Hg/mm.
 Another index of the left ventricular contractility, the maximum rate of pressure rise was also reduced.
 OKY-046 prevented decreases in end-systolic pressure/diameter relationship and maximum rate of pressure rise.
",13
2466,"Platelet fatty acids and function in two distinct regions of Belgium: relationship to age and dietary habits.
 We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and platelet function in two groups of healthy Belgian male subjects, known to differ in their mortality rate from coronary heart disease (CHD).
 In the Walloon subjects, there was a larger intake of saturated and a lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid composition of plasma and platelet phospholipids.
 While plasma HDL and total cholesterol were similar in the present samples of the two communities, platelet aggregation to epinephrine was significantly higher in the Walloon subjects.
 When the two populations were divided into younger (28-54 years) and older (55-73 years) age groups, the older Walloon subjects exhibited platelet hyper-aggregability to most of the agonists, compared to the other three groups.
 In addition to dietary fats, alcohol and smoking habits, age was an important determinant of platelet phospholipid fatty acids and platelet reactivity.
 The present results reinforce those of previous studies, indicating that platelet behaviour is significantly affected by the main risk factors for CHD.
",13
2467,"Potential complications of high-dose epinephrine therapy in patients resuscitated from cardiac arrest 
 Adults resuscitated from nontraumatic cardiac arrest who received intravenous epinephrine in doses chosen by the treating physician and who survived at least 6 hours were studied to determine if high-dose epinephrine produced more complications than standard-dose.
 A total of 68 patients were enrolled and evaluated for postresuscitation complications attributable to epinephrine, using a two-tailed t test, and contingency analysis.
 The 33 patients receiving high-dose epinephrine and 35 patients receiving standard-dose epinephrine were similar in demographics and variables known to affect outcome.
 There was no difference in potential complications between groups except serum calcium, which was 1.97 mmol/L (SD, 0.20) in the high-dose epinephrine group and 2.10 (SD, 0.20) in the standard-dose group.
 Hospital discharge rates (18% in the high-dose vs 30% in the standard-dose group) and neurological status on discharge were not significantly different.
 High-dose epinephrine did not produce increased direct complications in this cardiac arrest population compared with standard-dose epinephrine.
",13
2468,"Cardiomyopathy associated with the smoking of crystal methamphetamine.
 The smoking of crystal methamphetamine, or ""ice,"" is a growing drug abuse problem in the United States.
 The toxic effects of methamphetamine smoking have not been well described.
 We describe two patients with cardiovascular toxic effects associated with the smoking of crystal methamphetamine.
 In our first patient, the use of smokeable methamphetamine was associated with the subsequent development of pulmonary edema and a dilated cardiomyopathy.
 In our second patient, the smoking of crystal methamphetamine likely produced diffuse vasospasm that resulted in acute myocardial infarction, cardiogenic shock, and death.
 The recognition of potentially lethal cardiac complications associated with the smoking of crystal methamphetamine is of extreme significance and should be emphasized to potential abusers of this drug.
",13
2469,"Caloric expenditure, life status, and disease in former male athletes and non-athletes.
 This study examined the association between aerobic, caloric exercise expenditure and life status (living vs deceased) as well as the prevalence rates of hypertension (HBP) and cardiovascular disease (CVD) in former male athletes (ATH) and non-athletes (N-ATH).
 The initial survey for this study was done in 1952.
 Follow-up surveys of respondents were done in 1960, 1968, 1976, and 1984.
 The present study used all subjects who responded fully to activity and health questions in 1976 and who were reported as either dead or alive (not lost to follow-up) in 1984.
 A total of 348 subjects (185 ATH, 163 N-ATH) were assessed and caloric expenditure groups were established by kilocalories (kcal) of aerobic exercise per week; 0 kcal (group 1), 1-399 kcal (group 2), 400-899 kcal (group 3), 900-1499 kcal (group 4), 1500-2499 kcal (group 5), and 2500+ kcal (group 6).
 Only activity considered to be aerobic was used in the establishment of the aerobic categories.
 Death rate was highest in groups 1 and 2.
 Subjects in group 1 tended to be the oldest.
 Year of birth (age) (P less than 0.001) and CVD (P less than 0.05) as reported in 1976 were significantly related to mortality between 1976 and 1984.
 College athletic status and 1976 exercise level were not significantly related to mortality.
 Prevalence of CVD and HBP was highest in groups 1 and 6, suggesting a moderate amount of aerobic activity as optimal.
",13
2470,"Selective inhibition by a synthetic hirudin peptide of fibrin-dependent thrombosis in baboons.
 To determine the importance of the thrombin substrate recognition exosite for fibrinogen binding in the formation of both arterial and venous thrombi, we evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from residues 53-64 of hirudin (H peptide) in a nonhuman primate model.
 This peptide was studied because it inhibits thrombin cleavages of fibrinogen by simple competition without blocking enzyme catalytic-site function.
 When an exteriorized arteriovenous access shunt model was used in baboons (Papio anubis), thrombus formation was induced by placing a thrombogenic device made of (i) a segment of tubing coated covalently with type I collagen, which generated platelet-rich thrombi under arterial flow conditions, and (ii) two subsequent annular regions of flow expansion that produced fibrin-rich thrombi typically associated with venous valves and veins.
 Thrombus formation was quantified by measurements of 111In-labeled platelet and 125I-labeled fibrinogen deposition in both arterial-flow and venous-flow portions of the device.
 Continuous infusion of H peptide (0.5, 15, and 75 mg/kg) proximal to the device for 40 min interrupted, in a dose-response fashion, formation of fibrin-rich thrombus in the regions of disturbed flow and generation of fibrinopeptide A.
 In contrast, H peptide did not inhibit the capacity of platelets to deposit on the collagen surface (P greater than 0.2 at all doses) or to form hemostatic plugs (as assessed by measurements of bleeding time; P greater than 0.1 at all doses).
 These findings suggest that, by competitive inhibition of fibrinogen binding to thrombin, fibrin-rich venous-type thrombus formation may be selectively prevented.
 This strategy may be therapeutically attractive for preserving normal platelet function when conventional anticoagulant therapy is contraindicated.
",13
2471,"Home blood pressure readings in borderline hypertensive patients.
 Home blood pressure monitoring can provide valuable information for physicians managing borderline hypertensive patients.
 This study was conducted to compare office and home blood pressures in 36 borderline hypertensive subjects, and to determine the accuracy of the home monitoring unit used.
 The patients were very willing to record their home blood pressures for an extended period of time.
 The home blood pressure monitors were found to be quite accurate, and blood pressures measured at home were significantly lower than readings obtained in the office.
 In 39% (14 of 36) of the subjects studied, the average home blood pressures were more than 10 mmHg lower than their office readings.
 These findings support the hypothesis that home blood pressure monitoring can be useful in the management of borderline hypertensive patients.
",13
2472,"Vasodilatory beta-blockers: systemic and regional hemodynamic effects.
 The systemic and regional hemodynamic alterations in hypertension and of the beta-adrenergic receptor inhibiting agents are reviewed.
 Hemodynamically, hypertension may be regarded as persistent elevation of arterial pressure associated with increased total peripheral resistance.
 In early or mild essential hypertension, however, increased total peripheral resistance may not readily be recognized because of the overriding effect of increased cardiac output.
 Clearly, the hemodynamics of blood pressure control are complex, and the mechanisms of antihypertensive agents must be used appropriately.
 The early beta-blockers reduced heart rate and cardiac output immediately after intravenous administration without immediately reducing arterial pressure, and calculated total peripheral resistance was increased.
 With prolonged oral treatment, arterial pressure decreased while maintaining a reduced heart rate and cardiac output.
 Total peripheral resistance, however, remained elevated.
 Recent beta-blockers, such as celiprolol, provide an improved physiologic response by instantly reducing arterial pressure and total peripheral resistance without reducing heart rate or cardiac output or expanding intravascular volume.
",13
2473,"Angina, ischemia, and effort tolerance with vasodilating beta-blockers.
 beta-Blockers are known to suppress exercise-induced ischemia but give rise to such problems as fatigue or dyspnea on effort and also bradycardia.
 In a series of double-blind, placebo-controlled studies of celiprolol (a cardioselective beta 1-blocker with beta 2-agonist and vasodilatory properties) in patients with hypertension and angina and in normal volunteers, it was found that celiprolol did not produce bradycardia when given in combination with verapamil.
 Celiprolol did reduce exercise-induced ischemia, but there was no reduction in cardiac output at rest or on exercise compared with placebo.
 Compared with atenolol, celiprolol produced less dyspnea and fatigue at submaximal levels of exercise.
 It is concluded that celiprolol possesses certain differences, compared with conventional beta-blockers, that may be of direct clinical benefit.
",13
2474,"Cardiovascular risk factors and the effects of intervention.
 Cardiovascular risk factors can be substantially modified by changes in life-style such as diet, exercise, smoking cessation, and moderation of alcohol consumption.
 In turn, these can reduce blood pressure, heart rate at rest, and blood lipid concentrations.
 Epidemiologic evidence shows that for every 1% change in serum cholesterol levels, there is a 3% change in the likelihood of developing coronary heart disease.
 In addition, a long-term (5-year) change of 5 to 6 mm Hg in diastolic blood pressure can reduce the chances of stroke by 35 to 40% and of coronary heart disease by 20 to 25%.
 The full impact of this broad range of interventions on population health has still to be fully realized in many countries, including the United Kingdom, however it is likely to be considerable.
 Some of the recent evidence in support of such cardiovascular risk factor modification is selectively reviewed.
",13
2475,"Dialysis-induced alterations in left ventricular filling: mechanisms and clinical significance.
 Quantitative two-dimensional (2-D) and Doppler echocardiography were used to determine whether hemodialysis results in alterations in left ventricular (LV) diastolic filling that might contribute to dialysis-induced hypotension, as well as to assess whether any hemodynamic variables or indices of diastolic filling might be used to identify which patients were at the greatest risk of becoming hemodynamically unstable during dialysis.
 Sixteen male patients undergoing routine maintenance hemodialysis for end-stage renal disease were prospectively studied before and after hemodialysis.
 Following hemodialysis there was a significant prolongation (P less than 0.05) in LV isovolumetric relaxation time (IVRT), as well as a significant reduction in the rate and extent of early rapid ventricular filling (P less than 0.005); in contrast, late atrial-assisted filling did not change significantly.
 A multiple stepwise linear regression analysis of predialysis hemodynamic parameters and noninvasive indices of LV filling showed that there was a significant independent inverse relationship between the frequency of dialysis-related hypotensive episodes and the duration of early LV filling (r = -0.81; P less than 0.001).
 These results suggest that hemodialysis results in discrete alterations in early LV filling, with no significant compensatory increase in late atrial-assisted ventricular filling.
 Further, patients with the shortest early LV filling times appeared to have the greatest predilection for becoming hemodynamically unstable during dialysis.
",13
2476,"Use of the fistula assessment monitor to detect stenoses in access fistulae.
 Twenty-three unselected hemodialysis patients with functioning access arteriovenous fistulae were studied prospectively to determine the best technique for detecting stenoses within the fistulae.
 Combined clinical assessment and fistula assessment monitoring were compared with transbrachial angiography.
 Fistula assessment monitoring was more accurate (96%) than combined clinical assessment (accuracy, 52%) in stenosis detection.
 Complications of angiography occurred in 17% of patients; there were no complications of fistula assessment monitoring.
 Fistula assessment monitoring was better than combined clinical assessment in predicting clinical outcome for arteriovenous fistulae over 6 months and was as good as angiography.
 Routine fistula assessment monitoring could reduce inappropriate angiography and detect clinically significant silent stenoses.
 It is an ideal method for monitoring arteriovenous access fistulae.
",13
2477,"Cyclosporine-induced thrombotic microangiopathy resulting in renal allograft loss and its successful reuse: a report of two cases.
 Cyclosporine-induced thrombotic microangiopathy is a rare complication of renal transplantation.
 It commonly leads to graft loss.
 The mechanism of this entity is unknown.
 Factors intrinsic to the donor kidney appear to play an important role.
 We describe two cases of renal transplant patients who lost their first grafts secondary to cyclosporine-induced thrombotic microangiopathy.
 These patients were successfully retransplanted with an immunosuppressive protocol that included long-term cyclosporine.
 We conclude that graft loss from this entity is not a contraindication to subsequent successful transplantation with cyclosporine.
",13
2478,"Unsuspected mitral stenosis.
 PURPOSE AND PATIENTS AND METHODS: We observed a series of patients in whom the diagnosis of mitral stenosis was first discovered in the echocardiography laboratory.
 Because of this experience, we examined the records of 152 patients with echocardiographic evidence of rheumatic mitral stenosis to determine the clinical characteristics and course of patients with unsuspected mitral stenosis as well as those factors that may have obscured the diagnosis.
 RESULTS: Of these 152 patients, 18 had mitral stenosis that was unsuspected clinically until the echocardiogram.
 These patients were elderly, with a median age of 72 years.
 They were all referred for echocardiography because of cardiac symptoms.
 Eight patients were referred for evaluation of congestive heart failure.
 Five patients were referred for evaluation of aortic valve disease.
 Three patients were referred because of cerebrovascular accidents and atrial fibrillation.
 The Doppler-determined mean diastolic mitral gradient ranged from 4 to 15 mm Hg (mean: 7 mm Hg).
 Mitral stenosis ranged in severity from trivial to very severe.
 Eight patients had moderate to severe mitral stenosis with estimated mitral valve areas less than or equal to 1.5 cm2.
 Seven had mild or trivial mitral stenosis with estimated mitral valve areas greater than 1.5 cm2.
 After further evaluation, two patients underwent mitral valve surgery with improvement of congestive failure.
 In three patients, warfarin therapy was begun to prevent emboli.
 Thus, five of 18 patients had a significant immediate change in therapy because of the discovery of mitral stenosis.
 CONCLUSION: The diagnosis of mitral stenosis may not be suspected in the presence of advanced age, other serious cardiac and medical conditions, or mechanical factors that complicate the physical examination.
 In these patients, mitral stenosis may be hemodynamically significant and may cause significant symptoms.
",13
2479,"Prognostic significance of valvular regurgitation in patients with infective endocarditis.
 PURPOSE: Doppler ultrasound is a sensitive modality for detecting and quantitating valvular regurgitation in patients with infective endocarditis.
 Because valvular regurgitation leads to heart failure, we evaluated the prognostic significance of Doppler-detected valvular regurgitation in patients with endocarditis who had not yet developed clinical heart failure.
 PATIENTS AND METHODS: We reviewed the medical records of 65 patients with a clinical diagnosis of infective endocarditis from May 1985 to March 1990.
 A total of 49 patients were included in the study: 33 patients with native valve endocarditis and 16 patients with prosthetic valve endocarditis.
 The initial Doppler echocardiogram was examined in these patients to determine the presence and degree of valvular regurgitation.
 RESULTS: Significant (moderate to severe) valvular regurgitation was detected in 23 (47%) patients.
 The presence or absence of significant valvular regurgitation did not predict the development of congestive heart failure, the need for surgery, or death (p = NS).
 The development of congestive heart failure was significantly associated with the need for surgery (p less than 0.0001) and death (p less than 0.05).
 CONCLUSION: We conclude that the detection of significant valvular regurgitation in patients with infective endocarditis who have not yet developed heart failure is not predictive of future complications nor does the absence of significant valvular regurgitation identify a group of patients with a more favorable prognosis.
 In our series, patients who developed congestive heart failure had a significantly higher incidence of surgery and death.
 Therefore, decisions regarding clinical management in patients with infective endocarditis should not be made solely on the presence or absence of echocardiographically detected valvular regurgitation.
",13
2480,"Comparison of labetalol versus enalapril as monotherapy in elderly patients with hypertension: results of 24-hour ambulatory blood pressure monitoring.
 PURPOSE: This study compared the safety and efficacy of labetalol and enalapril as antihypertensive therapy for elderly patients.
 PATIENTS AND METHODS: A randomized, open-label, parallel controlled trial was conducted.
 After completing a 4-week placebo phase, 79 elderly (65 years or older) patients with an average standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less were randomized to receive a 12-week course of either labetalol or enalapril in an open-label design.
 The patients' BP and heart rate were evaluated biweekly by trained observers unaware of the treatment status, and drug dosage was titrated (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from baseline.
 Patients underwent 24-hour ambulatory BP monitoring (ABPM) at the end of the placebo phase and again after 8 weeks of active treatment.
 RESULTS: The treatment groups were comparable in their reduction of supine diastolic BP, with no significant differences between the two treatments.
 Labetalol demonstrated a significantly greater reduction (p less than 0.05) in standing diastolic BP at the end of the titration period compared to enalapril, but this difference was not significant by the end of the study period.
 Based on 24-hour ABPM readings, labetalol reduced mean 24-hour diastolic BP (p less than 0.05) and mean heart rate (p less than 0.05) more than enalapril.
 The labetalol-treated patients were significantly less often above their diastolic BP goal throughout the 24-hour ABPM period (p less than 0.01).
 The two treatments were equally well tolerated.
 CONCLUSIONS: The results indicate that labetalol and enalapril are equally effective in lowering supine diastolic BP in the elderly, but labetalol is more effective in lowering ambulatory BP and heart rate throughout the day.
",13
2481,"Elderly patients with congestive heart failure under prepaid care.
 PURPOSE: Because of concern about the quality of care received by Medicare patients in health maintenance organizations (HMOs), the care of patients with congestive heart failure (CHF) in eight HMOs was compared with the care of fee-for-service (FFS) Medicare cases.
 PATIENTS AND METHODS: We compared the care of 170 patients with CHF enrolled in one of eight Medicare HMOs with the care of 191 similar FFS patients.
 Panels of expert physicians developed criteria for evaluating quality of care, and specially trained nurse clinicians abstracted medical records.
 RESULTS: Outpatient evaluation and management were similar in both settings, although HMO patients were significantly more likely to be advised to restrict salt intake.
 However, FFS patients with uncontrolled hypertension were more likely to have their medication regimens changed (62% versus 36%, p less than 0.01).
 Ejection fractions were obtained equally as often, and inpatient management was similar for both groups.
 Nonetheless, HMO providers scheduled follow-up visits within 1 week of hospital discharge more often (42% versus 27%, p less than 0.01).
 CONCLUSIONS: This study suggests that financial incentives of prepaid care are not detrimental to most aspects of care for CHF patients.
 More rapid follow-up after hospital discharge for patients with CHF suggests that HMOs may be more effective in delivering continuity of care for patients with chronic illness.
",13
2482,"Emery-Dreifuss muscular dystrophy.
 Emery-Dreifuss syndrome is a rare form of muscular dystrophy associated with cardiac complications that lead to sudden death.
 The disorder and its potential anaesthetic implications in the management of a patient who presented for orthopaedic surgery is described.
",13
2483,"Drug-induced supraventricular tachycardia: a case report of fluoxetine.
 We report the occurrence of supraventricular tachycardia and hypotension in a 54-year-old woman after maintenance therapy with fluoxetine.
 Although cases of tachycardia and palpitations have been reported, supraventricular tachycardia and hypotension have not been directly attributed to fluoxetine.
",13
2484,"Torsades de pointes therapy with phenytoin.
 We present the case of a woman with myocardial infarction complicated by malignant ventricular arrhythmia and torsades de pointes.
 The torsades de pointes was refractory to conventional therapy but responsive to phenytoin.
 This case suggests the clinical usefulness of phenytoin for adjunct therapy of life-threatening ventricular arrhythmias when standard treatment modalities fail.
",13
2485,"Plasma concentrations of epinephrine during CPR in the dog.
 STUDY OBJECTIVE: The purpose of this study was to evaluate whether the marked increase in the plasma concentrations of epinephrine during cardiopulmonary arrest and basic life support (BLS) could be due in part to decreased distribution and/or elimination.
 DESIGN AND INTERVENTIONS: Dogs were randomly assigned to undergo adrenalectomy or sham-operation.
 Some adrenalectomized animals received an epinephrine infusion.
 MEASUREMENTS AND MAIN RESULTS: In the seven sham-operated dogs, the plasma epinephrine concentrations increased markedly during BLS as expected.
 In the seven adrenalectomized dogs receiving a constant infusion of epinephrine, cardiopulmonary arrest and BLS induced a three to sixfold increase in plasma epinephrine concentrations, with an increase in the mean plasma epinephrine concentrations (calculated from the area under the curve) of 1.21 +/- 0.12 ng/mL (P less than .05).
 In the seven adrenalectomized dogs receiving a constant epinephrine infusion but not subjected to cardiopulmonary arrest, the plasma epinephrine concentrations remained stable.
 Finally, in the seven adrenalectomized dogs not receiving an epinephrine infusion, the mean plasma epinephrine concentrations during BLS (calculated from the area under the curve) increased only by 0.05 +/- 0.04 ng/mL, significantly less than in adrenalectomized dogs receiving an epinephrine infusion (P less than .01).
 CONCLUSION: The increase in plasma epinephrine concentrations during cardiopulmonary arrest and BLS is due in part to an altered disposition of epinephrine.
",13
2486,"Demographic, social and stress correlates of hypertension among the urban poor.
 The relationship of demographic, social, and psychological variables to the diagnosis of hypertension in a population of urban, poor, predominantly black out-patients is reported.
 Subjects were 182 patients presenting for health care at Wayne State University Family Practice Clinic.
 Age, race, marital status, attendance at religious services, education, employment status, income, source of income and interpersonal stress were significantly related to a diagnosis of hypertension in this sample.
 Of those characteristics found to be significantly related to hypertension, discriminative analysis showed that age, race, education and frequency of church attendance were most important in predicting a diagnosis of hypertension among this out-patient sample of the urban poor.
 Implications for clinical care and for future research needs are considered.
",13
2487,"Strain differences in baroreflex inhibition by centrally infused enalapril in old rats.
 To determine whether inhibition of the brain renin-angiotensin system would affect baroreflexes similarly in old rats of different strains, we compared 24-month-old male Fischer 344 and Sprague-Dawley rats.
 Baroreflex sensitivity was tested while the rats were awake by recording reflex heart rate responses elicited as blood pressure was elevated with phenylephrine or lowered with sodium nitroprusside.
 Sprague-Dawley rats had higher blood pressures and lower heart rates initially.
 Chronic infusion of enalapril, a converting enzyme inhibitor, into a lateral cerebral ventricle (ICV) for two weeks lowered blood pressure in Sprague-Dawley but not in Fischer 344 rats.
 Furthermore, reflex bradycardia was unaffected in either rat strain, but reflex tachycardia was selectively suppressed in Fischer 344 rats.
 Thus, although time controls were not done to rule out spontaneous changes during the 14-day infusion period, these results suggest that central cardiovascular regulation does not change similarly with age in these two rat strains.
 As removal of the brain renin-angiotensin system lowered blood pressure in one strain and inhibited reflex tachycardia in the other, the divergence could mean that the brain renin-angiotensin system acts differently to keep blood pressure elevated in Sprague-Dawley rats and modulate reflex tachycardia in Fischer 344 rats.
",13
2488,"Prostacyclin production in myocardial infarction in the acute phase and during follow-up.
 Twenty-five patients with myocardial infarction were monitored in the acute phase and during follow-up with regard to the in vivo production of prostacyclin (PGI2) and thromboxane (TxA2), by measurement of their major urinary metabolites, 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TxB2, respectively.
 In 22 of these patients PGI2 and TxA2 production were also assessed before, during and after an exercise test performed 6 weeks after discharge.
 In approximately 24% of patients the in vivo production of prostacyclin did not increase during the acute phase of the infarction process.
 This inability was usually associated with a decrease in the release of heart muscle enzymes, and was mostly frequently observed in women.
 During the exercise tolerance test, none of the patients showed any increase in prostacyclin production, in contrast to healthy volunteers, in whom a significant increase was seen.
 There were no differences between patients with and without an increase in prostacyclin production during the acute phase.
 At the follow-up 2 years after the myocardial infarction, eight cardiac events had occurred, all of which were noted among patients who exhibited an expected increase in prostacyclin production in association with the infarction.
 This would seem reasonable, since most of the patients in this group had larger primary infarctions.
",13
2489,"Rapid and correct diagnosis of myocardial infarction: standardized case history and clinical examination provide important information for correct referral to monitored beds.
 The value of thorough examination of the case history as a diagnostic tool on hospitalization of patients with suspected myocardial infarction was investigated in three independent prospective studies.
 Use of a limited number of pain-related elements (= 'criteria'), that had already been obtained in the emergency room, could improve the decision on whether or not to admit patients to the coronary-care unit.
 As an example, in one of the studies, use of such criteria would have reduced the number of 'unnecessary' coronary-care-unit admissions from 298 to 162, a 46% reduction (P less than 0.001).
 In the same patient sample, use of the criteria could have reduced the number of patients with definite acute myocardial infarction, admitted to the general wards, from 47 to 22, a 53% reduction (P less than 0.01).
 These favourable results were confirmed in the two independent, smaller-scale studies.
",13
2490,"Serological arguments for classifying Raynaud's phenomenon as idiopathic.
 Twenty-five patients with idiopathic Raynaud's phenomenon were followed prospectively for a mean period of 48 months.
 Clinical and laboratory assessments were performed on admission and on followup.
 The sera were analyzed for the presence of autoantibodies (antinuclear, antiskeleton and antiorganelle antibodies).
 Sixteen patients were antinuclear antibody positive and 2 anticentromere antibody positive.
 Eight patients produced antivimentin, 5 antimitochondrial, 4 anti-Golgi complex, and 3 anticentriol antibodies.
 Eleven patients produced antidesmosome antibodies.
 Only one patient (anti-RNP and antidesmosome antibody positive) developed a systemic disease (mixed connective tissue disease) during followup.
 The initial screening of sera may help to classify Raynaud's phenomenon as idiopathic more accurately.
",13
2491,"Angiographic morphology in unstable angina and its relation to transient myocardial ischemia and hospital outcome.
 Complex stenosis morphology frequently occurs in patients with unstable angina pectoris.
 However, its relation to transient myocardial ischemia and hospital outcome has not been ascertained.
 To address this issue, 88 patients with significant (greater than or equal to 50%) coronary artery disease presenting with angina--new onset (n = 38), worsening (n = 20) or at rest (n = 30)-were studied.
 Patients with left main artery disease, normal coronary arteries or occlusion of the ischemia-related arteries were not included in the study.
 Continuous electrocardiographic recordings were obtained during the first 24 hours.
 Angiography was performed within 1 week from admission.
 Complex morphology was defined as any stenosis with irregular borders, overhanging edges or intracoronary thrombus.
 Only data referring to the in-hospital outcome were considered in this study.
 Adverse end points were sudden death, myocardial infarction and emergency revascularization.
 Analysis of the angiograms revealed a complex morphology in 58 patients (group 1).
 The remaining 30 patients served as control subjects (group 2).
 Thirty-two of the 58 group 1 patients had an unfavorable clinical outcome (positive predictive value, 55%).
 A similar outcome occurred in only 2 of the 30 group 2 patients (negative predictive value, 93%).
 Of the 32 group 1 patients who had an unfavorable clinical outcome, 29 had a cumulative duration of transient myocardial ischemia of greater than or equal to 60 minutes per 24 hours.
 A similar duration of ischemia, however, was observed in another 6 group 1 and in 8 group 2 patients.
",13
2492,"Anginal symptoms without ischemic electrocardiographic changes during ambulatory monitoring in men with coronary artery disease.
 Episodes of angina pectoris without electrocardiographic (ECG) signs of myocardial ischemia during 24-hour ambulatory monitoring were studied in 128 patients with a history of stable angina, angiographically proven coronary artery disease and positive exercise test results.
 In all, 341 episodes of ischemic ECG changes (ST-segment depression greater than 1 mm for greater than 1 minute) and 190 episodes of angina pectoris were observed: 86 episodes consisted of both ECG changes and angina pectoris, 255 episodes consisted only of ECG changes, and 104 episodes only of angina pectoris.
 Duration and magnitude of ST-segment deviation and heart rate at the onset of ischemia were similar in the 86 symptomatic and the 255 asymptomatic episodes with ECG changes.
 The 104 episodes of angina pectoris without ECG changes were detected in 44 patients (34%) (group A); 29 of them had only episodes with angina pectoris and 15 patients had both--episodes of angina pectoris with and without ECG changes.
 In 84 patients (66%) (group B) angina pectoris without ECG changes was not observed; all episodes were accompanied by ischemic ECG changes in these patients.
 No differences in the angiographic extent of coronary artery disease and in exercise test data were seen in both groups A and B; however, maximal ST-segment depression during exercise testing was significantly greater in group B than in group A patients (2.4 +/- 0.8 mm vs 1.9 +/- 0.9 mm; p less than 0.05).
",13
2493,"Dependence of Doppler echocardiographic transmitral early peak velocity on left ventricular systolic function in coronary artery disease.
 The influence of systolic function on pulsed Doppler echocardiographic transmitral flow velocity patterns was assessed before and after postextrasystolic (PES) potentiation in 12 normal subjects (control group) and in 25 patients with previous healed myocardial infarction (MI) group.
 Simultaneous high-fidelity left ventricular pressure measurements were performed in all patients.
 A programmed single-coupled right ventricular extrasystole was induced during echocardiographic and subsequent cineangiocardiographic recordings.
 Adequate angiograms for volumetric analysis in both baseline and PES beats were obtained in 23 patients (7 in the control group and 16 in the MI group).
 PES potentiation of contraction was more pronounced in the MI group than in the control group.
 PES changes in ejection fraction, stroke volume and end-systolic volume were significantly greater in the MI group than in the control group (11 vs 5%, p less than 0.005; 15 vs 5 ml/m2, p less than 0.005; and -13 vs -4 ml/m2, p less than 0.01, respectively).
 In contrast, PES potentiation prolonged the time constants of left ventricular pressure decline derived from exponential curve fits with a zero (Tw) and non-zero (Tb) asymptote pressure in the MI group to the same extent as in the control group (4 vs 5 ms, difference not significant [NS], and 9 vs 11 ms, NS, respectively).
 In the PES beat, peak E velocity remained unaltered (48 vs 49 cm/s, NS) in the control group, whereas it increased significantly (p less than 0.0001) from 47 to 51 cm/s in the MI group.
",13
2494,"Relation of serum lipoprotein cholesterol levels to presence and severity of angiographic coronary artery disease.
 To assess the relation of lipid levels to angiographic coronary artery disease (CAD), lipid profiles were obtained on 125 men and 72 women undergoing diagnostic coronary angiography.
 CAD, defined as greater than or equal to 25% diameter narrowing in a major coronary artery, was present in 106 men (85%) and 54 women (75%).
 Multiple regression analyses revealed that only high-density lipoprotein (HDL) cholesterol level in men, and age and total/HDL cholesterol ratio in women, were independently associated with the presence of CAD after adjustment for other risk factors.
 HDL cholesterol level and age were significantly correlated with both extent (number of diseased vessels) and severity (percent maximum stenosis) of CAD in men.
 In women, age was the only independent variable related to severity, whereas age and total/HDL cholesterol ratio were related to extent.
 Of 71 patients with total cholesterol less than 200 mg/dl, 79% had CAD.
 With multiple regression analyses, HDL cholesterol was the only variable independently related to the presence and severity of CAD in these patients after adjustment for age and gender; extent was significantly associated with age and male gender, and was unrelated to any of the lipid parameters.
 With use of multiple logistic and linear regression analyses of the group of 197 patients, HDL cholesterol was the most powerful independent variable associated with the presence and severity of CAD after adjustment for age and gender.
 HDL cholesterol was also an independent predictor of extent.
 Age was independently associated with each of the end points examined, and was the variable most significantly related to extent.
 These data add to the growing body of information demonstrating an important association between HDL and CAD.
",13
2495,"Edge detection versus densitometry for assessing coronary stenting quantitatively.
 The optimal method used to analyze quantitatively the immediate angiographic results of coronary stenting in the coronary arteries has not been studied.
 Accordingly, minimal luminal cross-sectional area was determined by 2 methods, edge detection and densitometry, in 19 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and then coronary stent implantation for symptomatic coronary stenoses.
 The correlation coefficient, 0.73 before angioplasty, decreased to 0.59 after coronary angioplasty and then increased to 0.83 after stent implantation.
 The mean differences between edge detection and densitometric determinations of minimal luminal cross-sectional area were 0.31 +/- 0.51 mm2 before PTCA, -0.38 +/- 1.22 mm2 after angioplasty and 0.35 +/- 0.79 mm2 after coronary stenting.
 It is concluded that, although the correlation and variability in the measurement of minimal luminal cross-sectional area between edge detection and densitometry deteriorate after PTCA, they are improved after stenting, probably because of smoothing of the vessel contours by the stent and remodeling of the stented segment into a more circular configuration.
 Therefore, in the stented coronary artery, edge detection and densitometry are equally acceptable methods of analysis.
",13
2496,"Frequency of success and complications of coronary angioplasty of a stenosis at the ostium of a branch vessel.
 The authors of this study hypothesized that percutaneous transluminal coronary angioplasty of a stenosis at the ostium of a branch vessel, whether isolated or associated with a bifurcation stenosis, was associated with reduced procedural success and increased in-hospital complications.
 One hundred six patients with 119 ostial branch stenoses were compared with 1,168 patients who underwent angioplasty of nonostial branch stenoses.
 An ostial branch stenosis was defined as a stenosis in the proximal 3 mm of a major branch vessel (diagonal [n = 58], posterior descending [n = 21], obtuse marginal [n = 34] and intermediate [n = 6]).
 The ostial branch stenosis was isolated in 61% of the patients and associated with a bifurcation stenosis in 39%.
 Despite a balloon to artery ratio of 1.05:1, angiographic success was 74% of ostial branch stenoses versus 91% of nonostial stenoses (p less than 0.01).
 Furthermore, angioplasty of ostial branch stenoses resulted in a complication rate of 13 versus 5% for angioplasty of nonostial branch stenoses (p less than 0.01).
 Therefore, angioplasty of ostial branch stenoses results in decreased procedural success and significant residual stenosis despite adequate balloon sizing, suggesting arterial elastic recoil and a significant increase in complications.
",13
2497,"Doppler echocardiographic comparison of the Carpentier and Duran anuloplasty rings versus no ring after mitral valve repair for mitral regurgitation.
 To compare the hemodynamic results of different anuloplasty techniques of primary valve repair for mitral regurgitation, 122 patients were prospectively studied with Doppler echocardiograms 5 to 10 days after operation.
 Seventy-seven patients had mitral valve prolapse, 27 had coronary artery disease, 13 patients had rheumatic mitral valve lesions and 5 patients had infective endocarditis.
 Forty-eight patients received the flexible Duran ring, 46 received the more rigid Carpentier ring and 28 patients received no ring.
 Doppler echocardiography demonstrated a significant decrease in mitral valve area estimated by the pressure half-time method in patients who received either a Carpentier (2.6 +/- 0.8 cm2) or Duran ring (2.8 +/- 0.8 cm2) when compared with patients who received no ring (3.2 +/- 0.7 cm2) (p = 0.01).
 No significant differences were observed for peak transmitral diastolic velocity, peak transmitral diastolic gradient, or the grade of mitral regurgitation by color flow Doppler mapping between patients with and without rings.
 The etiology of mitral disease and concomitant surgical procedures accompanying mitral valve repair did not significantly influence mitral valve area, peak velocity or peak gradient.
 These data suggest that Carpentier and Duran rings decrease the hemodynamic mitral valve area; however, the decrease in valve area is small and not associated with a clinically important increase in transvalvular gradient.
",13
2498,"Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease.
 Severe methylenetetrahydrofolate reductase (MTHFR) deficiency with less than 2% of normal enzyme activity is characterized by neurological abnormalities, atherosclerotic changes, and thromboembolism.
 We have discovered a ""new"" variant of MTHFR deficiency which is characterized by the absence of neurological abnormalities, an enzyme activity of about 50% of the normal value, and distinctive thermolability under specific conditions of heat inactivation.
 In this study, lymphocyte MTHFR specific activities in the thermolabile variant and control groups were 5.58 +/- 0.91 and 10.33 +/- 2.89 nmol formaldehyde formed/mg protein/h, respectively.
 The difference was significant (P less than .01).
 However, there was overlap among the individual values from the two groups.
 On the other hand, residual MTHFR activity after heat inactivation was 11.2 +/- 1.43% in the thermolabile variant and 36.3 +/- 5.18% in the controls.
 There was no overlap.
 Enzyme studies in 10 subjects with thermolabile MTHFR and their family members support the hypothesis that thermolabile MTHFR is inherited as an autosomal recessive trait.
 To elucidate the association of thermolabile MTHFR with the development of coronary artery disease, we determined the thermostability of lymphocyte MTHFR in 212 patients with proven coronary artery disease and in 202 controls without clinical evidence of atherosclerotic vascular disease.
 Thermolabile MTHFR was found in 36 (17.0%) cardiac patients and 10 (5.0%) controls.
 The difference in incidence between the two groups was statistically significant (P less than .01).
 The average age at onset of clinical coronary artery disease in 36 patients with thermolabile MTHFR was 57.3 +/- 7.6 years (35-72 years).
 The mean total plasma homocysteine concentration in patients with thermolabile MTHFR was 13.19 +/- 5.32 nmol/ml and was significantly different from the normal mean of 8.50 +/- 2.80 nmol/ml (P less than .05).
 There was no association between thermolabile MTHFR and other major risk factors.
 We conclude that thermolabile MTHFR is a variant(s) of MTHFR deficiency which is inherited as an autosomal recessive trait.
 In addition, it is positively associated with the development of coronary artery disease.
 Determination of in vitro thermostability of lymphocyte MTHFR is a reliable method for identifying subjects with this abnormality.
",13
2499,"The spectrum of portal vein thrombosis in liver transplantation.
 Thrombosis of the portal vein with or without patency of its tributaries used to be a contraindication to orthotopic liver transplantation (OLTX) until quite recently.
 Rapid progress in the surgical technique of OLTX in the last few years has demonstrated that most patients with portal vein thrombosis can be safely and successfully transplanted.
 Presented here is a series of 34 patients with portal vein thrombosis transplanted at the University of Pittsburgh since 1984.
 The various techniques used to treat various forms of thrombosis are described.
 The survival rate for this series was 67.6% (23 of 34 patients).
 Survival was best for patients who underwent phlebothrombectomy or placement of a jump graft from the superior mesenteric vein.
 The survival rate also correlated with the amount of blood required for transfusion during surgery.
 Overall it is concluded that a vast majority of the patients with thrombosis of the portal system can be technically transplanted and that their survival rate is comparable to that of patients with patent portal vein.
",13
2500,"Fibrous skeleton and ventricular outflow tracts in double-outlet right ventricle.
 Twenty-four hearts in which both great arteries arose from the right ventricle were studied to establish variations present within the fibrous skeleton and infundibular morphologies.
 Variations were also noted in the location of the ventricular septal defect and measurements were obtained of the outlet septum and the circumferences of the arterial valves.
 Completely muscular subarterial infundibulums were present in only 9 (37.5%) of the hearts, with varying degrees of fibrous continuity between the leaflets of the arterial and atrioventricular valves in the remainder.
 The aorta was rightward and posterior in 12 (50%) of the hearts, and subaortic and subpulmonary ventricular septal defects were present in equal numbers in this group.
 No subaortic defects were present when the aorta was side-by-side and right-sided.
 No subpulmonary defects were present in hearts with a posterior aorta.
 The mean ratio of 0.91 +/- 0.36 for the subpulmonary to subaortic length of the outlet septum was significantly less than the value of 1.54 +/- 0.41 noted previously in hearts with tetralogy of Fallot (p less than 0.001).
",13
2501,"Superiority of retrograde cardioplegia after acute coronary occlusion.
 Because antegrade cardioplegia may limit the distribution of cardioplegia beyond a coronary occlusion, this study was undertaken to determine whether retrograde coronary sinus cardioplegia provides superior myocardial protection during revascularization of an acute coronary occlusion.
 In 20 adult pigs, the second and third diagonal branches were occluded with a snare for 1 1/2 hours.
 Animals were then placed on cardiopulmonary bypass and underwent 30 minutes of ischemic arrest with multidose, potassium, crystalloid cardioplegia.
 In 10 animals, the cardioplegia was given antegrade through the aortic root, whereas in 10 others, it was given retrograde through the coronary sinus.
 After the arrest period, the coronary snares were released and all hearts were reperfused for 3 hours.
 Postischemic damage in the myocardium beyond the occlusions was assessed by wall motion scores using two-dimensional echocardiography (4 = normal to -1 = dyskinesia), the change in myocardial pH from preischemia, and the area of necrosis/area of risk (histochemical staining).
 Hearts protected with retrograde coronary sinus cardioplegia had less tissue acidosis (change in pH = 0.08 +/- 0.03 versus 0.41 +/- 0.13; p less than 0.05), higher wall motion scores (2.0 +/- 0.6 versus 1.3 +/- 0.3; not significant), and less myocardial necrosis (43.4% +/- 3.6% versus 73.3% +/- 3.5%; p less than 0.0001).
 We conclude that retrograde coronary sinus cardioplegia provides more optimal myocardial protection than is possible with antegrade cardioplegia after revascularization of an acute coronary occlusion.
",13
2502,"Efficacy of coronary sinus cardioplegia in patients with complete coronary artery occlusions.
 Myocardial areas distal to complete coronary artery occlusions are poorly protected by antegrade cardioplegia.
 We assessed the effects of coronary sinus cardioplegia in 30 patients undergoing bypass operations and at high risk of cardioplegic maldistribution because of the following anatomical patterns of coronary artery disease: critical (greater than or equal to 50%) stenosis of the left main trunk with total occlusion of the right coronary artery (16 patients) or critical (greater than or equal to 70%) stenosis of the right coronary artery with total occlusion of the left anterior descending (11 patients) or circumflex artery (3 patients).
 After induction of arrest through the aorta, coronary sinus cardioplegia was given intermittently during the cross-clamp period at a flow rate of 100 mL/min.
 Intraoperatively, occluded arteries were consistently found to be filled with the retrogradely infused solution.
 One patient died early postoperatively of low cardiac output and a second patient died later during his hospital stay, presumably of an arrhythmia.
 At autopsy, none of them had pathological evidence of inadequate myocardial protection.
 One patient sustained a myocardial infarction and 3 others required inotropes for more than 24 hours postoperatively.
 Postoperative values for right and left stroke volume indices were not significantly different from prebypass levels.
 Overall, these results are consistent with the occurrence of limited intraoperative ischemic damage and, by inference, suggest the efficacy of the coronary sinus route in preserving myocardial areas supplied by completely occluded coronary arteries and, hence, in jeopardy of inadequate cardioplegia delivery.
",13
2503,"Repair of posterior left ventricular aneurysm in a six-year-old boy.
 Left ventricular aneurysms and diverticula are rarely encountered in the pediatric age group.
 This paper reports a case of congestive heart failure and mitral regurgitation in a 6-year-old boy with a large posterolateral left ventricular aneurysm.
 Complete repair was successfully performed by excision of the aneurysm and Dacron patch reconstruction of the left ventricular free wall.
 The patch extended onto the posterior annulus of the mitral valve, thus restoring the mitral valve to normal geometry and correcting the mitral insufficiency.
 The surgical literature on congenital cardiac diverticula and acquired aneurysms in children is reviewed and summarized.
",13
2504,"Silicone pouch for protection of automatic implantable cardioverter-defibrillator leads.
 Automatic implantable cardioverter-defibrillator has become routine treatment for recurrent, drug-resistant ventricular tachycardia.
 Although there is documentation regarding clinical experience and device performance, there is little information on how to avoid complications related to the retrieval of sensing and defibrillation leads from the subcutaneous space.
 We are reporting our experience with a silicone pouch for protection of automatic implantable cardioverter-defibrillator leads that allows immediate and simple retrieval of the leads in case an automatic implantable cardioverter-defibrillator generator is needed.
",13
2505,"Dural spinal cord arteriovenous malformation.
 After multiple hospital admissions and an inpatient rehabilitation stay, a 68-year-old woman was transferred to our rehabilitation facility with a paraparesis of unknown etiology.
 Previous studies included four CT scans and three MRIs which did not demonstrate the lesion.
 A myelogram was noncharacteristic.
 The correct diagnosis, confirmed by selective angiography, was ultimately contingent upon recognition of the clinical features and natural history of dural spinal cord arteriovenous malformations (SCAVM).
 The unusual combination of this multitude of nondiagnostic imaging studies in the uncommon dural SCAVM served to delay diagnosis and treatment.
 Such delay may have great functional consequences.
 This report illustrates the importance of suspecting SCAVM and recognizing its features.
 Emphasis is placed on the physiatrist's role in assuring proper diagnosis to expedite a timely treatment and to obtain the best functional outcome.
 A brief review of the classification, clinical features, pathophysiology, diagnosis, and prognosis of SCAVM is presented.
",13
2506,"Detecting hypertension: screening versus case finding in Norway.
 OBJECTIVE--Evaluation of detection of hypertension in adults in the county of Nord-Trondelag, Norway.
 DESIGN--Cross sectional survey with clinical follow up examinations.
 SETTING--Health survey by screening teams from the national health screening service, and examinations by all 106 general practitioners in the county.
 SUBJECTS--During 1984-6, 74,977 persons (88.1% of those aged 20 years and over) participated in the health survey.
 MAIN OUTCOME MEASURES--Hypertension (when assessed by standardised recording and by questionnaires on drug treatment for hypertension) according to the blood pressure thresholds used in the Norwegian treatment programme.
 Subjects positive on screening were grouped after clinical examination into treatment groups.
 RESULTS--In all, 2399 subjects were positive for hypertension.
 Before screening 6210 (8.3%) patients reported taking antihypertensive drugs and another 3849 (5.1%) had their blood pressure monitored regularly.
 All who screened positive were referred to their general practitioner and evaluated according to a standard programme.
 As a result, drug treatment was started in 406 (0.5%) participants screened and blood pressure monitoring in another 1007 (1.3%).
 Of all patients taking antihypertensive drugs after the screening, 6399 (94.0%) had been diagnosed before screening, and of those whose blood pressure was monitored after the screening, 79.3% had been diagnosed before screening.
 CONCLUSIONS--At the blood pressure screening thresholds used, and when hypertension is defined by an overall clinical diagnosis, the results indicate that general practitioners can find and diagnose hypertensive patients with the case finding strategy.
",13
2507,"Treatment with deferoxamine during ischemia improves functional and metabolic recovery and reduces reperfusion-induced oxygen radical generation in rabbit hearts 
 BACKGROUND.
 Iron may play a central role in oxygen radical generation during myocardial ischemia and after reperfusion.
 Because conditions during ischemia may also liberate iron, we hypothesized that administration of the iron chelator deferoxamine during ischemia would result in improved functional and metabolic recovery after postischemic reperfusion.
 METHODS AND RESULTS.
 Isolated, perfused rabbit hearts were studied by phosphorus-31 nuclear magnetic resonance spectroscopy.
 The hearts received one of three treatments: deferoxamine at the onset of 30 minutes of global ischemia (n = 9), deferoxamine as a bolus followed by a continuous 15-minute infusion begun at reflow (n = 9), or standard perfusate (n = 7).
 Hearts treated with deferoxamine during ischemia showed better recovery of developed pressure than did control hearts (63.2 +/- 7.5% versus 41.2 +/- 2.9% of baseline) (p = 0.02) and better recovery of myocardial phosphocreatine content (92.4 +/- 10.3% versus 68.2 +/- 4.5% of baseline, p less than 0.05).
 These functional and metabolic benefits were comparable to those obtained with deferoxamine treatment during early reperfusion.
 In 15 additional hearts, intraischemic treatment with deferoxamine resulted in no reduction in oxygen radical concentrations as measured on frozen tissue by electron paramagnetic resonance spectroscopy at end ischemia, but the treatment eliminated the reperfusion-induced increase of free radical generation observed in control hearts (2.9 +/- 0.01 versus 7.0 +/- 0.07 microM, p less than 0.001).
 The magnitude of reduction was similar to that when deferoxamine was given at the onset of reflow (2.4 +/- 0.02 microM, p less than 0.001 versus control).
 CONCLUSIONS.
 These results demonstrate improved functional and metabolic recovery of myocardium treated with deferoxamine during ischemia, accompanied by a reduction in reperfusion-induced oxygen free-radical generation to the same degree as reflow treatment, confirming the importance of iron in the pathogenesis of myocardial reperfusion injury.
",13
2508,"Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit.
 BACKGROUND.
 The limiting effect of ischemic preconditioning on infarct size has been reported in canine hearts, which contain considerable amounts of xanthine oxidase, a free radical-producing enzyme.
 Furthermore, a recent study suggested that free radicals generated during preconditioning may contribute to the cardioprotective effect of preconditioning.
 The present study examined 1) whether preconditioning limits infarct size in rabbits, which, like humans, lack myocardial xanthine oxidase and 2) whether the cardioprotective effect of PC is mediated by free radicals.
 METHODS AND RESULTS.
 A branch of the circumflex coronary artery in rabbits was occluded for 30 minutes and then reperfused for 72 hours.
 Myocardial infarct size and area at risk were determined by histology and fluorescent particles, respectively.
 Five groups were studied: an untreated control group, a preconditioned group (PC group), a high-dose superoxide dismutase (SOD)-treated preconditioned group (high-dose SOD-PC group), a low-dose SOD-treated preconditioned group (low-dose SOD-PC group), and a SOD-plus-catalase-treated preconditioned group (SOD/CAT-PC group).
 Preconditioning was performed with four episodes of 5 minutes of ischemia and 5 minutes of reperfusion.
 The free radical scavengers (30,000 units/kg SOD for high-dose SOD-PC group, 15,000 units/kg SOD for low-dose SOD-PC group, and 30,000 units/kg SOD plus 55,000 units/kg catalase for SOD/CAT-PC group) were infused intravenously over 60 minutes starting 20 minutes before preconditioning.
 Infarct size as the percentage of area at risk was 45.1 +/- 3.5% (mean +/- SEM) in the control group (n = 11), 13.3 +/- 3.0% in the PC group (n = 12), 9.7 +/- 1.8% in the high-dose SOD-PC group (n = 8), 11.9 +/- 2.2% in the low-dose SOD-PC group (n = 6), and 9.6 +/- 2.3% in the SOD/CAT-PC group (n = 6) (p less than 0.05 versus control for the last four values).
 The differences in infarct size as the percent of area at risk among the PC, high-dose SOD-PC, low-dose SOD-PC, and SOD/CAT-PC groups were not significant.
 CONCLUSION.
 Ischemic preconditioning delays ischemic myocardial necrosis regardless of myocardial xanthine oxidase content.
 Free radicals are unlikely to have a major role in the mechanism of the preconditioning in rabbits.
",13
2509,"Transvascular intracardiac applications of a miniaturized phased-array ultrasonic endoscope. Initial experience with intracardiac imaging in piglets.
 BACKGROUND.
 Recent advances in miniaturization of phased-array and mechanical ultrasound devices have resulted in exploration of alternative approaches to cardiac and vascular imaging in the form of transesophageal or intravascular imaging.
 Preliminary efforts in adapting phased-array endoscopes designed for transesophageal use to a transvascular approach have used full-sized phased-array devices introduced directly into the right atrium in open-chested animals.
 The purpose of this study was to assess the feasibility of using a custom-made, very small phased-array endoscope for intracardiac imaging introduced intravascularly through a jugular venous approach in young piglets.
 METHODS AND RESULTS.
 Experimental atrial septal defects created in four piglets (3-4 weeks old) had been closed with a buttoned atrial septal defect closure device consisting of an occluder in the left atrium and a counteroccluder in the right atrium.
 Five to 15 days after atrial septal defect closure, the piglets were returned to the experimental laboratory, where a 6.3-mm, 17-element, 5-MHz phased-array probe mounted on a 4-mm endoscope was introduced through a cutdown incision of the external jugular vein and advanced to the right atrium.
 From the right atrium all four cardiac chambers, their inflows and outflows, and all four valves were well imaged with minimal superior and inferior rotation.
 High-resolution imaging of the atrial septum defined with anatomical accuracy, later verified by autopsy, the exact placement of both the occluder and counteroccluder in the left and right sides of the atrial septal defects and the absence of any shunting across the atrial septum in any of the four animals.
 CONCLUSIONS.
 Our efforts indicate that transvascular passage of small phased-array probes can be easily accomplished and is a promising technique for detailed visualization of cardiac structures.
 This approach may provide an alternative to transesophageal echocardiography, particularly for guiding interventional procedures such as placement of transcatheter closure devices in pediatric patients.
",13
2510,"Contractility and stiffness of noninfarcted myocardium after coronary ligation in rats. Effects of chronic angiotensin converting enzyme inhibition.
 BACKGROUND.
 Previous studies have shown that global left ventricular function is depressed after myocardial infarction.
 However, little is known about the effects of myocardial infarction on contractility and the passive-elastic properties of residual myocardium.
 METHODS AND RESULTS.
 We evaluated isometric function and passive myocardial stiffness in isolated, noninfarcted left ventricular papillary muscle from rats 6 weeks after sham operation or myocardial infarction.
 Maximal developed tension and peak rate of tension rise (+dT/dt) were significantly decreased in untreated rats with large myocardial infarction compared with controls (3.3 +/- 1.1 versus 4.3 +/- 0.6 g/mm2 and 49.5 +/- 17.5 versus 72.5 +/- 10.5 g/mm2/sec, respectively).
 Time to peak tension was prolonged (120 +/- 8 versus 102 +/- 4 msec) and myocardial stiffness was increased in untreated myocardial infarction rats compared with controls (35.2 +/- 4.9 versus 24.2 +/- 3.7).
 Rats with smaller myocardial infarctions differed from controls only with respect to a prolongation of time to peak tension.
 Papillary muscle myocyte cross-sectional area was increased by 44% (p less than 0.05), and myocardial hydroxyproline content was increased by 160% (p less than 0.05) in rats with large myocardial infarctions compared with controls.
 To determine whether treatment that improves left ventricular function after myocardial infarction also improves myocardial function, rats were treated with captopril beginning 3 weeks after myocardial infarction and continuing for 3 weeks.
 Treatment with captopril attenuated the prolongation in time to peak tension in the myocardial infarction rats; however, developed tension, +dT/dt, and muscle stiffness remained abnormal.
 Compared with untreated myocardial infarction rats, captopril-treated myocardial infarction rats had a 9% decrease in myocyte cross-sectional area (p = 0.1) but a persistent increase in myocardial collagen content.
 In summary, large myocardial infarction in rats causes contractile dysfunction, increased stiffness, myocyte hypertrophy, and increased collagen content in the residual noninfarcted myocardium.
 Treatment with captopril alters the process of cardiac remodeling and hypertrophy and improves one parameter of contractility in noninfarcted myocardium; however, myocardial collagen content and myocardial stiffness remain abnormal.
 CONCLUSIONS.
 These findings suggest that angiotensin converting enzyme inhibition in the rat infarct model of heart failure improves global cardiac performance via combined effects on myocardial function and the peripheral circulation.
",13
2511,"Coronary blood flow in dogs with contractile dysfunction due to experimental volume overload.
 BACKGROUND.
 Abnormalities in coronary blood flow are responsible for stress-induced reductions in contractile function in pressure overload hypertrophy.
 Less is known about coronary blood flow in volume overload.
 In this study, we tested the hypothesis that coronary blood flow abnormalities were responsible for contractile abnormalities in experimental volume overload hypertrophy.
 METHODS AND RESULTS.
 We examined coronary blood flow at rest and during pacing in seven dogs with contractile dysfunction secondary to chronic experimental mitral regurgitation (average regurgitant fraction at 3 months, 0.58 +/- 0.05).
 After 3 months of mitral regurgitation, left ventricular mass had increased from 92 +/- 8 g at baseline to 118 +/- 10 g (p less than 0.002).
 The slope of the end-ejection stress-volume relation, one of our indexes used to estimate contractile function, had fallen from 5.4 +/- 0.3 at baseline to 3.0 +/- 0.3 at 3 months of mitral regurgitation (p less than 0.001).
 In the mitral regurgitation dogs, coronary blood flow at rest was similar to that of control dogs (endocardial blood flow: control dogs, 1.33 +/- 0.12 ml/min/g; mitral regurgitation dogs, 1.16 ml/min/g, p = NS; epicardial blood flow at rest: control dogs, 1.30 +/- 0.16 ml/min/g; mitral regurgitation dogs 1.13 +/- 0.2 ml/min/g, p = NS).
 With pacing-induced stress, coronary blood flow increased appropriately in control and mitral regurgitation dogs.
 Ultrasonic dimension gauges placed in the endocardium and epicardium demonstrated no further deterioration in ventricular function during pacing in the mitral regurgitation dogs.
 In a separate group of five control dogs and five dogs with mitral regurgitation and left ventricular dysfunction, coronary blood flow was examined in the conscious closed-chest state at rest, during adenosine infusion, and during rapid atrial pacing (240 beats/min).
 Blood flow increased similarly in both groups during pacing and adenosine infusion.
 CONCLUSIONS.
 We conclude that in dogs with mitral regurgitation that have developed contractile dysfunction, abnormalities in coronary blood flow do not explain the resting contractile dysfunction.
 Furthermore, studies during pacing-induced stress and coronary vasodilation with adenosine demonstrate that substantial coronary blood flow reserve is present in this type of volume overload hypertrophy.
",13
2512,"Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation.
 Experimental studies demonstrate that short-term regional perfusion-contraction matching, in which the energy demands of regional myocardial contraction are reduced to match the diminished myocardial substrate supply, occurs during states of low coronary blood flow under resting conditions and during exercise-induced ischemia.
 This phenomenon is rapidly reversible and appears to occur in several clinical settings.
 Sustained perfusion-contraction matching is observed in states of partial experimental ischemia of intermediate duration lasting several hours.
 This condition might be called short-term hibernation and resembles clinical conditions such as unstable angina pectoris or myocardial infarction with some residual perfusion in which the contractile defect can be improved by reperfusion provided the ischemia is not severe enough to cause transmural necrosis.
 Such experimental and clinical observations may or may not relate to the setting of regional dysfunction at rest in patients with chronic coronary heart disease, in whom manifestations of acute ischemia may be absent but improvement of wall motion abnormalities occurs after CABG or balloon angioplasty.
 This condition may constitute the hypothetical state of chronic myocardial hibernation, for which tentative evidence exists from metabolic and perfusion studies using PET.
 Whether such a condition of prolonged perfusion-contraction matching might be associated with adaptive processes that could allow its persistence for long periods without manifest ischemia remains to be investigated.
",13
2513,"Ten-year incidence of myocardial infarction and prognosis after infarction. Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery 
 BACKGROUND.
 The 10-year incidence of myocardial infarction (fatal and nonfatal) and the prognosis after infarction were evaluated in 686 patients with stable angina who were randomly assigned to medical or surgical treatment in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery.
 METHODS AND RESULTS.
 Myocardial infarction was defined by either new Q wave findings or clinical symptoms compatible with myocardial infarction accompanied by serum enzyme elevations with or without electrocardiographic findings.
 Treatment comparisons were made according to original treatment assignment; 35% of the medical cohort had bypass surgery during the 10-year follow-up period.
 The overall cumulative infarction rate was somewhat higher in patients assigned to surgery (36%) than in medical patients (31%) (p = 0.13) due to perioperative infarctions (13%) and an accelerated infarction rate after the fifth year of follow-up (average, 2.4%/yr in the surgical group versus 1.4%/yr in the medical group).
 The 10-year cumulative incidence of death or myocardial infarction was also higher in surgical (54%) than in medical (49%) patients (p = 0.20).
 According to the Cox model, the estimated risk of death after infarction was 59% lower in surgical than in medical patients (p less than 0.0001).
 The reduction in postinfarction mortality with surgery was most striking in the first month after the event: 99% in the first month (p less than 0.0001) and 49% subsequently (p less than 0.0001).
 The estimated risk of death in the absence of infarction was nearly identical regardless of treatment (p = 0.75).
 Exclusion of perioperative infarctions did not alter the findings.
 CONCLUSIONS.
 Although surgery does not reduce the incidence of myocardial infarction overall, it does reduce the risk of mortality after infarction, particularly in the first 30 days after the event (fatal infarctions).
",13
2514,"Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure.
 BACKGROUND.
 Optimal timing of cardiac transplantation in ambulatory patients with severe left ventricular dysfunction is often difficult.
 To determine whether measurement of peak oxygen consumption (VO2) during maximal exercise testing can be used to identify patients in whom transplantation can be safely deferred, we prospectively performed exercise testing on all ambulatory patients referred for transplant between October 1986 and December 1989.
 METHODS AND RESULTS.
 Patients were assigned into one of three groups on the basis of exercise data: Group 1 (n = 35) comprised patients accepted for transplant (VO2 less than or equal to 14 ml/kg/min); group 2 (n = 52) comprised patients considered too well for transplant (VO2 greater than 14 ml/kg/min); and group 3 (n = 27) comprised patients with low VO2 rejected for transplant due to noncardiac problems.
 All three groups were comparable in New York Heart Association functional class, ejection fraction, and cardiac index (p = NS).
 Pulmonary capillary wedge pressure was significantly lower in group 2 than in either group 1 or 3 (p less than 0.05), although there was wide overlap.
 Patients with preserved exercise capacity (group 2) had cumulative 1- and 2-year survival rates of 94% and 84%, which are equal to survival levels after transplantation.
 In contrast, patients rejected for transplant (group 3) had survival rates of only 47% at 1 year and 32% at 2 years, whereas patients awaiting transplantation (group 1) had a survival rate of 70% at 1 year (both p less than 0.005 versus patients with VO2 greater than 14 ml/kg/min).
 All deaths in group 2 were sudden.
 By univariate and multivariate analyses, peak VO2 was the best predictor of survival, with only pulmonary capillary wedge pressure providing additional prognostic information.
 CONCLUSIONS.
 These data suggest that cardiac transplantation can be safely deferred in ambulatory patients with severe left ventricular dysfunction and peak exercise VO2 of more than 14 ml/min/kg.
",13
2515,"Catheter modification of the atrioventricular junction with radiofrequency energy for control of atrioventricular nodal reentry tachycardia.
 BACKGROUND.
 The utility of transcatheter application of radiofrequency energy to eliminate atrioventricular nodal reentrant tachycardia (AVNRT) was investigated.
 METHODS AND RESULTS.
 Thirty-nine patients (mean age, 53 +/- 20 years; range 14-86 years) with medically refractory AVNRT underwent perinodal ablation with radiofrequency energy.
 A custom-designed 6F catheter with a large (3-mm-long) distal electrode and interelectrode pacing of 2 mm was used in the majority of cases.
 The catheter used for ablation was initially positioned across the tricuspid anulus to obtain the largest His bundle electrogram, then withdrawn to obtain the largest atrial:ventricular electrogram ratio, with a small His bundle electrogram (less than or equal to 100 microV).
 Each application of radiofrequency energy (350-550 kHz, 16.2 +/- 5.2 W) was stopped after 60 seconds or if PR prolongation or an impedance rise was noted.
 The endpoints of the procedure were persistent modification of atrioventricular nodal conduction (either first-degree atrioventricular block or impairment of ventriculoatrial conduction) and noninducibility of AVNRT before and during isoproterenol administration.
 Radiofrequency energy was applied a mean of 6.8 +/- 3.5 times per session.
 After a mean follow-up of 8 +/- 3.0 months, 32 of the 39 patients (82%) have been free of AVNRT, and did not have high grade AV block.
 Three patients (8%) developed complete atrioventricular block and had pacemakers implanted.
 Two patients had unsuccessful initial procedures, and two patients had initially successful ablations but had recurrences of tachycardia 4-6 weeks later.
 Elimination of AVNRT appeared to be due to effects on the retrograde fast pathway in most patients.
 CONCLUSIONS.
 Radiofrequency ablation of the perinodal right atrium appears to be safe and effective for treatment of typical AVNRT.
",13
2516,"Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies 
 BACKGROUND.
 Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD).
 The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described.
 METHODS AND RESULTS.
 The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population.
 The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred.
 Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count.
 Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count.
 Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both.
 Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors.
 Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index.
 CONCLUSION.
 Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD.
",13
2517,"Upward shift of the lower range of coronary flow autoregulation in hypertensive patients with hypertrophy of the left ventricle 
 BACKGROUND.
 At any given perfusion pressure, coronary reserve is expressed by the difference between autoregulated and maximally vasodilated flow.
 In hypertension the raised coronary resistance reduces the steepness of the pressure-flow relationship at maximal vasodilatation.
 In the presence of cardiac hypertrophy the line of autoregulated flow becomes higher.
 For these reasons coronary reserve is reduced and the point at which baseline flow approaches the maximal achievable flow might be shifted to a higher perfusion pressure.
 Thus, any reduction below this elevated and critical value of pressure would lower the coronary flow.
 METHODS AND RESULTS.
 The investigated patients were normotensive (controls, nine) and hypertensive with normal (group I, seven) or augmented LV mass index because of concentric LV hypertrophy (group II, eight).
 All had effort-induced angina and angiographically normal left epicardial branches.
 Flow in the great cardiac vein was measured by thermodilution in the baseline and during stepwise (5 mm Hg every 5 minutes) decrease of the coronary perfusion pressure with a titrated nitroprusside i.v.
 infusion; perfusion pressures of 60 mm Hg in the controls and 70 mm Hg in the hypertensives were taken as end points.
 Baseline flow averaged 102 ml/min in normotensives, 104 ml/min in hypertensive group I and 148 ml/min in hypertensive group II.
 At the end points flow was similar to baseline in the controls and group I.
 In group II coronary flow started to decline and myocardial O2 extraction started to slightly but significantly rise at perfusion pressures of 90-80 mm Hg; at the end point flow was reduced by 26% (p less than 0.01 from baseline).
 The perfusion patterns did not seem to be related to the changes in tension-time index and heart rate.
 CONCLUSIONS.
 The association of high blood pressure (reduced ability of the coronary arterioles to dilate) and hypertrophy of the myocardium (augmented baseline coronary flow) may shift the point of exhaustion of coronary reserve to a higher perfusion pressure and make the myocardium vulnerable to treatment-induced relative hypertension.
",13
2518,"Concept of maximal flow ratio for immediate evaluation of percutaneous transluminal coronary angioplasty result by videodensitometry.
 BACKGROUND.
 In the setting of percutaneous transluminal coronary angioplasty (PTCA), immediate information about the result of the intervention is important, whereas morphological parameters are often less reliable than in diagnostic coronary arteriography.
 Recently, a new videodensitometric method was introduced and validated in animal experiments, which allows accurate comparison of maximal myocardial perfusion between situations with different degrees of stenosis.
 This method uses mean transit time (Tmn) of the contrast agent at maximal hyperemia as a parameter for maximal flow and is strictly in accordance with indicated dilation theory.
 METHODS AND RESULTS.
 In 40 patients with angina pectoris, single-vessel disease, and a positive exercise test at the time of acceptance for PTCA, this approach was applied for evaluation of the improvement of maximal flow achieved by the PTCA.
 Maximal vasodilation was induced immediately before and 15 minutes after PTCA by intracoronary administration of papaverine, and digital angiographic studies were performed.
 By special breath-holding instruction, almost motionless, triggered image acquisition was possible during 15-20 heartbeats.
 Excellent subtraction images could be obtained, and reliable determination of Tmn at maximal hyperemia was possible in 33 patients both before and after PTCA.
 The ratio between maximal flow after and before PTCA, called maximal flow ratio (MFR), was represented by the ratio between Tmn before and after the intervention and compared with the results of exercise testing 24-48 hours before and 7-10 days after the procedure.
 After correction for pressure changes, MFR was 2.2 +/- 1.5 for the 33 dilated vessels and 1.0 +/- 0.2 for 25 normal vessels serving as a control.
 In 94% of all patients, an MFR value of more than 1.6 or less than 1.6 discriminated between presence or absence of reversal of exercise test result from positive to negative.
 If on-line judgment of success was based upon angiographic parameters or measurement of trans-stenotic pressure gradient, the relation with noninvasive functional improvement was present only in 66% and 74% of all patients, respectively.
 A definite range of what can be called normal Tmn at maximal hyperemia could be distinguished, and post-PTCA values for successfully dilated arteries returned completely to this normal range.
 CONCLUSIONS.
 Accurate comparison of maximal myocardial perfusion before and after PTCA is possible in man, improvement of maximal flow is highly related to functional improvement as indicated by exercise test results, and, therefore, this method provides a straightforward way for on-line evaluation of the result of the intervention.
",13
2519,"Heart rate adjustment of exercise-induced ST segment depression. Improved risk stratification in the Framingham Offspring Study 
 BACKGROUND.
 Simple heart rate adjustment of ST segment depression during exercise (delta ST/HR index) and the pattern of ST depression as a function of heart rate during exercise and recovery (the rate-recovery loop) have been shown to improve the ability of the exercise electrocardiogram to detect the presence of coronary heart disease (CHD), but the performance of these methods for the prediction of future coronary events remains to be examined.
 METHODS AND RESULTS.
 We compared the delta ST/HR index and the rate-recovery loop with standard electrocardiographic criteria for prediction of CHD events in 3,168 asymptomatic men and women in the Framingham Offspring Study who underwent treadmill exercise electrocardiography and who, at entry, were free of clinical and electrocardiographic evidence of CHD.
 After a mean follow-up of 4.3 years, there were 65 new CHD events: four sudden deaths, 24 new myocardial infarctions, and 37 incident cases of angina pectoris.
 When a Cox proportional hazards model with adjustment for age and sex was used, a positive exercise electrocardiogram by standard criteria (greater than or equal to 0.1 mV horizontal or downsloping ST segment depression) was not predictive of new CHD events (chi 2 = 0.40, p = 0.52).
 In contrast, stratification according to the presence or absence of a positive delta ST/HR index (greater than or equal to 1.6 microV/beat/min) and a positive (counterclockwise) rate-recovery loop was associated with CHD event risk (chi 2 = 9.45, p less than 0.01) and separated subjects into three groups with varying risks of coronary events: high risk, when both tests were positive (relative risk 3.6; 95% confidence interval, 2.4-5.4); intermediate risk, when either the delta ST/HR index or the rate-recovery loop was positive (relative risk, 1.9; 95% confidence interval, 1.3-2.8); and low risk, when both tests were negative.
 After multivariate adjustment for age, sex, smoking, total cholesterol level, fasting glucose level, diastolic blood pressure, and electrocardiographic evidence of left ventricular hypertrophy, the combined delta ST/HR index and rate-recovery loop criteria remained predictive of coronary events (chi 2 = 5.45, p = 0.02).
 CONCLUSIONS.
 Heart rate adjustment of ST segment depression by the delta ST/HR index and the rate-recovery loop during exercise electrocardiography can improve prediction of future coronary events in asymptomatic men and women.
",13
2520,"Electrocardiographic body surface potential mapping in the Wolff-Parkinson-White syndrome. Noninvasive determination of the ventricular insertion sites of accessory atrioventricular connections.
 BACKGROUND.
 A reliable, noninvasive procedure to determine the location of accessory atrioventricular connections in patients with Wolff-Parkinson-White syndrome would add an important diagnostic tool to the clinical armamentarium.
 METHODS AND RESULTS.
 Body surface potential mapping (BSPM) using 180 electrodes in various-sized vests and displayed as a calibrated color map was used to determine the ventricular insertion site of the accessory atrioventricular (AV) connections in 34 patients with Wolff-Parkinson-White syndrome.
 Attempts were made to determine the 17 ventricular insertion sites described by Guiraudon et al.
 All 34 patients had an electrophysiologic study (EPS) at cardiac catheterization, and 18 had surgery so the ventricular insertion sites could be accurately located using EPS at surgery.
 A number of physiologic observations were also made with BSPM.
 CONCLUSIONS.
 The following conclusions were drawn: 1) BSPM using QRS analysis accurately predicts the ventricular insertion site of accessory AV connections in the presence of a delta wave in the electrocardiogram; 2) the ventricular insertion sites of accessory AV connections determined by BSPM and by EPS at surgery were identical or within one mapping site (1.5 cm or less) in all but four of 18 cases; three of the four exceptions had more than one accessory AV connection, and the other had a very broad ventricular insertion; 3) BSPM and EPS locations of the accessory AV connections correlated very well in the 34 cases despite the fact that BSPM determines the ventricular insertion site and EPS determines the atrial insertion site of the accessory AV connection; 4) as suggested by the three cases of multiple accessory AV connections, EPS and BSPM may be complementary since BSPM identified one pathway and EPS identified the other (in the case with a broad ventricular insertion, BSPM and EPS demonstrated different proportions of that insertion); 5) BSPM using ST-T analysis is very much less accurate in predicting the ventricular insertion site of accessory AV connections unless there is marked preexcitation; 6) standard electrocardiography using the Gallagher grid methodology (but with no attempt at stimulating maximal preexcitation) was not as accurate as QRS analysis of BSPM in predicting the ventricular insertion site of the accessory AV connection; however, exact comparison is hampered by the different number and size of the Gallagher and Guiraudon insertion sites; 7) BSPM using QRS analysis appears to be very accurate in predicting right ventricular versus left ventricular posteroseptal accessory AV connections; 8) typical epicardial right ventricular breakthrough, indicative of conduction via the specialized AV conduction system, occurs in all patients with left ventricular free wall accessory AV connections; 9) epicardial right ventricular breakthrough was not observed in cases with right ventricular free wall or anteroseptal accessory AV connections; 10) epicardial right ventricular breakthrough can occur in the presence of posteroseptal accessory AV connections, whether right or left ventricular; and 11) the delay in epicardial right ventricular breakthrough in cases with left ventricular insertion may provide a marker to estimate the degree of ventricular preexcitation.
",13
2521,"Diagnostic efficiency of troponin T measurements in acute myocardial infarction 
 BACKGROUND.
 The present study was designed to evaluate the efficiency of a newly developed troponin T enzyme immunoassay for the detection of acute myocardial infarction.
 METHODS AND RESULTS.
 The study comprised 388 patients admitted with chest pain and suspected myocardial infarction and 101 patients with skeletal muscle damage and additional suspected myocardial cell damage.
 Troponin T was elevated to more than twice the analytical sensitivity of the assay (0.5 microgram/l) in all patients with non-Q wave (range, 1.2-5 micrograms/l) and Q wave infarction (range, 3-220 micrograms/l).
 Troponin T appeared in serum as early as 3 hours after onset of pain in 50% of the patients and remained elevated in all patients for more than 130 hours, revealing release kinetics of both free cytosolic and structurally bound molecules.
 The diagnostic efficiency of troponin T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98% until 5.5 days after admission, if patients with unstable angina were excluded from analysis.
 In the 79 patients with unstable angina, troponin T was elevated (range, 0.55-3.1 micrograms/l) in at least one blood sample from each of 37 patients (56%).
 Circulating troponin T was correlated to the presence of reversible ST segment or T wave changes on the electrocardiogram (p less than 0.005) and to the frequency of in-hospital complications.
 In the 101 patients with skeletal muscle damage and suspected additional cardiac muscle damage, troponin T was the most useful test; its efficiency was 89% or 94% (depending on the discriminator value used) as compared with 63% for creatine kinase-MB.
 CONCLUSIONS.
 Thus, the data of the study indicate that the newly developed troponin T test improves the efficiency of serodiagnostic tools for the detection of myocardial cell necrosis as compared with conventionally used cardiac enzymes.
",13
2522,"Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens.
 BACKGROUND.
 Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas.
 METHODS AND RESULTS.
 A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec.
 The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media.
 The presence of dissection between the media and the atheroma was well visualized.
 These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations.
 The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques.
 Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo.
 Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2.
 The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area.
 At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media.
 CONCLUSIONS.
 Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification.
 Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty.
",13
2523,"Xanthine oxidase inhibition does not limit canine infarct size.
 BACKGROUND.
 Evidence supporting the role of xanthine oxidase in myocardial reperfusion injury is based on studies with pharmacological interventions used to inhibit enzyme function.
 Controversy exists, however, regarding the true role of xanthine oxidase in reperfusion injury.
 This study was performed to determine whether xanthine oxidase inhibition limits myocardial injury due to coronary artery occlusion and reperfusion.
 METHODS AND RESULTS.
 Anesthetized dogs underwent coronary artery occlusion (90 minutes) and reperfusion (6 hours).
 Oxypurinol (28 mg/kg) or amflutizole (30 mg/kg), chemically unrelated inhibitors of xanthine oxidase, or vehicle was infused intravenously 15 minutes before and 3 hours after reperfusion.
 Regional myocardial blood flow was determined with radiolabeled microspheres.
 Infarct size was determined with the tetrazolium method.
 Myocardial infarct size (percent of risk region) was less in oxypurinol-treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15%.
 Infarct size for the amflutizole-treated dogs, 40 +/- 21%, was not significantly different from that of the control group.
 There were no differences in rate-pressure product or collateral blood flow to account for differences in infarct size.
 Uric acid concentration in the coronary venous plasma increased after reperfusion in the dogs treated with vehicle but not in the drug-treated dogs.
 Xanthine oxidase inhibition was demonstrated in each of the drug treatment groups, but only oxypurinol limited the extent of myocardial injury.
 CONCLUSIONS.
 Previously reported cardioprotective effects of allopurinol, noted to occur only when the drug was administered chronically, may be related to a property of oxypurinol, a major metabolite of allopurinol.
 The beneficial effect of oxypurinol is unrelated to inhibition of superoxide formation during xanthine oxidase-catalyzed oxidation of xanthine and hypoxanthine.
",13
2524,"Pulmonary effects of ischemic limb reperfusion: evidence for a role for oxygen-derived radicals.
 OBJECTIVE: To evaluate the lung as a reperfusion target after limb ischemia-reperfusion, and to measure specifically the oxygen radical response to this reperfusion.
 DESIGN: Paired simple randomized, with continuous interval data in dependent variable and both continuous and nominal independent variables.
 SUBJECTS AND INTERVENTION: Sprague-Dawley male rats (n = 195) were anesthetized and both hind limbs occluded for 3.75 hr, the overnight LD50.
 Alveolar lavage was performed on the animals 1 hr after reperfusion or on survivors 20 hr after reperfusion.
 Groups were either undosed or pretreated with alpha-tocopherol as an antioxidant (50 mg/kg.day) 2 days before ischemia.
 MEASUREMENTS AND MAIN RESULTS: Luminol-enhanced chemiluminescence was measured in both phorbol myristate acetate-stimulated and unstimulated macrophages.
 Nanomoles of superoxide radicals per 10(6) alveolar cells/min were also measured using a cytochrome c reduction assay.
 A significant (p less than .01, Student's t-test), time-dependent increase in response of cells from ischemic-reperfused rats was seen.
 Pretreatment with antioxidant had no effect at 1 hr, but significant differences were seen in the 20-hr survivors.
 CONCLUSIONS: These studies show that alveolar lavage cells, 95% macrophages, reflect the reperfusion of ischemic-reperfused hind limbs by a significant increase in oxygen radical activity, an effect partly suppressed in antioxidant-dosed survivors.
",13
2525,"Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat.
 Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B2 when compared with normotensive (LN) and low blood pressure (LL) controls.
 Therefore, the effects of norepinephrine (1.2 x 10(-8) to 9.6 x 10(-7) M) and of phenylephrine (5 x 10(-8) to 1.9 x 10(-6) M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats.
 In addition, the effects of norepinephrine were assessed before and during thromboxane A2/prostaglandin H2 receptor blockade by AH23848 (4 x 10(-6) M).
 Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E2 and F2 alpha, of 6-ketoprostaglandin F1 alpha, and of thromboxane B2 was similar in the three strains.
 The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced.
 Norepinephrine and phenylephrine induced a 10- to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B2 only.
 AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys.
",13
2526,"Kinetic abnormalities of the red blood cell sodium-proton exchange in hypertensive patients.
 The present study was designed to examine the kinetics of Na(+)-H+ exchange in red blood cells of normotensive and hypertensive subjects and its relation to the previously reported abnormalities in Na(+)-Li+ exchange.
 The Na(+)-H+ antiporter activation kinetics were studied by varying cell pH and measuring net Na+ influx (mmol/l cell x hr = units) driven by an outward H+ gradient.
 The Na(+)-Li+ exchange was determined at pH 7.4 as sodium-stimulated Li+ efflux.
 Untreated hypertensive patients (n = 30) had a higher maximal rate of Na(+)-Li+ exchange (0.43 +/- 0.05 versus 0.26 +/- 0.02 units, p less than 0.0003), a higher maximal rate of Na(+)-H+ exchange (62.3 +/- 6.2 versus 47 +/- 4 units; p less than 0.02), but a similar affinity for cell pH compared with normotensive subjects (n = 46).
 The cell pH activation of the Na(+)-H+ antiporter exhibited a lower Hill coefficient than that of normotensive subjects (1.61 +/- 0.12 versus 2.56 +/- 0.14; p less than 0.0001).
 This index of occupancy of internal H+ regulatory sites was found reduced in most of the hypertensive patients (73%) whether their hypertension was untreated or treated.
 Hypertensive patients with Na(+)-Li+ exchange above 0.35 units (0.68 +/- 0.057 units, n = 16) did not exhibit elevated maximal rates of Na(+)-H+ exchange (57.3 +/- 10 units, NS) in comparison with those with Na(+)-Li+ exchange below 0.35 units (66.4 +/- 7.6 units, n = 26), but both groups exhibited reduced Hill coefficients.
 Hypertensive patients with enhanced Na(+)-H+ exchange activity (more than 90 units) had normal maximal rates of Na(+)-Li+ exchange.
",13
2527,"Specific supersensitivity of the mesenteric vascular bed of Dahl salt-sensitive rats.
 Dahl salt-sensitive (DS) and salt-resistant (DR) rats were maintained on a diet containing normal (0.45%) or high (7%) salt for 5 days.
 The DS rats had slightly higher systolic blood pressures than DR rats, although a high salt diet failed to significantly elevate pressure in either group when compared with their appropriate (low salt diet) controls.
 The sensitivity of the isolated, perfused mesenteric vasculature from DS rats fed a high salt diet to nerve stimulation was greater when compared with all other groups in the presence or absence of cocaine (1 microM).
 A similar difference in sensitivity between high salt DS rats and high salt DR rats to bolus injections of norepinephrine was observed only in the presence of cocaine.
 The change in sensitivity was characterized by a leftward shift of the dose-response curve without a change in maximum response.
 No difference in sensitivity between the high salt DS group and any other treatment group was observed in response to the pressor agents KCl, angiotensin II, 5-hydroxytryptamine or the depressor agent acetylcholine.
 These data indicate that DS rats on a short-term, high salt diet possess a significant and specific elevation in sensitivity to nerve stimulation and norepinephrine in the absence of an increase in blood pressure.
 Differences in the effectiveness of cocaine among the groups suggest that differences may exist in neuronal uptake (uptake 1).
",13
2528,"High NaCl diet enhances arterial baroreceptor reflex in NaCl-sensitive spontaneously hypertensive rats.
 Previous studies from our laboratory have shown that arterial baroreceptor reflex control of lumbar sympathetic nerve activity is blunted in the NaCl-sensitive spontaneously hypertensive rat (SHR-S) compared with either the NaCl-resistant spontaneously hypertensive rat (SHR-R) or the normotensive Wistar-Kyoto (WKY) rat.
 In the current study, the effect of dietary NaCl supplementation on arterial baroreceptor reflex control of lumbar sympathetic nerve activity and heart rate was assessed in SHR-S and control SHR-R and WKY rats.
 Male SHR-S, SHR-R, and WKY rats were fed diets containing either 1% or 8% NaCl beginning at 7 weeks of age and were studied at age 9-10 weeks.
 Arterial baroreceptor reflex-mediated changes in lumbar sympathetic nerve activity and heart rate were recorded in conscious, unrestrained rats during phenylephrine-induced (15-40 micrograms/kg/min) and nitroprusside-induced (15-300 micrograms/kg/min) changes in mean arterial pressure.
 SHR-S maintained on a 1% NaCl diet had blunted baroreceptor reflex control of lumbar sympathetic nerve activity during acute increases in MAP compared with SHR-R and WKY rats (p less than 0.05).
 After ingestion of the 8% NaCl diet, this blunting was absent, indicating enhancement of baroreceptor reflex control of lumbar sympathetic nerve activity.
 SHR-S maintained on a 1% NaCl diet also had blunted arterial baroreceptor control of lumbar sympathetic nerve activity during nitroprusside-induced decreases in mean arterial pressure compared with WKY rats, but this was not significantly altered during ingestion of the 8% NaCl diet.
",13
2529,"Effect of age on coronary circulation after imposition of pressure-overload in rats.
 We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old).
 Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load.
 In the two age groups, similar increases in peak left ventricular pressure were observed (113 +/- 7 mm Hg in sham-operated rats versus 160 +/- 11 mm Hg in banded rats of the young adult group; 103 +/- 7 mm Hg in sham-operated rats versus 156 +/- 11 mm Hg in banded rats of the old group).
 After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin.
 Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions.
 In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level.
 Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly.
 In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats.
 However, minimal coronary vascular resistance increased, and flow reserve decreased significantly.
 Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy.
",13
2530,"Systolic Hypertension of the Elderly Program (SHEP). Part 10: Analysis.
 The SHEP is a randomized, placebo-controlled trial that will follow standard clinical trial principles in analyzing data relating to its proposed hypotheses.
 The protocol has stated a priori the main objective as well as the secondary subgroup hypotheses.
 Sample size calculations for SHEP have accounted for dropins to and drop-outs from active therapy as well as for the risk of nonstroke death.
 The sample size achieved (4,736 participants) should be adequate to address the proposed questions.
 Monitoring procedures have been described and established.
 A data and safety monitoring board that uses these procedures is closely following the data from the trial.
 The board will periodically examine the data to determine whether termination of the study is warranted.
",13
2531,"Arterial mechanical properties in dilated cardiomyopathy. Aging and the response to nitroprusside.
 The effects of aging on arterial mechanical properties and the response to nitroprusside were examined in 25 patients with dilated cardiomyopathy.
 High-fidelity pressures were recorded with a multisensor catheter.
 Pulse wave velocity was determined between two sensors in the thoracic aorta.
 Arterial compliance was determined by an analysis of the diastolic waveform and cardiac output.
 At baseline, despite a similar systemic vascular resistance, the pulsatile load (e.g., arterial compliance) and wave transmission characteristics (e.g., pulse wave velocity) were altered with aging.
 Arterial compliance was reduced in older (greater than 50 yr, n = 8) versus younger (less than 35 yr, n = 8) patients (0.51 +/- 0.17 vs.
 1.33 +/- 0.63 ml/mmHg, P less than 0.01) and intermediate in those 35-50 yr of age (n = 9, 0.72 +/- 0.40 ml/mmHg).
 There was a positive correlation between age and pulse wave velocity (r = +0.90).
 Nitroprusside infusion decreased resistance, increased arterial compliance, and lowered pulse wave velocity in all groups.
 Yet, advancing age was associated with a greater fall in wave velocity for a given fall in aortic pressure.
 The slope (K) of the relation between pulse wave velocity and aortic diastolic pressure progressively increased with age (0.01 +/- 0.03, 0.06 +/- 0.02, and 0.09 +/- 0.03 m/s-mmHg).
 Multiple linear regression analysis revealed a significant relation between K and age.
 These data demonstrate that in older patients with dilated cardiomyopathy the left ventricle is coupled to an arterial circulation that has a greater pulsatile load, despite a similar steady load.
 Furthermore, these age-related changes in the arterial system affect the hemodynamic response to pharmacologically-induced vasodilatation.
",13
2532,"Diastolic dysfunction in hypertrophic cardiomyopathy. Effect on active force generation during systole.
 We tested the hypothesis that intracellular Ca++ [( Ca++]i) overload underlies the diastolic dysfunction of patients with hypertrophic cardiomyopathy.
 Myocardial tissue was obtained at the time of surgery or transplantation from patients with hypertrophic cardiomyopathy and was compared with control myocardium obtained from patients without heart disease.
 The isometric contractions and electrophysiologic properties of all myocardial specimens were recorded by standard techniques and [Ca++]i was measured with the bioluminescent calcium indicator aequorin.
 In contrast to the controls, action potentials, Ca++ transients, and isometric contraction and relaxation were markedly prolonged in the hypertrophic myocardium, and the Ca++ transients consisted of two distinct components.
 At 38 degrees C and 1 Hz pacing frequency, a state of relative Ca++ overload appeared develop, which produced a rise in end-diastolic [Ca++]i, incomplete relaxation, and fusion of twitches with a resultant decrease in active tension development.
 We also found that drugs with increase [Ca++]i, such as digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i, such as verapamil, or agents that increase cyclic AMP, such as forskolin, prevented them.
 These results may explain why patients with hypertrophic cardiomyopathy tolerate tachycardia poorly, and may have important implications with regard to the pharmacologic treatment of patients with hypertrophic cardiomyopathy.
",13
2533,"Thrombosis-related markers in unstable angina pectoris.
 While thrombus formation has been implicated in the pathogenesis of unstable angina, the value of thrombus-related markers for distinguishing unstable from stable angina is not well defined.
 Fibrin D-dimer and plasminogen activator inhibitor were prospectively analyzed in the peripheral blood of 46 patients (26 with unstable angina and 20 with stable angina or normal coronary arteries).
 Baseline blood samples were drawn within 24 h after rest pain in patients with unstable angina and in 19 of these 26 patients in less than 6 h.
 In patients with unstable angina, mean +/- SD (median) values for fibrin D-dimer and plasminogen activator inhibitor values measured 0.09 +/- 0.06 (0.07) microgram/ml and 9.1 +/- 9.6 (5.9) IU, respectively, compared to 0.11 +/- 0.10 (0.05) microgram/ml and 5.5 +/- 1.9 (5.0) IU/ml, in patients in the control group (p = NS for all comparisons between the two groups).
 Recurrent in-hospital pain, coronary anatomy and need for intervention showed no relation to the levels of these markers.
 In 19 additional patients (9 with unstable angina and 10 control patients) samples from the coronary sinus and the peripheral blood were also analyzed.
 Again, in patients with unstable angina all samples were drawn less than 24 h after rest pain; in six of nine patients samples were drawn in less than 6 h.
 A coronary sinus to peripheral blood gradient for either of these markers could not be demonstrated.
 The differences between peripheral and coronary sinus D-dimer and plasminogen activator inhibitor concentrations were also similar in patients with unstable angina and control patients.
",13
2534,"Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied myocardium of patients with hypertrophic cardiomyopathy: a study with nitrogen-13 ammonia and positron emission tomography.
 To assess regional coronary reserve in hypertrophic cardiomyopathy, regional myocardial blood flow was measured in 23 patients with hypertrophic cardiomyopathy and 12 control subjects by means of nitrogen-13 ammonia and dynamic positron emission tomography.
 In patients with hypertrophic cardiomyopathy at baseline study, regional myocardial blood flow was 1.14 +/- 0.43 ml/min per g in the hypertrophied (20 +/- 3 mm) interventricular septum and 0.90 +/- 0.35 ml/min per g (p less than 0.05 versus septal flow) in the nonhypertrophied (10 +/- 2 mm) left ventricular free wall.
 These were not statistically different from the corresponding values in control subjects (1.04 +/- 0.25 and 0.91 +/- 0.21 ml/min per g, respectively, p = NS).
 After pharmacologically induced coronary vasodilation (dipyridamole, 0.56 mg/kg intravenously over 4 min), regional myocardial blood flow in patients with hypertrophic cardiomyopathy increased significantly less than in control subjects both in the septum (1.63 +/- 0.58 versus 2.99 +/- 1.06 ml/min per g, p less than 0.001) and in the free wall (1.47 +/- 0.58 versus 2.44 +/- 0.82 ml/min per g, p less than 0.001).
 In addition, patients with hypertrophic cardiomyopathy who had a history of chest pain had more pronounced impairment of coronary vasodilator reserve than did those without a history of chest pain.
 After dipyridamole, coronary resistance in the septum decreased by 38% in patients without a history of chest pain, but decreased by only 14% in those with such a history (p less than 0.05).
 Coronary resistance in the free wall decreased by 45% in patients without and by 27% in those with a history of chest pain (p = 0.06).
",13
2535,"Mechanisms for left ventricular systolic dysfunction in aortic regurgitation: importance for predicting the functional response to aortic valve replacement 
 To test the hypothesis that the combined use of the time-varying elastance concept and conventional circumferential stress-shortening relations would elucidate differential mechanisms for left ventricular systolic dysfunction in severe, chronic aortic regurgitation and therefore predict the functional responses to aortic valve replacement, 31 control patients and 37 patients with aortic regurgitation were studied.
 The studies included micromanometer left ventricular pressure determinations, biplane contrast cineangiograms under control conditions and radionuclide angiograms under control conditions and during methoxamine or nitroprusside infusions with right atrial pacing.
 The patients with aortic regurgitation were classified into three groups: Group I had normal Emax and stress-shortening relations, Group II had abnormal Emax but normal stress-shortening relations and Group III had abnormal Emax and stress-shortening relations.
 The left ventricular end-diastolic and end-systolic volumes showed a progressive increase and the ejection fraction showed a progressive decrease from Group I to III; these values differed from those in the control patients (p less than 0.001).
 In Group I, there was a decrease in left ventricular volumes (p less than 0.05) but no significant change in ejection fraction (61 +/- 7% versus 63 +/- 4%) after aortic valve replacement.
 In contrast, in Group II, reduction in left ventricular volumes (p less than 0.01) was associated with an increase in ejection fraction from 50 +/- 8% to 64 +/- 11% (p less than 0.01).
 Finally, in Group III, reduction in left ventricular volumes (p less than 0.05) was associated with a further decrement in ejection fraction from 35 +/- 13% to 30 +/- 13%.
 Group I patients had compensated adequately for chronic volume overload.
 However, Group II had left ventricular dysfunction that was associated with an increase in the left ventricular volume/mass ratio compared with that in the control patients and Group I (p less than 0.05 for both), suggesting inadequate hypertrophy and assumption of spherical geometry.
 Finally, irreversible myocardial dysfunction had supervened in Group III.
 In conclusion, a combined analysis of left ventricular chamber performance using the time-varying elastance concept and myocardial performance using conventional circumferential stress-shortening relations provides complementary information that elucidates differential mechanisms for left ventricular systolic dysfunction and therefore predicts the functional response to aortic valve replacement.
",13
2536,"Impact of orifice geometry on the shape of jets: an in vitro Doppler color flow study.
 To investigate the influence of orifice geometry on the three-dimensional shape of jets, an in vitro Doppler color flow study was performed.
 Jets were formed by discharging blood through round orifices and through orifices with major/minor axis ratios of 2:1, 3:1 and 5:1.
 These were repeated with orifice areas of 0.1, 0.3 and 0.5 cm2.
 For turbulent and laminar jets formed by these orifices, Doppler color flow images were obtained from two orthogonal scanning planes aligned with the major and minor orifice axes.
 Jet width was measured at 1 cm intervals from 0 to 5 cm from the orifice and used to calculate jet eccentricity (ratio of major to minor axis widths) and the rate of divergence of the jet walls.
 Jets were observed to diverge more rapidly along walls aligned with the orifice minor axis rather than along the major axis.
 This differential spreading led to the development of circular symmetry at a short distance from the orifice.
 Jet divergence (theta) occurred more rapidly for turbulent jets and for jets formed by larger orifices: theta (zero) = 0.80 + 6.3.A + 7.0.T + 0.47.E-OR (r = 95, p less than 0.0001, n = 48), where A is orifice area (cm2); T is 0 for laminar jets, 1 for turbulent jets and E-OR combines orifice eccentricity and scanning orientation, ranging from -5 for 5:1 orifices imaged along the major axis, 0 for circular orifices to 5 for 5:1 orifices imaged along the minor axis.
 Within the jet, eccentricity decayed approximately exponentially with distance from the orifice, more rapidly for turbulent jets, more slowly for the larger and more eccentric orifices.
",13
2537,"Patient age and results of balloon aortic valvuloplasty: the Mansfield Scientific Registry experience. The Mansfield Scientific Aortic Valvuloplasty Registry Investigators.
 Patients enrolled in the Mansfield Scientific Aortic Valvuloplasty Registry were followed up a mean of 7 months after balloon aortic valvuloplasty.
 Results were compared for patients less than 70, 70 to 79 and greater than or equal to 80 years of age at time of valvuloplasty.
 As assessed by aortic valve area indexed to body surface area, stenosis was more severe in the older patients and the incidence of congestive heart failure was also greater in those aged greater than or equal to 80 years.
 The results of valvuloplasty were comparable in all three age groups, and indexed final valve area was not significantly different among the groups.
 In-hospital mortality ranged from 4.2% to 9.4%, but this and other complications were not significantly different among the groups.
 Total 7 month mortality was 23%.
 As performed in this registry study, balloon aortic valvuloplasty produced similar results in older and younger patients, despite initially more severe disease in the older patients.
",13
2538,"Drug response at electropharmacologic study in patients with ventricular tachyarrhythmias: the importance of ventricular refractoriness.
 The clinical and electrophysiologic predictors of successful antiarrhythmic drug therapy for patients with inducible ventricular tachycardia were evaluated in 59 consecutive patients undergoing serial electropharmacologic trials.
 Structural heart disease was less frequently present in patients for whom effective therapy was found (p less than 0.05).
 The presence of coronary artery disease and a history of prior myocardial infarction were significantly more frequently present in patients for whom antiarrhythmic drug therapy could not be found (p less than 0.05).
 The corrected QT interval and ventricular effective refractory period measured at a pacing cycle length of 400 ms were significantly shorter in responders compared with nonresponders (QT interval 428 +/- 52 versus 460 +/- 59 ms; ventricular effective refractory period 237 +/- 28 versus 254 +/- 24 ms; (p less than 0.05).
 In addition, the interelectrogram coupling interval of the ventricular extrastimulus initiating ventricular tachycardia was significantly shorter in responders compared with nonresponders (223 +/- 37 versus 251 +/- 33 ms; p = 0.003).
 Logistic regression analysis identified a short ventricular interelectrogram coupling interval (p less than 0.01) and absence of prior myocardial infarction (p less than 0.05) as the only independent predictors of antiarrhythmic drug suppression of the induction of ventricular tachycardia.
 Greater drug-induced increments in the ventricular effective and functional refractory periods were observed in responders than in nonresponders as was the shortest ventricular interelectrogram coupling interval.
 Thus, baseline electrophysiologic measurements identify patients with inducible ventricular tachycardia who are likely to respond to antiarrhythmic drug therapy.
 Furthermore, these patients demonstrate greater drug-induced electrophysiologic changes.
",13
2539,"Tricuspid valve dysplasia or displacement in intrauterine life.
 In 450 cases of structural heart disease diagnosed prenatally, 38 fetuses (8.5%) had either a dysplastic or a displaced tricuspid valve.
 The tricuspid valve was dysplastic in 22 fetuses, all of which had evidence of tricuspid regurgitation resulting in right atrial dilation and increased cardiothoracic ratio.
 An associated abnormality of the pulmonary valve occurred in 16 fetuses.
 The remaining 16 fetuses had Ebstein's malformation, 14 with evidence of tricuspid incompetence at presentation and 10 with an associated abnormality of the pulmonary valve.
 Of the 38 cases, the pregnancy was interrupted in 17, spontaneous intrauterine fetal death occurred in 8, 11 infants died postnatally and 2 infants are still alive; additional abnormalities were found in 8 cases (chromosomal anomalies in 2, ventricular septal defects in 2, corrected transposition in 2, the Chiari malformation in 2, supraventricular tachycardia in 1 case and coarctation of the aorta in 1).
 Fetuses with severe abnormalities are selected for fetal echocardiography by the four chamber screening program and a high rate of natural loss both in intrauterine life and immediately after birth was observed in the 21 cases in which pregnancy was continued.
 This would explain the higher incidence of tricuspid valve disease in our prenatal compared with postnatal series.
 Although increased cardiothoracic ratio and associated lesions of the right ventricular outflow tract contribute to the poor outcome in the cases detected prenatally, the absence of these features does not always indicate a good prognosis because progression of disease can occur with advancing gestational age.
 No absolute measurement or single echocardiographic feature emerged as a consistent predictive factor of prognosis.
",13
2540,"Anti-ischemic effects of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia.
 The anti-ischemic effects of atenolol and nifedipine were compared in a randomized double-blind crossover manner in 24 patients with stable exertional angina and transient silent ischemia during ambulatory electrocardiographic (ECG) monitoring.
 Both atenolol and nifedipine were effective (p less than 0.005) in reducing the average number and duration of transient ischemic events, but therapy with atenolol was associated with a significantly greater reduction in the mean number (p less than 0.05) and duration (p less than 0.01) of silent ischemic events.
 Analyses of the silent ischemic activity during the morning hours revealed that only therapy with atenolol produced a significant reduction in the average duration per patient (139 +/- 54 vs.
 1,609 +/- 468 s, p less than 0.01) and in the average duration of silent ischemia per event between 6 AM and 12 noon (62 +/- 21 vs.
 208 +/- 24 s, p less than 0.005).
 There were fewer adverse experiences during therapy with atenolol.
 These results show that although both atenolol and nifedipine are effective in reducing silent ischemic events, treatment with atenolol is associated with significantly greater efficacy, particularly on the morning surge of silent myocardial ischemia.
",13
2541,"Value of ventricular electrogram recordings in the diagnosis of arrhythmias precipitating electrical device shock therapy.
 An antitachycardia pacemaker-cardioverter-defibrillator that is capable of storing ventricular electrograms before and after delivery of device shock therapy was implanted in 16 patients.
 Three of the patients experienced out-of-hospital device shock therapy preceded by minimal symptoms.
 Although limitations of electrogram analysis exist and are discussed, careful analysis and registration of electrograms during all supraventricular and ventricular rhythms observed during in-hospital testing served as an important reference for subsequent arrhythmia diagnosis.
 By analyzing the electrogram rate and RR interval stability and configuration, a definitive diagnosis was established in all three patients (atrial fibrillation, polymorphic ventricular tachycardia and rate-sensing lead disruption, respectively).
 Thus, the ability to store ventricular electrograms before shock therapy represents a major advance in the management of patients who receive an electrical device to treat ventricular tachyarrhythmia.
",13
2542,"Case finding, data quality aspects and comparability of myocardial infarction registers: results of a south German register study.
 The population-based Augsburg Coronary Event Register (330,000 residents, age 25-74 years) has registered a total of 1012 cases of acute myocardial infarction (AMI) in 1985 and 1021 AMI in 1986 and categorized them on the basis of the current WHO diagnostic algorithm for AMI.
 The register is designed for longitudinal comparisons of annual AMI risk (incidence, attack rate, death rate), and the risk to the AMI patients themselves (28-day case fatality).
 The methodology and specific issues encountered during registration and data evaluation are described.
 With an estimated 95% completeness of case finding, the quality control data review which the register conducts annually shows a consistency of specific data structures which indicate stable case finding and validation procedures.
 However, local conditions which affect case finding and data completeness per case are responsible for the creation of subsets of AMI which are in turn distinguished by differences in diagnostic category structures.
 With regard to the study objectives, the differences among subsets appear to have the least effect on rate calculations if DEFINITE and POSSIBLE AMI are combined.
 The implications of methodological variations and subset differences within and across registers on annual rate calculations and result comparisons are discussed.
",13
2543,"Sequential or fixed sample trial design? A case study by stochastic simulation.
 The properties of Wilcoxon's rank sum test for fixed sample size and a Wilcoxon-type two-sample sequential test have been illustrated and compared by means of stochastic simulation.
 Data from a real fixed sample trial have been used, both for resampling from the original data, and for construction of an idealized theoretical distribution.
 The sequential and the fixed sample test obtain equal power, but the sequential test mostly includes considerably fewer patients to reach a conclusion, i.e.
 the mean and median number of patients included are both much lower than the fixed sample size.
 Under the hypotheses only a small fraction of the simulation runs exceed the fixed sample size.
 These findings exemplify results obtained in theoretical analyses and simulation studies covering a wide range of distributions.
 In our opinion sequential tests have obvious advantages and are in many cases better alternatives than fixed sample tests in clinical trials.
",13
2544,"Inability to demonstrate physiologic correlates of subjective improvement among patients taught the relaxation response.
 OBJECTIVE: To assess whether the regular elicitation of the relaxation response produces sustained physiologic changes coincident with symptomatic relief or improved psychological state.
 DESIGN: Prospective, cohort pilot study.
 SETTING: Clinical research center within a teaching hospital.
 PATIENTS: Thirteen athletic men, mean age 44.8 years, with borderline or labile hypertension, taking no medication.
 All 13 completed the study.
 INTERVENTIONS: Three baseline assessments of psychological state, symptom checklist, and assessment of autonomic response to infusion of beta agonist (isoproterenol).
 Daily relaxation response exercises for five consecutive weeks followed by repeat assessment of all parameters.
 Discontinuation of relaxation exercises for subsequent five weeks followed by repeat assessment of all parameters.
 Measurements and main results: After eliciting the relaxation response, subjects demonstrated significant decreases in anxiety (p less than 0.014) and somatic symptoms (p less than 0.02).
 Psychological and somatic variables returned toward baseline after the subsequent discontinuation of relaxation exercises.
 No significant concomitant change in urinary catecholamines, heart rate response to isoproterenol, blood pressure, pulse rate, or serum cholesterol was demonstrated.
 CONCLUSION: The regular elicitation of the relaxation response can improve psychological performance and reduce symptoms.
 However, the physiologic mechanism whereby these psychological and symptomatic improvements occur remains poorly understood and warrants further investigation.
",13
2545,"Cardiac performance in infants referred for extracorporeal membrane oxygenation.
 We performed cardiac evaluations in 59 infants referred for severe lung disease to determine whether cardiac performance was impaired in those requiring extracorporeal membrane oxygenation (ECMO).
 Infants were divided into two groups: group 1 (n = 25) received conventional therapy and group 2 (n = 34) received ECMO therapy after meeting established criteria.
 Ventilatory and oxygenation indexes and estimates of right ventricular systolic pressure were measured.
 Load-dependent and load-independent echocardiographic indexes of cardiac performance were also measured.
 The infants in the two groups had similar diagnoses, age, weight, inotropic support, ventilator and oxygenation indexes on admission, and survival.
 Heart rate and estimates of preload and afterload were similar in the two groups.
 Ventricular shortening fraction was 36.1 +/- 7.6% in group 1 and 40.5 +/- 8.8% in group 2 (p value was not significant).
 Velocity of circumferential fiber shortening (VCF/sec) was 1.41 +/- 0.35 in group 1 and 1.58 +/- 0.39 in group 2 (p value was not significant).
 The relationship between wall stress and ventricular shortening was similar in the two groups.
 There were no differences in cardiac output.
 Pulmonary artery pressure was estimated to be 56 +/- 13 mm Hg in group 1 and 63 +/- 10 mm Hg in group 2 (p = 0.017).
 Thus no significant differences were found in load-dependent or load-independent measures of cardiac performance in infants with severe lung disease treated with ECMO or conventional therapy.
 We conclude that cardiac failure is not the primary cause of clinical deterioration in infants with severe lung disease who require ECMO therapy.
",13
2546,"Abdominal aortic aneurysm: results of a family study.
 Data pertaining to abdominal aortic aneurysm among first-degree relatives of 91 patients with abdominal aortic aneurysm are presented.
 The percentage of families with at least one affected first-degree relative of the proband (multiplex families) was 15.4%.
 In 21.4% of multiplex families parent-offspring transmission of abdominal aortic aneurysm was noted; in the remaining families only siblings were affected.
 The mean age at onset among probands was 67.3 years; that among all affected was 67.4 years.
 No statistically significant difference in the mean ages at onset between genders was noted.
 Among affected siblings of probands, the sex ratio, male:female, was 1.33:1, which is not significantly different from 1:1.
 The relative risk of developing an abdominal aortic aneurysm was 3.97 for fathers, 4.03 for mothers, 9.92 for brothers, and 22.93 for sisters.
",13
2547,"Revascularization of an ischemic limb by use of a muscle pedicle flap: a rabbit model.
 A rabbit model of hind limb ischemia was designed to demonstrate that new, hemodynamically significant arterial connections will develop between ischemic skeletal muscle and an independently perfused muscle pedicle flap.
 The right common iliac artery was divided in 15 rabbits.
 In eight rabbits a muscle flap based on the left deep inferior epigastric artery was transposed to the right thigh (flap group).
 In seven rabbits a sham operation was performed where the flap was sutured to the abdominal wall (sham group).
 After 7 days angiography demonstrated arterial connections between the flap and the native limb circulation in all of the flap group animals.
 The flap increased muscle perfusion in the ischemic limb (2.99 ml/100 gm muscle/minute in the flap group, vs 2.06 ml/100 gm muscle/minute in the sham group, p less than 0.005).
 Hemodynamically significant vascular connections will develop between a well-perfused muscle flap and an ischemic limb.
 The augmentation in perfusion provided by these connections can be quantified.
",13
2548,"Limitations of magnetic resonance imaging and ultrasound-directed (duplex) scanning in the diagnosis of subclavian vein thrombosis.
 To investigate the potential role of magnetic resonance imaging and duplex scanning in the diagnosis of catheter-induced subclavian vein thrombosis, we correlated the results of 43 arm phlebograms with duplex scans; 28 of these phlebograms were also correlated with magnetic resonance imaging scans of the thoracic veins.
 Eighteen of the 43 phlebograms were normal, and all had normal magnetic resonance imaging and duplex studies.
 Eleven subclavian veins were totally occluded on phlebography; all had duplex scans, and five were also scanned with magnetic resonance imaging.
 Duplex scans detected 6 of 11 occlusions, whereas magnetic resonance imaging detected 4 of the 5 occlusions scanned.
 The five occlusions that were not detected by either magnetic resonance imaging or duplex scans were short segmental occlusions of the medial one third of the left subclavian vein.
 Of 14 nonocclusive thrombi seen on phlebography, duplex scans correctly identified 8.
 Magnetic resonance imaging was done on eight nonocclusive thrombi but identified only two.
 All abnormal findings on duplex scanning and magnetic resonance imaging were confirmed by phlebography.
 Short occlusions of the proximal portion of the left subclavian vein were often undetected by duplex scanning but occasionally seen with magnetic resonance imaging.
 Neither modality was sensitive to the presence of nonocclusive mural thrombi.
 Magnetic resonance imaging is highly reliable in ruling out the presence of a thrombotic process in the subclavian vein, but it may on occasion fail to detect the presence of subclavian thrombi.
 For this reason, in cases with suspected subclavian vein thrombosis magnetic resonance imaging cannot be used as the only diagnostic modality.
",13
2549,"Skewflap versus long posterior flap in below-knee amputations: multicenter trial.
 A multicenter trial of alternative techniques for below-knee amputation is described in which surgeons in 11 centers randomized 191 patients with end-stage occlusive vascular disease to two different methods of stump construction.
 The skewflap technique was performed in 98 and the long posterior flap was performed in 93.
 The two groups were well matched in respect to age, sex, smoking, diabetes, and indications for amputation.
 Early outcome was compared in terms of 30-day mortality rate: skew 11 (11%) deaths versus long posterior flap 16 (17%); the state of the wound at 1 week (primary healing 60% in both groups); the need for surgical revision at the same level 7 (7%) versus 7 (8%), and revision to a higher level 10 (10%) versus 7 (8%).
 Follow-up information at 6 months was available from records or by mailed questionnaire in 188 (98%) at 6 months, 20 died during that interval.
 It showed that a prosthetic limb was fitted to 64 (84%) of skew flaps and 50 (77%) of long posterior flaps.
 Walking, alone or with support, was achieved in 59 (78%) and 46 (71%), respectively.
 None of these differences reached statistical significance.
 It is concluded that the skew flap is just as effective as the long posterior flap and is an excellent option for below-knee amputation.
",13
2550,"Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery.
 The literature on arterial aneurysms is subject to potential misinterpretation because of inconsistencies in reporting standards.
 The joint councils of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery appointed an ad hoc committee to address this issue.
 This communication, prepared in response to the need for standardized reporting, defines and classifies arterial aneurysms and recommends standards for describing the causes, manifestations, treatment, and outcome criteria that are important when publishing data on aneurysmal disease.
",13
2551,"Antihypertensive therapy. To stop or not to stop?
 The benefits of continuous antihypertensive therapy have been extensively documented.
 However, lack of compliance with the prescribed regimen, excessive cost, and troublesome adverse effects of some antihypertensive agents led to the consideration of intermittent therapy or even complete discontinuation of therapy as an effective alternative to lifelong medication.
 Prospective studies dealing with this subject reported inconsistent results.
 Nevertheless, they allowed us to identify selection criteria of candidates for step-down or discontinuation of antihypertensive therapy.
 Such candidates include patients with mild essential hypertension who have one or more of the following characteristics: young age, normal body weight, low salt intake, no alcohol consumption, low pretreatment blood pressure, successful therapy with one drug only, and no or only minimal signs of target organ damage.
 Stopping antihypertensive therapy without subsequent rise in arterial pressure was shown to be possible in a subset of patients with mild essential hypertension for a period of months to years.
 This approach appears to be safe, provided that blood pressure is monitored frequently, and may improve compliance, save treatment costs, and reduce adverse effects of certain drugs, although its long-term consequences for morbidity and mortality remain to be determined.
",13
2552,"Comparison of two levels of anticoagulant therapy in patients with substitute heart valves 
 After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom).
 An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications.
 Final evaluation included 51 and 48 patients, respectively.
 The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient).
 The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years).
 There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02).
 Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment.
 We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves.
",13
2553,"Analysis and predictors of pulmonary vascular resistance after cardiac transplantation.
 Elevated pulmonary vascular resistance is a known risk factor for early death from acute right ventricular failure after orthotopic cardiac transplantation.
 Patients in whom the elevated pulmonary vascular resistance is due primarily to increased left atrial pressure (""reactive"") frequently have normalization of resistance after transplantation, but few studies have detailed the time course and magnitude of these changes.
 To analyze the response of pulmonary vascular resistance to cardiac transplantation, we analyzed data from 4353 right heart catheterizations on all 182 patients undergoing cardiac transplantation between 1981 and Jan.
 1, 1990.
 Before transplantation 18% of patients had a pulmonary vascular resistance greater than 4 WU, 16% had a pulmonary artery systolic pressure greater than 60 mm Hg, and 16% had a transpulmonary gradient greater than 14 mm Hg.
 In the overall group of patients, pulmonary vascular resistance (mean value 2.63 WU), transpulmonary gradient (mean value 9.9 mm Hg), and pulmonary artery systolic pressure (mean value 48.0 mm Hg) were normalized within 1 week of cardiac transplantation.
 In patients with a high preoperative pulmonary vascular resistance (greater than or equal to 4 WU), the resistance fell promptly within 1 week of transplantation but continued to be slightly elevated throughout the period of follow-up.
 By multiple regression analysis, pulmonary vascular resistance at 1 week and 1 year after transplantation was significantly correlated with the pretransplantation resistance.
 Pulmonary vascular resistance anytime after transplantation was related to preoperative resistance, body surface area, and pulmonary artery diastolic pressure.
 Inferences: (1) As a group, cardiac transplant recipients have a normal pulmonary vascular resistance, transpulmonary gradient, and pulmonary artery systolic pressure within 1 week after transplantation with little change thereafter for at least several years.
 (2) Patients with reversible elevation of pulmonary vascular resistance before cardiac transplantation typically have a reactive and a fixed component.
 Cardiac transplantation relieves the reactive but not the fixed component.
 As a result, pulmonary vascular resistance early (within 1 week) and late after transplantation will have fallen but not completely normalized.
",13
2554,"The mechanism of heart failure caused by cardiac allograft rejection.
 Rejection of the cardiac allograft is often associated with reversible myocardial failure, the mechanism of which is not understood.
 We have examined this phenomenon in a small animal model that provides the opportunity for multimodality study of the rejection process.
 Heterotopic cardiac transplantation was performed in the Lewis rat with Lewis X Brown-Norway (allografts) or Lewis (isografts) donors.
 Without immunosuppression, allografts are completely rejected in 6 to 8 days.
 At 3 days cardiac grafts were explanted and mounted on a modified Langendorff apparatus for functional measurements or submitted for pathologic examination and biochemical determination of high-energy phosphates.
 Three-day isografts (n = 9) had minimal histologic changes.
 Pathologic examination of 3-day allografts (n = 13) showed lymphocytic infiltrate and myocyte necrosis, histologic features for which antirejection treatment is usually given clinically.
 For grafts subjected to functional studies (n = 11), heart rate, cardiac output, coronary flow, and stroke work were determined at baseline and in response to isoproterenol (3 x 10(-8) mol/ml).
 Three-day allografts (n = 6) and isografts (n = 5) had similar baseline function.
 The chronotropic response to isoproterenol was similar in allografts and isografts, but allografts had diminished cardiac output and stroke work after isoproterenol.
 Adenosine triphosphate levels were normal (41.9 nmol/mg) in 3-day allografts (n = 4).
 We have evaluated functional, biochemical, and pathologic changes associated with myocardial dysfunction during heterotopic cardiac transplant rejection in a small animal.
 This model reproducibly demonstrates diminished contractile reserve in 3-day allografts with normal baseline function and high-energy stores but histologically significant rejection.
",13
2555,"Mitral valve repair by replacement of chordae tendineae with polytetrafluoroethylene sutures.
 Expanded polytetrafluoroethylene sutures have been used for replacement of diseased chordae tendineae during reconstructive procedures on the mitral valve in 43 patients.
 There were 28 men and 15 women whose mean age was 55 years, range 21 to 76.
 Three fourths of the patients were in New York Heart Association class III or IV.
 Replacement of primary chordae tendineae of the anterior leaflet was performed with 4-0 or 5-0 polytetrafluoroethylene sutures.
 A double-armed suture was passed twice through the fibrous portion of the papillary muscle head and tied down.
 Each arm of the suture was brought up to the free margin of the leaflet and passed through the area where the native chorda was attached.
 After the lengths of the two arms were adjusted, the ends were tied together on the ventricular side of the leaflet.
 Thirty patients had degenerative disease of the mitral valve; the incompetence was due to prolapse of the anterior leaflet in 14 patients and prolapse of the anterior and posterior leaflets in 16.
 Eleven patients had rheumatic mitral valve disease: four had stenosis, three had regurgitation, and four had mixed lesions.
 Two patients had ischemic mitral regurgitation caused by rupture of a papillary muscle head.
 There were no operative deaths.
 Patients have been followed up from 5 to 61 months, mean 13.
 Doppler echocardiographic studies were performed at regular intervals after the operation and revealed normal mitral valve function in most patients There were two failures that necessitated mitral valve replacement: one because of acute mitral regurgitation and the other because of hemolysis.
 There have been two late deaths, neither one valve related.
 Replacement of chordae tendineae with polytetrafluoroethylene sutures is simple and allows for reconstruction of the mitral valve in many patients who would otherwise require mitral valve replacement.
 Because our patients have been followed up for a limited time, the long-term results of this procedure remain unknown.
",13
2556,"Alcohol and pyruvate cardioplegia. Twenty-four-hour in situ preservation of hamster hearts.
 Isolated hamster hearts were first perfused with a normal Krebs-Henseleit medium to demonstrate comparable viability of hearts before perfusing and storing them for 24 hours in one of three solutions.
 The three solutions were a physiologic saline with pyruvate as the substrate and 4% alcohol to arrest the heart (group 1), a standard cardioplegic solution (group 2), and an alcohol-free physiologic saline with pyruvate as the substrate (group 3).
 Recovery in terms of rate/pressure product and oxygen consumption after 30 minutes of reperfusion was 81% and 93%, respectively, for group 1, 13% and 32% for group 2, and 70% and 72% for group 3.
 Percent of physiologic recovery was not related to recovery of adenosine triphosphate.
 The adenosine triphosphate level returned to approximately 40% control level in all three groups, and in all three groups inorganic phosphate remained approximately 320% over control level after 30 minutes of reperfusion.
 Phosphocreatine level significantly higher in groups 1 and 3 than in group 2, as a result of improved oxygen consumption.
 Intracellular pH, determined by phosphorous 31 nuclear magnetic resonance spectroscopy, was physiologic in groups 1 and 3 but alkaline in group 2.
 This alkalinity may have been caused by leaky membranes.
 Pyruvate helped preserve mitochondrial function during depressed oxygen delivery, such as was seen during the 24-hour storage period.
 Four percent alcohol arrested the heart; combined with pyruvate plus alcohol solution were better than a standard cardioplegic solution for maintaining functional capability.
",13
2557,"The dynamics of antegrade cardioplegia with simultaneous coronary sinus occlusion. Effects on aortic root infusion pressure, coronary sinus pressure, and myocardial cooling.
 It has been suggested that antegrade cardioplegia with coronary sinus occlusion improves homogeneous myocardial cooling and reduces myocardial injury in the presence of coronary artery occlusion.
 Little data are available on the exact relationships among the basic elements or this intervention, including antegrade infusion rate, aortic root pressure, the degree of coronary sinus occlusion, coronary sinus pressure, and myocardial cooling.
 The purpose of this study was to determine these relationships and to provide some basic guidelines for better understanding of this intervention.
 Twenty-two sheep were placed on cardiopulmonary bypass, the distal left anterior descending artery was occluded, and the proximal coronary sinus was snared.
 Sixteen combinations of infusion rate (3, 5, 7, or 9 ml/kg/min) and coronary sinus occlusion (total, subtotal, or moderate occlusion or no occlusion) were adopted for each 2 minutes of antegrade cardioplegia, yielding 96 measurements.
 Myocardial temperatures in the occluded and nonoccluded regions, aortic root infusion pressure, and coronary sinus pressure were measured during each infusion of cardioplegic solution.
 Coronary sinus occlusion was then released, and the whole heart was reperfused for 30 minutes for another infusion of cardioplegic solution and measurements.
 Results showed good degrees of linearity between infusion rate and aortic root infusion pressure for all coronary sinus occlusion and noninfusion groups (p less than 0.01).
 A positive effect of coronary sinus occlusion on aortic root infusion pressure was observed.
 The graded increases in infusion rate with various degrees of coronary sinus occlusion were constantly associated with elevation of coronary sinus pressure (p less than 0.01).
 It was also noted that myocardial temperatures in the region of the occluded left anterior descending artery were significantly lower in coronary sinus occlusion groups than in nonocclusion groups (p less than 0.01 or 0.05).
 Myocardial temperature in the nonoccluded region decreased significantly with the stepwise increases in infusion rate (p less than 0.01), but not with the increases in coronary sinus occlusion (not significant).
 Based on this and previous studies, we recommend that the induced coronary sinus pressure be safely maintained in the range of 25 to 35 mm Hg and that further studies be focused on the infusion rate of 5 ml/kg/min with subtotal or total coronary sinus occlusion for the intervention of antegrade cardioplegia plus coronary sinus occlusion.
",13
2558,"Freehand allograft aortic valve replacement and aortic root replacement. Utility of intraoperative echocardiography and Doppler color flow mapping.
 Seventeen consecutive patients undergoing 20 planned aortic valve replacements with allograft valves at Stanford University Medical Center were studied with intraoperative epicardial echocardiography and Doppler color flow mapping before and after cardiopulmonary bypass.
 Native aortic valves were replaced in 12 of the 20 patients, and eight patients underwent second aortic valve procedures.
 In 17 of 20 patients allograft selection was guided by prebypass echocardiographic estimates of annular diameter and/or length of allograft aortic root required.
 Other prebypass findings included unanticipated severe mitral regurgitation in one patient (which precluded allograft aortic valve replacement), left-to-right shunts in five patients, ascending aortic dissection in one, and aortic root disease necessitating coronary reimplantation or bypass in two.
 Postbypass echocardiography demonstrated acceptable competency of 18 of 19 allograft valves (mild or no aortic insufficiency).
 Postbypass echocardiography also documented successful repair of four of five shunts and mild mitral regurgitation in 15 of 19 patients (versus 11 of 19 before bypass).
 Conclusions: Intraoperative echocardiography-Doppler mapping is a useful adjunct for allograft aortic valve or aortic root replacement; it allows confident selection of appropriate tissue size before aortic cross clamping, which minimizes delay from allograft thawing procedures.
 It also provides helpful information about the extent of aortic root disease and coronary ostial anatomy before bypass, confirms allograft competency after bypass, and detects accompanying valvular and other hemodynamic lesions before and after allograft valve replacement.
",13
2559,"Deprivation in infancy or in adult life: which is more important for mortality risk? 
 Previous ecological studies have suggested that early life factors are important causes of adult cardiovascular and respiratory disease, by showing geographic correlations between past infant mortality rates and present adult mortality rates.
 However, these studies inadequately take account of the fact that areas which were severely deprived earlier this century remain the most deprived today.
 Thus the ecological relation between infant and adult mortality rates could simply reflect persistence in the geographic distribution of poor socioeconomic circumstances.
 To explore this hypothesis further infant mortality rates for 1895-1908 for 43 counties in England and Wales were correlated with cause-specific adult mortality for 1969-73 in people aged 65-74 years, with and without adjustment for present-day social deprivation and social class.
 The strong simple correlations found between infant mortality in 1895-1908 and adult mortality from various causes in 1969-73 were generally much attenuated or abolished by controlling for indices of present-day socioeconomic circumstances.
 Our results suggest that previous studies give no strong support for any direct influence of factors acting in early life on adult coronary heart disease mortality risk.
 Studies which gather data about infancy, childhood, and the full course of adult life are required to clarify this issue.
",13
2560,"Raynaud's syndrome. Using a range of therapies to help patients.
 Raynaud's syndrome is a common medical problem.
 Approach to diagnosis must involve a search for underlying causes.
 Treatment includes avoidance of precipitating factors, biofeedback, and possibly pharmacologic therapy, after careful consideration of risks.
",13
2561,"Heart transplantation in patients with severe pulmonary hypertension and increased pulmonary vascular resistance.
 Irreversibly increased pulmonary vascular resistance is a contraindication for cardiac transplantation.
 At our hospital patients referred for recipient evaluation with systolic pulmonary artery pressure greater than 50 mmHg and pulmonary vascular resistance greater than 2 Wood units (Wu) are tested with intravenous sodium nitroprusside for reversibility.
 In 23 patients whose increased systolic pulmonary artery pressure (67.4 +/- 10.4 mmHg) and resistance (4.8 +/- 2.4 Wu) were reduced by nitroprusside, orthotopic heart transplantation was performed without early mortality.
 Right heart catheterization after transplantation revealed a significant and persistent fall of the elevated pulmonary artery pressure and pulmonary vascular resistance.
 We conclude that if severe pulmonary hypertension and elevated pulmonary vascular resistance are reversible with nitroprusside, the patient can safely undergo heart transplantation.
",13
2562,"Ultrastructural changes in rat hearts following cold cardioplegic ischemia of differing duration and differing modes of reperfusion.
 Morphologic consequences of prolonged global hypothermic (15 degrees C), cardioplegic ischemia and two reperfusion techniques were studied in Langendorff-perfused rat hearts.
 A 'gentle' reperfusion technique, with gradual rise in perfusate temperature and pressure to physiologic levels over 30 min, was used for 12 hearts following 2-hour or 3 1/2-hour (6 in each group) ischemia.
 Abrupt reperfusion, with perfusate at 37 degrees C and 70 mmHg, was performed on 13 hearts (6 ischemic for 2 hours and 7 for 3 1/2 hours).
 Six nonischemic, perfused hearts served as controls.
 Randomly selected specimens from the left ventricle after 45-60 min reperfusion were prepared for transmission electron microscopy.
 Volume fractions of myocardial structural components were calculated from stereologic point-counting on the electron micrographs.
 Two-way analysis of variance revealed that interstitial edema developed with increasing ischemic time and was not influenced by reperfusion technique.
 The degree of endothelial damage was independent of ischemic time, but was lessened by 'gentle' reperfusion.
 Both mitochondrial injury and myocyte edema were less when perfusate temperature and pressure were slowly raised after 3 1/2-hour ischemia.
",13
2563,"Coronary trapping of a complement activation product (C3a des-Arg) during myocardial reperfusion in open-heart surgery.
 Accumulation of complement factors has been found to occur in the myocardium after infarction.
 We studied the possibility that the complement activation product C3a des-Arg is trapped within the coronary circulation during reperfusion of the ischemic myocardium.
 In 11 patients undergoing routine coronary artery bypass grafting, arterial blood was sampled before, during and after cardiopulmonary bypass.
 Blood was drawn from the coronary sinus concomitantly with arterial blood sampling 5 and 30 min after release of the aortic cross-clamp (n = 10).
 From a preoperative value of 92 +/- 13 ng/ml, C3a des-Arg rose during CPB to a maximum of 1816 +/- 393 at the end of CPB.
 Following reperfusion for 5 min, C3a des-Arg was 1284 +/- 232 ng/ml in arterial and 1106 +/- 100 in coronary sinus blood, a significant difference (p less than 0.05).
 The amount of C3a des-Arg trapped in the heart at 5-min reperfusion showed positive correlation with its arterial concentration (p less than 0.05).
 No significant difference was found after 30 min of reperfusion.
 Complement activation products trapped in the heart in the early reperfusion period may play a pathogenetic role in myocardial ischemia-reperfusion injury.
",13
2564,"Subacute poisoning with phosalone, an organophosphate insecticide.
 An illness characterized by weakness, dizziness, and gastrointestinal symtoms was identified among a crew of 30 migrant field-workers employed by a grape grower in Madera County, California, during August 1987.
 The onset of symptoms occurred between August 24 and August 30 and a median of 9 days from the date of first employment.
 The first crew member sought medical treatment on August 26, and 10 crew members were admitted to hospital between August 27 and August 30.
 For most workers, gastrointestinal and constitutional symptoms resolved shortly after admission, but 4 patients had episodes of severe sinus bradycardia persisting for several days.
 On the day of admission, transient atrioventricular dissociation developed in 2 persons.
 Interviews with 16 crew members not admitted to the hospital identified only 1 additional worker ill with gastrointestinal symptoms, but all 16 had moderate to severe inhibition of both plasma and red blood cell cholinesterase.
 Four other workers who were tested but not interviewed also had cholinesterase depression.
 The crew had had exposure since August 19 to the organophosphate insecticide phosalone, which was last applied to the vineyard on July 21, or 29 days earlier.
 Although this is the first report unequivocally linking phosalone to field-worker poisoning, the delayed onset and nonspecific nature of the symptoms associated with subacute poisoning may have hindered the recognition of previous similar episodes.
",13
2565,"New developments in cardiopulmonary resuscitation.
 Since the last revision of the American Heart Association's guidelines in 1985, several new developments of clinical importance have occurred in the field of cardiopulmonary resuscitation.
 These include enhanced access to and earlier use of defibrillation, the use of high-dose epinephrine when standard doses fail, the assessment of resuscitative efforts with end-tidal CO2 monitoring and the addition of two new drugs, amiodarone (for refractory ventricular fibrillation) and adenosine (for paroxysmal supraventricular tachycardia).
 Time will determine the ultimate role of these advancements in the management of cardiac arrest.
",13
2566,"Late streptokinase infusion and antithrombotic treatment in myocardial infarction reduce subsequent myocardial ischemia.
 Of 255 consecutive patients with acute myocardial infarction, 111 were eligible for attempted late thrombolysis.
 They were randomly assigned to either thrombolytic and antithrombotic treatment (treatment group) or routine treatment (control group).
 Patients in the treatment group received streptokinase initiated late (mean 32 hours; range 12 to 49) after the onset of symptoms, followed by heparin infusion for at least 5 days and warfarin and dipyridamole for at least 3 months.
 Patients were examined clinically and by bicycle ergometry on discharge from the hospital and after 3 and 12 months.
 The two groups did not differ with respect to deaths or reinfarctions.
 There was a trend toward a lower incidence of angina pectoris in the treatment group.
 Exercise tolerance in this group was significantly higher than in the control group (at 3 months 124 +/- 39 W vs 107 +/- 41 W; p less than 0.05).
 The difference was entirely accounted for by patients with no previous history of infarction or angina pectoris (at 3 months 142 +/- 37 W vs 112 +/- 45 W; p = 0.01).
 ECG signs of myocardial ischemia, silent or symptomatic, occurred at significantly lower levels of exercise among patients in the control group compared with patients in the treatment group.
 The results support the notion that thrombolytic therapy given as late as 12 to 49 hours after the onset of symptoms may reduce the incidence of residual ischemia during the postinfarction period.
",13
2567,"Immediate regional endocardial surface expansion following coronary occlusion in the canine left ventricle: disproportionate effects of anterior versus inferior ischemia.
 The exact time of onset of functional expansion after acute myocardial infarction/ischemia remains unclear in spite of its potential link to chronic pathologic infarct expansion and its potential implications for therapy.
 To examine this early change in ventricular morphology, 14 open-chest dogs were studied with two-dimensional echocardiography before and after occlusion (10 minutes) of the left anterior descending coronary artery (LAD, n = 7) or circumflex artery (CIRC, n = 7).
 The endocardial surface area (ESA) and the area of abnormal wall motion (AWM) were reconstructed from the echocardiographic data using a previously reported technique for quantitatively mapping the ESA and extent of AWM.
 For the total group (N = 14), the mean ESA before occlusion was 48.9 +/- 9.8 cm2, increasing to 65.7 +/- 18.9 cm2 at 10 minutes occlusion (p less than 0.001).
 For the LAD subgroup, the mean ESA before occlusion was 50.7 +/- 9.3 cm2, increasing to 79.1 +/- 14.1 cm2 at 10 minutes following occlusion (p less than 0.001).
 For the CIRC subgroup, the mean ESA before occlusion was 47.1 +/- 10.8 cm2, increasing to 52.3 +/- 12.6 cm2 at 10 minutes after occlusion (p less than 0.001).
 The ESA increase for the LAD subgroup was significantly larger than that of the CIRC subgroup (LAD range 14.5 to 49.9 cm2 versus CIRC range 1.5 to 9 cm2, p less than 0.0001).
 Coronary occlusion resulted in similarly sized regions of AWM for both subgroups (LAD, 31.3 +/- 12.2 cm2 versus CIRC, 25.9 +/- 10.3 cm2, p = n.s.).
 For the LAD group, the largest increase in endocardial circumference occurred within the zone of AWM at the apex (39.9 +/- 12%).
 The endocardial surface area therefore expands immediately after coronary occlusion and the magnitude of this process is primarily related to the site (anteroapical) rather than to the extent of AWM.
",13
2568,"Detection of myocardial infarction in the presence of Wolff-Parkinson-White syndrome by QRST isoarea map in dogs.
 The possibility of detecting myocardial infarction (MI) in the presence of Wolff-Parkinson-White (WPW) syndrome by means of body surface QRST isoarea maps was studied in eight dogs.
 Eighty-seven body surface ECGs were recorded simultaneously.
 Recordings were taken during right atrial (RA) and right atrial and right ventricular (RA + RV) sequential pacing, which simulated WPW syndrome, during control periods and at 1-hour intervals for up to 5 hours after occlusion of the left anterior descending coronary artery.
 In ECGs during the RA drive, diagnostic findings of MI such as abnormal Q waves were observed but became obscure during the RA + RV drive.
 On the contrary, the QRST values over the anterior chest during both drives were positive soon after coronary occlusion, decreased gradually as time passed, and became abnormally negative after 5 hours.
 The QRST isoarea maps during RA and RA + RV pacing showed quite similar patterns and were highly correlated with each other throughout this study (r greater than 0.95).
 These findings demonstrate that localized abnormalities resulting from MI are evident in QRST isoarea maps even in the presence of preexcitation and fusion.
",13
2569,"Acute reduction of mitral valve area after percutaneous balloon mitral valvuloplasty: assessment with Doppler continuity equation method.
 Mitral valve areas before and after balloon mitral valvuloplasty were serially determined by the Doppler continuity equation method in 16 patients.
 Ultrasound examinations were performed before and immediately after balloon inflation and 24 hours, 1 week, and 1 month after valvuloplasty.
 Mitral valve area determined by the Doppler continuity equation method correlated well with that determined at catheterization by the Gorlin formula, not only before but also immediately after balloon inflation (y = 0.87 x + 0.05, standard error of estimate = 0.22 cm2, r = 0.90).
 Serial calculation of mitral valve area by the Doppler continuity equation method showed a slight but significant decrease in the valve area at 24 hours after balloon mitral valvuloplasty but no change after that.
 We conclude that the Doppler continuity equation method provides an accurate estimation of mitral valve area before and even after balloon valvuloplasty.
 Mitral valve area dilated by balloon inflation is decreased slightly within 24 hours after the procedure, which corroborates valve stretch as one mechanism for increasing mitral valve area with balloon valvuloplasty.
 Estimation of mitral valve area immediately after balloon mitral valvuloplasty may overestimate the long-term efficacy of the procedure.
",13
2570,"Acute hemodynamic effects of intravenous diperdipine, a new dihydropyridine derivative, in coronary heart disease.
 The acute hemodynamic effects of a new dihydropyridine calcium channel blocker, diperdipine, which is suitable for intravenous administration, were studied by right and left cardiac catheterization in 16 patients with coronary heart disease.
 Diperdipine markedly reduced systemic vascular resistance and improved stroke index and left ventricular ejection fraction.
 Mean pulmonary artery and wedge pressures were slightly increased as a possible consequence of enhanced venous return, whereas right atrial and left ventricular end-diastolic pressures were not significantly changed.
 Nevertheless, an increase in preload was clearly indicated by an augmented left ventricular end-diastolic volume index after administration of diperdipine.
 Left ventricular contractility, which was estimated by the end-systolic pressure-volume ratio and by dP/dt max was not significantly changed, though analysis of individual data suggests a minimally negative inotropic effect.
 However, such a minor effect on left ventricular contractility was largely counterbalanced by the marked reduction of afterload, which produced a sharp improvement of stroke index.
 Enhancement of left ventricular ejection fraction and reduction in systemic vascular resistance were inversely and directly correlated to control values.
 Overall, diperdipine was well tolerated, but one patient had a major untoward reaction that consisted of an ischemic episode that was possibly related to drug administration.
 In conclusion, intravenous diperdipine appears to be a potent arteriolar dilating agent that does not affect left ventricular contractility.
",13
2571,"Ultra short-acting intravenous beta-adrenergic blockade as add-on therapy in acute unstable angina.
 To assess the efficacy and safety of the ultra short-acting beta-blocking agent, esmolol, in acute unstable angina, we administered esmolol to 21 patients who had persistent angina despite conventional medical therapy.
 Following a baseline Doppler echocardiographic examination, esmolol was titrated to reduce the rate-pressure product by at least 20%.
 Once the patients had been receiving a maintenance dosage for 30 minutes, Doppler echocardiographic studies were repeated.
 Mean esmolol dose at target response was 17 +/- 16 mg/min, with the dosage range of 8 to 24 mg/min.
 Esmolol was effective in alleviating anginal chest pain in 18 of the 21 patients.
 Seven patients eventually underwent percutaneous transluminal coronary angioplasty (PTCA) and eight had coronary bypass surgery.
 The remainder were discharged receiving medical therapy including oral beta-blockade.
 During esmolol therapy, heart rate and blood pressure decreased significantly (86 +/- 14 to 68 +/- 12 beats/min and 125 +/- 16 to 103 +/- 20 mm Hg, both p less than 0.001).
 Cardiac output decreased from 5.4 +/- 1.3 to 4.5 +/- 1.1 L/min (p less than 0.001) secondary to a decrease in heart rate as stroke volume remained unchanged.
 Left ventricular ejection fraction increased from 47 +/- 12 to 49 +/- 13 with esmolol therapy, although this change was not statistically significant.
 Both the one third filling fraction as well as E/A ratio (ratio of early-to-late diastolic filling velocities) increased with esmolol therapy (35 +/- 8% to 38 +/- 8% and 0.73 +/- 0.2 to 0.85 +/- 0.23, both p less than 0.005), indicating improvement in left ventricular diastolic function.
",13
2572,"Improvement of systolic and diastolic left ventricular wall motion by serial echocardiograms in selected patients treated for unstable angina.
 The purpose of the study was to evaluate the effect of antiischemic treatment on left ventricular function in selected patients with unstable angina pectoris that was due to severe proximal left anterior descending coronary artery narrowing and to identify subgroups liable to an adverse outcome (mean term 2.7 years).
 Effect of antiischemic treatment on systolic and diastolic left ventricular wall motion was studied in 35 patients who had unstable angina pectoris and an electrocardiogram that indicated severe proximal left anterior descending coronary artery narrowing.
 Treatment consisted of either a revascularization procedure (17 patients) or antianginal drug therapy (18 patients).
 All patients underwent a two-dimensional echocardiographic study within 48 hours (mean 20 hours) of entry into the study.
 This study semiquantitatively analyzed systolic performance of the ischemia-related segments by calculation of a total wall motion score.
 In 16 patients this investigation was combined with a continuous detailed recording of only the apical interventricular septal wall motion.
 This detailed study included measurements for regional function by providing a typification of the pattern of systolic and early diastolic excursion of the endocardial border of the apical interventricular septum.
 A repeat ultrasonic study was performed at least 1 month (median 2 months, 7 days) after admission.
 Results of the systolic wall motion analyses of all 35 patients showed, in both treatment groups, a significant improvement in systolic wall motion of the anterior and apical segments (mean total wall motion score at early study vs late study: revascularization, 6.9 vs 2.2 and medical therapy, 4.6 vs 1.0).
",13
2573,"Identification of the rate-dependent functional refractory period of the atrioventricular node in simulated atrial fibrillation.
 We continuously observed successive pairs of R-R intervals during atrial fibrillation and hypothesized that the shortest R-R interval for a given preceding R-R interval in a pair represents the functional refractory period of the atrioventricular node at that preceding interval.
 To test this hypothesis we simulated atrial fibrillation in 28 isolated cross-perfused canine hearts and obtained an R-R interval scatterplot by plotting the R-R intervals as a function of the immediately preceding R-R interval.
 This scatterplot enabled us to detect a series of the shortest R-R intervals for a wide range of preceding R-R intervals, and this allowed us to estimate the rate-dependent functional refractory period of the atrioventricular node in simulated atrial fibrillation.
 The estimated functional refractory periods correlated well with those measured by the conventional method (r = 0.93).
 We conclude that the proposed method makes it possible to estimate the rate-dependent functional refractory periods of the atrioventricular node in atrial fibrillation.
",13
2574,"Septal ventricular pacing in the immature canine heart: a new perspective.
 Cardiac pacing initiated from epicardial or transvenous apical right ventricular electrodes causes asynchronous ventricular contraction.
 This alters myocardial stress vectors and results in adverse cellular and subcellular changes in the experimental animal.
 Clinically, such changes may contribute to the adverse hemodynamics reported with long-term ventricular pacing.
 To determine the feasibility of direct stimulation of the ventricular specialized conduction systems and therefore the potential for maintenance of normalized depolarization patterns, 13 beagle puppies were studied.
 Baseline ventricular activation and contraction patterns were obtained using intracardiac electrograms and multigated nuclear acquisition (MUGA) imaging.
 Septal electrode insertion from the aortoatrial groove was accomplished by use of two-dimensional echocardiography and continuous electrocardiographic (ECG) monitoring of the surface ECG during pacemaker implantation in five puppies.
 Standard right ventricular epicardial electrodes were implanted in five additional animals, with three remaining as age-matched non-paced controls.
 After 4 months of observation, repeat MUGA imaging and intracardiac electrograms demonstrated nearly normal biventricular activation and contraction patterns among the septal-paced group.
 Histopathologic examination illustrated normal cellular morphology in the septal-paced animals.
 This study demonstrates that pacing electrode insertion into the proximal interventricular septum is feasible and results in utilization of the normal ventricular conduction pathway.
 Such an approach to initiation of ventricular stimulation may attenuate the adverse effects of long-term ventricular pacing.
",13
2575,"Noninvasive estimation of left atrial pressure in patients with congestive heart failure and mitral regurgitation by Doppler echocardiography.
 A completely noninvasive method for estimating left atrial pressure in patients with congestive heart failure and mitral regurgitation has been devised with the use of continuous-wave Doppler echocardiography and brachial sphygmomanometry.
 Of 46 patients studied with mitral regurgitation, 35 (76%) had jets with distinct Doppler spectral envelopes recorded.
 The peak ventriculoatrial gradient was obtained by measuring peak mitral regurgitant velocity in systole and using the modified Bernoulli equation.
 This gradient was then subtracted from peak brachial systolic blood pressure, an estimate of left ventricular systolic pressure, to yield left atrial pressure (left atrial pressure = systolic blood pressure - mitral regurgitant pressure gradient).
 Noninvasive estimates of left atrial pressure from 35 patients were plotted against simultaneous recordings of mean pulmonary capillary wedge pressure resulting in the correlation y = 0.88x + 3.3, r = 0.88, standard error of estimate = +/- 4 mm Hg (p less than 0.001).
 Therefore, continuous-wave Doppler echocardiography and sphygmomanometry may be used in selected patients with congestive heart failure and mitral regurgitation for noninvasive estimation of left atrial pressure.
",13
2576,"Myocardial imaging with Tc-99m teboroxime: technique and initial results.
 This study examined the results of Tc-99m teboroxime imaging in 22 patients aged 59 +/- 9 years and compared the results with those of thallium-201.
 The exercise and rest teboroxime studies were obtained within 3 hours of each other using a dose of 15 mCi/study.
 Because of the very short wash-out half-life of teboroxime, imaging was begun within 1 to 2 minutes after injection.
 Both SPECT and planar images were obtained; the SPECT protocol was modified by changing the number of frames, the time per frame, or the filters used for reconstruction of images.
 The planar images were obtained in the supine or upright position.
 Shorter acquisition time for SPECT (10 sec/frame) and the use of a Butterworth filter with a frequency cutoff of 0.3 cycle/cm and a power of 10 yielded best image quality.
 There was a close agreement with thallium results in identifying an abnormal or normal perfusion pattern in 89% of vascular territories.
 The scans were abnormal by both techniques in 12 patients, normal in nine patients, and discordant in only one patient.
 Thus Tc-99m teboroxime myocardial imaging is feasible at rest and during exercise using either SPECT or planar imaging.
 Shorter acquisition time and appropriate filtering for SPECT imaging and the upright position in planar imaging improve image quality and are convenient for the patient.
",13
2577,"Future directions in vasodilator therapy for heart failure.
 Vasodilator therapy has become a major pharmacologic approach for improving left ventricular function, and consequently, vasodilator drugs are being used increasingly in the treatment of heart failure.
 Ideally, vasodilator drugs used in the long-term management of heart failure should show clearly defined pharmacodynamic effects.
 These include reduced impedance to left ventricular ejection, increased venous capacitance, increased left ventricular ejection fraction and reduced heart size, absence of neurohormonal stimulation, and slowed progression of left ventricular dysfunction.
 The mechanisms of action and sites of activity of the various vasodilator drugs currently available vary considerably, and none as yet has proved ideal for the treatment of heart failure or hypertension.
 The complexity surrounding the multiple vasoconstrictor mechanisms involved in heart failure has led to a rationale for combined vasodilator therapy and certain combinations are discussed.
 From a therapeutic standpoint, the development of drugs with multiple mechanisms of action is particularly attractive.
 Flosequinan is a new vasodilator agent whose cellular mechanism of action remains uncertain.
 Flosequinan has the advantage of being able to relax both arterial and venous beds and as such may be particularly beneficial in the treatment of heart failure.
",13
2578,"Clinical efficacy of flosequinan in heart failure.
 The effects of the new arterial and venous vasodilator flosequinan have been evaluated in a variety of ways in different groups of patients with chronic heart failure.
 Flosequinan improved the central hemodynamic effects of heart failure in one group, with benefits still apparent up to 24 hours after a single oral dose.
 In another group it also improved calf blood flow and, therefore, blood flow to skeletal muscle.
 Also, using a number of different tests, it improved the exercise performance of the patients.
 In a further group the improvement in exercise tolerance produced was similar to that of captopril.
 Flosequinan has the necessary properties of a drug that is likely to be of benefit in the treatment of patients with chronic heart failure.
",13
2579,"Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction.
 The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI).
 Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later.
 Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions.
 In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05).
 The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001).
 As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant).
 At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients.
 This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported.
 The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region.
 The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering.
",13
2580,"Effects of nisoldipine on myocardial ischemia during exercise and during daily activity.
 The antiischemic properties of nisoldipine, a dihydropyridine calcium antagonist, were assessed in a multicenter, double-blind, placebo-controlled trial by repeated exercise testing and 72-hour ambulatory electrocardiographic monitoring in 82 patients with coronary artery disease.
 Patients with positive treadmill stress test results and greater than or equal to 2 ischemic episodes per 24 hours were included in this study.
 Administration of all chronic antiischemic medications except beta blockers were discontinued.
 During the first week all patients received placebo twice daily.
 During the second and third weeks, 41 patients received nisoldipine 10 mg and 41 patients received placebo twice daily.
 In the placebo group there were no changes in exercise parameters or in ambulatory electrocardiographic parameters.
 In the nisoldipine group, exercise duration increased from 403 to 448 seconds (p = 0.0035), time to 1 mm of ST depression increased from 224 to 298 seconds (p = 0.002), time to pain increased from 241 to 321 seconds (p = 0.01), and maximal ST depression was reduced from 2.6 to 2.3 mm (p = 0.002).
 Among the ambulatory electrocardiographic parameters in the nisoldipine group, only the number of episodes was reduced, from 14.4 to 11.6 (p = 0.0013) per patient.
 There was no significant reduction in total ischemic time (132 vs 120 minutes per patient).
 No significant side effects were observed.
 This is the largest clinical trial to date on the effects of nisoldipine on myocardial ischemia.
 The results indicate that nisoldipine was effective in improving all exercise parameters and only partially effective in suppressing ischemia during daily activity.
",13
2581,"Usefulness of blood lactate as a predictor of shock development in acute myocardial infarction [published erratum appears in Am J Cardiol 1991 Apr 15;67(9):912]
 Data were obtained and analyzed in 229 patients admitted to the coronary care unit from November 1988 through July 1989.
 The patients were classified into 2 groups: patients without or with only mild left ventricular failure (Killip class I or II) during their hospital stay (group I), and patients who were in Killip class I or II on admission but developed cardiogenic shock during hospitalization (group II).
 Discriminant function analysis was performed using the following variables: patients' age, history of previous myocardial infarction, diabetes mellitus, blood lactate, urea, creatinine, creatine kinase, aspartate aminotransferase, lactate dehydrogenase concentrations, and chest x-ray cardiothoracic ratio.
 Variables that were found to significantly discriminate the 2 groups of patients were age, previous infarction, x-ray cardiothoracic ratio, blood urea and lactate concentrations.
 The risk index was computed, and blood lactate was the variable with the greatest predictive power for shock development.
 The sensitivity, specificity and predictive value of the risk index, taking various cutoff points, were calculated.
 With a cutoff value of 1, sensitivity was 65%, specificity 91%, positive predictive value 36% and negative predictive value 97%.
 With a cutoff value of 2, sensitivity was 53%, specificity 99%, positive predictive value 82% and negative predictive value 96%.
",13
2582,"Capabilities of supine exercise electrocardiography versus exercise radionuclide angiography in predicting coronary events.
 The ability of supine exercise electrocardiography and exercise radionuclide angiography to predict time to subsequent cardiac events (cardiac death, nonfatal myocardial infarction or late coronary bypass grafting or angioplasty) were compared in 265 patients with normal resting electrocardiograms who were not taking digoxin.
 All patients had undergone coronary catheterization and were initially treated medically.
 Follow-up study was performed at a median of 51 months.
 Separate logistic regression models, which had been previously developed to predict 3-vessel or left main coronary artery disease (CAD), were compared using a Cox regression analysis to predict time to a subsequent cardiac event.
 The exercise electrocardiography model, consisting of the magnitude of ST depression, exercise heart rate and patient gender, was a powerful predictor (chi-square = 30.8, p less than 0.0001) of subsequent events.
 The exercise radionuclide angiography model, which included the exercise response of the pressure-volume ratio in addition to the exercise electrocardiography variables, had similar prognostic power (chi-square = 31.8, p less than 0.0001).
 In a separate analysis considering only cardiac death and nonfatal myocardial infarction, the exercise electrocardiography model remained a significant predictor of events (chi-square = 12.2, p less than 0.001).
 None of the radionuclide angiography variables added significantly to the prognostic power of the exercise electrocardiography model.
 Thus, in patients with a normal resting electrocardiogram who are not taking digoxin, the supine exercise electrocardiography model that predicts 3-vessel or left main CAD also predicts future cardiac events.
 Exercise radionuclide angiography does not provide any additional prognostic information in such patients.
",13
2583,"Relation of cardiac output at rest and during exercise to age in essential hypertension.
 It has been suggested that the decline of cardiac output with age is due to increased prevalence of disease, particularly occult coronary artery disease.
 Therefore, the relation of cardiac output (direct oxygen Fick method) to age was analyzed in 110 sixteen- to 64-year-old men with World Health Organization stage I or II essential hypertension at the time of the hemodynamic study, who were alive and free of cardiovascular complications 7 years later.
 At supine and seated rest, during upright bicycle exercise at 50 W and and at peak work load, cardiac output was inversely (p less than 0.01) related to age.
 These relations were independent of weight and mean intraarterial pressure.
 Stroke volume decreased with advancing age at supine rest, but not at rest and during exercise in the seated position.
 Heart rate was not affected by age in the supine position, but was slower in older patients during upright rest and at peak exercise.
 In conclusion, in patients with essential hypertension who remained free of cardiovascular complications for 7 years, cardiac output was independently and inversely related to age at various levels of activity.
 These findings suggest that occult cardiovascular disease does not explain the decline in cardiac output with age in patients with essential hypertension.
",13
2584,"Comparison of the effects of guanadrel sulfate and propranolol on blood pressure, functional capacity, serum lipoproteins and glucose in systemic hypertension.
 In a controlled, double-blind, crossover study, the effects of guanadrel sulfate and propranolol on blood pressure (BP) and selected cardiopulmonary and metabolic variables were compared in 15 physically active and moderately hypertensive subjects.
 Guanadrel sulfate reduced systolic and diastolic BP at rest by -16 and -15 mm Hg, and at maximal exercise by -33 and -13 mm Hg, respectively (p less than 0.005), without affecting submaximal oxygen consumption (VO2), maximal VO2, ventilatory threshold, forced vital capacity, forced expiratory volume in 1 second, or fatigue, as assessed by perceived exertion.
 In contrast, propranolol significantly decreased diastolic BP at rest (-16 mm Hg) and systolic BP at maximal exercise (-44 mm Hg); however, it significantly decreased submaximal VO2 (-3.9 ml.kg-1.min-1), maximal VO2 (-3.9 ml.kg-1.min-1), ventilatory threshold (-0.3 liters.min-1), minute ventilation at submaximal exercise (-7.3 liters.min-1), forced expiratory volume in 1 second (-0.27 liters), and concomitantly increased the rating of perceived exertion at maximal exercise (1.9 U).
 Guanadrel sulfate was also associated with significant decreases in mean fasting plasma glucose and total serum cholesterol, whereas propranolol resulted in an increase in serum triglycerides (p less than 0.05).
 In contrast to propranolol, guanadrel sulfate appears to decrease BP without evoking negative metabolic consequences or impairing exercise tolerance.
",13
2585,"Abnormal baroreflex control of heart rate in decompensated congestive heart failure and reversal after compensation.
 Congestive heart failure (CHF) causes impairment of baroreflex control of heart rate (HR).
 To determine if this derangement is reversible, the cardiac chronotropic control was assessed in 10 patients with class IV chronic CHF of various etiologies before and after compensation achieved by bed rest, salt restriction, diuretics and vasodilators.
 Mean time between the 2 studies was 15 +/- 3 days.
 The management was modified 3 days before the second autonomic evaluation, so as to reestablish the same diet and pharmacologic conditions of the previous study.
 Compensation led to significant reduction in symptom-based class, body weight, and pulmonary and systemic congestion.
 Mean +/- standard error of the mean HR responses (beats/min) before and after compensation were, respectively: (1) to atropine (0.04 mg/kg): 10 +/- 2 and 27 +/- 2 (p less than 0.01); (2) to handgrip (30% maximum capacity, 1 minute): 9 +/- 2 and 19 +/- 3 (p less than 0.005); (3) to headup tilt (5 minutes): 4 +/- 3 and 20 +/- 4 (p less than 0.005).
 Mean +/- standard error of the mean baroreflex sensitivity (ms/mm Hg) of RR responses to phenylephrine and amyl nitrate-induced changes in systolic pressure was, respectively, in each condition: phenylephrine, 0.9 +/- 0.2 and 8 +/- 2.3 (p less than 0.05); amyl nitrate, 0.3 +/- 0.2 and 4.1 +/- 1.1 (p less than 0.05).
 A significant correlation between improvement in HR responses to atropine and tilt and changes in body weight was obtained.
 These findings show a reversible component of impaired baroreflex control of HR in severe CHF, possibly due to its congestive effects.
",13
2586,"Doppler echocardiographic study of porcine bioprosthetic heart valves in the aortic valve position in patients without evidence of cardiac dysfunction.
 To study the natural history of the hemodynamic performance of bioprosthetic heart valves, Doppler echocardiograms were recorded in a group of clinically stable patients at 2 and 5 years after replacement of native aortic valves with bioprosthetic valves.
 Eighteen patients completed a 2-year and 26 patients a 5-year follow-up examination.
 The effective orifice areas of identical models of bioprosthetic valves (Hancock II) were determined in vitro in a left-sided heart pulse duplicator system.
 In vivo Doppler-derived effective orifice areas were compared with the in vitro measurements for the same valve size.
 At both the 2- and 5-year follow-up examinations, the Doppler-derived effective orifice area was significantly less than the in vitro area (p less than 0.0001 at each interval).
 Ten of 16 valves evaluated serially decreased greater than 0.20 cm2 in the Doppler-derived effective orifice area between studies.
 The mean decrease in effective orifice area in valves evaluated serially was 0.25 +/- 0.29 cm2 (p less than 0.005).
 The peak transaortic gradient increased from 21 +/- 6 to 27 +/- 8 mm Hg (p less than 0.01).
 The mean transaortic gradient increased from 12 +/- 4 to 15 +/- 7 mm Hg (p less than 0.05).
 It is concluded that serial Doppler echocardiographic studies demonstrate a deterioration in the hemodynamic performance of bioprosthetic valves over time in patients with no symptoms or signs of valvular dysfunction and that Doppler echocardiography may be useful for identifying subclinical bioprosthetic valvular dysfunction.
",13
2587,"Effects of the phospholipase inhibitor mepacrine on injury in ischemic and metabolically inhibited adult isolated myocytes.
 The phospholipase inhibitor mepacrine has been shown to delay cell death of metabolically inhibited cultured cardiomyocytes.
 The present study was initiated to determine if mepacrine also delays cell death and development of osmotic fragility of both metabolically inhibited and ischemic adult rat cardiomyocytes.
 Isolated myocyte suspensions were incubated with 3 mmol/l (millimolar) iodoacetic acid and 6 mmol/l amytal (inhibited) or were pelleted into a slurry and layered with oil (ischemic) in the presence and absence of 10 or 50 mumol/l (micromolar) mepacrine.
 Rates of contracture, cell viability as determined by trypan blue permeability, cell viability after osmotic swelling in 170 mOsm media (osmotic fragility), and cell morphology were monitored.
 Mepacrine had no effects on rates of contracture, but was found to significantly delay cell death during isotonic incubations of both metabolically inhibited and ischemic cells.
 In contrast, mepacrine had no effect on the development of osmotic fragility.
 Incubation of metabolically inhibited myocytes in calcium-free media did not delay contracture or cell injury, but did attenuate the protective effects of mepacrine.
 This study confirms previous reports that mepacrine protects cells from injury, extends the observations of protection to ischemic isolated adult myocytes, but shows that development of osmotic fragility is not inhibited by mepacrine.
",13
2588,"Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit.
 Lipoprotein-associated coagulation inhibitor produces feed-back inhibition of tissue factor (tissue thromboplastin)-induced coagulation in the presence of factor Xa Recombinant lipoprotein-associated coagulation inhibitor (rLACI) was tested for its ability to modify thromboplastin-induced intravascular coagulation in a rabbit model that allows monitoring of iodine-125 fibrin accumulation/disappearance in the lung and sampling of blood for the measurement of coagulation parameters.
 Infusion of thromboplastin into the rabbit caused a rapid increase of radioactivity over the lungs, possibly due to the accumulation of 125I fibrin in the lungs, followed by a rapid decline of radioactivity, suggestive of removal of fibrin from the lungs.
 Thromboplastin also caused a rapid decrease of systemic fibrinogen that was accompanied by a lengthening of the activated partial thromboplastin time and prothrombin time.
 The effect of coinfusion of rLACI with thromboplastin or bolus injection of rLACI before thromboplastin infusion was studied.
 At a high dose of rLACI (800 micrograms/kg body weight), the thromboplastin-induced radioactivity increase in the lungs and the systemic fibrinogen decrease were completely suppressed.
 The activated partial thromboplastin time and prothrombin time of the plasma samples lengthened, possibly due to the presence of thromboplastin in circulation.
 The thromboplastin-induced radioactivity increase over the lungs was not completely suppressed by lower doses of rLACI (135 to 270 micrograms/kg body weight), but these doses of rLACI prevented systemic fibrinogen decrease.
 At a bolus dose of 23 micrograms/kg body weight, rLACI provided 50% protection of the fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in rabbits treated with thromboplastin alone).
 These results show that rLACI is effective in the inhibition of thromboplastin-induced coagulation in vivo.
",14
2589,"Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia.
 Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA).
 The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin, Candida albicans, and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied.
 Samples were collected before (baseline) and twice during the rhGM-CSF administration.
 The absolute number of circulating lymphocytes remained relatively constant during the first period, but experienced a significant increase (P less than .001) during the second period.
 The increase was most prominent in the B cells (P less than .001), but the T cells (P less than .016) also increased.
 Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17), HLA-DR, and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation.
 The NK cell activity was suppressed (P less than .008) throughout the treatment.
 However, proliferative responses to phytohemagglutinin, Candida antigen, and tetanus toxoid were unaffected.
 Although the mechanism is not yet defined, GM-CSF does induce activation and increase in absolute lymphoid cell number, especially B cells, together with a decrease in NK cytotoxicity.
 The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established.
",14
2590,"Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia.
 We studied 10 cutaneous telangiectatic lesions of hereditary hemorrhagic telangiectasia (HHT), ranging in size from pinpoint to 2 mm, by light and electron microscopy.
 Four representative lesions were reconstructed by computer from serial 1- or 2-mm plastic embedded sections.
 The earliest clinically detectable lesion of HHT is a focal dilatation of postcapillary venules, which continue to enlarge and eventually connect with dilated arterioles through capillaries.
 As the vascular lesion increases in size, the capillary segments disappear and a direct arterio-venous communication is formed.
 This entire sequence of morphologic events is associated with a perivascular mononuclear cell infiltrate in which the majority of cells are lymphocytes and the minority are monocytes/macrophages by ultrastructure.
 Comparison of these findings with the telangiectatic mats of scleroderma and cherry angiomas revealed that the former, previously shown to be composed of dilated postcapillary venules, are also associated with perivascular infiltrates, but the latter, which are produced by capillary loop aneurysms, are not.
",14
2591,"Isolation and quantitation of human erythrocyte deformability classes.
 A new technique is described that fractionates erythrocytes according to their deformability.
 The method is a modification of the method of Beutler et al.
 (J Lab Clin Med 1976;88:328-33), in which small cellulose columns are used to remove white cells from blood samples.
 We find that when the length-to-width ratio of the columns is increased, the mixed cellulose bed also fractionates the red cells.
 Measurement of mean cell volume, mean corpuscular hemoglobin concentration, hemoglobin level, deformability index, and cell density showed that deformability is the physical property of the erythrocyte that forms the basis for the fractionation.
 This is a separation modality that complements the numerous density gradient techniques for red cells.
 The following experimental results can be obtained by using the technique: (1) The number of cells with a defined degree of rigidity can be quantitated in an erythrocyte population.
 (2) Large numbers of cells that differ with respect to their deformability can be isolated.
 (3) Application of the method to sickle cells has quantitated the remarkable heterogeneity of these cells with regard to their deformability.
",14
2592,"Immune activation is associated with phenylhydrazine-induced anemia in the rat.
 Long-term phenylhydrazine (PHZ) treatment caused pronounced anemia and a concomitant increase in the numbers of circulating leukocytes in Long-Evans rats.
 The leukocytosis was caused mainly by an elevation in mononuclear cells, most notably in the lymphocyte population.
 PHZ has been reported to cause the direct lysis of erythrocytes by nonimmune mechanisms.
 However, recent reports indicate that PHZ can cross-link red cell band 3 protein (senescent antigen), resulting in the binding of autologous immunoglobulin G (IgG).
 Recognition of this complex by macrophage Fc receptor mechanisms triggers rapid erythrophagocytosis-in the spleen and possibly the liver as well.
 In our study, analysis of the blood, bone marrow, and spleen cells of long-term (1 to 6 weeks) PHZ-treated rats was performed by using flow cytometry.
 Total serum IgG levels were determined by radial immunodiffusion, and antibodies reactive with red cells that were sensitized to PHZ either in vivo or in vitro were titered by using the indirect Coombs' method.
 Serum prostaglandin E2 titers also were determined at different time intervals after PHZ administration.
 The results indicate that PHZ induces an increase in circulating antibody and prostaglandin E2 titers that correlates with the onset of anemia and that the serum of PHZ-treated rats can induce anemia in normal recipients after passive transfer.
 Cytofluorographic studies revealed a marked increase in the B-cell population of the peripheral blood and spleen and an altered ratio T-helper to T-suppressor cells at certain time intervals after PHZ injection.
 The results indicate that in addition to inducing senescence-like alterations in erythrocyte membrane proteins, PHZ stimulates the production of the autologous IgG that recognizes these sites and promotes lymphoid blastogenesis, most notably in the B-cell lineage.
",14
2593,"Benefits and risks of anemia correction with recombinant human erythropoietin in children maintained by hemodialysis.
 Ten children with renal failure (age range 2 years 6 months to 18 years 9 months; median 11 years 10 months), maintained by long-term hemodialysis, had successful correction of their anemia after intravenous administration of recombinant human erythropoietin in a dosage escalating every 2 weeks (75 to 150 to 300 to 450 IU/kg/wk).
 Mean hemoglobin concentration increased from 6.4 +/- 0.9 to 11.5 +/- 1.0 gm/dl.
 Blood cell counts used to evaluate the correction of anemia were done after dialysis; this was especially important for children less compliant with water restriction.
 The higher hemoglobin concentration resulted in improvement of the quality of life, a greater tolerance for physical effort (exercise tolerance doubled and the ventilatory anaerobic threshold increased significantly), correction of some subclinical central nervous system abnormalities detected by evoked potentials testing, and reduction of bleeding time.
 Few side effects were noted; severe hypertension developed in one patient when postdialysis hematocrit was only 28%, and there were two episodes of hypertransaminasemia with no other evidence of liver dysfunction.
 We conclude that in children with renal failure the use of recombinant human erythropoietin to correct anemia is safe and strongly advisable, because of the resolution of many of the symptoms correlated with anemia.
",14
2594,"Rapid detection and prenatal diagnosis of beta-thalassaemia: studies in Indian and Cypriot populations in the UK.
 The application of the amplification refractory mutation system (ARMS) to the detection of individual beta-thalassaemia mutations in heterozygous parents and ""at risk"" fetuses has been assessed in Indian and Cypriot immigrant populations in the UK.
 100 first trimester prenatal diagnoses have been done, entailing the detection of 17 different mutations.
 The method, which allows the determination of the mutations in both parental and fetal DNA on the same day, should have wide application to the carrier detection and prenatal diagnosis of monogenic diseases with heterogeneous molecular defects.
",14
2595,"The twin-twin transfusion syndrome.
 Twin-twin transfusion syndrome is a complication of monozygotic-monochorionic twinning with serious perinatal implications.
 An extensive literature review revealed that our current understanding of the anatomy and pathogenesis of the syndrome has not changed over the last 3 decades.
 However, modern diagnostic modalities, such as sonography and Doppler studies, allow antenatal diagnosis and therefore may change the current definition of the syndrome.
 Based on these data, a new composite definition of the syndrome is suggested.
 This definition includes the following criteria: 1) sonographic signs (inter-twin differences in abdominal circumference greater than 18 mm, polyhydramnios-oligohydramnios, and signs of monozygosity), 2) Doppler velocimetry of the umbilical arteries (inter-twin difference in systolic/diastolic ratios above 0.4), 3) demonstration of a transplacental vascular shunt, 4) inter-twin birth weight difference of 15% or more, and 5) inter-twin hemoglobin difference of 5 g/dL or more.
 In addition, prenatal diagnosis may help in the management of this complication, and it seems that intrauterine treatment of the placental vascular anomalies may be more effective than other antenatal therapeutic options.
",14
2596,"Iron deficiency in the young athlete.
 Although overt anemia is uncommon, depletion of body iron stores is common among adolescent female athletes.
 Poor dietary iron intake, menstruation, and increased iron losses associated with physical training all appear to be important factors.
 Whether nonanemic iron deficiency can impair exercise performance is uncertain.
 Nonetheless, athletes with low ferritin levels are at risk for impaired erythropoiesis and should receive therapeutic iron supplementation.
",14
2597,"Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding alpha-mannosidase II.
 Congenital dyserythropoietic anemia type II, or hereditary erythroblastic multinuclearity with a positive acidified-serum-lysis test (HEMPAS), is a genetic anemia in humans inherited by an autosomally recessive mode.
 The enzyme defect in most HEMPAS patients has previously been proposed as a lowered activity of N-acetylglucosaminyltransferase II, resulting in a lack of polylactosamine on proteins and leading to the accumulation of polylactosaminyl lipids.
 A recent HEMPAS case, G.C., has now been analyzed by cell-surface labeling, fast-atom-bombardment mass spectrometry of glycopeptides, and activity assay of glycosylation enzymes.
 Significantly decreased glycosylation of polylactosaminoglycan proteins and incompletely processed asparagine-linked oligosaccharides were detected in the erythrocyte membranes of G.C.
 In contrast to the earlier studied HEMPAS cases, G.C.
 cells are normal in N-acetylglucosaminyltransferase II activity but are low in alpha-mannosidase II (alpha-ManII) activity.
 Northern (RNA) analysis of poly(A)+ mRNA from normal, G.C., and other unrelated HEMPAS cells all showed double bands at the 7.6-kilobase position, detected by an alpha-ManII cDNA probe, but expression of these bands in G.C.
 cells was substantially reduced (less than 10% of normal).
 In Southern analysis of G.C.
 and normal genomic DNA, the restriction fragment patterns detected by the alpha-ManII cDNA probe were indistinguishable.
 These results suggest that G.C.
 cells contain a mutation in alpha-ManII-encoding gene that results in inefficient expression of alpha-ManII mRNA, either through reduced transcription or message instability.
 This report demonstrates that HEMPAS is caused by a defective gene encoding an enzyme necessary for the synthesis of asparagine-linked oligosaccharides.
",14
2598,"Haemopoietic growth factors.
 The availability of recombinant haemopoietic growth factors has permitted more precise in vitro experiments and human in vivo studies to be performed.
 In general, the results have been in accord with expectations from previous in vitro studies.
 The clinical exploitation of the haemopoietic growth factors offers great promise but careful studies are required to define their value.
 The effects of some growth factors are multiple and complex, and it cannot be assumed that improvements in blood cell counts are per se beneficial to the patient under all circumstances.
 Randomized controlled trials with clinical end-points are now essential.
 In the situation of chemotherapy-induced neutropenia, large studies would be required to show an improvement in mortality although lesser morbidity would be easier to demonstrate.
 In the field of cancer therapy the major benefit of the haemopoietic growth factors will be if they permit dosage escalation and there is a consequent improvement in response rate and long-term survival.
 This will require careful patient selection and large, probably multicentre, trials.
 It is also likely that such studies will be limited by the development of severe thrombocytopenia and an effective means to ameliorate this (perhaps the elusive thrombopoietin) will be required.
 The possibility of using haemopoietic growth factors as an adjunct to the treatment of severe infections is enticing, but designing a trial to evaluate this possibility is fraught with difficulties.
 Finally, it must be noted that all the studies reported to date use single factors.
 This is just the beginning and the use of other factors and synergistic combinations may give greater efficacy without increased toxicity.
",14
2599,"Sarcoidosis: abdominal manifestations at CT.
 There are few data in the literature on the abdominal manifestations of sarcoidosis at computed tomography (CT).
 To determine whether differences in nodal distribution and appearance can be reliably used to distinguish between sarcoidosis and non-Hodgkin lymphoma (NHL), the authors retrospectively reviewed the abdominal and pelvic CT scans of 16 patients with biopsy-proved sarcoidosis and 20 patients with biopsy-proved NHL.
 Eleven of the 16 patients with sarcoidosis had abdominal and/or pelvic lymphadenopathy, which was common at all nodal sites except for the retrocrural and pelvic locations.
 There was a statistically significant lower frequency of retrocrual adenopathy in sarcoidosis than in NHL.
 Mean nodal size was significantly greater in NHL.
 Nodes tended to be confluent in NHL and discrete in sarcoidosis.
 Hepatomegaly was seen in six of the 16 patients (38%) with sarcoidosis and splenomegaly was present in nine of 15 (60%).
 CT depicted hepatic lesions in only three of eight patients (38%) with biopsy-proved hepatic involvement.
 Splenic lesions were seen at CT in five of the 15 patients (33%).
 The authors believe that the overlap in nodal appearance and distribution poses a limitation for use of these criteria in accurate disease characterization.
",14
2600,"Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity.
 Increased extracellular concentrations of uridine (Urd) have been reported to reduce, in vitro, azidothymidine (AZT)-induced inhibition of human granulocyte-macrophage progenitor cells without impairment of its antihuman immunodeficiency virus (HIV) activity.
 Because of the clinical toxicities associated with chronic Urd administration, the ability of benzylacyclouridine (BAU) to effect, in vivo, AZT-induced anemia and leukopenia was assessed.
 This agent inhibits Urd catabolism and, in vivo, increases the plasma concentration of Urd in a dose-dependent manner, without Urd-related toxicity.
 In mice rendered anemic and leukopenic by the administration of AZT for 28 days in drinking water (1.5 mg/mL), the continued administration of AZT plus daily BAU (300 mg/kg, orally) partially reversed AZT-induced anemia and leukopenia (P less than .05), increased peripheral reticulocytes (to 4.9%, P less than .01), increased cellularity in the marrow, and improved megaloblastosis.
 When coadministered with AZT from the onset of drug administration, BAU reduced AZT-induced marrow toxicity.
 In vitro, at a concentration of 100 mumol/L, BAU possesses minimal anti-HIV activity and has no effect on the ability of AZT to reverse the HIV-induced cytopathic effect in MT4 cells.
 The clinical and biochemical implications of these findings are discussed.
",14
2601,"Isolation and characterization of an acquired antithrombin antibody.
 A 68-year-old man, following mitral valve replacement, presented with a low-grade chronic consumptive coagulopathy.
 Laboratory analysis showed mild fibrinolysis, minimal effect of coumadin therapy, and a prolonged thrombin time (greater than 150 seconds using bovine IIa).
 When purified human IIa was used the thrombin time normalized to within 17 seconds of controls, suggesting a possible inhibitor of bovine IIa.
 An anti-IIa antibody was isolated by protein A-Sepharose (Sigma, St Louis, MO) chromatography followed by affinity chromatography using a bovine IIa-Sepharose column.
 The effects of this purified anti-IIa antibody on both bovine and human IIa procoagulant and anticoagulant functions were studied.
 The isolated immunoglobulin G (IgG) was observed to inhibit bovine IIa in all assays tested.
 This IgG was also able to slightly prolong fibrinogen clotting by human IIa.
 Using an enzyme-linked immunosorbent assay it was observed that the IgG bound to bovine IIa, bovine II, human IIa, but not to human II.
 Further, binding was detectable at approximately 50-fold lower concentrations to bovine IIa (1 nmol/L IgG concentration) than to human IIa (50 nmol/L IgG concentration).
 The effect of the antibody on the reaction between IIa and AT III/heparin was investigated.
 Human IIa was found to be protected from AT III/heparin neutralization in the presence of this antibody.
 These results suggest that this patient developed an antibody that strongly binds to and inhibits the bovine IIa in all assays tested.
 However, the antibody only significantly affects human IIa neutralization by AT III/heparin, and has little effect on the human IIa procoagulant activity.
 These data suggest that the decreased effect of AT III/heparin on this patient's IIa may have been a contributing factor in his coagulopathy.
 The exact cause of this antibody development is unclear, but the role of bovine topical thrombin used during cardiac valve replacement surgery is suspect.
",14
2602,"Fibrinogen Baltimore I: polymerization defect associated with a gamma 292Gly----Val (GGC----GTC) mutation.
 Fibrinogen Baltimore I is one of the very first congenital abnormal fibrinogens reported over several decades ago; however, the molecular defect of this dysfibrinogen has eluded identification.
 In fact, several reports misidentified the functional defect of Baltimore I, which has impaired fibrin monomer polymerization.
 Reversed-phase high-performance liquid chromatography analysis of lysyl endopeptidase digest of the purified Baltimore I gamma-chain showed an abnormal peptide not found in the co-existing normal gamma-chain of this heterozygote.
 Amino acid sequencing of this peptide indicated that gamma-chain Gly292 is replaced by valine.
 This observation was confirmed, and the genetic defect was determined by direct nucleotide sequencing of a polymerase chain reaction product containing codon gamma 292, which is mutated: GGC----GTC.
 The molecular defect of Fibrinogen Baltimore I lies in a region of the gamma-chain required for fibrin polymerization, suggesting that the integrity of gamma Gly292 is critical for fibrin assembly.
",14
2603,"Sra, a private platelet antigen on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia.
 A new platelet alloantigen, Sra, is described that was defined by an alloantibody detected in the serum of a healthy mother who delivered a child with typical clinical signs of neonatal alloimmune thrombocytopenia (NAIT).
 The antibody reacted strongly with the child's and father's platelets, but not with platelets of the mother or with those of a highly selected panel representing all known platelet alloantigens.
 Platelets from 300 unselected normal blood donors also tested negative, suggesting a phenotype frequency in the German population of less than 0.01.
 The antigen was present in 9 of 20 members within three generations of the paternal family, indicating autosomal codominant inheritance.
 By immunochemical analysis using a glycoprotein (GP)-specific immunoassay and a variety of GP IIb/IIIa-specific monoclonal antibodies for antigen immobilization (MAIPA assay), radioimmunoassay, and Western blotting, we could show that the antigen resides on a 68-Kd proteolytic fragment of GP IIIa.
 Immunogenetic data and gene dosage studies revealed that the Sra antigen is not related to any of the other known platelet alloantigens.
 In accordance with established criteria, the Sra antigen represents the first example of a ""private"" platelet alloantigen that bears significance in rare instances of NAIT.
",14
2604,"Human neutrophils release the Leu-8 lymph node homing receptor during cell activation.
 The Leu-8 molecule, the human homologue of the murine MEL-14 peripheral lymph node homing receptor, is expressed on neutrophils in both species and may be important in localization of cells to sites of inflammation.
 Most circulating human neutrophils express the Leu-8 molecule, and activation of neutrophils with phorbol myristate acetate causes a rapid decline in Leu-8 membrane fluorescence staining within 15 minutes.
 Northern blot analysis of total cellular RNA from neutrophils demonstrated two species of Leu-8 messenger RNA, a major one of 2.4 kb and a minor one of 1.9 kb.
 Because two different Leu-8 cDNA clones were obtained from human lymphocytes that were predicted to encode both transmembrane and phosphatidylinositol (PI)-anchored forms of the molecule, experiments were conducted to determine whether Leu-8 is anchored to neutrophils by a PI-anchor.
 There was a slight decrease in expression of Leu-8 on neutrophils when they were treated with PI-specific phospholipase C (PI-PLC).
 However, Leu-8 was abundant on neutrophils obtained from a patient with paroxysmal nocturnal hemoglobinuria.
 To determine the fate of the Leu-8 molecule during cell activation, neutrophils were labeled with 125I-anti-Leu-8.
 During activation antibody was rapidly lost from the cell surface and was not internalized, suggesting that Leu-8 is released from the cell membrane during cell activation.
 When cell extracts of neutrophils were compared with extracts of lymphoid cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting, the Leu-8 species expressed on neutrophils had a significantly higher and more variable relative mobility (70 to 120 Kd for neutrophils v 70 Kd for Jurkat T cells).
 In addition, Leu-8 molecules were detected in the supernatants of activated neutrophils.
 These results indicate that human neutrophils express a high-molecular-weight form of the Leu-8 molecule that has a conventional transmembrane anchor and is rapidly released from the membrane during activation.
 The loss of the Leu-8 membrane glycoprotein during activation may be a mechanism for rapid alteration of neutrophil adhesion characteristics.
",14
2605,"Molecular basis of spectrin and ankyrin deficiencies in severe hereditary spherocytosis: evidence implicating a primary defect of ankyrin.
 While varying degrees of spectrin deficiency have been found in the majority of patients with hereditary spherocytosis (HS), a combined severe deficiency of both spectrin and the spectrin-binding protein, ankyrin, has been reported only in two patients with severe HS.
 To elucidate the molecular basis of these protein deficiencies, we have studied the synthesis, assembly, and the mRNA levels of spectrin and ankyrin in peripheral blood reticulocytes in one of the previously reported probands.
 Pulse-labeling studies showed that in HS reticulocytes, the synthesis of alpha-spectrin was comparable with control reticulocytes while that of beta-spectrin was increased about fourfold, presumably reflecting increased erythropoietic drive.
 On the HS reticulocyte membrane, the amount of newly assembled spectrin was reduced to about half of the control values, presumably reflecting a decrease in the synthesis of the spectrin binding protein, ankyrin: the ankyrin synthesis was nearly absent in the cytosol and the amounts of membrane-associated ankyrin were reduced to about half of the normal values.
 The changes in the amounts of spectrin and ankyrin mRNAs quantitated by slot blot and Northern blot analyses were comparable with changes in the synthesis of these proteins: The alpha spectrin mRNA was within a control range and the beta-spectrin mRNA was slightly increased, while the amounts of ankyrin mRNA were reduced to about 50% of control values.
 We conclude that the primary defect underlying the combined spectrin and ankyrin deficiency is a deficiency of ankyrin mRNA leading to a reduced synthesis of ankyrin which, in turn, underlies the decreased assembly of spectrin on the membrane.
",14
2606,"Variation in hemoglobin F production among normal and sickle cell adults is not related to nucleotide substitutions in the gamma promoter regions.
 Single nucleotide substitutions in the promoter regions of the A gamma- and G gamma-globin genes have been associated with increased fetal hemoglobin (HbF) production.
 We wished to determine whether these or other unrecognized substitutions in the gamma promoter regions are responsible for the 20-fold variation in HbF production in sickle cell patients or normal adults.
 From a random sampling of 250 sickle cell (SS) patients and 125 normal adults, 17 individuals representing the highest and lowest HbF producers were selected for study.
 All three common restriction fragment length polymorphism beta-globin region haplotypes (Benin, Central African Republic, and Senegal) were found in both the highest and lowest HbF producers with SS disease.
 Using the polymerase chain reaction amplification and direct sequencing of the amplified DNA product, we examined the promoter regions of both the A gamma and G gamma genes from -350 bp to +50 bp of the CAP site.
 No mutations were found in either gamma gene promoter region.
 We conclude that nucleotide substitutions in the promoter regions (-350 to +50 bp) of both gamma genes are not responsible for the marked variation in HbF production among SS or normal individuals.
",14
2607,"Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel.
 Glanzmann thrombasthenia is a rare, inherited disorder of the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) complex.
 We previously identified two distinct populations with this disorder in Israel, Iraqi-Jews and Arabs.
 The groups are indistinguishable in hemorrhagic symptoms and platelet GP IIB/IIIa receptor deficiency, but they differ in their platelet immunodetectable GP IIIa (beta 3), with the Iraqi-Jewish population expressing no detectable GP IIIa and the Arab population expressing small amounts.
 We have now examined the platelets of these two populations as well as normal platelets for the alpha v beta 3 vitronectin receptor.
 Normal platelets contained between approximately 50 to 100 alpha v beta 3 vitronectin receptors as judged by the binding of antibodies to both alpha v (LM142) and the intact alpha v beta 3 vitronectin receptor complex (LM609).
 In addition, normal platelets bound to immobilized vitronectin in the presence of 1 mmol/LMnCl2; the adhesion was mediated predominantly through GP IIb/IIIa, but with a distinct contribution by the alpha v beta 3 vitronectin receptor, as determined by monoclonal antibody inhibition studies.
 Iraqi-Jewish patients' platelets had a profound decrease in immunodetectable alpha v beta 3 vitronectin receptors, and their platelets did not adhere well to vitronectin.
 In contrast, Arab patients' platelets had normal or increased numbers of platelet alpha v beta 3 vitronectin receptors, and these receptors functioned well in the vitronectin adhesion assay, taking over much of the adhesion mediated by GP IIb/IIIa in normal platelets.
 These studies define further the heterogeneity of the molecular basis of Glanzmann thrombasthenia; they also have more widespread implications for understanding the synthesis and function of the beta 3 family of integrin receptors.
",14
2608,"A mathematical model of the volume, pH, and ion content regulation in reticulocytes. Application to the pathophysiology of sickle cell dehydration.
 We developed a mathematical model of the reticulocyte, seeking to explain how a cell with similar volume but much higher ionic traffic than the mature red cell (RBC) regulates its volume, pH, and ion content in physiological and abnormal conditions.
 Analysis of the fluxbalance required by reticulocytes to conserve volume and composition predicted the existence of previously unsuspected Na(+)-dependent Cl- entry mechanisms.
 Unlike mature RBCs, reticulocytes did not tend to return to their original state after brief perturbations.
 The model predicted hysteresis and drift in cell pH, volume, and ion contents after transient alterations in membrane permeability or medium composition; irreversible cell dehydration could thus occur by brief K+ permeabilization, transient medium acidification, or the replacement of external Na+ with an impermeant cation.
 Both the hysteresis and drift after perturbations were shown to depend on the pHi dependence of the K:Cl cotransport, a major reticulocyte transporter.
 This behavior suggested a novel mechanism for the generation of irreversibly sickled cells directly from reticulocytes, rather than in a stepwise, progressive manner from discocytes.
 Experimental tests of the model's predictions and the hypothesis are described in the following paper.
",14
2609,"Evidence for a direct reticulocyte origin of dense red cells in sickle cell anemia.
 To explore our hypothesis of a direct reticulocyte origin of irreversibly sickled cells (ISCs), we fractionated light, reticulocyte-rich, and discocyte-rich sickle anemia red cells on Stractan gradients, and examined the effects of deoxygenation-induced sickling, external Ca2+, acidification, and replacing external Na+ by impermeant N-methyl-D-glucamine (NMG+).
 Sickling permeabilized light reticulocyte-rich cells to cations (Na+, K+, and Ca2+) more than discocytes; without external Ca2+, Na+ influx matched K+ efflux, with stable cell volume; with Ca2+, many light, low hemoglobin (Hb) F reticulocytes dehydrated rapidly (preventable by quinine, a Ca2(+)-dependent K+ channel inhibitor).
 Acidification of oxygenated discocytes (high mean Hb F) and reticulocyte-rich fractions yielded denser, reticulocyte-enriched cells with lower Hb F (as in light reticulocyte or dense ISC-rich fractions).
 Light cells shrank when NMG+ replaced Na+, supporting predictions of a Na(+)-dependent volume control system.
 Demonstration of sickling-induced, Ca2(+)-dependent dehydration of Hb F-free reticulocytes, and conservation of acid-stimulated K:Cl cotransport among low Hb F, reticulocyte-enriched cells in discocyte fractions support the hypothesis.
 Ancillary new findings included heparin stimulation of sickling-induced Na+ and K+ permeabilizations, and Ca2+ inhibition of the Na+ leak.
",14
2610,"Neutrophil nicotinamide adenine dinucleotide phosphate oxidase assembly. Translocation of p47-phox and p67-phox requires interaction between p47-phox and cytochrome b558.
 Two of the cytosolic NADPH oxidase components, p47-phox and p67-phox, translocate to the plasma membrane in normal neutrophils stimulated with phorbol myristate acetate (PMA).
 We have now studied the translocation process in neutrophils of patients with chronic granulomatous disease (CGD), an inherited syndrome in which the oxidase system fails to produce superoxide due to lesions affecting any one of its four known components: the gp91-phox and p22-phox subunits of cytochrome b558 (the membrane-bound terminal electron transporter of the oxidase), p47-phox, and p67-phox.
 In contrast to normal cells, neither p47-phox nor p67-phox translocated to the membrane in PMA-stimulated CGD neutrophils which lack cytochrome b558.
 In one patient with a rare X-linked form of CGD caused by a Pro----His substitution in gp91-phox, but whose neutrophils have normal levels of this mutant cytochrome b558, translocation was normal.
 In two patients with p47-phox deficiency, p67-phox failed to translocate, whereas p47-phox was detected in the particulate fraction of PMA-stimulated neutrophils from two patients deficient in p67-phox.
 Our data suggest that cytochrome b558 or a closely linked factor provides an essential membrane docking site for the cytosolic oxidase components and that it is p47-phox that mediates the assembly of these components on the membrane.
",14
2611,"Preferential expression of human Fc gamma RIIIPMN (CD16) in paroxysmal nocturnal hemoglobinuria. Discordant expression of glycosyl phosphatidylinositol-linked proteins.
 The isoform of Fc gamma RIII (CD16) expressed on PMN has a GPI membrane anchor, and in paroxysmal nocturnal hemoglobinuria (PNH) there is a deficiency in Fc gamma RIII expression on PMN.
 Contrary to expectation, however, CD16 expression is preserved (albeit at reduced levels) in all affected PNH PMN that completely lack the GPI-anchored proteins DAF (CD55) and CD59.
 Fc gamma RIII negative PMN are not observed in any of the six PNH patients examined in this study.
 Analysis of the molecular weight of both glycosylated and deglycosylated Fc gamma RIII from PMN with reduced Fc gamma RIII expression indicates no variations in size relative to normal donor Fc gamma RIIIPMN.
 Indeed, the Fc gamma RIII expressed at intermediate levels is phosphatidylinositol-specific phospholipase C (PI-PLC)-sensitive.
 Thus, there is no evidence suggestive of expression of a transmembrane isoform and all data indicate that Fc gamma RIIIPMN on affected cells in PNH is a GPI-linked isoform.
 With Fc gamma RIIIPMN expression preserved at reduced levels on affected cells in PNH, PMN from PNH patients retain the capacity to internalize the Fc gamma RIIIPMN-specific probe E-ConA (at reduced levels) as well as IgG-opsonized erythrocytes.
 Reduced expression of GPI-anchored molecules on PNH PMN is not restricted to Fc gamma RIIIPMN since intermediate levels of CD59 were observed in the PNH PMN that were decay-accelerating factor (DAF)-negative and Fc gamma RIIIPMN intermediate.
 In addition, discordant expression of GPI-linked molecules in individual cells is not restricted to PMN since DAF+/CD14- monocytes were observed in one PNH patient.
 These data suggest that, when analyzed on an individual cell level, the GPI anchor defect in PNH is not absolute and must involve either a hierarchy of access of different protein molecules to available GPI anchors, distinct anchor biochemistries for the different proteins, or differential regulation of protein-anchor assembly.
",14
2612,"Erythroid colony growth from peripheral blood and bone marrow in polycythaemia.
 Erythroid colony growth in the presence and absence of erythropoietin was compared in 23 patients with primary proliferative polycythaemia (PPP), nine with idiopathic erythrocytosis, 10 with secondary polycythaemia, 15 with pseudopolycythaemia and in 76 normal subjects.
 Erythroid colonies growing without erythropoietin stimulation (endogenous erythroid colonies) from peripheral blood (BFU-E) were found in 20 of 22 patients with PPP and in two of seven with idiopathic erythrocytosis.
 None was found in secondary polycythaemia, pseudopolycythaemia, or in normal subjects.
 Small numbers of endogenous colony forming units-erythroid (CFU-E) (though not BFU-E) were cultured from the bone marrow of three of 24 normal subjects, suggesting that peripheral blood cultures provide a more specific indicator of clonal erythropoiesis.
 Peripheral blood endogenous erythroid colony growth is an effective and convenient means of distinguishing patients with clonal erythrocytosis and may be of particular value when iron deficiency obscures the diagnosis of PPP on conventional criteria.
",14
2613,"Fetal hemoglobin, sickling, and sickle cell disease.
 Increased numbers of F cells and large amounts of Hb F/F cell appear to produce clinical benefit in rare variants of sickle cell disease and probably in more commonly encountered patients.
 Fetal hemoglobin interferes with polymerization of Hb S in vitro, but laboratory studies carried out with homogeneous hemoglobin solutions are inadequate models of events in vivo, because RBCs are heterogeneous in their MCHC and Hb F content.
 Studies of hemoglobin switching in sheep, in tissue culture, and then in baboons led to use of 5-azacytidine for induction of increased Hb F synthesis in SS patients.
 Drug trials were successful but the theory that led to them was not.
 An alternate theory, not without flaws, led to the use of hydroxyurea.
 Chronic administration of the drug can lead to very impressive increases in Hb F synthesis and apparent clinical benefit.
 It is not clear that such clinical benefit is real rather than a placebo effect.
 Nor is it entirely clear that all of the effect of hydroxyurea can be related to increased production of F cells and increased F/F cell.
 Controlled clinical trials and studies of the properties of RBCs from treated patients may answer those questions.
 It is also likely that they will not only raise still other questions but probably show that our current understanding of the biology and treatment of sickle cell disease is far from complete.
",14
2614,"Erythrocyte membrane protein deficiencies in paroxysmal nocturnal hemoglobinuria.
 Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder characterized by intermittent hemolytic anemia.
 Membrane abnormalities of blood cells from patients with PNH are the reason for the unusual sensitivity to lysis by autologous plasma complement.
 A patient with typical clinical disease consistent with PNH is described together with a few strategies and pitfalls for treatment.
 Commonly used in vitro assays are discussed that document the complement-mediated lysis of aberrant PNH erythrocytes.
 Membrane-associated proteins that are abnormal in PNH cells, the characteristics of these proteins, and their mechanism(s) of action are described; these include the decay accelerating factor that inhibits the C3/C5 convertases of both complement pathways on cell surfaces, the C8 binding protein that modulates a step in terminal complement lysis, and other proteins that regulate complement-mediated lysis at early or late steps of the complement cascade.
",14
2615,"Chloramphenicol toxicity: 25 years of research.
 Significant progress has been made in recent years in the understanding of the pathogenesis of the two types of hematologic toxicity from chloramphenicol.
 The common, dose-dependent, reversible bone marrow suppression from chloramphenicol is a consequence of mitochondrial injury.
 The greater erythroid susceptibility to chloramphenicol appears to be a function of the endogenous mitochondrial amino acid pools.
 The pathogenesis of aplastic anemia from chloramphenicol treatment remains uncertain.
 A large body of indirect evidence favors a complex mechanism involving metabolic transformation of the p-NO2 group of chloramphenicol by the predisposed subject, leading to the production of a toxic intermediate causing stem cell damage.
 A concept is presented wherein metabolites of chloramphenicol generated by intestinal bacteria undergo further metabolic transformation in the bone marrow with in situ production of toxic intermediate.
 This concept of the marrow being both the metabolic site for the offending agent as well as the target for its toxic metabolites will likely apply to other potential myelotoxins.
",14
2616,"Danazol.
 Danazol is a synthetic attenuated androgen that can interfere with normal interactions between the pituitary-hypothalamic axis and the gonads.
 These effects are mediated by complex mechanisms, including those in which danazol can compete with natural steroids in binding to androgen receptors or to sex hormone-binding globulin, possibly displacing natural steroids from this protein, and in binding to reactive sites of enzymes required for synthesis of natural steroids, thereby depressing synthesis.
 Because of danazol's impairment of the pituitary-hypothalamic interactions with gonads, it is an effective therapeutic agent for treatment of endometriosis and cystic disease of the breast.
 It is effective in the treatment of hereditary angioneurotic edema, but the mechanism of this therapeutic success is unclear.
 Danazol has been used, without universal success, in the treatment of other gynecologic and certain hematologic disorders.
",14
2617,"Nitrogen metabolism in sickle cell anemia: free amino acids in plasma and urine.
 Twenty-four hour urinary levels and fasting plasma concentrations of free amino acids (AA) were evaluated in adult sickle cell anemia (HbSS) and age-matched HbAA subjects with comparable daily energy (E) and protein (N) intake.
 HbSS elicited significant reduction in the sum of plasma indispensable (EAA) with no change in the dispensable (NAA) amino acids, resulting in a prominent (P less than 0.01) reduction in the EAA/NAA ratio from 71% to 55%.
 Arg (-38%), Leu (-32%), Val (-28%) and His (-32%) were among the AA most severely affected.
 Despite a twofold increase in 24-hour urine volume in HbSS compared with HbAA subjects, total urinary losses of EAA and NAA were markedly reduced in the former group, with Arg (-53%) and Gly (-56%) levels most prominently affected.
 Compared with HbAA controls, HbSS subjects showed a three-fourfold increase in 24-hour urinary orotate excretion that had no relationship to amount of N intake.
 The results indicated that adult subjects with HbSS, who consumed adequate N and E as per the RDA for healthy individuals, behaved like normal HbAA controls on a low protein diet.
 There was evidence that the HbSS subject might be in a precarious state with respect to sufficiency of several amino acids, particularly L-Arg, which is now classified as conditionally indispensable for the human.
",14
2618,"Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases.
 The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied.
 These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used.
 Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants.
 Warfarin assays were negative.
 We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide.
 The coagulopathies responded to long-term therapy with large doses of vitamin K1.
 The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients.
 The anticoagulant effect is of long duration, requiring chronic vitamin K treatment.
 With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.
",14
2619,"Immunochemical and electrophoretic analyses of phosphorylated native and recombinant neutrophil oxidase component p47-phox.
 Human polymorphonuclear neutrophils (PMNs) possess a potent oxygen-dependent microbicidal system that depends on the activity of a stimulus-activated multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
 Patients with chronic granulomatous disease (CGD) lack activity of this oxidase and consequently suffer severe and frequent infections.
 Components of the oxidase include both membrane-bound factors (most notably, cytochrome b559, which is absent in the X-linked form of CGD) and at least two cytosolic factors, one or the other of which is absent in autosomal CGD.
 Patients with CGD, particularly the autosomal type, have defective phosphorylation of proteins in the 44 to 48 Kd range.
 A polyclonal antiserum (B-1) that recognizes cytosolic oxidase components of 47 and 67 Kd was used to identify phosphoproteins in a cell-free oxidase system.
 Two-dimensional gel electrophoresis showed the identity of the 47-Kd cytosolic protein (p47-phox) recognized by B-1 and the cationic 47-Kd protein that is phosphorylated in normal but not p47-phox-deficient CGD cytosol during activation of the NADPH-dependent oxidase.
 All full-length and C-terminal recombinant p47-phox proteins augmented the superoxide-generating capacity of the cell-free system and were phosphorylated when added to cytosol from normal subjects or from a patient with p47-deficient autosomal CGD.
 These studies provide compelling evidence that the 47-Kd cationic protein that is a substrate for phosphorylation during the activation of PMNs is, in fact, p47-phox, a cytosolic protein previously shown to be critical for normal activity of the NADPH-dependent oxidase of PMNs.
",14
2620,"Molecular basis for alpha-thalassemia associated with the structural mutant hemoglobin Suan-Dok (alpha 2 109leu----arg) [published erratum appears in Blood 1991 Mar 15;77(6):1404].
 Hemoglobin (Hb) Suan-Dok (alpha 109Arg) is a rare alpha-globin structural mutation that is linked to an alpha-thalassemia (alpha-thal) determinant.
 When inherited in trans to an alpha-thal-1 mutation (-), it results in Hb H disease associated with low levels (9%) of the Suan-Dok Hb.
 The nature of the thalassemic defect associated with the alpha SD mutation has been investigated by structural and functional studies.
 Sequence analysis of the cloned Suan-Dok allele showed a missense mutation (T----G) at codon 109 in an otherwise normal alpha 2-globin gene.
 When the alpha 2SD-globin gene was introduced into mouse erythroleukemia cells, the steady state alpha-globin messenger RNA (mRNA) level was equivalent to the alpha A-globin gene control.
 Although in vitro translation of a synthetic alpha 2SD-globin mRNA generated levels of alpha globin equivalent to alpha 2A-globin mRNA at early time points, the ratio of alpha SD to alpha A globin decreased markedly at later time points.
 These data suggest that the thalassemic defect associated with the Suan-Dok mutation results from a significant instability of the alpha SD globin.
",14
2621,"Molecular defect in coagulation factor XFriuli results from a substitution of serine for proline at position 343.
 Our previous findings suggested that coagulation factor XFriuli could be functionally defective owing to a point mutation in the portion of the factor X gene coding for the fully activated heavy chain.
 To verify the existence of this postulated change, we analyzed all eight exons of the normal and Friuli factor X gene.
 Each exon was amplified from genomic DNA using the polymerase chain reaction and cloned into the plasmid pUC19.
 The amplified DNA inserts were subjected to direct sequencing by the dideoxy chain termination method with forward and reverse oligonucleotide sequencing primers.
 A point mutation (C to T transition at nucleotide position 19,297) that results in coding for serine (TCC) in place of proline (CCC) at amino acid position 343 was found.
 This substitution involves a highly conserved proline residue oriented spatially close to both the cleavage site of the zymogen and the active site of the enzyme and explains the previous observations of discrete biochemical and functional differences between factor XFriuli and normal factor X.
 The mutation abolished an HgiCI restriction site present in the normal factor X gene, and this change constitutes the basis for a convenient method for screening individuals carrying this molecular defect.
 Proline343 is in conserved region 5 of the serine protease superfamily to which factor X belongs and is part of a 14-residue L*****P******C motif that occurs in at least 16 other enzymes.
 Computer analysis suggests that the motif may be an essential aspect of conformational features important to functional properties of factor X as well as other serine proteases.
",14
2622,"Hemoglobin Cagliari (beta 60 [E4] Val----Glu): a novel unstable thalassemic hemoglobinopathy.
 This report describes a patient with thalassemia intermedia-like phenotype born to normal parents in whom globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T to A substitution at codon 60 of the beta-globin gene arising as a de novo mutation.
 Normal sequences were detected at the homologous beta-globin locus.
 This mutation results in the substitution of a polar (glutamic acid) for a nonpolar (valine) residue near the corner of the heme pocket of the beta-globin chain.
 The novel variant has been designated Hb Cagliari, from the place of birth of the propositus.
 Kinetics of globin synthesis performed following splenectomy suggest that this new Hb variant is synthesized at a near normal rate but undergoes rapid breakdown.
 The extreme lability of the variant explains the clinical and hematologic picture characterized by marked ineffective erythropoiesis, thalassemia-like bone changes, iron overload, high proportion of Hb F in the peripheral blood, reduced beta/alpha-globin chain synthesis ratio in peripheral blood reticulocytes, and absence of the abnormal Hb in peripheral blood at extensive protein structural analysis before splenectomy.
 This case indicates that a thalassemic hemoglobinopathy should be suspected in the presence of a patient with a thalassemia intermedia-like phenotype born to normal parents, even when protein structural analysis fails to detect an abnormal Hb.
 DNA sequencing may allow to define the mutation, thus making the proper diagnosis.
",14
2623,"Trimethoprim-sulphamethoxazole-associated blood dyscrasias. Ten years' experience of the Swedish spontaneous reporting system.
 During the 10-year period 1976-1985, a total of 154 cases of blood dyscrasia were reported in Sweden which were evaluated as having a probable or possible causal relationship with trimethoprim-sulphamethoxazole (T-SM).
 There were 61 cases of leucopenia (of which 16 had agranulocytosis), 28 cases of thrombocytopenia, and two of non-haemolytic anaemia.
 There were also 32 cases of bicytopenia and 31 cases of tricytopenia.
 The median age varied from 38 years in the leucopenia group to 81 years in those with tricytopenia.
 The overall fatality rate was 17%, ranging from 2% in the group with mild leucopenia to 52% in the group with tricytopenia.
 In relation to sales and prescription data, the overall incidence of reported T-SM blood dyscrasias was 5.3 per million defined daily doses, and among out-patients the incidence was one case per 18,000 prescriptions.
 Thus the overall incidence of any blood reaction to T-SM appears to be low.
 In relation to prescription data, elderly people were overrepresented among the serious reactions.
",14
2624,"A clinico-pathological and follow up study of 10 cases of essential type II cryoglobulinaemic neuropathy.
 Ten patients with essential cryoglobulinaemia type II were examined for peripheral nerve damage.
 In six cases distal symmetrical nerve involvement was present, while in three other cases abnormalities restricted to single nerves were found.
 Electrophysiological and morphological data were consistent with axonal damage, the larger myelinated fibres being most affected.
 Although active signs of vasculitis and immunoperoxidase staining for immunoglobulins were not present, endoneurial vessels were widely damaged, with abnormally thick endothelial cells and redundant basal membranes.
 These findings, together with a patchy distribution of myelinated fibre loss, suggest ischaemia as a cause of peripheral neuropathy during essential cryoglobulinaemia type II.
 A follow up examination, performed one year after haematologial remission, revealed that no further peripheral nerve damage had occurred.
",14
2625,"Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis.
 Assessment of gallium-67 (67Ga) uptake in the salivary and lacrimal glands and intrathoracic lymph nodes was made in 605 consecutive patients including 65 with sarcoidosis.
 A distinctive intrathoracic lymph node 67Ga uptake pattern, resembling the Greek letter lambda, was observed only in sarcoidosis (72%).
 Symmetrical lacrimal gland and parotid gland 67Ga uptake (panda appearance) was noted in 79% of sarcoidosis patients.
 A simultaneous lambda and panda pattern (62%) or a panda appearance with radiographic bilateral, symmetrical, hilar lymphadenopathy (6%) was present only in sarcoidosis patients.
 The presence of either of these patterns was particularly prevalent in roentgen Stages I (80%) or II (74%).
 We conclude that simultaneous (a) lambda and panda images, or (b) a panda image with bilateral symmetrical hilar lymphadenopathy on chest X-ray represent distinctive patterns which are highly specific for sarcoidosis, and may obviate the need for invasive diagnostic procedures.
",14
2626,"Development of a new radioimmunoassay for erythropoietin using recombinant erythropoietin.
 The development of a 24 hour radioimmunoassay for erythropoietin (EPO) using EPO derived from recombinant DNA as both immunogen and ligand is described in the present paper.
 Mixed breed rabbits immunized with 10 micrograms/kg of EPO derived from a stably transfected cell line (Elanex Pharmaceuticals Inc., Bothel, Washington, USA, through McDonnell Douglas Corp., St.
 Louis, Missouri, USA; ""MD"") produced antibodies to EPO with high titer (up to 1:896,000 final dilution in the tube), high affinity (8.4 x 10(11) liter/M), and good specificity.
 Purified EPO from the above source or from AmGen Biologicals (Thousand Oaks, California, USA; ""AG"") were successfully radioiodinated with the chloramine-T method and used as ligand in the radioimmunoassay.
 Standard dose-response curves prepared with EPO from both commercial sources were not significantly different and showed a sensitivity of 0.75 to 0.96 mU/tube.
 The dose-response curves in both systems also showed parallelism with serially diluted serum from a patient with aplastic anemia.
 Within-assay and between-assay precision were determined by assaying multiple replicates of a serum pool.
 Recovery of exogenous EPO added to a serum pool averaged 97% for both systems.
 The range of normal human serum EPO was determined by assaying the sera of 153 hematologically-normal adult subjects and was found to be 1.1 to 27.3 mU/ml for MD EPO and 0.5 to 16.7 mU/ml for AG EPO.
 Sera from several patients with hematologic abnormalities were also assayed, including those of 36 patients with anemia of end-stage renal disease (mean +/- SEM, 29.5 +/- 4.0 mU/ml; P less than 0.01).
 In conclusion, this new, more rapid and sensitive radioimmunoassay system can be used to measure EPO levels in sera from normal human subjects and patients with several types of anemia, and should also be very useful in therapeutic drug monitoring of patients receiving EPO from various commercial sources.
",14
2627,"Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan.
 beta-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the beta-globin gene.
 Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally.
 The present study constitutes an extensive molecular characterization of this disease in a small, highly inbred ethnic group with a high incidence of beta-thalassemia--the Jews of Kurdistan.
 An unusual mutational diversity was observed.
 In 42 sibships 13 different mutations were identified, of which 3 are newly discovered: a C----A transversion at -88 to the cap site, a frameshift in codon 36/37, and an A----G transition in the polyadenylylation signal.
 Four of the mutations are unique to Kurdish Jews and have not been discovered in any other population.
 A fifth was found outside Kurdish Jews only in an Iranian from Khuzistan, a region bordering Kurdistan.
 Two-thirds of the mutant chromosomes carry the mutations unique to Kurdish Jews.
 We traced the origin of the mutations to specific geographic regions within Kurdistan.
 This information, supported by haplotype analysis, suggests that thalassemia in central Kurdistan (northern Iraq) has evolved primarily from multiple mutational events.
 In Turkish Kurdistan, the primary mechanism is genetic admixture with the local population.
 In Iranian Kurdistan, a founder effect appears to be partly responsible.
 We conclude that several evolutionary mechanisms contributed to the evolution of beta-thalassemia in this small ethnic isolate.
",14
2628,"Antibiotic-associated hypoprothrombinemia: a review of prospective studies, 1966-1988.
 Many antimicrobial agents have been associated with hypoprothrombinemia.
 The precise mechanisms are unknown, but alteration in vitamin K status or utilization is involved.
 The two postulated mechanisms implicate either direct inhibition of biosynthesis of the vitamin K-dependent clotting factors by the N-methylthiotetrazole (NMTT) moiety found in certain antimicrobial agents or eradication of vitamin K-producing intestinal microflora in patients with reduced oral intake of vitamin K.
 An English-language review of all prospective studies reported between 1966 and 1988 in which serial prothrombin times were monitored in adult patients revealed that the incidence of hypoprothrombinemia varied from 3.7% to 64% with NMTT-containing regimens and from 0% to 24% with non-NMTT-containing regimens.
 Detailed evaluation of these and other studies suggests that certain risk factors, including malnutrition, hepatic and renal dysfunction, older age, and severity of illness, may be the major determinants of hypoprothrombinemia.
 The hypothesis that the NMTT side chain is primarily responsible for hypoprothrombinemia may not be justified.
 We conclude that patients at high risk for coagulopathy should be carefully monitored and that serious consideration should be given to the use of prophylactic vitamin K in such cases.
",14
2629,"Venous Doppler ultrasonography in the fetus with nonimmune hydrops.
 Eighteen pregnancies with nonimmune hydrops fetalis were referred for fetal echocardiography to rule out congenital heart disease.
 In 14 of these cases, pulsating blood velocities were recorded in the umbilical vein, which in a normal population had a nonpulsatile blood velocity pattern.
 The four cases without pulsations in the umbilical vein were found to have intrauterine viral infections.
 In the last 10 cases examined, the umbilical venous pulsations were found to reflect abnormal central venous pulsations during atrial systole suggesting increased fetal central venous pressure.
 Right ventricular shortening fraction was significantly decreased in the group with umbilical venous pulsations compared with those without (0.18 versus 0.32, p less than 0.05).
 All the fetuses without venous pulsations survived, but only four of the 14 with pulsations survived (p less than 0.05).
 The results suggest that blood velocity recordings in the umbilical and central veins of the fetus can give valuable clinical information with regard to the presence of fetal congestive heart failure and differentiate between this physiologic state and other causes of nonimmune hydrops fetalis.
 This may have implications for fetal diagnostic work-up and prognosis.
",14
2630,"Combined use of fine-needle aspiration cytologic examination and tuberculin skin test in the diagnosis of cervical tuberculous lymphadenitis. A prospective study.
 A prospective study to evaluate the efficacy of combined use of fine-needle aspiration (FNA) cytologic examination and Mantoux test in the diagnosis of cervical tuberculous lymphadenitis was carried out.
 Tuberculin reactions were determined in 59 control subjects.
 Preoperative FNA cytologic examinations and Mantoux tests were performed on 74 patients with cervical lymphadenopathy.
 The lymph nodes were then excised and examined histologically and cultured for mycobacteria.
 Forty-eight, 22, and 4 patients had histologically confirmed tuberculous, non-specific, and malignant lymphadenopathy.
 Fine-needle aspiration cytologic examination alone could detect cervical tuberculous lymphadenitis in 37 patients (77%).
 The predictive value of a strong tuberculin reaction for mycobacterial infection was 100%.
 The combined use of a Mantoux test and FNA cytologic examination was able to diagnose 43 (90%) of 48 cases of tuberculous lymphadenitis cervical preoperatively.
 Combined use of FNA cytologic examination and Mantoux test was efficient in the diagnosis of tuberculous lymphadenitis.
",14
2631,"Morphology of sickle cells produced in solutions of varying osmolarities.
 The effect of varying osmolarities (0.6% to 1.5% NaCl solutions, 213 to 492 mOsm/kg H2O) on the morphology of deoxygenated sickle cells was studied quantitatively with a computer-assisted image analysis system.
 Discocyte-rich, less dense fractions of sickle cells (density less than or equal to 1.11) were suspended in buffered NaCl solutions (pH 7.4) of various osmolarities, deoxygenated at room temperature for up to 5 hours, and stained by Wright's solution.
 Microscopic images were analyzed by circular shape factor (CSF = 4 pi x [area]/[perimeter]2) and elliptical shape factor (ESF = [short axis]/[long axis]).
 Since these two parameters yield different values for elongated cells and for cells of other shapes, such as maple-leaf- or star-shaped cells, the morphologic changes of sickle cells can be analyzed numerically.
 We found that both the rate and the degree of deformation depended highly on the osmotic pressure of the media in which the cells were suspended.
 In hypertonic solution, most sickle cells assumed a maple-leaf shape.
 The deformation occurred quickly, but the degree of deformation (circular shape factor and elliptical shape factor) was lower than that found in isotonic and slightly hypotonic solutions.
 Although elongated cells were formed in hypotonic and isotonic solutions, deformation was slower in these solutions than in hypertonic solutions.
 These results indicate that the shape and the degree of deformation of deoxygenated sickle cells are highly dependent on the osmolarity of the suspending medium and that the rate of deformation is inversely related to osmolarity.
 The relationship between morphology of deoxygenated sickle cells and osmotic pressure of the suspending media is discussed.
",14
2632,"Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high-dose interleukin-2 immunotherapy.
 High-dose interleukin-2 (IL-2) immunotherapy can cause hypotension, respiratory distress, interstitial edema, and thrombocytopenia, similar to endotoxic shock.
 We have observed that IL-2 has no direct effect on coagulation factors in vitro, but it has been observed to alter the coagulant properties of vascular endothelium.
 Accordingly, we investigated the possibility that IL-2 infusions initiate plasma fibrinolysis and disseminated intravascular coagulation (DIC).
 We studied the clinical course, platelet count, and coagulation profile in response to IL-2 infusion in seven patients, two with metastatic melanoma and five with metastatic renal cell carcinoma.
 Every patient experienced hemodynamic instability and thrombocytopenia, and one patient suffered an unusual complication, mesenteric thrombosis.
 No patient had appreciable changes in the prothrombin time or the partial thromboplastin time, nor did factors V or VIII decline in the two patients observed.
 In four patients examined, we found decreased titers of Hageman factor (factor XII), high molecular weight kininogen, prekallikrein, and plasma thromboplastin antecedent, as if these had been consumed by reactions of the intrinsic pathway of thrombin formation.
 Circulating D-dimer fragments were found in the plasma of every patient at some point during each infusion cycle, and we observed decreased titers of plasminogen in the four patients just mentioned, suggesting that IL-2 infusions initiated fibrinolysis.
 Taken together, the clotting factor derangements and related toxicity phenomena cannot be ascribed firmly to DIC.
 Activation of the intrinsic (contact) system of coagulation, however, may provide one link between the vascular endothelial surface alterations caused by IL-2 infusions and the development of the systemic toxicity that resembles septic shock.
",14
2633,"Middle cerebral artery blood velocity and cerebral blood flow in sickle cell disease.
 To understand better the relationship between blood velocity measured by transcranial Doppler and cerebral blood flow measured by the 133Xe inhalation method, we examined 23 patients undergoing evaluation in the Comprehensive Sickle Cell Center at Columbia University.
 Blood velocity in the middle cerebral artery was directly related to cerebral flow (r = 0.77; p less than 0.05).
 A multivariate analysis in this sample made it possible to improve this correlation to account for more than 90% of the variability in cerebral blood flow by the use of transcranial Doppler measures of velocity and pulsatility along with the patient's age and hematocrit (r = 0.95; p less than 0.001).
 It is likely that the combination of Doppler and clinical or demographic variables in other diseases will similarly improve the quantitative estimation of cerebral blood flow.
",14
2634,"Platelet aggregation in platelet-rich plasma and whole blood in 120 patients with myeloproliferative disorders.
 In vitro platelet aggregation in platelet-rich plasma (PRP) and in whole blood (WB) was assessed in 31 patients with idiopathic myelofibrosis, 32 with essential thrombocytosis, 23 with polycythemia vera, and 34 with chronic myelogenous leukemia.
 In PRP most subjects showed normal or reduced platelet aggregation, whereas in WB the majority of patients showed increased platelet function.
 Spontaneous platelet aggregation (SPA) was observed frequently in WB, whereas it was seldom observed in PRP.
 SPA in WB was inhibited by in vitro addition of aspirin and apyrase, and SPA was only partially dependent on high platelet count because it also occurred in samples with normal platelet content (at variance with 13 subjects with reactive thrombocytosis, in which SPA was observed only in samples with high platelet concentration).
 Platelets from patients with idiopathic myelofibrosis had the highest tendency to undergo SPA.
",14
2635,"Polycythemia vera and other polycythemic states.
 The diagnosis of polycythemia requires an accurate and independent assessment of both plasma volume and red blood cell mass.
 Patients with an increased red cell mass (absolute polycythemia) may be hypoxic or have an erythropoietin-secreting tumor or space-occupying lesion compressing the kidney.
 Those with a reduced plasma volume (relative polycythemia) most often are tobacco smokers, are taking diuretic or cardiac medications, or ingest increased quantities of caffeine-containing beverages.
 On the other hand, polycythemia vera is a systemic disease with multiple complications, which is best diagnosed through a complex of findings as outlined by the Polycythemia Vera Study Group.
",14
2636,"Platelet abnormalities in myeloproliferative disorders.
 A large number of various platelet abnormalities are described in patients with MPD.
 These abnormalities serve diagnostic purposes only.
 They appear to have little or no predictive value regarding the clinical manifestations of the patients or the progress of the disease.
 Those platelet characteristics most consistently reported to be defective include a decrease in the platelet content of serotonin and adenine nucleotides, decreased platelet density, an abnormal ultrastructure characterized by paucity of granules and hypertrophy of the surface connecting canicular system, an altered membrane glycoprotein profile that includes reduced levels of GPIb, and reduced lipoxygenase activity and aggregation response with epinephrine.
 These abnormalities may originate at the megakaryocyte level.
 Furthermore, the released abnormal platelets may undergo modification of their functional and biochemical characteristics as a result of episodes of intravascular thrombosis or aging in circulation or as a result of the progression and treatment of the disease, thus creating the paradoxic and often conflicting relationship between the thrombotic and hemorrhagic events and the results of platelet functional tests as observed in this disorder.
",14
2637,"Sarcoidosis of the cauda equina: a report of three cases.
 Three cases of sarcoidosis of the cauda equina are presented.
 In two there was no previous history suggestive of sarcoidosis and the presentation was one of a painful flaccid paralysis; in these the diagnosis was made after myelography and laminectomy with subsequent histology.
 The third patient had a previous diagnosis of lupus pernio and magnetic resonance imaging (MRI) was used to aid diagnosis.
 Only two previous cases have been reported of sarcoidosis presenting in the cauda equina with no other systemic manifestations.
 This is the first report of the use of MRI in sarcoidosis of the lower meninges.
",14
2638,"Hemoglobin Columbia Missouri or alpha 2[88 (F9) Ala----Val]beta 2: a new high-oxygen-affinity hemoglobin that causes erythrocytosis.
 A previously undescribed hemoglobin variant, hemoglobin Columbia Missouri, alpha 88 (F9) Ala----Val, was detected in a 22-year-old white man who was undergoing assessment for erythrocytosis.
 This new hemoglobin variant does not separate from hemoglobin A by electrophoresis in conventional media, by isoelectric focusing, or by electrophoresis of purified globin chains in 8 M urea.
 It exhibits a high oxygen affinity, with a P50 (oxygen tension at 50% saturation) of 19.3 torr for the patient's whole blood.
 The substitution of hemoglobin Columbia Missouri is an internal residue near the end of the F helix of the alpha chain.
 Hemoglobin Okazaki has an arginyl residue substitution for a cysteinyl residue at F9 (beta 93) in the beta chain.
 In comparison with hemoglobin Okazaki, the substitution in hemoglobin Columbia Missouri has a more pronounced effect on oxygen affinity.
 Consequently, hemoglobin Columbia Missouri is associated with erythrocytosis, whereas hemoglobin Okazaki is not.
",14
2639,"Transfusion requirements and effects in patients with thalassaemia major. Cooleycare Programme.
 Analysis of data available in 1985 on 3468 Italian and Greek patients registered in Cooleycare, an international cooperative programme of quality assessment of treatment delivery in thalassaemia, gave the following picture of treatment requirements and effects.
 The proportion of patients undergoing splenectomy has progressively decreased, and age at splenectomy has increased with time over the past 20 years.
 Age at first transfusion exceeds 4 years in a small but important group of patients, which indicates that a milder form of thalassaemia exists in this group.
 Children receiving modern treatment remain of near-normal stature until age 11 but later tend to be stunted.
 The mean blood requirement is 35% higher in non-splenectomised than in splenectomised patients.
 Differences in transfusion interval of 2 to 4 weeks have no measurable effect on blood requirement.
 Mean blood requirement rises gradually with mean haemoglobin concentration, possibly in a non-linear fashion.
 The prevalence of red cell alloimmunisation rises with delay in start on transfusion.
 Transfusion reactions were reported in 1% of transfusions (90% of which were leucocyte-depleted), from 17% of patients.
",14
2640,"A three-point approach to anemia.
 Anemia is a sign of underlying disease that is causing blood loss, sequestration of red blood cells (RBCs), impaired RBC production, or primary marrow dysfunction.
 The most efficient clinical approach to a patient with anemia is to ask the following three questions: Is the anemia microcytic, macrocytic, or normocytic? Is pancytopenia present? Is the marrow response appropriate for the anemia as determined by the reticulocyte count? Answers to these questions focus laboratory evaluation on a logical progression and avoid a costly shotgun approach.
",14
2641,"Contemporary use of the disease concept: III. A pedantic failure to change behavior regarding the problem of anemia.
 The frequency with which house staff noticed their patients to be anemic, the frequency with which they tried to find out why the patients were anemic, and the diagnostic accuracy of such endeavors were measured.
 Next, an intervention was conducted in which the teams were lectured on the subject of anemia, given reading materials on the subject, and given social encouragement to solve the problem.
 At follow-up no improvement was found in any of the outcome variables.
",14
2642,"Ventilation and gas exchange during exercise in sickle cell anemia.
 Adults with sickle cell anemia (SCA) have restrictive lung impairment, increased alveolar dead space, and hypoxemia.
 These factors, together with increased anaerobic metabolism, are thought to cause exercise hyperventilation.
 To assess the role of each of these in children, 34 patients with SCA and 16 control subjects performed pulmonary function and exercise tests.
 Twenty-eight patients with SCA had spirometric values and lung volumes, and all but two patients with SCA had arterial saturation greater than 91% during exercise.
 Despite a low VO2max (30.07 +/- 6.55 ml/min/kg), the ventilatory anaerobic threshold (VAT) in the patients occurred at a similar %VO2max as in the control subjects (69 +/- 9% versus 63 +/- 12%).
 The slope of the delta VE/delta VCO2 relationship for sub-VAT work was steeper in the patients (29.4 +/- 6.5 versus 24.7 +/- 5.2, p = 0.01), and the ventilatory equivalent for CO2 (VE/VCO2) in steady-state exercise was greater in the patients than in the control subjects (33.2 +/- 3.5 versus 30.8 +/- 3.5, p = 0.03).
 End-tidal PCO2 did not differ (38.3 +/- 3.0 versus 39.2 +/- 3.1), indicating equivalent alveolar ventilation.
 The patients had a higher dead space:tidal volume ratio (VD/VT) than did the control subjects (0.204 +/- 0.033 versus 0.173 +/- 0.024, p = 0.0005).
 The PaCO2 was significantly lower in those with lower Hb, but there was no difference in pH.
 In conclusion, children with SCA have an increased exercise ventilatory response caused in part by increased physiologic dead space, and in part by their low Hb.
 The greater dead space may be the result of sickle cells impairing capillary perfusion to ventilated alveoli.
",14
2643,"Cardiac output and oxygen delivery during exercise in sickle cell anemia.
 Desaturation in patients with sickle cell anemia (SCA) can lead to intravascular sickling and vascular occlusion.
 The increased metabolic demands of exercise tend to increase oxygen extraction, giving rise to a fall in saturation in the capillary bed that may predispose to sickling.
 This could be minimized with an increase in cardiac output.
 The aims of this study were to assess the role of increased stroke volume (SV) in augmenting cardiac output (Q) and to estimate the role of enlarged arteriovenous O2 content difference in maintaining O2 transport in children with SCA.
 A group of 30 children with SCA (Hb 65 to 133 g/L) and 16 healthy controls of the same racial group and of similar height and weight performed incremental and steady-state exercise at 50% Wmax.
 Cardiac output (Q) was measured by the indirect (CO2) Fick method during steady state.
 The slope of delta HR/delta VO2 during incremental exercise was higher in SCA subjects compared with controls (4.01 +/- 1.73 versus 2.80 +/- 0.61 bpm per ml/min/kg VO2, p = 0.001).
 Q for VO2 was abnormally high in patients, particularly older ones with lower Hb levels.
 HR (% predicted) was higher in patients than in controls (106 +/- 11 versus 92 +/- 8% predicted, p less than 0.0001), as was SV (113 +/- 16 versus 98 +/- 14% predicted, p = 0.002).
 Multiple linear regression of Q % predicted and SV % predicted on Hb and age showed a positive correlation with age and a negative correlation with Hb (r = 0.84 for Q and r = 0.76 for SV).
",14
2644,"Prenatal detection of foramen ovale obstruction without hydrops fetalis.
 A case of prenatal echocardiographic diagnosis of obstruction of the foramen ovale is described.
 Presentation was the ultrasound detection of unexplained marked right atrial and right ventricular dilation without fetal hydrops.
 It is speculated that fetal outcome depends on the severity and time of onset of foramen ovale obstruction in utero.
",14
2645,"Abnormal megakaryocytopoiesis in the Belgrade laboratory rat.
 The Belgrade laboratory (b/b) rat has a hereditary hypochromic microcytic anemia because of defective transmembrane iron transport into erythroblasts.
 The present study was prompted by our previous work in which we showed that the b/b rat has hypomegakaryocytic thrombocytopenia associated with increased megakaryocyte size.
 To define the basic mechanism underlying this abnormality in the b/b rat we have studied both megakaryocytopoiesis and granulopoiesis in anemic b/b rats, chronically transfused b/b rats, iron-treated b/b rats, and controls.
 We have found decreased concentrations of megakaryocyte and granulocyte progenitors in the marrow of b/b rats.
 Full correction of the severe anemia by chronic transfusion resulted in normalization of megakaryocyte progenitors, small acetylcholinesterase positive cells, megakaryocyte size, and platelet counts, along with granulocyte progenitors.
 In contrast, the partial correction of anemia obtained by iron treatment resulted in improvement, but not normalization, of these parameters.
 These findings indicate that abnormal megakaryocytopoiesis in the b/b rat can be best interpreted as a consequence of hypoxia because of the severe anemia.
 Because we have recently shown that the number of erythroid progenitors in b/b rats is also low, we propose that abnormal megakaryocytopoiesis in this animal is a reflection of an acquired stem cell disorder induced by the prolonged hypoxia resulting from the severe anemia.
",14
2646,"Polycythemia vera blood burst-forming units-erythroid are hypersensitive to interleukin-3.
 Because polycythemia vera (PV) is a clonal hematopoietic stem cell disease with a trilineage hyperplasia, and interleukin-3 (IL-3) stimulates trilineage hematopoiesis, we have studied the response of highly purified PV blood burst-forming units-erythroid (BFU-E) to recombinant human IL-3 (rIL-3).
 Whereas the growth of normal blood BFU-E in vitro rapidly declined by 40 and 60% after 24 and 48 h of incubation without 50 U/ml of rIL-3, the growth of PV BFU-E declined by only 10 and 30% under the same conditions, demonstrating a reduced dependence on rIL-3.
 A reduced dependence of PV BFU-E on recombinant human erythropoietin (rEP) was also present.
 Dose-response experiments showed a 117-fold increase in PV BFU-E sensitivity to rIL-3, and a 6.5-fold increase in sensitivity to rEP, compared to normal BFU-E, whereas blood BFU-E from patients with secondary polycythemia responded like normal BFU-E.
 Endogenous erythroid colony (EEC) formation, which is independent of the addition of rEP, was reduced by 50% after erythroid colony-forming cells were generated from PV BFU-E in vitro without rIL-3 for 3 d, whereas rEP-stimulated erythroid colonies were unaffected.
 These studies demonstrate a striking hypersensitivity of PV blood BFU-E to rIL-3, which may be the major factor in the pathogenesis of increased erythropoiesis without increased EP concentrations.
",14
2647,"Angiolymphoid hyperplasia with eosinophilia.
 Angiolymphoid hyperplasia with eosinophilia is a rare condition and is poorly recognized in the otolaryngological literature.
 The condition is characterized by the appearance of cutaneous nodules within the head and neck region especially around the external ear.
 Variable lymphadenopathy and peripheral eosinophilia can occur and the condition can mimic neoplasia.
 It is important to be aware of this disease entity in order to avoid overtreatment.
 Surgical removal is the treatment of choice; however, this often multilobulated and poorly delineated lesion often precludes initial wide excision and local recurrence is common.
 We present three cases of this unusual condition and a brief resume of the literature.
",14
2648,"Long-term follow-up after heterotopic splenic autotransplantation for traumatic splenic rupture 
 The trapping function of the heterotopic splenic autotransplants (HSA) in 13 polytraumatized patients, aged 5-38 yr, was evaluated using heat damaged technetium-99m-labeled autologous red blood cells in early (1-7 mo) and late (3-4.5 yr) period after heterotopic autotransplantation to the omentum.
 The intensity of tracer accumulation was graded in comparison to the liver uptake.
 The splenic tissue surface was calculated on anterior projection each time.
 The shapes of the transplants were compared and new uptake foci suggesting spontaneous splenosis were looked for on both scans.
 The average surface of HSA was 28.2 (+/- 14.7) cm2 on early and 44.1 (+/- 14.3) cm2 on late examination (p less than 0.003) and the increase in intensity of tracer accumulation on both occasions was significant as well (p less than 0.0001).
 In three patients, some additional splenotic foci were found on follow-up scans.
 Howell-Jolly bodies in peripheral blood were detected in six of eight patients in early and remained detectable in lower number in three of eight patients on follow-up.
 No serious infection was noticed in our group of patients.
 Our work confirmed the excellent survival rates of HSA with improving trapping function and no important spread from original implantation site on long-term follow-up.
",14
2649,"Cold-induced granulocyte agglutination. A cause of pseudoleukopenia.
 Transient cold agglutination of her granulocytes developed in a 60-year-old woman with a left upper lobe pneumonia during the acute phase of her illness.
 This phenomenon was manifested by pseudogranulocytopenia, multiple clumps of granulocytes on her peripheral blood smear, and abnormal distribution of granulocytes and monocytes on the white blood cell histogram when measured on an automated hematology analyzer (Coulter S-Plus IV, Coulter Electronics Inc, Hialeah, Fla).
 The cause is postulated to be an IgM autoantibody directed against components of the granulocyte membranes.
 Spurious leukopenia is encountered infrequently with automated hematology analyzers.
 Cold-induced granulocyte agglutination should be recognized as a potential cause of pseudogranulocytopenia so that white blood cell counts can be accurately reported and unnecessary evaluation of patients for leukopenia can be avoided.
",14
2650,"Cyclosporine therapy for advanced Langerhans cell histiocytosis.
 Prompted by evidence that Langerhans cell histiocytosis (LCH) is a nonmalignant disorder of immune regulation, we used cyclosporine (12 mg/kg/d orally) to treat three young children with advanced multisystem LCH.
 All three patients had partial responses to cyclosporine within 2 months of therapy, as evidenced by complete resolution of organ dysfunction and regression of the majority of lesions.
 Complete responses were attained by adding relatively nontoxic chemotherapy (ie, prednisone and vinblastine).
 Toxicity from cyclosporine comprised mild and reversible elevations of the serum creatinine and blood urea nitrogen.
 These results indicate that further evaluation of cyclosporine for the treatment of patients with advanced LCH is warranted.
",14
2651,"Transmembrane mobility of phospholipids in sickle erythrocytes: effect of deoxygenation on diffusion and asymmetry.
 We studied the effect of sickling on the transmembrane reorientation and distribution of phospholipids in the red blood cells of patients homozygous for sickle cell anemia (SS).
 To this purpose, we followed the redistribution kinetics of trace amounts of spin-labeled analogues of natural phospholipids first introduced in the membrane outer leaflet of normal or sickle erythrocytes exposed to air or nitrogen.
 Deoxygenation had no effect on the lipid redistribution kinetics in normal (AA) cell membranes.
 At atmospheric pO2, unfractionated SS cells were not different from normal cells.
 However, on deoxygenation inducing sickling, phosphatidylcholine passive diffusion was accelerated and the rate of the adenosine triphosphate-dependent transport of aminophospholipids was reduced, especially for phosphatidylserine.
 The stationary distribution of the aminophospholipids between the two leaflets was slightly less asymmetric, a phenomenon more pronounced with phosphatidylethanolamine.
 These changes were rapidly reversible on reoxygenation.
 When SS cells were separated by density, both dense and light cells exhibited the properties cited above.
 However, dense cells exposed to air possessed a lower aminophospholipid transport rate.
 These data favor the relationship between aminophospholipid translocase activity and phospholipid transmembrane asymmetry.
 Sickle cell disease is the first case of aminophospholipid translocase pathology.
",14
2652,"Iron deficiency anemia in the elderly: the diagnostic process.
 OBJECTIVE: To determine the effectiveness of physician probability estimates calculated on the basis of findings from history-taking and physical examination in the diagnosis of iron deficiency anemia in elderly patients.
 DESIGN: Prospective study.
 SETTING: Two community hospitals offering secondary and tertiary care.
 PATIENTS: A total of 259 patients over 65 years of age found to have previously undiagnosed anemia.
 MEASURES: Physician estimates of the likelihood of iron deficiency before (pretest probability) and after (post-test probability) the laboratory test results were available.
 The hemogram was available to the physicians when they made their pretest probability estimates.
 Because the serum ferritin level proved to be the most powerful of the laboratory test results studied, the likelihood ratios associated with the post-test estimates were compared with the ratios associated with the serum ferritin level.
 MAIN RESULTS: The post-test probability estimates were influenced by the serum ferritin level and the pretest estimates.
 The post-test estimates derived from the findings obtained through history-taking and physical examination and the laboratory test results (including the serum ferritin level) were slightly less accurate in predicting iron deficiency than the serum ferritin level alone.
 Nevertheless, a model in which the pretest estimates were used in addition to the serum ferritin level to predict iron deficiency proved to be more powerful than the serum ferritin level alone (p = 0.006).
 This indicated that the limitations of the post-test estimates were due to a misinterpretation of the serum ferritin level and that the findings from history-taking and physical examination added important diagnostic information.
 CONCLUSIONS: Physicians must be aware of test properties to provide optimal care to their patients.
 If test results are properly interpreted, pretest probabilities derived from findings obtained through history-taking and physical examination can add useful information that will lead to more accurate diagnoses.
",14
2653,"The clinical spectrum of thrombocytosis and thrombocythemia.
 Platelet production is the result of a highly ordered maturation of a developmental hierarchy of megakaryocytic progenitor cells regulated by a variety of cytokines.
 GM-CSF, II-3 and II-6 have a stimulatory effect and several cytokines (TGF-beta, platelet released glycoprotein, platelet factor 4 and interferons) have inhibitory effects down regulating platelet production perhaps as part of an autocrine control loop.
 Excess platelet production can be clinically characterized as pseudothrombocytosis, thrombocytosis or thrombocythemia; the clinical features and criteria for each are defined.
 The term thrombocytosis infers its reactive nature and, in the absence of arterial disease or prolonged immobility, it poses little risk regardless of platelet numbers.
 By contrast, in thrombocythemia, whether primary or associated with other myeloproliferative lesions, significant thrombohemorrhagic events occur.
 The natural history, rationale, and approach to platelet reduction and control of clinical sequela are reviewed.
 Clinical therapeutic options include a new agent, Anagrelide.
",14
2654,"Methaemoglobinaemia after ingestion of amyl nitrite.
 We report a case of methaemoglobinaemia in a 2 year old girl after ingestion of an 'aphrodisiac' containing nitrite.
 The availability of these products, their poor labelling, and their intended presence in domestic bedrooms all serve to increase the hazard they pose to young children.
",14
2655,"Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor.
 Twenty children (aged 1 to 17 years) with severe or moderate aplastic anemia were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at a dose of 400 micrograms/m2 per day administered as a 30-minute intravenous (IV) infusion daily for 2 weeks.
 This treatment increased the neutrophil counts (2.7- to 28.0-fold) in 12 of the 20 patients.
 Increasing doses (800 or 1,200 micrograms/m2 per day) were administered to five patients who had not responded to the initial dose, and three showed an increase in neutrophil count.
 Differential counts of bone marrow (BM) aspirates showed an increase in the myeloid/erythroid ratio.
 The response was transient, however, and the neutrophil count returned to baseline within 2 to 10 days of discontinuing treatment.
 No severe toxicity attributable to rhG-CSF was observed.
 The results suggest that this agent is effective in stimulating granulopoiesis in children with aplastic anemia.
 Our study also indicates that rhG-CSF will be particularly useful in managing patients with aplastic anemia complicated by bacterial or fungal infection.
",14
2656,"Prophylactic effect of self-administered pump-driven subcutaneous IgG infusion in patients with antibody deficiency: a triple-blind cross-over study comparing P-IgG levels of 3 g l-1 versus 6 g l-1.
 Eight adult patients with hypoimmunoglobulinaemia were randomly allocated to initiation of low- or high-level IgG-substitution.
 IgG was administered subcutaneously, at 50 or 150 mg ml-1, 20 ml per infusion, by means of a pocket-portable electric infusion pump.
 Infusions were given 2 to 4 times weekly for 24 months, with a change of dose regimen after 12 months.
 The desired plasma IgG levels were reached after a mean lag phase of 3 months (range 1-5 months).
 The median (and ranges) of the individual mean plasma IgG levels during the ensuing 9-month periods were as follows: high-level period, 6.5 g l-1 (range 6.2-7.8 g l-1); low-level period, 3.2 g l-1 (range 3.0-4.0 g l-1).
 During the high-level period, compared to the low-level period, there was a significant decrease in the following parameters: 'days in bed at home', 'days missed work' and 'days with fever'.
 No serious side-effects were observed.
 It is concluded that a plasma IgG concentration of 6 g l-1 can readily be achieved by subcutaneous IgG substitution, and the prophylactic effect is superior to that obtained with a plasma IgG concentration of 3 g l-1.
",14
2657,"A fatal case of ceftriaxone (Rocephin)-induced hemolytic anemia associated with intravascular immune hemolysis.
 Fatal hemolytic anemia developed in a 52-year-old woman who was treated with a cephalosporin, ceftriaxone.
 The patient's red cells (RBCs) were coated with C3, but no RBC-bound IgG, IgA, or IgM was detected.
 Her serum contained an antibody that did not react with cephalosporin-coated RBCs but reacted strongly with RBCs in vitro when her serum was added to drug and RBCs.
 This is the first case of immune hemolytic anemia associated with ceftriaxone, the first case of fatal cephalosporin-induced hemolytic anemia, and the second case in which a cephalosporin antibody showed in vitro and in vivo characteristics usually thought to be associated with the so-called immune complex mechanism.
",14
2658,"Ceftazidime-induced hemolysis in a patient with drug-dependent antibodies reactive by immune complex and drug adsorption mechanisms.
 A 35-year-old woman developed acute intravascular hemolysis within five days of beginning a course of ceftazidime.
 The direct antiglobulin test became strongly positive with both anti-IgG and anticomplement.
 The serum contained an antibody that, in the presence of ceftazidime, sensitized unmodified reagent cells with IgG and complement (immune-complex type).
 The serum also agglutinated ceftazidime-pretreated cells at room temperature and 37 degrees C (drug-adsorption type).
 Retrospective testing disclosed that the drug adsorption antibody, which had been present before the current course of antibiotics, was not demonstrable during the hemolysis.
 The reactivity of the immune complex antibody, which developed by the second day of ceftazidime, paralleled the degree of hemolysis and the strength of the direct antiglobulin test.
 The authors believe that this patient had two separate ceftazidime-dependent antibodies and that the antibody reactive by immune complex mechanism mediated an episode of acute intravascular hemolysis.
",14
2659,"A comparison of the performance of 20 pulse oximeters under conditions of poor perfusion 
 The performance of 20 pulse oximeters with finger probes was evaluated by comparison of their readings with directly measured arterial blood oxygen saturations.
 The samples were taken from patients who had undergone cardiac surgery under hypothermic cardiopulmonary bypass and had poor peripheral perfusion.
 The mean difference (bias, accuracy), standard deviation (precision) and drop-out rate for each pulse oximeter was determined.
 An overall ranking of performance of each pulse oximeter was calculated using five criteria (accuracy, precision, number of readings within 3% of standard, percentage of readings given within 3% of standard, expected overread limit in 95% of cases).
 Two pulse oximeters achieved a combination of accuracy and precision such that 95% of measurements would be expected to be within 4% of the co-oximeter value; these two also had the lowest drop-out rate.
",14
2660,"Acquired methemoglobinemia. The relationship of cause to course of illness [published erratum appears in Am J Dis Child 1991 Feb;145(2):158]
 To better characterize methemoglobinemia in children, we reviewed the charts of 17 patients who were admitted to a children's hospital over the last 10 years.
 Two distinct groups were identified: (1) The endogenous group (n = 9) included patients with methemoglobinemia associated with an intercurrent illness.
 (2) The exogenous group (n = 8) included patients with methemoglobinemia secondary to drug exposure.
 Despite similar initial methemoglobin levels in the endogenous (mean, 29%) and exogenous (mean, 28%) groups, children in the endogenous group had more acidosis (serum bicarbonate levels of 5.9 vs 19.1 mmol/L and arterial pH of 7.01 vs 7.35).
 All the children in the exogenous group with methemoglobinemia secondary to an accidental ingestion stayed only 1 day in the hospital, while children in the endogenous group were admitted for an average of 19 days.
 Children with methemoglobinemia secondary to a drug exposure have a more benign illness with a shorter duration than children with methemoglobinemia associated with an intercurrent illness.
 It appears that the absolute level of methemoglobin is not as important as the underlying cause in determining both the course and severity of illness.
",14
2661,"Prenatal screening for hemoglobinopathies. I. A prospective regional trial.
 Prenatal hemoglobinopathy screening was chosen as a model system for the study of patient receptivity to unsolicited genetic information.
 Providers of prenatal care in Rochester, NY, were offered free testing of all their prenatal patients and genetic counseling of women found positive.
 The 18,907 prenatal samples tested in a 5-year period represented 35.1% of the pregnancies in the Rochester metropolitan region.
 A hemoglobinopathy was found in 810 pregnancies (4.3%).
 Of the 21 different types of hemoglobinopathies detected, the most common were sickle cell trait (59%), hemoglobin C trait (19%), beta-thalassemia trait (11%), and hemoglobin E trait (5%).
 At the time of phlebotomy, 75% of the pregnancies were of less than 18 wk duration.
 Sixty-six percent of the pregnancies occurred in patients unaware of their diagnosis, and 80% occurred in patients unaware that they might be at risk for a child with a serious blood disorder.
 Of the 810 positive pregnancies, 551 (68%) occurred in patients who came for counseling.
 Of 453 women counseled during their first screened pregnancy, 390 (86%) said they wanted their partners tested and 254 (55%) had their partner tested.
 In the 77 pregnancies thus found to be at risk, the couple was too late for prenatal diagnosis in 12 cases, and the condition for which the fetus was at risk was too mild in 12 cases.
 Prenatal diagnosis was offered in the remaining 53 pregnancies and was accepted by 25 couples (47%).
 These results indicate that unselected patients in the primary care setting in this region, even though pregnant, are receptive to and utilize genetic information.
",14
2662,"Prenatal screening for hemoglobinopathies. II. Evaluation of counseling 
 Learning during genetic counseling is often below expectations, especially in the context of genetic screening.
 In this report we describe learning as a result of genetic counseling of 298 pregnant women identified as hemoglobinopathy carriers, 234 with sickle cell trait and 64 with beta-thalassemia trait.
 Counseling was designed to provide the information needed in a simple, clear, and nondirective manner.
 A special videotape produced for this purpose provided dramatization and a role model illustrating an appropriate response.
 After viewing the videotape the counselee had an opportunity to question the counselor and to have any misconceptions corrected.
 Questionnaires revealed significantly increased knowledge as a result of counseling in each of the three hemoglobinopathy subject areas tested-namely, clinical manifestations, genetics, and prenatal diagnosis.
 Five factors correlated with higher knowledge scores after counseling-namely, a younger patient age, more years of education, knowledge of having trait before this identification, knowledge of the baby's father having trait before counseling, and having no prior children.
",14
2663,"Prenatal screening for hemoglobinopathies. III. Applicability of the health belief model.
 A comprehensive prenatal hemoglobinopathy screening program in Rochester, NY, has been described in a preceding paper in this issue of the Journal.
 A woman identified as a carrier may face three decisions.
 The first is whether to accept the offer of counseling.
 The second is whether to have her partner tested.
 If her partner also tests positive, then the third decision is whether to accept the offer of prenatal diagnosis.
 This report analyzes factors affecting her decision, with special attention being given to factors invoked by the Health Belief Model.
 Factors predicting that a patient who we identified as a carrier would come for counseling included the following: patient had no prior knowledge that she is a carrier (P less than .001), a gestational age less than 18 wk (P less than .01), and Caucasian race (P less than .05).
 For sickle cell trait counselees and beta-thalassamia trait counselees, factors found to predict patient's intent to have partner tested were the following: a greater postcounseling knowledge of the disease (P less than .009), a lesser perceived burden of intervention (P less than .011), and belief that the partner is also a carrier (P less than .008).
 Also for sickle cell trait counselees and beta-thalassemia trait counselees, factors predicting that the partner actually will be tested were the following: living with the partner (P less than .001), gestational age at identification less than or equal to 18 wk (P less than .001), a lesser perceived burden of intervention (P less than .002), and a greater perceived seriousness of the disease (P less than .05).
",14
2664,"Decreased content and surface expression of alpha-granule membrane protein GMP-140 in one of two types of platelet alpha delta storage pool deficiency.
 To determine whether alpha-granule membranes are present in platelets of patients with storage pool deficiencies of both alpha and dense granules (alpha delta-SPD), we examined the content and surface expression of the alpha-granule membrane protein GMP-140 in one patient (J.C.) with a severe alpha-granule deficiency and in three members of a family (family C) with milder alpha-granule deficiencies.
 Surface expression of GMP-140 in stimulated platelets, assessed by flow cytometric measurements of the binding of two anti-GMP-140 monoclonal antibodies, was 24-38% of normal values in platelets from patient J.C., vs.
 60-95% of normal values in family C.
 Total platelet content of GMP-140, determined in platelet lysates by antigen-capture ELISA, was 49% of normal in patient J.C., but normal in the members of family C.
 Platelets of patient J.C.
 were found to be heterogeneous with respect to GMP-140 content and surface expression by both flow cytometry and immunogold electron microscopy.
 Approximately 80% of her platelets expressed little or no GMP-140 after stimulation, whereas the remaining 20% expressed normal amounts of GMP-140 and showed extensive immunogold labeling of typical alpha-granules and clear vacuoles.
 No such heterogeneity was found in platelets from family C.
 These findings in the severe alpha delta-SPD patient are in clear contrast to the observations of normal GMP-140 content in the three other alpha delta-SPD patients, and in patients with the gray platelet syndrome, reported previously by others.
 These results illustrate the phenotypic heterogeneity of alpha-granule deficiencies in human platelets, and suggest that a defect in granule formation in the megakaryocytes may account for the alpha-granule defect in at least one form of alpha delta-SPD.
",14
2665,"Successful treatment of cat-scratch disease with ciprofloxacin.
 Cat-scratch disease is usually a benign, self-limited disease.
 Infection may be asymptomatic but is commonly associated with painful regional lymphadenitis.
 Occasionally, disease may result in systemic symptoms and dissemination.
 Five adult patients, aged 24 to 57 years, were diagnosed as having cat-scratch disease, based on a positive history of cat scratches followed by typical symptoms including painful regional lymphadenitis, malaise, and positive cat-scratch skin tests.
 Diagnostic evaluations revealed no other cause for the lymphadenitis.
 Three patients had not received prior treatment with antibiotics, and two patients had failed to improve on other antibiotics.
 All five were treated with oral ciprofloxacin, 500 mg by mouth, twice daily.
 All patients had dramatic improvement in symptoms within a few days and none has relapsed during follow-up.
 This is the first report of successful treatment of cat-scratch disease with ciprofloxacin, which appears to be an effective therapy for cat-scratch disease in adults.
",14
2666,"Aplastic anemia associated with antithyroid drugs.
 Prognosis in aplastic anemia is usually linked to the degree of hypoplasia in the bone marrow and pancytopenia in the blood.
 The authors were, therefore, intrigued when a patient with methimazole-associated aplastic anemia who satisfied criteria for severe disease recovered rapidly and completely once her drug was withdrawn.
 Review of the English language literature revealed ten fully documented cases of aplastic anemia associated with use of the antithyroid drugs methimazole, carbimazole, and propylthiouracil.
 Analysis of the ten and of an eleventh case presented here indicated that the disorder is typically characterized by severe pancytopenia and profound marrow hypoplasia, yet surprisingly good prognosis, ie, minimum survival of more than 70% with partial or complete recovery from symptoms and cytopenias in survivors within 2-5 weeks.
 The only deaths, both in the 1950s, were from brain hemorrhage in patients who were not transfused with platelets.
 The discrepancy between the clinical and laboratory severity of antithyroid drug-associated aplasia, on the one hand, and its relatively good prognosis and short term course, on the other, should be kept in mind when considering these patients for bone marrow transplantation or for therapy with antithymocyte globulin.
",14
2667,"Dystrophin analysis in the differential diagnosis of autosomal recessive muscular dystrophy of childhood and Duchenne muscular dystrophy.
 We report 2 patients with childhood autosomal recessive muscular dystrophy.
 Both patients had slight muscle weakness without enlargement of the calf muscles or involvement of the facial muscles.
 Their clinical courses are static.
 Muscle histology revealed characteristic features of muscular dystrophy.
 Dystrophin was identifiable in the sarcolemma of both patients by immunocytochemical staining with an antidystrophin antibody.
 At an early age, immunocytochemical analysis with antidystrophin antibody was useful in distinguishing between childhood autosomal recessive and Duchenne muscular dystrophies.
",15
2668,"Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa.
 BACKGROUND.
 Night blindness is an early symptom of retinitis pigmentosa.
 The rod photoreceptors are responsible for night vision and use rhodopsin as the photosensitive pigment.
 METHODS AND RESULTS.
 We found three mutations in the human rhodopsin gene; each occurred exclusively in the affected members of some families with autosomal dominant retinitis pigmentosa.
 Two mutations were C-to-T transitions involving separate nucleotides of codon 347; the third was a C-to-G transversion in codon 58.
 Each mutation corresponded to a change in one amino acid residue in the rhodopsin molecule.
 None of these mutations were found in 106 unrelated normal subjects who served as controls.
 When the incidence of these three mutations was added to that of a previously reported mutation involving codon 23, 27 of 150 unrelated patients with autosomal dominant retinitis pigmentosa (18 percent) were found to carry one of these four defects in the rhodopsin gene.
 All 27 patients had abnormal rod function on monitoring of their electroretinograms.
 It appears that patients with the mutation involving codon 23 probably descend from a single ancestor.
 CONCLUSIONS.
 In some patients with autosomal dominant retinitis pigmentosa, the disease is caused by one of a variety of mutations of the rhodopsin gene.
",15
2669,"Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells 
 The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique.
 Expression of CFTR, but not of a mutant form of CFTR (delta F508), corrected the Cl- channel defect.
 Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease.
",15
2670,"Expression and characterization of the cystic fibrosis transmembrane conductance regulator 
 Cystic fibrosis (CF) is a common lethal genetic disease that manifests itself in airway and other epithelial cells as defective chloride ion absorption and secretion, resulting at least in part from a defect in a cyclic AMP-regulated, outwardly-rectifying Cl- channel in the apical surface.
 The gene responsible for CF has been identified and predicted to encode a membrane protein termed the CF transmembrane conductance regulator (CFTR).
 Identification of a cryptic bacterial promoter within the CFTR coding sequence led us to construct a complementary DNA in a low-copy-number plasmid, thereby avoiding the deleterious effects of CFTR expression on Escherischia coli.
 We have used this cDNA to express CFTR in vitro and in vivo.
 Here we demonstrate that CFTR is a membrane-associated glycoprotein that can be phosporylated in vitro by cAMP-dependent protein kinase.
 Polyclonal and monoclonal antibodies directed against distinct domains of the protein immunoprecipitated recombinant CFTR as well as the endogenous CFTR in nonrecombinant T84 cells.
 Partial proteolysis fingerprinting showed that the recombinant and non-recombinant proteins are indistinguishable.
 These data, which establish several characteristics of the protein responsible for CF, will now enable CFTR function to be studied and will provide a basis for diagnosis and therapy.
",15
2671,"Evaluation of a perinatal autopsy protocol: influence of the Prenatal Diagnosis Conference Team.
 This study was designed to evaluate changes in the perinatal autopsy following the adoption of a new autopsy protocol.
 The University of Utah Medical Center has a Prenatal Diagnosis Conference Team composed of obstetricians, pediatricians, geneticists, and other health care professionals.
 These individuals are involved in the care of patients whose pregnancies are at risk for congenital malformations.
 An autopsy protocol was designed to increase the interaction of the pathologist with the Prenatal Diagnosis Conference Team in the evaluation of perinatal death.
 Two years, 1982 and 1987, before and after the protocol was implemented, were selected for retrospective review.
 The autopsies in 1987 made more specific diagnoses compared with those in 1982.
 Additional congenital anomalies were diagnosed, and increased numbers of patients were found to have well-described congenital disorders.
 The number of attempted postnatal autopsy chromosome studies increased and more chromosomal abnormalities were detected.
 The final autopsy diagnoses made in 1987 have provided more information to the physician for genetic or other patient counseling.
 After the protocol was adopted, increased numbers of cases were referred to the Medical Center for evaluation at autopsy.
 More of those who came to autopsy had been evaluated during life by members of the Prenatal Diagnosis Conference Team.
 Premortem sonograms had been done at an earlier gestational age and a greater number of anomalies were detected.
 Fewer of the fetuses had intrauterine death and more had pregnancy terminated by induction of labor.
 The gestational age at delivery declined.
",15
2672,"""Macrosomic"" twinning: a study of growth-promoted twins.
 We evaluated 56 twin pregnancies representing the tenth decile of the mean twin birth weight distribution to investigate whether larger twins face the same increased perinatal risk as do macrosomic singletons.
 Compared with pregnancies in the ninth decile, no significant difference was found between the means of maternal age, parity, and gestational age; between the rates of presentation combinations and cesareans; or between the neonatal sex ratios.
 However, the incidence of growth-discordant pairs was significantly higher in the heavier group (P = .034).
 Compared with the general twin population, the tenth-decile group contained significantly fewer primiparas (P = .0023).
 Maternal obesity and diabetes were infrequent and could not explain the increased birth weight.
 The neonatal outcome was excellent.
 Although the comparison revealed insignificant differences, it is possible that the combination of higher parity, malpresentation rate, and male-to-female ratio may be operative in the genesis of large twins.
",15
2673,"The modified superior based pharyngeal flap technique. Part II. An anatomic study.
 There is little in the literature on the topographic and/or applied surgical anatomy related to superior based pharyngeal flap surgery.
 Herein we report on the applied surgical anatomy of pharyngeal flap surgery, especially as it applies to critical anatomic relationships to vessels, muscles, and nerves.
",15
2674,"Single- versus multiple-dose surfactant replacement therapy in neonates of 30 to 36 weeks' gestation with respiratory distress syndrome.
 To assess the efficacy of a multiple-dose protocol of surfactant replacement therapy in neonates of 30 to 36 weeks' gestation, 75 neonates were randomly assigned to control, single-dose surfactant, or multiple-dose surfactant groups.
 Neonates at less than 6 hours of age with a diagnosis of respiratory distress syndrome were eligible.
 Subjects were randomly assigned to receive either 100 mg/kg of bovine surfactant or air placebo.
 Neonates in the multiple-dose group were eligible to receive up to three additional doses as indicated.
 Neonates in both surfactant groups showed a positive response to treatment, with marked improvement in oxygenation by 10 minutes postinstillation (P less than .0001).
 Both surfactant groups had better oxygenation than control subjects at lower ventilatory parameters over the first 24 hours.
 A deterioration in oxygenation and ventilatory requirements was seen in both treatment groups starting 6 to 12 hours after the first dose.
 The deterioration in oxygenation could be minimized by the use of multiple doses; however, extra doses had no effect on diminishing ventilatory requirements or time to extubation.
 It is concluded that surfactant therapy at less than 6 hours of age is effective in acutely reducing oxygen and ventilatory requirements in neonates of 30 to 36 weeks' gestation with respiratory distress syndrome.
 It appears that multiple doses of surfactant have a greater effect on sustaining improvements in oxygenation than on ventilatory requirements.
 Further study is required to determine optimal dosage and retreatment strategy.
",15
2675,"The cloacal malformation: radiologic findings and imaging recommendations.
 The imaging studies and records of 65 patients with the cloacal malformation seen from 1969 to 1989 were reviewed.
 The malformations were described according to cloacal configuration (urethral, vaginal), type of urinary-cloacal communication (urethral, vesical), and level of rectal communication (vaginal, cloacal, vesical, other).
 Lower urinary tract abnormalities were frequent (reflux, ureteral ectopia, bladder diverticula, bladder duplication, urachal remnants, urethral duplication), as were genital abnormalities (uterine duplication, vaginal duplication, uterine atresia, vaginal atresia), abnormalities of the bony pelvis (partial sacral agenesis, pubic diastasis), and renal abnormalities (agenesis, obstruction, horseshoe kidney).
 Contrast material studies of the cloaca and the distal limb of the colostomy with fluoroscopy in various projections were essential for diagnosis.
 Voiding cystourethrography was important for detecting vesicoureteric reflux.
 Sonography was of limited value for evaluation of the malformation but was valuable for imaging the kidneys.
 MR imaging revealed that spinal cord abnormalities cannot be predicted based on the appearance of the lumbosacral spine and are more common than previously thought.
",15
2676,"Neonatal screening and staggered early treatment for congenital dislocation or dysplasia of the hip.
 In 14 264 consecutive newborn babies the results of screening and early treatment for congenital dislocation and/or dysplasia of the hip (CDH) were evaluated in a prospective follow-up study.
 Barlow's test was done and the family history was recorded.
 Babies who were positive (n = 140) were immediately given abduction treatment.
 If the screening result was doubtful (133) or if the test was negative but the family history positive (685) the child was radiographed at 5 months and abduction treatment was started if any form of CDH was seen.
 Among Barlow-negative children with no family history (13,306), two reference groups were selected--at age 5 months (596) and at age 2 years (4365).
 Dislocation was missed at screening in 0.02%.
 Dysplasia was seen at 5 months in 15% of Barlow-negative children with a positive family history and in 2-3% of the reference group children.
 Crude estimates of the lower limits of validity indices for the screening test showed that the test is efficient in the identification of dislocation but probably has no value for dysplasia.
 Of the babies in whom treatment was started immediately 17% had relapse dysplasia after withdrawal of therapy, 3% had avascular necrosis, and 78% were normal at 2 years.
 When treatment was started at 5 months we found no relapse dysplasia, only 1% avascular necrosis, and 53-63% success at 2 years.
 In children with dislocatable hips we propose a wait-and-see treatment strategy, with early ultrasonography or radiography at 5 months.
",15
2677,"Controlled trial of immediate splinting versus ultrasonographic surveillance in congenitally dislocatable hips.
 79 infants with congenitally dislocatable hips diagnosed clinically soon after birth were examined sonographically and randomised in a controlled trial to immediate splinting (n = 41) or sonographic surveillance for 2 weeks (38).
 Infants from this second group were splinted at age 2 weeks if instability persisted (11 of 38) or if sonographic abnormality had shown no improvement (4 of 38).
 Sonographic findings or clinical outcome did not differ between the two groups at birth or at 6 and 12 months' follow-up.
 We conclude that dislocatable hips may be safely watched for 2 weeks after birth to allow spontaneous resolution, but that this approach requires considerable resources and attention to detail.
 Our experience confirms the importance of the dynamic sonographic scan.
 The low specificity (70%) of sonographic examination in the first week of life makes it an unsatisfactory primary method of screening at birth, but it is a most useful adjunct to the clinical screening and management of congenital dislocation of the hip.
",15
2678,"Body composition in myelomeningocele.
 Body composition and measures of obesity were evaluated in 59 subjects with myelomeningocele (MMC), aged 0.3-29 y, by anthropometry and measures of body cell mass (BCM) and intra- and extracellular water (ICW and ECW), derived from total body potassium and deuterium-isotope dilution; these results were compared with reference data.
 Body composition was normal in preambulatory children with MMC.
 Beyond ages 3-4 y there was significant depletion of BCM and total body water, with maldistribution of water (increased ECW and decreased ICW) and increased percentage body fat above that expected for age and sex.
 These findings were more pronounced in females and in those with high lesions, and were less pronounced in those who remained ambulatory.
 These changes may result in metabolic and nutritional maladaption during stress.
 The relation of BCM, total body water depletion and increased ECW to decreasing ambulatory activity suggests that early nutritional and mobility programs warrant further study.
",15
2679,"The effect of maternal hyperoxia on behavioral activity in growth-retarded human fetuses.
 Thirteen pregnant women who subsequently were delivered of infants with birth weights less than the 3rd percentile were studied for examination of fetal heart rate and fetal activity patients during maternal administration of oxygen at a concentration of 50% or room air for 2 hours.
 None of the fetuses was acidotic at birth.
 Maternal transcutaneous PO2 levels increased from 79 +/- 3 mm Hg to 158 +/- 10 mm Hg for the 2 hours of observation.
 The results indicated that maternal hyperoxia produced sustained fetal breathing activity that was almost 100% higher than that in room air (analysis of variance, p = 0.024).
 Gross fetal body movements, fetal heart rate accelerations, and fetal heart rate variability increased significantly with increasing observation time (analysis of variance, p less than 0.01), but were not significantly altered by maternal hyperoxia or room air.
 We conclude that despite significant change in fetal breathing activity, ultrasonographic observation of fetal behavioral activity during maternal hyperoxia could not be used to differentiate severely growth-retarded from normally grown human fetuses.
 We speculate that altered fetal heart rate and fetal body movement patterns usually associated with intrauterine growth retardation might be related to altered development of the fetal central nervous system and are not reversible during prolonged maternal administration of oxygen.
",15
2680,"Color matching and foveal densitometry in patients and carriers of an X-linked progressive cone dystrophy.
 We describe a family with an as yet undescribed form of X-linked progressive cone dystrophy in a five-generation pedigree, from which we report here the results of 17 male patients and 31 obligate and 13 possible female carriers.
 The affected males showed the characteristic picture of cone dystrophy.
 Foveal cone photopigment density was impaired (judged from anomaloscope settings and foveal densitometry), even at an early stage of the disease.
 The carriers showed no fundus abnormalities, except occasional changes due to myopia.
 The anomaloscope demonstrated mild pseudoprotanomaly in 27 of 31 obligate carriers and in six of 13 possible carriers.
 Foveal densitometry findings performed in 11 carriers always agreed with the anomaloscope findings.
 We conclude that the findings of pseudoprotanomaly and abnormal density differences in females of this family were the only ocular abnormalities and thus are indicative of the carrier state.
",15
2681,"Ultrasound in the diagnosis of congenital dysplasia and dislocation of the hip joints in children older than two years.
 To evaluate the use of ultrasound in the diagnosis to congenital dysplasia and dislocation of the hip (CDH) in children older than two years of age, 64 patients with normal hip joints and 47 patients with present or previous CDH were examined.
 Lateral and anterior ultrasound scanning was employed, and the coverage of the femoral head by the acetabular roof was assessed.
 The ultrasound measurements were compared with standard roentgenography, and a good accordance between the methods was found.
 A lateral projection of the femoral head in relation to the bony acetabular rim of more than 8 mm in children younger than ten years of age indicated subluxation and more than 15 mm at age two to four years indicated dislocation.
 Reliable images were obtained by ultrasound at any age between two and 18 years.
 Ultrasound is recommended as the primary imaging technique in the evaluation of hip joints, even in older children, and ultrasound should replace roentgenography in most of the follow-up examinations of children with previous CDH.
",15
2682,"Pulmonary atresia with ventricular septal defect. Selection of patients for systemic-to-pulmonary artery shunt based on echocardiography.
 From January 1987 to December 1988, in 22 infants with PAVSD, the diagnostic results obtained with echocardiography (two-dimensional, Doppler, and color) were prospectively compared to the angiocardiographic findings.
 We classified into group 1 patients with confluent and good-sized pulmonary (greater than or equal to 3 mm) arteries, single ductus arteriosus, and normal pulmonary venous connections (""favorable pattern"").
 The other patients with PAVSD were classified into group 2 (""unfavorable pattern"").
 The intracardiac anatomy, the morphology of the pulmonary arteries, and the pattern of pulmonary blood supply and pulmonary venous connection were correctly identified with echocardiography in all but one patient, who was erroneously considered to be in group 2.
 No false-positive of the ""favorable pattern"" (group 1) was detected.
 Echocardiography is an effective tool in infants with PAVSD, in order to discriminate cases with ""favorable"" and ""unfavorable"" patterns of pulmonary arteries, pulmonary blood supply, and pulmonary veins.
 The first group with the ""favorable pattern"" may be considered for systemic-to-pulmonary shunt surgery without angiocardiography.
 Based on this experience from January to December 1989, four patients with this ""favorable pattern"" underwent a successful systemic-to-pulmonary artery shunt with an echocardiographic diagnosis alone.
",15
2683,"Di George anomaly with atrioventricular canal.
 We report the first case of Di George anomaly associated with atrioventricular canal.
 This combination of anomalies may represent a chance occurrence of two situations happening in the same patient or, alternatively, the result of a single unknown embriogenetic mechanism.
",15
2684,"Helping a child to understand her own testicular feminisation 
 Children do not think as adults do.
 They would therefore be less worried than adults are about a diagnosis with serious or ominous implications, yet they are commonly left uninformed until someone judges that they are old enough to understand.
 For most, this means delivery of painful information during the very vulnerable teenage years.
 A better approach is to unfold the truth stage by stage, matching simple statements to the child's conceptual growth until the personal implications are finally realised as part of a maturing process.
 Use of this approach for a child with testicular feminisation is described.
",15
2685,"Characterization of a splicing mutation in group A xeroderma pigmentosum.
 The molecular basis of group A xeroderma pigmentosum (XP) was investigated by comparison of the nucleotide sequences of multiple clones of the XP group A complementing gene (XPAC) from a patient with group A XP with that of a normal gene.
 The clones showed a G----C substitution at the 3' splice acceptor site of intron 3, which altered the obligatory AG acceptor dinucleotide to AC.
 Nucleotide sequencing of cDNAs amplified by the polymerase chain reaction revealed that this single base substitution abolishes the canonical 3' splice site, thus creating two abnormally spliced mRNA forms.
 The larger form is identical with normal mRNA except for a dinucleotide deletion at the 5' end of exon 4.
 This deletion results in a frameshift with premature translation termination in exon 4.
 The smaller form has a deletion of the entire exon 3 and the dinucleotide at the 5' end of exon 4.
 The result of a transfection study provided additional evidence that this single base substitution is the disease-causing mutation.
 This single base substitution creates a new cleavage site for the restriction nuclease AlwNI.
 Analysis of AlwNI restriction fragment length polymorphism showed a high frequency of this mutation in Japanese patients with group A XP: 16 of 21 unrelated Japanese patients were homozygous and 4 were heterozygous for this mutation.
 However, 11 Caucasians and 2 Blacks with group A XP did not have this mutant allele.
 The polymorphic AlwNI restriction fragments are concluded to be useful for diagnosis of group A XP in Japanese subjects, including prenatal cases and carriers.
",15
2686,"Mothers' postcounseling beliefs about the causes of their children's genetic disorders.
 Mothers' postcounseling beliefs about the causes of their children's genetic disorders were investigated by means of a Q-sort consisting of 54 statements of possible beliefs that were sorted into nine groups of six items each on the basis of congruence with the subject's beliefs.
 The subjects were well educated, knowledgeable about the genetics of their child's disorder, and indicated a high level of belief in genetic causes.
 Differences in beliefs were associated with differences in genetic etiology, indicating that beliefs were affected by the specific information provided in genetic counseling.
 Factor analysis identified a cluster of Q-sort items characterized by a highly personal relationship to the cause of the disorder (e.g., personal attributes, being selected and blessed, and God's actions).
 Subjects who rated these items low had a belief pattern, designated impersonal, that was consistent with a scientific worldview and that indicated psychological distancing from the cause of the child's disorder.
 Subjects who rated these items high, the personal belief pattern, had a mixture of scientific and nonscientific beliefs that indicated a sense of personal involvement in the cause of the child's disorder.
 Subjects with the two belief patterns were equally knowledgeable about the genetics of the disorder.
 Thus, the personal belief pattern did not appear to interfere with acceptance or understanding of the information provided in genetic counseling.
",15
2687,"Waardenburg syndrome (WS): the analysis of a single family with a WS1 mutation showing linkage to RFLP markers on human chromosome 2q.
 Waardenburg syndrome type I (WS1; MIM 19350) is caused by a pleiotropic, autosomal dominant mutation with variable penetrance and expressivity.
 Of individuals with this mutation, 20%-25% are hearing impaired.
 A multilocus linkage analysis of RFLP data from a single WS1 family with 11 affected individuals indicates that the WS1 mutation in this family is linked to the following four marker loci located on the long arm of chromosome 2: ALPP (alkaline phosphatase, placental), FN1 (fibronectin 1), D2S3 (a unique-copy DNA segment), and COL6A3 (collagen VI, alpha 3).
 For the RFLP marker loci, a multilocus linkage analysis using MLINK produced a peak lod (Z) of 3.23 for the following linkage relationships and recombination fractions (theta i): (ALPP----.000----FN1)----.122----D2S3----.267----CO L6A3.
 A similar analysis produced a Z of 6.67 for the following linkage relationships and theta i values among the markers and WS1: (FN1----.000----WS1----.000----ALPP)----.123----D2S 3----.246----COL6A3.
 The data confirm the conclusion of Foy et al.
 that at least some WS1 mutations map to chromosome 2q.
",15
2688,"Ocular clinicopathologic study of gyrate atrophy.
 We performed a histopathologic study of whole globes obtained post mortem from a patient with well-documented, vitamin B6-responsive gyrate atrophy.
 The retina in the posterior pole had focal areas of photoreceptor atrophy with adjacent retinal pigment epithelial hyperplasia.
 An abrupt transition from the near normal retina to a zone of near total atrophy of the retina, retinal pigment epithelium, and choroid was present in the fundus midperiphery.
 Electron microscopic examination disclosed abnormalities of the mitochondria of the corneal endothelium and the non-pigmented ciliary epithelium.
 Similar, but less severe, mitochondrial abnormalities were present in the photoreceptors.
",15
2689,"Staged repair of pulmonary atresia with ventricular septal defect and major systemic to pulmonary artery collaterals 
 Fifty-eight consecutive patients with pulmonary atresia, ventricular septal defect, hypoplastic pulmonary arteries with arborization defects, and major aortopulmonary collaterals were entered into a program for staged surgical repair between January 1979 and July 1989.
 Prerepair preparatory procedures were designed to (1) encourage native pulmonary artery growth by increasing blood flow and (2) unifocalize pulmonary blood supply by transplanting or ligating major collaterals.
 A total of 121 staging procedures were performed with an overall mortality of 10.3%.
 One hundred thirty-four major collaterals were either ligated or transplanted.
 Thirty patients eventually underwent hemodynamic repair with an early mortality of 3.3% and late mortality of 10.0%.
 Twenty-six current survivors of repair remain clinically well after a mean follow-up of 3.6 years.
 Ten patients are currently in various stages of preparation.
 Twelve patients (20.7%) failed to achieve minimum requirements for repair after staging and await further palliation or heart-lung transplantation.
 The principles of management have evolved over the years and are discussed.
",15
2690,"Abnormal fucosylation of ileal mucus in cystic fibrosis: I. A histochemical study using peroxidase labelled lectins.
 Peroxidase conjugated lectins were used to analyse the glycoproteins of small intestinal mucins in normal infants and those with cystic fibrosis to ascertain whether there are any detectable histochemical differences in saccharide composition.
 A significant decrease in Lotus tetragonolobus (LTG) binding fucose was shown in normal small intestinal mucin starting around 36 weeks' gestation with total absence of staining at term and beyond.
 In contrast, the age matched patients with cystic fibrosis showed persistent and intense LTG binding of fucose.
 These results provide the first clear histochemical evidence that cystic fibrosis mucin is abnormal and confirm the findings of previous biochemical studies.
",15
2691,"Abnormal fucosylation of-ileal mucus in cystic fibrosis: II. A histochemical study using monoclonal antibodies to fucosyl oligosaccharides.
 Abnormal fucosylation of cystic fibrosis mucin was previously shown using peroxidase conjugated lectins on ileal tissue sections.
 These abnormally fucosylated glycoproteins were investigated further using monoclonal antibodies to fucosyl oligosaccharides based on type 1 and type 2 blood group precursor chains.
 The results of this study, using monoclonal antibodies to blood group glycoproteins in cystic fibrosis, were negative, yet abnormal fucosylation had been found using lectin histochemistry.
 Using monoclonal antibodies, lectins, and appropriate enzymes, such as glycosyl hydrolases, it should be possible to delineate further the abnormality found in glycoproteins in cystic fibrosis on appropriately fixed ileal sections, obtained from infants at term presenting with meconium ileus.
",15
2692,"Quelprud's nodule: a post-auricular cartilaginous nodule.
 A number of minor variations to the configuration of the external ear are well recognized.
 This paper brings attention to one entity which is characterized by a small cartilaginous nodule or prominence arising from the posterior surface of the pinna and which we have named Quelprud's nodule.
 A prospective clinical survey of 208 patients attending an ENT clinic revealed that nearly one-third of the population studied possess this nodule.
 There was an equal sex incidence.
 The Quelprud's nodule was identified within families in a distribution which suggests an autosomal dominant inheritance with variable expressivity.
",15
2693,"Cardiovascular abnormalities in infants prenatally exposed to cocaine.
 This study utilized a historical cohort to examine the relationship between maternal cocaine use during pregnancy and the occurrence of congenital cardiovascular abnormalities.
 All neonatal drug screens performed at Boston City Hospital during an 18-month period were reviewed (n = 554); for 214 (39%) screened high-risk neonates, results of toxicologic screens were positive for cocaine, and 340 (61%) neonates had no detectable cocaine.
 We compared the occurrence of cardiovascular malformations and electrocardiographic abnormalities in these two groups.
 Matches were sought between these 554 infants and our pediatric cardiology data base, which consisted of inpatient consultation, outpatient consultation, and electrocardiography.
 Forty-nine patients had drug screens and were also entered into our cardiology data base: 25 had both consultations and electrocardiograms, and 24 had electrocardiograms only.
 The rate of cardiac anomalies among the cocaine-positive infants was significantly higher (relative risk = 3.7; 95% confidence interval: (1.4, 9.4)) than the rate of these anomalies among the cocaine-negative comparison group (65/100 vs 18/1000); the rate for cocaine-positive infants was also significantly higher than published rates for general populations of infants.
 Several electrocardiographic abnormalities, high-grade ventricular ectopy, and cardiorespiratory arrests were also noted in our study population.
 We conclude that cocaine exposure during prenatal life appears to predispose infants to structural cardiovascular malformations, electrocardiographic abnormalities, and, possibly, cardiopulmonary autonomic dysfunction.
",15
2694,"Genetic disease detection and DNA amplification using cloned thermostable ligase.
 Polymerase chain reaction, using thermostable DNA polymerase, has revolutionized DNA diagnostics.
 Another thermostable enzyme, DNA ligase, is harnessed in the assay reported here that both amplifies DNA and discriminates a single-base substitution.
 This cloned enzyme specifically links two adjacent oligonucleotides when hybridized at 65 degrees C to a complementary target only when the nucleotides are perfectly base-paired at the junction.
 Oligonucleotide products are exponentially amplified by thermal cycling of the ligation reaction in the presence of a second set of adjacent oligonucleotides, complementary to the first set and the target.
 A single-base mismatch prevents ligation/amplification and is thus distinguished.
 This method was exploited to detect 200 target molecules as well as to discriminate between normal beta A- and sickle beta S- globin genotypes from 10-microliters blood samples.
",15
2695,"Double-blind comparison of oral transmucosal fentanyl citrate with oral meperidine, diazepam, and atropine as preanesthetic medication in children with congenital heart disease.
 The effectiveness of oral transmucosal fentanyl citrate (OTFC) as preanesthetic medication was compared with oral meperidine, diazepam, and atropine (MDA) in 40 pediatric patients scheduled to undergo repair of congenital heart defects.
 In a double-blinded manner, patients received a fentanyl lollipop (20-25 micrograms/kg) and a placebo oral solution (0.4 ml/kg) (n = 20) or a placebo lollipop and an oral solution (0.4 ml/kg) of meperidine (1.5 mg/kg), diazepam (0.2 mg/kg), and atropine (0.02 mg/kg) (n = 20).
 The patient's vital signs, systolic and diastolic blood pressures, heart rate, respiratory rate, and oxyhemoglobin saturation (SpO2), as well as activity and apprehension scores were evaluated and recorded at baseline and at 10-min intervals.
 The patient's emotional status at the time of parental separation and at induction of anesthesia were also assessed.
 Side effects and onset of action were observed.
 After OTFC, onset of sedation was significantly faster than with the oral solution of meperidine, diazepam, and atropine.
 In both groups there was no significant change in heart rate.
 Although systolic blood pressure, diastolic blood pressure, and respiratory rate showed statistically significant decreases, these changes were not clinically significant.
 The child's emotional status at the time of separation from the parents and during induction was similar in both groups.
 Side effects with OTFC were more frequent: nose itching occurred in 65%, body itching in 10%, and vomiting in 30%.
 Two patients (10%) in the OTFC-treated group became hypoxemic (SpO2 less than 90) and required supplemental oxygen.
 In the group receiving oral meperidine, diazepam, and atropine, 10% had mild facial pruritus and 5% complained of a dry mouth.
",15
2696,"Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting.
 Evidence suggests that insulin-like growth factors-I and -II (IGF-I and II) play a role in regulating fetal growth and development.
 In the fetus, IGF-I and -II are complexed with two specific binding proteins (IGFBP-1 and -2), which are thought to modulate the actions of the IGFs in target tissues.
 We examined regulation of the genes for IGF-I, IGF-II, IGFBP-1, and IGFBP-2 in fetal rat liver in an experimental model for intrauterine growth retardation caused by maternal fasting on days 17-21 of gestation.
 The mean weight of fetuses from the fasted dams was 27-32% lower than the mean weight of fetuses from the fed dams.
 The concentration of immunoreactive IGF-I was decreased by 71% in serum of fetuses from the fasting dams.
 The concentration of immunoreactive IGF-II was slightly decreased (by 12%) in serum of fetuses from the fasting dams, whereas the concentration of immunoreactive pro-IGF-II E-domain peptide was decreased by 31%.
 The abundance of hepatic IGF-I mRNA was decreased by 55% in fetuses from the fasting dams.
 In contrast, the abundance of IGF-II mRNA in fetal liver was not significantly decreased by maternal fasting.
 Maternal fasting caused a 2-fold increase in the abundance of IGFBP-1 mRNA in fetal liver, whereas it did not change the abundance of IGFBP-2 mRNA.
 The induction of IGFBP-1 mRNA in liver of the growth-retarded fetuses is similar to the induction that occurs in liver of fasting adults, while the lack of regulation of IGFBP-2 mRNA differs from the strong induction of IGFBP-2 mRNA that occurs in liver of fasting adults.
 In summary, these results indicate that maternal fasting causes a decrease in fetal IGF-I gene expression, a decrease in fetal serum IGF-I, and a slight decrease in fetal serum IGF-II and pro-IGF-II E-domain peptide concentrations.
 Maternal fasting also causes an increase in fetal IGFBP-1 gene expression.
 Changes in fetal insulin and glucose may be related to changes in expression of the IGF-I and IGFBP-1 genes in the growth-retarded fetuses.
 The decreased expression of IGF-I and -II and increased expression of the IGFBP-1 gene may contribute to the fetal growth retardation observed in this model system.
",15
2697,"Control of the sperm-oocyte switch in Caenorhabditis elegans hermaphrodites by the fem-3 3' untranslated region.
 In the Caenorhabditis elegans hermaphrodite germ line, sperm and then oocytes are made from a common pool of germ-cell precursors.
 The decision to differentiate as a sperm or an oocyte is regulated by the sex-determining gene, fem-3.
 Expression of fem-3 in the hermaphrodite germ line directs spermatogenesis and must be negatively regulated to allow the switch to oogenesis.
 In adult hermaphrodites (which are producing oocytes), most fem-3 RNA is found in the germ line, consistent with both the requirement for fem-3 in hermaphrodite spermatogenesis and the maternal effects of fem-3 on embryonic sex determination.
 Whereas loss-of-function mutants in fem-3 produce only oocytes, hermaphrodites carrying any of nine fem-3 gain-of-function (gf) mutations make none; instead sperm are produced continuously and in vast excess over wild-type amounts.
 Genetic analyses suggest that fem-3(gf) mutations have escaped a negative control required for the switch to oogenesis.
 Here we report that all nine fem-3(gf) mutants carry sequence alterations in the fem-3 3' untranslated region (3' UTR).
 There is no increase in the steady-state level of fem-3(gf) RNA over wild-type, but there is an increase in the polyadenylation of fem-3(gf) RNA that is coincident with the unregulated fem-3 activity.
 Results of a titration experiment support the hypothesis that a regulatory factor may bind the fem-3 3' UTR.
 We speculate that fem-3 RNA is regulated through its 3' UTR by binding a factor that inhibits translation, and discuss the idea that this control may be part of a more general regulation of maternal RNAs.
",15
2698,"Autosomal dominant sectoral retinitis pigmentosa. Two families with transversion mutation in codon 23 of rhodopsin.
 A cytosine-to-adenine transversion in codon 23 of rhodopsin, the rod visual pigment gene, was reported recently by Dryja et al in 17 of 148 unrelated patients with autosomal dominant retinitis pigmentosa, but the clinical findings associated with this deletion have not been reported in detail.
 In screening our patients with autosomal dominant retinitis pigmentosa for the codon 23 transversion, we found positive results in four affected individuals from two families with sectoral retinitis pigmentosa, while 12 patients with sectoral retinitis pigmentosa from different families had negative results, suggesting that other gene sites or locations may give this same phenotypic change.
 From our patients' history of light exposure and the location of degeneration in the retina, we hypothesize that light phototoxicity may be playing an expressive role in this point mutation of the rhodopsin gene.
 This is the first report in which a type of retinitis pigmentosa has been associated with a specific molecular gene defect, although the actual pathophysiologic mechanism currently is unknown.
",15
2699,"Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (Pro-23-His).
 Ocular findings are presented from 17 unrelated patients with a form of autosomal dominant retinitis pigmentosa and the same cytosine-to-adenine transversion in codon 23 of the rhodopsin gene corresponding to a substitution of histidine for proline in the 23rd amino acid of rhodopsin (designated rhodopsin, Pro-23-His).
 On average, these patients (mean age, 37 years) had significantly better visual acuity and larger electroretinographic amplitudes than 131 unrelated patients (mean age, 32 years) with autosomal dominant retinitis pigmentosa without this mutation.
 However, these 17 patients from separate families, as well as 12 relatives with the mutation from four of these families, showed interfamilial and intrafamilial variability with respect to severity of their ocular disease, suggesting that some factor(s) other than this gene defect itself is involved in the expression of their condition.
 This form of retinitis pigmentosa can now be detected by testing leukocyte DNA from peripheral blood.
 Some mechanisms by which this mutation in the rhodopsin gene could lead to rod photoreceptor cell death are suggested.
",15
2700,"Anomalous subaortic position of the brachiocephalic vein (innominate vein): an echocardiographic study.
 In 24 (0.98%) of 2457 patients with congenital heart disease the brachiocephalic vein was in an anomalous position below the aortic arch.
 This is a much higher proportion of such cases than reported so far.
 This high frequency may arise from differences in the study population and the method of diagnosis.
 This venous anomaly was more common in patients with tetralogy of Fallot or ventricular septal defect with pulmonary atresia.
 Patients with the venous anomaly were more likely to have a right aortic arch.
 The anomalous course of the brachiocephalic vein from the neck to the junction of the superior vena cava was shown by cross sectional echocardiography.
 In doubtful cases, Doppler study usually clarified the anatomical arrangement.
",15
2701,"Polyorchidism: case report and review of literature.
 Polyorchidism is a rare anomaly with approximately 70 cases reported in the literature.
 It may result from transverse division of the urogenital ridge, a hypothesis that best explains the anatomical features of the supernumerary testicle.
 The primary accompanying disorders and anomalies include maldescended testis, inguinal hernia and torsion.
 Malignancy has been reported in 3 cases.
 In the absence of any concomitant disorder and if testicular tumor can be ruled out by magnetic resonance imaging and ultrasonography, surgical exploration with biopsy is unnecessary.
",15
2702,"""Woven"" right coronary artery: case report and therapeutic implications.
 We report an unusual anomaly of the right coronary artery consisting of proximal branching of the artery and subsequent interweaving of the branches, referred to as a ""woven"" coronary artery.
 Implications and differential diagnosis are discussed.
",15
2703,"Cystic fibrosis transmembrane conductance regulator: nucleotide binding to a synthetic peptide.
 Multiple mutations in the gene responsible for cystic fibrosis are located within a region predicted to encode a nucleotide-binding fold in the amino terminal half of the cystic fibrosis transmembrane conductance regulator protein.
 A 67-amino acid peptide (P-67) that corresponds to the central region of this putative nucleotide binding site was chemically synthesized and purified.
 This peptide bound adenine nucleotides.
 The apparent dissociation constants (Kd's) for the trinitrophenyl (TNP) adenine nucleotides, TNP-adenosine triphosphate, TNP-adenosine diphosphate, and TNP-adenosine monophosphate, were 300 nanomolar, 200 nanomolar, and greater than 1 micromolar, respectively.
 The Kd for adenosine triphosphate was 300 micromolar.
 Circular dichroism spectroscopy was used to show that P-67 assumes a predominantly beta sheet structure in solution, a finding that is consistent with secondary structure predictions.
 On the basis of this information, the phenylalanine at position 508, which is deleted in approximately 70 percent of individuals with cystic fibrosis, was localized to a beta strand within the nucleotide binding peptide.
 Deletion of this residue is predicted to induce a significant structural change in the beta strand and altered nucleotide binding.
",15
2704,"Tuberous sclerosis.
 Tuberous sclerosis is an inherited disorder characterized by a triad of signs--mental retardation, seizures and adenoma sebaceum.
 The hamartomas that commonly affect multiple organ systems can be seen on plain film radiography.
 Computed tomography and ultrasonography are useful for assessing whether lesions are present in the abdomen, kidneys and brain.
 The hamartomas tend to bleed, causing symptoms and prompting the need for evaluation.
",15
2705,"A dimorphic 4-bp repeat in the cystic fibrosis gene is in absolute linkage disequilibrium with the delta F508 mutation: implications for prenatal diagnosis and mutation origin.
 The gene causing cystic fibrosis (CF) has been recently cloned, and the major mutation (delta F508) accounting for approximately 70% of CF chromosomes has been uncovered.
 We have identified at the 3' end of intron 6 in the CF gene a 4-bp tandem repeat (GATT) that exhibits interesting features.
 First, PCR screening of 103 normal individuals revealed that the repeat exists only in two polymorphic allelic forms, either as a hexamer or a heptamer.
 These two alleles are in Hardy-Weinberg equilibrium and predict a heterozygote frequency of 41% (p[seven repeats] = .71; q [six repeats] = .29).
 Second, the allele with six repeats was found linked to delta F508 on all 76 CF chromosomes investigated, demonstrating strong linkage disequilibrium and suggesting that delta F508 had originated on the gene bearing six repeats.
 Third, when the repeat alleles are linked to the DNA markers XV2c and KM19, extended haplotypes are generated.
 These new haplotypes become informative in situations in which prenatal diagnosis cannot be performed solely with XV2c and KM19.
 Since this repeat marker is located in the CF gene and would be very less likely to recombine with the gene, it can serve as a valuable DNA marker for haplotype analysis.
 A possible crossover, however, was identified between XV2c and KM19, transferring delta F508 to a different haplotype.
",15
2706,"Two frameshift mutations in the cystic fibrosis gene.
 Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene.
 We have identified in exon 7 two frameshift mutations, one caused by a two-nucleotide insertion and the other caused by a one-nucleotide deletion; these mutations--CF1154insTC and CF1213delT, respectively, are predicted to shift the reading frame of the protein and to introduce UAA(ochre) termination codons at residues 369 and 368.
",15
2707,"Closure of the ductus arteriosus with indomethacin in ventilated neonates with respiratory distress syndrome. Effects of pulmonary compliance and ventilation.
 The reported effects of indomethacin on pulmonary compliance are variable depending upon the patient population and on the degree to which indomethacin resulted in successful ductal closure.
 Eleven fluid-restricted, furosemide-treated premature infants being mechanically ventilated for respiratory distress syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had pulmonary function testing performed before and after successful closure of the PDA.
 The diagnosis of a significant PDA was made by clinical and echocardiographic criteria.
 Indomethacin was administered at a dosage of 0.2 mg/kg/dose every 12 to 18 h for 1 to 3 doses.
 To control for the 48-h time interval to achieve ductal closure, nine premature infants being ventilated for RDS but who did not have a significant PDA also had pulmonary function evaluations performed before and after the 48 h.
 Also, to control for the independent effect of fluid restriction and diuretic therapy on pulmonary compliance, eight such premature infants with a PDA had pulmonary function evaluations performed at a 48-h interval.
 Successful closure of the ductus with indomethacin was associated with an improvement in compliance and ventilation parameters in all infants in the indomethacin-treated infants.
 In the indomethacin-treated group, the mean percent improvements were noted in the following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%.
 There were no significant changes in the pulmonary functions in the 48-h RDS or the 48-h PDA fluid-restricted, furosemide-treated control groups.
 In conclusion, successful closure of the ductus with indomethacin causes a significant improvement in compliance and ventilation parameters in infants being mechanically ventilated for RDS.
",15
2708,"Lectin binding sites in normal, scarred, and lattice dystrophy corneas.
 Normal, scarred, and dystrophic corneas were histochemically probed with a panel of 16 lectins by means of an avidin-biotin revealing system.
 Normal corneal epithelial cells, keratocytes, and endothelial cells expressed at least two distinct N-linked oligosaccharide subsets, of the non-bisected, biantennary and bisected, bi-/triantennary types.
 Corneal scars stained variably with the lectin subsets described above, and with Maclura pomifera agglutinin.
 Lattice dystrophy corneas showed a loss of the oligosaccharide expression observed on the plasma membranes of normal epithelial cells, and there was concurrent deposition of extracellular glycoprotein within the corneal stroma, which was of the same oligosaccharide subsets as were lost from the epithelial cell plasma membranes.
 This extracellular stromal glycoprotein was far more widely deposited than the amyloid and extended well beyond the stromal scarring.
 We propose that these observations are related and that in lattice corneal dystrophy a glycoprotein(s) is shed from the plasma membranes of epithelial cells and sequestrated within the corneal stroma, where it subsequently stimulates amyloid deposition.
",15
2709,"Requirement for the replication protein SSB in human DNA excision repair.
 Replication and repair are essential processes that maintain the continuity of the genetic material.
 Dissection of simian virus 40 (SV40) DNA replication has resulted in the identification of many eukaryotic replication proteins, but the biochemistry of the multienzyme process of DNA excision repair is less well defined.
 One protein that is absolutely required for semiconservative replication of SV40 DNA in vitro is human single-stranded DNA-binding protein (SSB, also called RF-A and RP-A).
 SSB consists of three polypeptides of relative molecular mass 70,000, 34,000 and 13,000, and acts with T antigen and topoisomerases to unwind DNA, allowing the access of other replication proteins.
 Human SSB can also stimulate the activity of polymerases alpha and delta, suggesting a further role in elongation during DNA replication.
 We have now found a role for human SSB in DNA excision repair using a cell-free system that can carry out nucleotide excision repair in vitro.
 Monoclonal antibodies against human SSB caused extensive inhibition of DNA repair in plasmid molecules damaged by ultraviolet light or acetylaminofluorene.
 Addition of purified SSB reversed this inhibition and further stimulated repair synthesis by increasing the number of repair events.
 These results show that a mammalian DNA replication protein is also essential for repair.
",15
2710,"Detection of tuberous sclerosis in parents by magnetic resonance imaging.
 We performed a detailed physical examination and MRI without gadolinium DTPA contrast in 60 couples with at least 1 child having tuberous sclerosis (TS).
 Eight parents had TS diagnosed by physical examination, family history, or various diagnostic procedures including MRI.
 Eight additional subjects and 6 control subjects had nonspecific high-signal white matter changes on MRI.
 MRI confirmed the diagnosis of TS in only 1 parent without physical findings of the disease, similar to the results of earlier studies using computed cranial tomography.
 CT may be less sensitive than MRI but is probably more specific for TS.
 Either CT or MRI may occasionally help substantiate the diagnosis of TS in a parent with few other findings.
 Both studies may need to be done in some parents to maximize the accuracy of genetic counseling.
",15
2711,"Brain growth among fetuses exposed to cocaine in utero: asymmetrical growth retardation.
 Fetal growth retardation may be associated with maternal cocaine use during pregnancy.
 The pattern of fetal growth retardation was analyzed in infants born to 80 women who used cocaine, but not alcohol, during pregnancy, and in two comparison groups: 100 infants born to mothers who used neither alcohol nor cocaine during pregnancy and 67 infants whose mothers used alcohol but not cocaine during pregnancy.
 There were statistically significant differences in head size between the unexposed and cocaine-exposed infants (P less than .001).
 Notably, head circumference was reduced proportionately more than birth weight in cocaine-exposed infants, a pattern similar to that observed in alcohol-exposed infants.
 Alcohol- and cocaine-exposed infants were not statistically different in head circumference.
 We conclude that brain growth of cocaine-exposed infants is similar to that reported for alcohol-exposed infants, and that cocaine-exposed infants may be characterized as having asymmetrical growth retardation.
",15
2712,"A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi.
 The karyotypes of 144 spontaneous abortuses were determined using direct chromosome preparations from chorionic villi.
 The frequency of chromosome abnormality was 69.4%, which is considerably higher than figures cited in most previous cytogenetic surveys using the conventional method of cell culturing.
 Autosomal trisomy was the predominant abnormality (64%), followed by polyploidy (9%), monosomy X (7%), structural rearrangements (6%), mosaicism (6%), double trisomy (4%), and double chromosome anomaly (3%).
 Direct preparations have advantages in that results can be obtained rapidly, the success rate of karyotyping is satisfactory, and maternal-cell contamination is minimal.
",15
2713,"First- and second-trimester diagnosis of fetal ocular defects and associated anomalies: report of eight cases.
 Ocular cataract, hypertelorism, hypotelorism, anophthalmos, and microphthalmos are rare malformations commonly associated with other fetal anomalies.
 Previously, ocular malformations were detected only after mid-gestation.
 Transvaginal sonography allows the detection of many structural fetal anomalies.
 We describe the case reports of eight ocular anomalies among 1600 fetal screenings by transvaginal sonography at 12-18 weeks' gestation.
 Severe cataract was correctly diagnosed by transvaginal sonography.
 However, transvaginal sonography failed to detect moderate cataract in a case of repeat cataract in a subsequent gestation.
 Anophthalmia may sometimes be secondary to a degenerative process in middle and late pregnancy.
 In five of the eight described cases, the eye malformations were associated with defects of the central nervous system.
",15
2714,"Postterm infants: too big or too small?
 Concern over the postterm pregnancy has shifted from that of the difficult delivery of an excessively large fetus to the current concern with death in utero of an undernourished, small-for-date fetus.
 Studies of postterm pregnancy before the availability of ultrasonography may have included a large proportion of erroneous menstrual dates.
 The present study of 7000 infants was undertaken to reassess fetal growth in postterm pregnancies in which the expected date of confinement from last normal menstrual period dating was confirmed (+/- 7 days) by early ultrasonography.
 Results show a gradual shift toward higher birth weight and greater crown-heel length and head circumference between 273 and 300 days of gestational age.
 No evidence of postterm weight loss or lower weight for length could be demonstrated.
 Concern in postterm pregnancy should be for fetal macrosomia, not for intrauterine growth retardation.
",15
2715,"Cerebral blood flow, cross-brain oxygen extraction, and fontanelle pressure after hypoxic-ischemic injury in newborn infants.
 The relationship between mean arterial pressure, intracranial pressure, cerebral blood flow, cross-brain oxygen extraction, cerebral metabolic rate, and outcome was studied during therapy in nine neonates on 3 consecutive days after severe hypoxic-ischemic cerebral injury.
 Cross-brain oxygen extraction was significantly higher (5.06 +/- 0.5 vs 2.05 +/- 0.8 ml/dl; p = 0.012) in the five neonates who survived with normal neurologic outcome than in the four who died or sustained severe brain damage.
 In contrast, global cerebral blood flow in the five neonates with normal neurologic outcome was significantly lower (25.6 +/- 8.2 vs 83.2 +/- 44.9 ml/100 gm brain/min; p less than 0.05) during the study period.
 The differences in cross-brain oxygen extraction and global cerebral blood flow between infants who had neurologic recovery and those who died or sustained brain damage occurred in the presence of acceptable values for intracranial pressure, mean arterial pressure, and cerebral perfusion pressure.
 Our preliminary data suggest that cross-brain oxygen extraction and possibly global cerebral blood flow may be important variables associated with severe neuronal injury and death after hypoxic-ischemic cerebral injury.
",15
2716,"Enamel pitting: a common symptom of tuberous sclerosis.
 Dental enamel pitting as a diagnostic sign of tuberous sclerosis is explored, and a protocol for the oral examination of patients and persons at risk is described.
 In this study 50 patients with tuberous sclerosis and 250 control patients were examined for dental enamel pitting.
 A simple clinical protocol was established for examination with the use of a dental disclosing solution swabbed on dry teeth.
 The incidence of enamel pitting in the adult dentition of patients with tuberous sclerosis was 100%, whereas that in the adult dentition of the control group was 7%.
 The simplicity of the test and the high probability of occurrence in tuberous sclerosis make such an examination useful in the diagnosis of this serious genetic disease.
",15
2717,"Changes in left ventricular diastolic filling patterns by Doppler echocardiography in cystic fibrosis.
 The onset of cor pulmonale is a common terminal finding in patients with cystic fibrosis.
 Since Doppler echocardiography can detect changes in diastolic filling patterns prior to the onset of either systolic dysfunction or clinical symptoms, we utilized this technique to determine whether detectable changes in left ventricular diastolic filling patterns exist in patients with cystic fibrosis.
 Among 25 patients, the proportion of left ventricular filling attributable to atrial contraction was significantly increased when compared with age-matched control individuals.
 When filling patterns were compared with severity of pulmonary disease, worsening pulmonary disease was directly correlated to shifts in left ventricular filling patterns.
 We conclude that changes in left ventricular patterns of relaxation are detectable early in the course of cystic fibrosis and that such changes are probably progressive.
 Early detection could lead to therapeutic trials designed to improve left ventricular filling and delay the onset of overt cor pulmonale.
",15
2718,"Single nucleotide primer extension to detect genetic diseases: experimental application to hemophilia B (factor IX) and cystic fibrosis genes.
 In this report, we describe an approach to detect the presence of abnormal alleles in those genetic diseases in which frequency of occurrence of the same mutation is high (e.g., cystic fibrosis and sickle cell disease), and in others in which multiple mutations cause the disease and the sequence variation in an affected member of a given family is known (e.g., hemophilia B).
 Initially, from each subject, the DNA fragment containing the putative mutation site is amplified by the polymerase chain reaction.
 For each fragment two reaction mixtures are then prepared.
 Each contains the amplified fragment, a primer (18-mer or longer) whose sequence is identical to the coding sequence of the normal gene immediately flanking the 5' end of the mutation site, and either an alpha-32P-labeled nucleotide corresponding to the normal coding sequence at the mutation site or an alpha-32P-labeled nucleotide corresponding to the mutant sequence.
 Single nucleotide primer extensions are then carried out and analyzed by denaturing polyacrylamide gel electrophoresis and autoradiography.
 As predicted by the Watson-Crick base-pair rule, in the wild type only the normal base, in an affected member only the mutant base, and in carriers both the normal and the mutant base are incorporated into the primer.
 Thus, an essential feature of the present methodology is that the base immediately 3' to the template-bound primer is one of those altered in the mutant, since in this way an extension of the primer by a single base will give an extended molecule characteristic of either the mutant or the wild type.
 The method is rapid and should be useful in carrier detection and prenatal diagnosis of every genetic disease with a known sequence variation.
",15
2719,"Neonatal screening for cystic fibrosis in Wales and the West Midlands: clinical assessment after five years of screening.
 Screening of the newborn for cystic fibrosis by measurement of immunoreactive trypsin has been undertaken on alternate weeks in Wales and the West Midlands for five years since 1985 to evaluate the possible clinical benefits of early diagnosis.
 Patients detected by screening and those diagnosed by clinical symptoms alone were assessed annually for differences in clinical, anthropometric, and biochemical variables.
 Fifty eight infants not considered to be at risk of cystic fibrosis (they did not present with meconium ileus and do not have a sibling with cystic fibrosis) have been detected by screening and they have been compared with 44 children who were diagnosed clinically.
 This latter group includes nine children whose screening was negative but who were recognised subsequently to have cystic fibrosis.
 The mean age at diagnosis of the screened group was significantly lower than that of the group diagnosed clinically.
 Excluding admissions for diagnostic tests for cystic fibrosis, the screened group spent a significantly shorter time in hospital during the first year of life.
 The results of all other comparisons made between the screened group and those diagnosed clinically were similar up to the age of 4 years.
",15
2720,"Controversies in the management of gastroschisis: a study of 40 patients.
 Forty infants with gastroschisis were referred to two paediatric surgeons during a 13 year period.
 Overall survival was 90%.
 Nine patients were transferred in utero and 31 were referred postnatally.
 Birth weights, gestational ages, and Apgar scores were similar for both groups.
 Primary closure of the defect was successfully achieved in seven (78%) patients in the prenatally transferred group compared with 17 (55%) in the postnatal group.
 Significantly less postoperative assisted ventilation, and a trend in favour of early discharge home, were noted after prenatal transfer.
 Problems arising during postnatal transfer may have contributed to these differences.
 No major differences resulting from the mode of delivery were identified.
 Patients treated by primary closure fared significantly better than those undergoing staged repairs with prosthetic material.
 Prospective randomised studies are required to confirm these findings.
",15
2721,"Endotracheal resuscitation of neonates using a rebreathing bag.
 Thirty asphyxiated neonates were resuscitated endotracheally with an anaesthetic rebreathing bag.
 The system was not limited either by pressure or by volume and chest movement was used as the criterion for adequate inflation.
 Inflation pressure and flow were recorded during resuscitation, and flow was integrated to obtain volume.
 Median mean pressure over the first 10 inflations was 40 cm H2O and this dropped during later resuscitation to 29 cm H2O.
 The volume delivered did not change significantly, so volume divided by pressure increased from a median of 0.18 to 0.35 ml/kg/cm H2O.
 Fourteen infants formed part of their functional residual capacity with artificial ventilation and five with spontaneous breaths.
 Eleven infants showed no evidence of functional residual capacity formation.
 In the 22 preterm infants there was a strong association between absence of functional residual capacity formation and later hyaline membrane disease that required ventilation.
 We suggest that pressures of more than than 30 cm H2O may be helpful during initial resuscitation and that there should be further study of devices using positive end expiratory pressure for resuscitation of preterm infants.
",15
2722,"Pelvic support osteotomy in an unusual congenital dislocation of the hip. A 52-year follow-up study.
 Structural changes in the anatomy of the soft tissues as a result of long-standing congenital dislocation of the hip (CDH) are seldom described in the literature.
 Similarly, the anatomy of a hip 52 years after a pelvic support osteotomy for CDH seems not to have been previously observed.
 A long-term follow-up autopsy study of bilateral pelvic support osteotomies performed in a 91-year-old autopsy subject showed unexpectedly flattened sciatic nerves.
",15
2723,"Chemical dependency in women: a description of its effects and outcome on adequate parenting.
 The purpose of this article is to define chemical dependency in women as a maladaptive response to inadequate upbringing.
 A description of the situational and psychological variables that characterize chemically dependent women is offered as well as attributes these women lack that are necessary for effective parenting.
 The dysfunctional child-rearing patterns and the consequential outcome for the children are also described.
 Suggestions for clinical intervention are provided.
",15
2724,"Radiographic manifestations of congenital heart disease in the adult patient.
 Improvements in the preoperative evaluation, surgical treatment, and postoperative care of patients with congenital cardiac disease have allowed a large patient population with congenital cardiac abnormalities to reach adolescence and adulthood.
 Noninvasive diagnostic imaging procedures (e.g., plain film radiography, echocardiography, computed tomography, and magnetic resonance imaging) are playing an increasingly important role in the evaluation and management of adults with both treated and untreated congenital cardiac disease.
 The role of plain film radiology is emphasized.
",15
2725,"A mutation in the second nucleotide binding fold of the cystic fibrosis gene.
 The discovery last year of the deletion of a phenylalanine residue at amino acid position 508 of the cystic fibrosis (CF) gene has meant that approximately 70% of mutant chromosomes associated with CF can be accounted for.
 We report the finding of a substitution at nucleotide position 4041 of the CF gene, resulting in a change from asparagine to lysine at amino acid position 1303.
 We believe that this is a disease-causing mutation, as it involves a nonconservative amino acid change and has only been found on CF chromosomes with a consistent haplotype background.
 The mutation was detected using direct sequencing of PCR-amplified genomic DNA and was confirmed by dot hybridization to both normal and mutant allele-specific oligonucleotides.
 The mutation was detected on three chromosomes from four individuals but not on any normal chromosome.
 Its presence in the heterozygous state is not correlated with the clinical status of the individual patients.
",15
2726,"Epidermolysis bullosa simplex (Koebner) is a keratin disorder. Ultrastructural and immunohistochemical study.
 A skin biopsy specimen was obtained from a 1-month-old female with epidermolysis bullosa simplex (Koebner).
 Histologically, an intraepidermal separation was seen and considered to be formed by cytolysis of the epidermal basal cells.
 Ultrastructurally, the basal cells were lacking in cytoplasmic tonofilaments, and the initial change of the cytolysis seemed to be cleavages of the cytoplasm.
 Immunohistochemically, a basal cell keratin was expressed in a suprabasal cell layer but not in the basal cell layer, and a panepithelial keratin was not detected in the basal cell layer.
 These findings suggest that keratin production of the epidermal cells may be delayed, resulting in a weakness of the basal cells against minor trauma to the skin.
",15
2727,"Autogenous atrial tunnel for direct cavopulmonary connection in infants and small children.
 A technique is described for construction of an autogenous right atrial tunnel for direct cavopulmonary connection in infants and small children requiring Fontan operation.
 Advantages, in this subset of patients, of this method over others previously described using prosthetic or growth-limited materials are suggested.
",15
2728,"A mutation in the DNA-binding domain of the androgen receptor gene causes complete testicular feminization in a patient with receptor-positive androgen resistance.
 Androgen resistance is associated with a wide range of quantitative and qualitative defects in the androgen receptor.
 However, fibroblast cultures from approximately 10% of patients with the clinical, endocrine, and genetic features characteristic of androgen resistance express normal quantities of apparently normal androgen receptor in cultured genital skin fibroblasts (receptor-positive androgen resistance).
 We have analyzed the androgen receptor gene of one patient (P321) with receptor-positive, complete testicular feminization and detected a single nucleotide substitution at nucleotide 2006 (G----C) within the second ""zinc finger"" of the DNA-binding domain that results in the conversion of the arginine residue at position 615 into a proline residue.
 Introduction of this mutation into the androgen receptor cDNA and transfection of the expression plasmid into eukaryotic cells lead to the synthesis of a receptor protein that displays normal binding kinetics but is inactive in functional assays of receptor activity.
 We conclude that substitution mutations in the DNA-binding domain of the androgen receptor are one cause of ""receptor-positive"" androgen resistance.
",15
2729,"Neuronal ceroid-lipofuscinosis: preferential metabolic alterations in thalamus and posterior association cortex demonstrated by PET.
 Regional brain glucose utilisation was investigated with positron emission tomography (PET) and fluorodeoxyglucose (FDG) in four siblings with neuronal ceroid-lipofuscinosis.
 A consistent pattern was found, namely a decrease of glucose utilisation in all grey structures but more marked at the level of the thalamus and posterior association cortex.
 The severity of metabolic anomalies was correlated with the degree of clinical impairment and with disease duration; they were the most severe in the oldest patient, who was also the most affected clinically, intermediate in two others, and minimal in the subject with the shortest period of development of the disease.
 These observations suggest that PET is useful for the definition of anatomical targets of metabolic diseases and for the investigation of their pathophysiology.
",15
2730,"Maternal age and birth defects: a population study.
 Since more and more women in developed countries are delaying childbearing to an older age, it is important to find out whether birth defects, other than those resulting from chromosomal anomalies, are related to maternal age.
 We have studied all 26,859 children with birth defects of unknown aetiology identified among 576,815 consecutive livebirths in British Columbia.
 All these cases' records were linked with provincial birth records to allow determination of maternal age at birth.
 We excluded children with chromosomal anomalies and those with other birth defects of known aetiology.
 Only 3 of the 43 birth defect categories studied showed significant maternal-age-specific trends: there were decreasing linear trends with maternal age for patent ductus arteriosus (chi 2 = 36.65, 1 df, p less than 0.01) and hypertrophic pyloric stenosis (chi 2 = 4.90, 1 df, p less than 0.05) and a bell-shaped curve (risk increasing to maternal age 30 then falling) for congenital dislocatable hip/hip click.
 The findings from this population-based analysis of no association between the incidence of birth defects of unknown aetiology and advancing maternal age should be reassuring to healthy women who opt to delay childbearing.
",15
2731,"Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase.
 Cystic fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells.
 These channels in normal cells are activated by cyclic AMP-dependent protein kinase and protein kinase C.
 In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels.
 But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10).
 We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase.
 We find that intracellular application of activated kinase and ATP activates a Cl- current similar to that activated by a Ca2+ ionophore, that peptide inhibitors of either the kinase or calmodulin block Ca2(+)-dependent activation of Cl- channels, and that a peptide inhibitor of protein kinase C does not block Ca2(+)-dependent activation.
 Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis.
",15
2732,"Spatially localized magnetic resonance spectroscopy of the brains of normal and asphyxiated newborns.
 Phase-modulated rotating frame imaging is a modification of magnetic resonance spectroscopy, which uses a linear radiofrequency field gradient to obtain spatially localized biochemical information.
 Phase-modulated rotating frame imaging was used to study regional cerebral energy metabolism in the brains of 9 normal newborns and 25 newborns after birth asphyxia.
 Relative concentrations of phosphorus-containing metabolites and intracellular pH were determined for brain tissue at three specified depths below the brain surface for all neonates.
 Wide variations in metabolite ratios were seen among normal neonates, and considerable metabolic heterogeneity was demonstrated in individual neonates by depth-resolved spectroscopy.
 Asphyxiated neonates with severe hypoxic-ischemic encephalopathy and a poor neurodevelopmental outcome showed the expected rise in inorganic orthophosphate and fall in phosphocreatine concentrations in both global and spatially localized spectra.
 Phase-modulated rotating frame imaging showed that metabolic derangement was less in superficial than in deeper brain tissue.
 The inorganic orthophosphate-adenosine triphosphate ratio from 1 to 2 cm below the brain surface was more accurate than any global metabolite ratio for the identification of neonates with a poor short-term outcome.
 These data are consistent with the known vulnerability of subcortical brain tissue to hypoxic-ischemic injury in the full-term neonate.
",15
2733,"Neuropsychological outcome of pediatric liver transplantation.
 Children with end-stage liver disease who undergo liver transplantation may have unrecognized neuropsychological and academic deficits, for which remediation programs may be available.
 Intellectual, academic, and neuropsychological measures of 28 pediatric patients who had received successful liver transplantation at least 1 year previously were compared with those of 18 patients with cystic fibrosis (to control for effects of growth retardation and chronic illness) matched for age, age at diagnosis, physical growth, and parents' socioeconomic status.
 Liver transplant patients had significantly lower scores on nonverbal intelligence tests (mean +/- SD for liver transplant vs cystic fibrosis patients: 89.1 +/- 19.1 vs 105.8 +/- 17.6), lower academic achievement, and lower zeta scores for age in the areas of learning and memory (-0.68 +/- 1.09 vs 0.19 +/- 1.24), abstraction and concept formation (-1.73 +/- 1.58 vs -0.79 +/- 1.37), visual-spatial function (-0.66 +/- 1.09 vs 0.10 +/- 0.69), and motor function (-0.13 +/- 0.85 vs 0.36 +/- 0.57).
 No differences were found on tests of verbal intelligence, or in alertness and concentration, perceptual-motor, and sensory-perceptual areas.
 Cyclosporine levels were found to correlate positively with motor speed (r = .41, P less than .05).
 Thorough psycho-educational and neuropsychological evaluations should be considered for pediatric patients who receive liver transplantation to allow these children to maximize their potential.
",15
2734,"Bovine surfactant replacement therapy in neonates of less than 30 weeks' gestation: a randomized controlled trial of prophylaxis versus treatment.
 The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age).
 Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water.
 All treated neonates were eligible to receive up to three additional doses during the first 5 days of life.
 The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group.
 Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours.
 There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001).
 Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age).
 There were no differences between early and late surfactant groups in any of these parameters.
 The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005).
 Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters.
 It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS).
",15
2735,"Congenital orthopedic anomalies and their impact on the family.
 A baby born with a congenital limb deficiency presents a challenge to parents and health care professionals.
 Lack of information about treatment options can exacerbate the crisis for the family.
 The treatment modalities available to the family generally depend on the child's specific limb deficiency or deficiencies.
 Surgery to reconstruct the deficiency is not a workable option for many patients because of abnormal joints and soft tissues.
 Amputation may be recommended for patients whose deficiency is difficult or impossible to manage prosthetically.
 Limb lengthening is an option only for patients whose bones are smaller than normal.
 Prosthetics are the most widely used treatment modality because they immediately equalize limb lengths and improve function.
 When a baby is born with a congenital limb deficiency, the initial response of the parents is shock and denial.
 In adjusting to their newborn, they must first mourn the loss of the baby they expected.
 Once the adjustment process begins, specific information about the limb deficiency and the treatment options should be available.
 Family adjustment to the child is a continual process.
 As the child grows, management strategies need to change to adjust to the child's changing needs.
 With appropriate and timely health care and family intervention, a child with a congenital limb deficiency can be a happy, successful person.
",15
2736,"Pediatric cardiac surgery guided by echocardiography. Established indications and new trends.
 Cardiac surgery in 602 children was not preceded by cardiac catheterization, the diagnosis being based on clinical findings and two-dimensional and Doppler echocardiography.
 In the 355 operations without cardiopulmonary bypass there were nine major and seven minor diagnostic errors (2.5% and 2%).
 Among the 247 cases with open-heart surgery there were no major and eight (3.2%) minor errors.
 The malformations most suitable for nonbypass surgery without catheterization seem to be those with reduced pulmonary blood flow requiring systemic-pulmonary artery shunt, aortic coarctation and patent ductus arteriosus.
 For open-heart surgery without invasive investigation, atrial septal defect, partial atrioventricular canal, aortic and pulmonary stenosis, cardiac tumor and isolated valve disorder are 'classic' candidates.
 Recent experience indicated that selected cases of complete atrioventricular canal, tetralogy of Fallot, truncus arteriosus, total anomalous pulmonary venous connection and transposition of the great arteries may safely undergo primary repair without cardiac catheterization.
 Because of its diagnostic potentialities, pediatric cardiac surgeons must become familiar with echocardiography.
",15
2737,"Antagonistic and agonistic effects of transforming growth factor-beta and IL-1 in rheumatoid synovium.
 We investigated potential mechanisms by which lymphocytes infiltrating rheumatoid synovium become immunosuppressed.
 In 20 of 22 synovial fluids and 12 of 13 synovial tissue culture supernatants, no IL-1 bioactivity could be detected in the thymocyte proliferation assay.
 These same preparations could, however, support proliferation of fibroblast monolayers, consistent with the presence of IL-1 and/or other fibroblast growth factors.
 Addition of either rheumatoid synovial fluids or synovial culture supernatants to exogenous IL-1 in the IL-1 bioassay caused marked inhibition of the assay indicative of an IL-1 inhibitor.
 This inhibition of IL-1 could be reversed by treating the effusions or supernatants with a neutralizing antibody to transforming growth factor-beta (TGF-beta).
 Furthermore, monocyte-macrophages isolated from rheumatoid synovial fluid constitutively released both latent and active TGF-beta in culture at levels sufficient to completely block the biologic activity of 100 U/ml IL-1.
 The production of substantial levels of TGF-beta by synovial macrophages, as well as the apparent ability of these inflammatory macrophages to activate latent TGF-beta, implicates TGF-beta not only as an important inhibitor of IL-1-induced lymphocyte proliferation, but also as a key cytokine in promoting synovial fibroblast hyperplasia and pathology.
",16
2738,"Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization.
 These studies address the hypothesis that Ag-bearing epidermal Langerhans cells migrate to the regional lymph node during contact sensitization and function as APC.
 Skin from C3H mice was grafted onto BALB/c nude mice, and 7 or 14 days later, the recipients were sensitized with FITC through the grafts.
 APC from lymph nodes draining the site of sensitization were capable of sensitizing C3H recipients to FITC.
 Because sensitization is MHC restricted, only cells reaching the lymph node from the grafted skin could have induced contact hypersensitivity in C3H mice.
 Examination of the FITC+ draining lymph node cells by immunofluorescence and immunoelectron microscopy demonstrated that all were Ia+, most were F4/80+, and some contained Birbeck granules.
 These studies demonstrate that Ia+, FITC+ cells from the skin, at least some of which are Langerhans cells, leave the skin after epicutaneous sensitization with FITC and participate in the initiation of the contact hypersensitivity response within the regional lymph node.
",16
2739,"Aberrant proliferation of lumen-forming cells in stratified epithelium of porokeratosis skin.
 The present investigation was based on the postulate, first proposed by Reed and Leone in 1970, that porokeratosis lesions represent clonal growth of epidermal cells.
 Comparative studies using immunocytochemical staining, epidermal cell culture, and non-equilibrium pH gradient (NEpHG) gel electrophoresis analysis of the keratins extracted were carried out on five patients with various types of porokeratosis.
 Positive type IV collagen staining on the stratum corneum was found in lesional skin specimens of all patients, but not in normal controls.
 A search for connections between type IV collagen in the basement membrane of epidermis and the skin surface disclosed infrequent intra-epidermal streaking of type IV collagen and one positively stained trans-epidermal acrosyringium.
 Positive intra-epidermal laminin staining in porokeratosis lesions confirmed the trans-epidermal passage of basement-membrane materials.
 Epidermal cells cultured from lesional skin showed low plating efficiency, and all colonies exhibited intracytoplasmic vacuole formation and excessive top cell shedding.
 NEpHG gel electrophoresis of keratins extracted showed that lesional profiles not only contained keratins normally present in glabrous skin, but also possibly K9 and some additional proteins.
 K9 had been immunolocalized to periductal cells in previous studies.
 Our findings, taken together, strongly suggest that porokeratosis epidermis consists of epithelial cells with lumen-forming ability.
",16
2740,"The innermost cell layer of the outer root sheath is positive with Ki-67.
 The expression of a cell proliferation-associated human nuclear antigen was immunohistochemically studied in human anagen hair and hair follicles using the monoclonal antibody Ki-67.
 The reaction of Ki-67 in mature anagen hair follicles was observed in the hair matrix cells and outer root sheath (ORS) cells.
 Nuclear staining was seen in a small number of matrix cells and in some ORS cells; this finding corresponded to the thymidine or bromodeoxyuridine labeling studies previously reported.
 In addition, there were two different patterns of cytoplasmic staining in the ORS: strong staining of the innermost cells (IMC) and weaker staining of the other ORS cells in the isthmus.
 Ki-67 reactivity of the IMC layer was observed at each stage of anagen and was regularly seen from the upper bulb to the isthmus.
 Ki-67 is a commercially available antibody that detects cycling cells.
 However, the IMCs in anagen hair follicles showed cytoplasmic labeling by Ki-67 from the matrix cells in the upper bulb to the distal portion of the isthmus.
",16
2741,"Increased phospholipase C-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate and 1,2-sn-diacylglycerol content in psoriatic involved compared to uninvolved and normal epidermis.
 Evidence suggests that the phospholipase C/protein kinase C signal transduction system participates in the regulation of epidermal cell growth and differentiation.
 Psoriatic epidermis is characterized by hyperproliferation, defective differentiation, and inflammation.
 In this report, we have determined the activity of phospholipase C-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) and 1,2-diacylglycerol content in normal and psoriatic involved and uninvolved epidermis.
 1,2-diacylglycerol is formed from phospholipase C-catalyzed hydrolysis of PIP2 and is the physiologic activator of protein kinase C.
 PIP2 hydrolysis was assayed in soluble and particulate fractions prepared from keratome biopsies of normal and psoriatic skin.
 Total lipids were extracted from normal and psoriatic epidermis and 1,2-diradylglycerol (a mixture of 1,2-diacylglycerol and 1-ether, 2-acyl-glycerol) quantitated by enzyme assay.
 Because 1,2-diacylglycerol is a more potent activator of protein kinase C, the relative proportions of 1,2-diacyl and 1-ether, 2-acylglycerol in uninvolved and involved psoriatic epidermis were determined.
 This was accomplished by separation of acetate derivatives of 1,2-diacylglycerol and 1-ether, 2-acyl-glycerol by thin layer chromatography.
 Soluble and membrane-associated phospholipase C-catalyzed PIP2 hydrolysis were increased 3.7 times (p less than 0.001) and 3 times (p less than 0.004), respectively, in psoriatic involved compared to uninvolved and normal epidermis.
 1,2-diradylglycerol content was also significantly elevated (3 times, p less than 0.01) in psoriatic involved versus uninvolved and normal epidermis.
 Analysis of the acetate derivatives of 1,2-diradylglycerol in psoriatic uninvolved and involved epidermis revealed that 1,2-diacylglycerol was the major species (86% and 95%, respectively).
 There were no significant differences in either phospholipase C-catalyzed PIP2 hydrolysis or 1,2-diacylglycerol content between uninvolved and normal epidermis.
 1,2-diacylglycerol purified from normal and involved psoriatic epidermis was capable of activating protein kinase C from normal epidermis in vitro.
 In epidermal slices, activation of protein kinase C by addition of 12-0-tetradecanoylphorbol-13-acetate and 1,2-diacylglycerol (1,2-dioctanoylglycerol) resulted in subsequently decreased protein kinase C activity, a process termed down-regulation.
 These data are consistent with the possibility that the elevation in lesional 1,2-diacylglycerol content may account, in part, for the previously reported reduction of protein kinase C activity in psoriasis (Horn, Marks, Fisher, et al: J Invest Dermatol 88:220-222, 1987).
",16
2742,"Successful culture of adult human melanocytes obtained from normal and vitiligo donors.
 The development of growth conditions for human melanocytes from uninvolved skin from vitiligo patients and age-matched normal adults is a prerequisite to understanding the etiology of this pigmentary disorder.
 By using new growth conditions, pure melanocyte cultures were prepared from normal adults and the pigmented skin of vitiligo donors.
 Both cell types grew without a lag period and were maintained for more than six months (4-8 passages).
 The cultures could be expanded from several thousand melanocytes in the original cell suspension to several million cells (2-7 x 10(6] in pure culture.
 To obtain these results, the current standard conditions for the culture of fetal melanocytes were substantially modified.
 MEM-S medium was less satisfactory than MCDB-153.
 Adult normal and vitiligo cells also required the presence of exogenous catalase (20 micrograms/ml) during isolation and primary seeding.
 Thereafter, this enzyme was not necessary.
 Melanocytes grew best and gave the highest yields if the concentrations of both calcium (200 microM) and the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) were low (4-8 nM).
 Other growth factors included in the MCDB-153 media were bFGF, crude bovine pituitary extract, insulin, transferrin, hydrocortisone, 5% FCS, and the antioxidant alpha-tocopherol.
 Cholera toxin and isobutylmethylxanthine (IBMX) were omitted from the MCDB-153 growth medium because they slowed down growth even at very low concentrations.
 The results indicate adult and vitiligo melanocytes can be cultured.
 Preliminary studies of the normal and vitiligo cells indicate that vitiligo melanocytes retain some of the ultrastructural abnormalities observed in skin even when grown in culture.
",16
2743,"The clinical significance of immune reactions with some streptococcal antigens in rheumatoid arthritis.
 The level of antibodies and delayed-type hypersensitivity to the group specific polysaccharides and cell wall proteins of groups A, B, C and G streptococci was determined in 247 patients with rheumatoid arthritis (RA) as well as in healthy persons and in patients with other articular disorders by means of an enzyme linked immunosorbent assay, passive hemaglutination and leukocyte migration inhibition tests.
 An increase of the immune response to antigens of group B streptococcus was found in patients with RA.
 The greatest sensitization against these antigens was typical for high disease activity of short duration, and a rapidly progressive course of RA.
 High titers of antibodies to polysaccharide of group B streptococcus appeared in the synovial fluid in the early stages of the clinical development of RA.
 Values of immune response to streptococcal antigens correlated well with the titer of rheumatoid factor and the concentration of immunoglobulins and immune complexes.
 The presence of group B streptococcus in the urogenital tract appeared more often in patients with RA than in healthy persons.
 The possibility of a triggering role for immune reactions with antigens of group B streptococcus in the immunopathological process of RA is discussed, as well as the diagnostic significance of our results.
",16
2744,"Antibodies to denatured type II collagen in rheumatoid arthritis: negative association with IgM rheumatoid factor.
 Serum samples from 129 patients with definite or classic rheumatoid arthritis (RA) were assayed by ELISA for antibodies to denatured bovine type II collagen (dII).
 All patients had active disease at the time of serum sampling.
 Anti-dII antibodies were found in 18 (14%) of 129 patients (95% confidence intervals: 8-20%).
 The only clinical or laboratory feature associated with the presence of anti-dII antibodies was seronegativity for IgM rheumatoid factor (IgM RF): 6 (37.5%) of 16 seronegative patients had anti-dII antibodies vs 12 (10.6%) of the 113 seropositive patients (OR = 5, p less than 0.01).
 There were no associations of anti-dII antibodies with age, sex, race, disease activity, disease duration, functional class, or the presence of HLA-DR1, DR4, or DQw3 in these patients.
 Antibodies to type II collagen may have a pathophysiologic role in RA, especially in patients seronegative for RF.
",16
2745,"Pulsed suppressive treatment in rheumatoid arthritis: intravenous methylprednisolone and nitrogen mustard.
 Persistent polyarticular rheumatoid arthritis (RA) and aggressive disease flares resistant to conventional therapy can effectively be controlled by intravenous pulse methylprednisolone (IVMP) or nitrogen mustard (HN2).
 The efficacy, toxicity and immunologic effects of each agent are reviewed.
 Clinical response is evident within days of the start of therapy for both; persisting up to 6 weeks for IVMP and at least 59 days for HN2.
 Morbidity from both agents is minimal when appropriate precautions are taken.
 No mortalities directly related to either modality have been reported in RA.
",16
2746,"Elevated serum levels of soluble interleukin 2 receptor, interleukin 2 and neopterin in diffuse and limited scleroderma: effects of chlorambucil.
 In a study of 48 patients with systemic sclerosis (SSc).
 elevated serum levels of soluble interleukin 2 receptor (IL-2R), interleukin 2 (IL-2) and neopterin (indicators of lymphocyte/monocyte activation) were noted in 100, 44 and 40% of early untreated patients with SSc (11 diffuse, 5 Limited).
 Levels of IL-2R, but not IL-2 or neopterin, were lower in patients with longer duration of disease and possibly with chlorambucil therapy.
 Pharmacologic alterations of markers of humoral or cell mediated immunity may not be an accurate reflection of clinical efficacy of chlorambucil.
",16
2747,"A double blind placebo controlled trial of low dose clotrimazole in rheumatoid arthritis.
 Seventy-three patients with rheumatoid arthritis were randomized in a double blind study to receive either clotrimazole (20 mg/kg/day) 2 days a week for 12 weeks or matching placebo.
 Patients receiving clotrimazole had significant improvements (p less than 0.05) from baseline in measurements of grip strength, joint count, and patient assessment of pain, but did not show significant improvement over patients treated with placebo.
 More adverse experiences, predominantly gastrointestinal complaints, occurred in patients taking clotrimazole resulting in 9 patients discontinuing therapy.
",16
2748,"Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis.
 Low dose methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis.
 Current product recommendations accompanying MTX preparations advise against concurrent usage of nonsteroidal antiinflammatory drugs (NSAID), and adverse pharmacokinetic interactions have been reported with this combination.
 Six patients who were receiving MTX were studied with both oral and parenteral MTX, 10-25 mg/dose, without NSAID and with ibuprofen (2400 mg/day) and flurbiprofen (300 mg/day) for 6 weekly doses.
 Serum MTX levels were obtained at frequent intervals.
 Serum was separated and MTX analyzed using a radioimmunoassay (RIA).
 There was no observable interaction between MTX and either ibuprofen or flurbiprofen, with respect to the area under the curve per unit dose, Cmax, Cmax/dose, Tmax, and serum half-life.
 The pharmacokinetic indices were not significantly influenced by the route of administration.
",16
2749,"Psychological screening in rheumatoid arthritis.
 Our objective was to examine the utility of the Symptom Checklist-90-R (SCL-90-R) as a psychological screening instrument for patients with rheumatoid arthritis (RA).
 Subjects were 81 male and 3 female patients with classic or definite RA who were categorized into 3 anatomic stage groups based on roentgenograms.
 Erythrocyte sedimentation rates, joint counts, and the SCL-90-R were obtained on all subjects.
 In addition, rheumatologists were surveyed, and items were analyzed to identify potential disease related items on the SCL-90-R.
 Both the survey and the item analyses supported the utility of the SCL-90-R as a psychological screening instrument in a population with RA.
",16
2750,"Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis.
 The assessment of a measure of chronic pain, should be reliable, valid and sensitive to change.
 Our study evaluated the reliability of 3 pain scales, visual analogue scale (VAS), numerical rating scale (NRS) and verbal rating scale (VRS) in literate and illiterate patients with rheumatoid arthritis (RA).
 Patients with RA attending an outpatient rheumatology clinic were interviewed and asked to score their pain levels on the 3 pain scales.
 The scales were presented in random order, twice, before and just after a regular medical consultation.
 Ninety-one patients were studied (25 illiterate and 66 literate).
 The Pearson product moment correlation between first and second assessment was 0.937 for VAS, 0.963 for NRS and 0.901 for VRS in the literate patient group and 0.712 for VAS, 0.947 for NRS and 0.820 for VRS in the illiterate patient group.
 These results indicate that the NRS has the higher reliability in both groups of patients.
",16
2751,"Estimating the incidence and prevalence of rare rheumatologic diseases: a review of methodology and available data sources [editorial]
 Where the need for descriptive epidemiology is great, population based registries can be established, at considerable cost, to provide the desired data.
 In many instances, however, there may be existing data and information systems that provide morbidity information on sufficiently large, well defined populations to allow reasonable estimates of the incidence and prevalence of rare rheumatologic diseases.
",16
2752,"Successful pregnancy outcome in association with lipoatrophic diabetes mellitus.
 Lipoatrophic diabetes mellitus is a rare syndrome characterized by lipoatrophy and insulin-resistant diabetes mellitus.
 Partial lipodystrophy without clinical diabetes mellitus has been associated with intrauterine growth retardation and fetal death.
 We report successful pregnancy outcomes in two women with lipoatrophic diabetes mellitus.
",16
2753,"Vancomycin-induced red man syndrome.
 A total of 11 cases of red man syndrome collected among 650 children who had received vancomycin in our hospital between 1986 and 1988 (estimated prevalence 1.6%) were retrospectively analyzed.
 These 11 children were compared with 11 age-matched children who received vancomycin in whom red man syndrome did not develop.
 Of the patients with red man syndrome, 73%, and of the patients with no reaction, 45.4% received vancomycin for penicillin-resistant Staphylococcus epidermidis-positive cultures, or because of history of penicillin allergy.
 No difference was observed in the dose per kilogram given to both groups (12.9 +/- 3.5 mg/kg per dose in those with red man syndrome vs 12.3 +/- 6.9 mg/kg per dose in control children.
 The duration (mean +/- standard deviation) of vancomycin infusion was 45.9 +/- 16.7 minutes (range 10 to 90 minutes) in patients with red man syndrome and 54.5 +/- 7.6 minutes (range 45 to 65 minutes) in the control group (P = .07).
 In the 5 children with red man syndrome rechallenged with vancomycin, slower infusion rates prevented or reduced the syndrome, which emphasized the fact that the rate of administration is the important determinant of red man syndrome in susceptible cases.
 Clinically, the syndrome developed at the end of the infusion in most patients, but appeared as early as 15 minutes after initiation of the infusion.
 It was mostly manifested as a flushed, erythematous rash on the face, neck, and around the ears.
 Less frequently, the rash was distributed all over the body.
 Pruritus was usually localized to the upper trunk but was also generalized (2 of 11 children).
",16
2754,"Major histocompatibility complex haplotype studies in Ashkenazi Jewish patients with pemphigus vulgaris.
 Of 26 Ashkenazi Jewish patients with pemphigus vulgaris, 24 (92.3%) carried the major histocompatibility complex (MHC) class II alleles HLA-DR4, DQw3, of which all were of the subtype DR4, DQw8.
 From studies of the patients and their families, haplotypes were defined.
 It was found that, of the patients who carried HLA-DR4, DQw8, 75% carried one or the other (and in one case, both) of two haplotypes [HLA-B38, SC21, DR4] or HLA-B35, SC31, DR4.
 The former is a known extended haplotype among normal Jews, with a frequency of 0.102, and the latter may also be an extended haplotype in this ethnic group, with a frequency of 0.017 among normal haplotypes from Jews.
 Of the remaining DR4-positive patients, all but one had a presumed D-region segment (defined as SC21, DR4, DQw8 or SC31, DR4, DQw8 with variable HLA-B) of these haplotypes.
 Only one patient had DR4, DQw8 without any other markers of the extended haplotypes.
 The number of homozygotes and heterozygotes for DR4, DQw8 was consistent with dominant but not recessive (P less than 0.01) inheritance of a class II or a class II-linked susceptibility gene for the disease.
 Since the disease is entirely attributable to the presence of an antibody to an intraepidermal intercellular cement substance, it is likely that the class II susceptibility gene (on [HLA-B38, SC21, DR4, DQw8], HLA-B35, SC31, DR4, DQw8, or their segments, in Jewish patients) controls the production of the antibody as a dominantly expressed immune response gene.
",16
2755,"The source and significance of raised serum enzymes in rheumatoid arthritis.
 Hepatobiliary dysfunction in rheumatoid arthritis has been suggested on the basis of raised serum activity of alkaline phosphatase, 5-nucleotidase, lactic dehydrogenase and gamma-glutamyl transferase, but a specific pathological lesion has not been demonstrated and serum transaminases and bilirubin are almost invariably normal.
 This paper reports a series of studies designed to determine the tissues of origin of the enzymes and offers an alternative interpretation of the enzymological findings.
 The results suggest that only alkaline phosphatase originates from the liver, while lactic dehydrogenase and 5-nucleotidase originate from synovial fluid polymorphs and synovial lining cells, respectively.
 Serum alkaline phosphatase may be induced by inflammatory mediators such as interleukin-1 because it correlates with the acute phase response.
 Serum lactic dehydrogenase is an integrated measure of polymorph lysis in all joints and offers a marker of joint inflammation more specific than measures such as the ESR.
 Levels of serum 5-nucleotidase provide information about the activity of the synovium.
 Finally, because hepatic necrosis does not normally occur, the transaminases may be used to monitor drug toxicity.
",16
2756,"Immunopathology of cicatricial pemphigoid affecting the conjunctiva.
 Conjunctival biopsy specimens from 13 patients with cicatricial pemphigoid and from 13 age-matched healthy individuals undergoing cataract surgery were analyzed by light microscopy and immunohistochemical techniques, including a panel of monoclonal antibodies used to characterize inflammatory mononuclear cell phenotypes.
 Results of histologic examination of cicatricial pemphigoid specimens showed typical squamous metaplasia, vasculopathy, increased numbers of mast cells, and abundant plasma cells.
 All cicatricial pemphigoid specimens demonstrated immunoreactants at the epithelial basement membrane zone (BMZ).
 Epithelium of cicatricial pemphigoid conjunctiva showed significantly more T-helper cells (CD4+), dendritic cells (CD1+), and macrophages (CD14+), and a significantly higher helper/suppressor ratio than did controls.
 In the substantia propria, pemphigoid specimens showed dramatically increased inflammatory infiltrate with significantly more cells staining, in order of frequency, for T cells (CD3+, CD5+), T-helper cells (CD4+), T-suppressor cells (CD8+), macrophages (CD14+, Mac-1+), and dendritic cells (CD1+, HLA-DR+).
 Ten percent of these cells expressed interleukin-2 receptor protein (CD25+), indicating T-cell activation.
",16
2757,"A case of sideburn reconstruction using a temporoparieto-occipital island flap.
 A preliminary case is reported in which a large temporal bald scar including the sideburn was successfully reconstructed using a temporoparieto-occipital island flap in combination with a tissue expander.
 This flap is considered to be a kind of reverse-flow island flap of the occipital artery by means of the fine vascular connections with the temporal branch of the superficial temporal artery.
 This new method is potentially a good solution for sideburn reconstruction.
",16
2758,"Individual patterns of immediate skin reactivity to mold extracts.
 One hundred atopic patients were skin tested intradermally over a 2-year period with 30 different mold extracts.
 Subjects were monitored for immediate reactions.
 Data suggest that to evaluate mold sensitivity in atopic patients one must use multiple mold extracts.
",16
2759,"Anogenital warts in children. Clinical and virologic evaluation for sexual abuse 
 Seventy-three children with anogenital warts were examined for sexual abuse during a 2-year period.
 Our data suggest that nonsexual transmission is common, particularly in children under 3 years of age.
 Approximately 25% of these children were younger than age 1 year, and another 50% were between the ages of 1 and 3 years.
 No evidence of sexual abuse was detected in 66 children.
",16
2760,"Type VII collagen and 19-DEJ-1 antigen. Comparison of expression in inversa and generalized variants of recessive dystrophic epidermolysis bullosa.
 The expression of type VII collagen and 19-DEJ-1 antigen was examined in 73 and 71 patients, respectively, with recessive dystrophic epidermolysis bullosa (RDEB), comprising gravis, mitis, inversa, and indeterminant subsets, to better determine the specificity and sensitivity of two monoclonal antibodies directed against these dermoepidermal junction-specific epitopes.
 Type VII collagen (LH 7:2 epitope) was usually absent (in 90%) in patients with the gravis variant of RDEB, whereas its expression was most often diminished (in 67%) in those with the mitis form of the disease.
 Only 2% and 5% of patients with gravis and mitis variants, respectively, had apparent normal amounts of type VII collagen within their skin.
 In contrast, six (86%) of seven patients with the inversa variant had normal expression of the antigen.
 Only 25% of all patients with RDEB lacked the 19-DEJ-1 antigen; of these, however, most had the gravis variant, although absence or diminution was also infrequently observed in those with the mitis and inversa forms.
 Intermediate findings were noted in patients classified as having indeterminant forms of RDEB.
 Some variability in antigen expression was also noted among affected siblings.
 We conclude that assessment of expression of the LH 7:2 epitope of type VII collagen may be diagnostically useful, although considerable overlap does exist between individual patients with gravis and mitis forms.
 19-DEJ-1 expression is a far less sensitive probe in RDEB, although such data may prove useful in the assessment of newborns lacking the characteristic features of gravis disease.
 In addition, based on our experience with inversa RDEB, it would appear that altered expression of type VII collagen cannot be attributed to blister formation in this latter rare subset, since this antigen is usually strongly detected along the dermoepidermal junction, even in perilesional skin sites.
",16
2761,"Synovial fluid polymorphonuclear leucocytes from patients with rheumatoid arthritis have reduced MPO and NADPH-oxidase activity.
 Synovial fluid (SF) polymorphonuclear leucocytes (PMN) from patients with rheumatoid arthritis (RA) were compared to RA and normal circulating blood PMN.
 RA SF PMN were as viable as blood PMN and remained viable for up to 24 h in culture.
 Measurement of myeloperoxidase indicated that RA SF PMN had degranulated and secreted their myeloperoxidase prior to isolation, 26.5 +/- 11.7% being found extracellularly compared to less than 2.9% in RA and normal blood PMN.
 RA SF PMN alone showed a decrease in basal NADPH-oxidase activity as well as an increase in responsiveness to stimulation by chemotactic peptide during culture.
 Stimulation of PMN with phorbol-12-myrisitate-13-acetate evoked equivalent responses in each population before and after culture.
 These results demonstrate a major difference in resting and receptor-mediated activation of superoxide release by RA SF PMN.
 Together, these results have important implications in identifying the role of the activated PMN in RA.
",16
2762,"Limiting dilution analysis of autocytotoxic and autosuppressor T-cells in rheumatoid arthritis.
 Limiting dilution analysis has shown that the autologous mixed lymphocyte reaction is regulated by at least two cell populations, the autocytotoxic and the autosuppressor.
 Limiting dilution analysis in nine patients with rheumatoid arthritis has shown that there is a significant decrease in both populations when compared to 10 control subjects.
 The mechanism and the consequences of this decrease are not known.
",16
2763,"A laboratory and clinical study of pneumatic 'grip strength' devices.
 The use of inflated bags or cuffs to measure grip strength is now a well established technique.
 The method does have a number of problems.
 Bags of different diameter and volume were seen to give statistically significantly different pressure readings when squeezed by the same subjects.
 Different initial pressures (from 20 mmHg to 60 mmHg) also gave significantly different results both in laboratory tests on a materials testing machine and when patients with rheumatoid arthritis squeezed the bag.
 The technique of squeezing also affected the results.
 Despite the intrinsic drawbacks of the system, it is likely to remain in general use because of familiarity and convenience.
 We recommend the minimum details required when pneumodynamometer-derived data are published.
",16
2764,"The cycling of combination antirheumatic drug therapy in rheumatoid arthritis.
 In this open pilot study a combination of hydroxychloroquine, prednisolone and alternating months of treatment with sulphasalazine or oral weekly pulse methotrexate has been investigated in 16 patients with rheumatoid arthritis (RA) refractory to a total of 67 disease suppressive medications.
 Results at 3 months indicated significant improvements in visual analogue score for pain, joint count, Ritchie index, scale of disability related to activities of daily living, ESR, rheumatoid factor and C-reactive protein.
 This degree of improvement, however, was not maintained 6 and 12 months after commencement of treatment.
 Pain score, Ritchie index and ESR were the only parameters demonstrating significant improvement at 12 months.
 Therapy was terminated in eight patients, half due to lack of efficacy and half because of side effects.
",16
2765,"Methylsulphasalazine in rheumatoid arthritis.
 Methylsulphasalazine, which differs from sulphasalazine by the addition of one methyl group, may provide the benefits of the parent drug with fewer side-effects in rheumatoid arthritis (RA).
 We describe the outcome of its use in RA.
 Of 21 patients entered into the study, 10 successfully completed 6 months of therapy; five developed adverse effects, four withdrew for reasons unrelated to drug treatment and two stopped because of inefficacy.
 No serious adverse effects were reported.
 A statistically significant improvement in most clinical assessments was observed from weeks 8-12 onwards.
 Significant improvement in plasma viscosity was observed and there was a trend towards improvement in serum CRP, histidine and IgM concentrations.
 There was a good correlation between mean serial changes in clinical and biochemical assessments indicating that the drug may exhibit the properties of a second-line agent.
 Median steady-state serum concentrations of methylsulphasalazine and methylsulphapyridine were 26.6 micrograms/ml and 2.85 micrograms/ml respectively.
",16
2766,"Analysis of IL-1 and TNF-alpha gene expression in human rheumatoid synoviocytes and normal monocytes by in situ hybridization.
 Human IL-1 alpha, IL-1 beta, and TNF-alpha mRNA expression was examined in peripheral blood monocytes (PBM) from normal individuals and in primary synoviocytes isolated from patients with rheumatoid arthritis by Northern blot and in situ hybridization.
 Cells cultured in the presence or absence of LPS were analyzed using in vitro synthesized 35S-labeled sense or antisense RNA probes to determine the relative abundance and the cell type expressing each of the mRNA for these potent inflammatory mediators.
 The results indicated that 72% of the LPS-stimulated PBM expressed detectable levels of IL-1 alpha mRNA, 89% IL-1 beta mRNA, and 10% TNF-alpha transcripts.
 Thus, the majority of activated PBM produced both IL-1 alpha and IL-1 beta.
 Experiments combining immunofluorescence for IL-1 beta protein with in situ hybridization for TNF-alpha mRNA demonstrated that monocytes expressing TNF-alpha mRNA also produced IL-1 beta.
 Primary synoviocytes from four patients with RA were also examined for the mRNA expression of each cytokine.
 Northern blot analyses of total RNA isolated from 0 to 72 h after LPS- or mock-stimulation showed that IL-1 beta mRNA was the most abundantly expressed, followed by TNF-alpha.
 In situ hybridization revealed that IL-1 beta and TNF-alpha transcripts were detected exclusively in synovial tissue macrophages.
 IL-1 alpha mRNA was not detected in these cultures by either method.
",16
2767,"Evidence for an epidermal cytokine network.
 Cytokines are (glyco)proteins that are synthesized and secreted by various cells, which bind to specific receptors on target cells and which regulate activation, proliferation, and differentiation of immune as well as non-immune cells.
 Keratinocytes upon injury release interleukin (IL)-1, IL-6, IL-8, colony-stimulating factors, and tumor-necrosis factor, as well as growth and suppressor factors.
 There is also strong evidence for a network of interacting cytokines, which has been only partially characterized so far, maintaining a proper balance.
 However, excessive or insufficient production of these mediators may contribute to certain disease states, particularly those with infectious and autoimmune genesis.
 Therefore the understanding of cytokine interactions may be helpful in elucidating the pathomechanisms of such diseases.
 Moreover, certain cytokines, as well as their analogues and antagonists, may prove to be of therapeutic value.
",16
2768,"Leukocyte chemoattractant cytokines of the epidermis.
 The constitutive production of interleukin-1 alpha-like material in normal human epidermis, its inflammatory properties, and the mechanism of its inflammatory action are briefly reviewed.
 The isolation of interleukin-8 from psoriatic lesions, its in vitro production, and leukocyte chemoattractant properties are also described.
 Available evidence suggests that interleukins-1 and -8 are inflammatory cytokines of major potential importance in the induction of leukocyte infiltrates in human skin.
",16
2769,"Interleukin-1 and interleukin-6 in psoriasis.
 We report on the levels of expression of IL-1 and IL-6 in skin from psoriasis patients.
 Different approaches were pursued.
 Initially, the levels of IL-1 beta and IL-6 were measured in suction blister fluid from lesional and uninvolved skin from psoriasis patients, using a sensitive enzyme-linked immunoabsorbent assay (ELISA) and bio-assay.
 Skin sections were also examined for the presence of IL-1 and IL-6 using IL-1 beta- and IL-6-specific antibodies.
 Finally, the expression of IL-1 and IL-6 mRNA was determined in cultured keratinocytes (KC) and fibroblasts from psoriasis skin.
 Suction blister fluid from lesional and uninvolved psoriasis skin and from skin of healthy individuals did not contain detectable levels (greater than 100 pg/ml) of IL-1 beta.
 Blister fluid from psoriasis lesions contained low but significant levels of IL-6, whereas the serum levels of IL-6 in these patients was undetectable.
 Using cryostat skin sections and an IL-1 beta-specific monoclonal antibody (MoAb) in an indirect immunoperoxidase technique, a diffuse staining in the entire epidermis was observed in sections of uninvolved skin from psoriasis patients.
 In cryostat sections of psoriasis lesions, a faint diffuse staining of the epidermis and a pronounced ""dot-like"" intracellular staining pattern was observed.
 On the other hand, the same IL-1 beta-specific MoAb showed, in a indirect immunofluorescence technique using unfixed epidermal cells, bright membrane staining in epidermal cell suspensions from psoriasis lesions.
 Slightly elevated levels of IL-1 beta and IL-1 alpha mRNA were observed in cultured KC from psoriasis lesions as compared to those in normal KC and in the HEp-2 cell line.
 Very low levels of IL-6 mRNA were expressed in KC from psoriasis lesions and healthy individuals.
 Fibroblasts from psoriasis lesions expressed extremely low levels of IL-1 alpha and IL-1 beta, but high levels of IL-6 mRNA.
 The results point to a paradoxical situation in psoriatic skin: blister fluid from psoriasis lesions contains no IL-1 beta, whereas IL-1 beta is overexpressed on the plasma membrane and in the intracellular compartment of epidermal cells.
 This finding may help in explaining the observed absence of IL-1 in aqueous extracts of psoriatic scales.
 Because cultured KC from psoriasis lesions express minimal levels of IL-6 mRNA.
 dermal fibroblasts, probably together with the inflammatory infiltrate, may represent a major source of IL-6 in psoriasis lesions in vivo.
",16
2770,"A possible role for transforming growth factor-beta in systemic sclerosis.
 The cause of systemic sclerosis remains unknown, but cellular and molecular mechanisms possibly responsible for the characteristic clinical manifestations of fibrosis and vascular damage (Raynaud's phenomenon, telangiectasis, digital infection, and renal arteriopathy) are becoming understood in greater detail.
 One possibly important cytokine is transforming growth factor-beta (TGF-beta); its involvement is reviewed here.
 With regard to vascular lesions, TGF-beta has variably been shown to inhibit endothelial cell growth in vitro but to promote angiogenesis in vivo, a paradox that remains unresolved.
 Nonetheless, an injurious activity of TGF-beta on microvascular endothelial cells could help to explain the intimal proliferation and microvascular obliteration seen.
 Whether as a result of or as a cause of endothelial cell damage, platelet activation has been well documented in systemic sclerosis and the platelet alpha granule pool contains a large quantity of TGF-beta.
 TGF-beta is also produced by activated macrophages and T cells, both of which are known to occur within systemic sclerosis lesions.
 An important effect of TGF-beta is its stimulation of fibroblast collagen and fibronectin synthesis and their deposition into the extracellular matrix.
 Stimulation by TGF-beta may therefore account for the fibrosis seen in the dermis and in the internal organs.
 Direct evidence of TGF-beta involvement in systemic sclerosis is scanty, and awaits discovery of either an abnormal expression of or response to TGF-beta.
 The biologic effects of TGF-beta appear to be regulated at the level of activation from a latent polypeptide precursor form.
 Descriptions of the importance of this cytokine in pathologic conditions will need to account for this activation and its regulation.
 Nonetheless, the physiologic effects so far attributed to TGF-beta make its involvement in systemic sclerosis an attractive possibility to explain some of the manifestations of this enigmatic disease.
",16
2771,"Abnormal cutaneous topobiology: the molecular basis for dermatopathologic mononuclear cell patterns in inflammatory skin disease.
 Because of the identification and characterization of various adhesion molecules (lymphocyte function associated antigen-1, intercellular adhesion molecule-1), chemotactic factors (interleukin-8, monocyte chemotactic/activating factor), and their modulatory cytokines (gamma interferon, tumor necrosis factor), it is possible to begin to ascribe specific molecules to cutaneous cellular reaction patterns.
 The abnormal topobiology, or altered spatial distribution, of mononuclear cells, which gives rise to disease-specific patterns, was described in molecular terms.
 A large number of diverse skin diseases were classified into six different groups, with each group highlighting distinctive cell types, adhesion molecules, chemotactic factors, and cytokines.
 The diseases within each group, which share functional anatomical reaction zones, were postulated to share common pathophysiologic pathways.
 Thus, it is now possible, as one scans the microscopic field, to look past the static images of red- and blue-stained cells and appreciate a dynamic and detailed medley of molecularly defined events emanating from the eyepiece.
",16
2772,"Response of discoid and subacute cutaneous lupus erythematosus to recombinant interferon alpha 2a.
 Ten patients suffering from discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) were treated with interferon alpha 2a.
 A marked improvement or clearing of cutaneous lupus erythematosus lesions was observed in eight of them.
 However, the response to interferon was of short duration and within a few weeks after interferon withdrawal all patients who were improved or cleared relapsed.
 This study suggests that interferon alpha 2a represents a new interesting approach in the treatment of DLE and SCLE.
 Ongoing trials will define the optimal treatment schedule for the maintenance of interferon-induced improvement of cutaneous lupus erythematosus.
",16
2773,"Application of beta-interferon in virus-induced papillomas.
 Eighty patients with bilateral common warts of the extremities were treated at weekly intervals with intralesional injections of either human fibroblast interferon or placebo.
 Lyophilized interferon (3 X 10(6) units) was diluted with 3 ml of normal sterile saline matched with identical vials of placebo.
 Eighty sets of three vials of human fibroblast interferon or placebo were labeled either A or B by a controller who maintained the code until the experiment was completed.
 Each patient received 0.1 X 10(6) units of interferon into the warts on one side and placebo injections into those on the matching extremity.
 Warts were measured each week and the progress or lack thereof was scored on a scale of -1 (worse) to 3 (cured).
 Therapy continued until either at least one extremity had cleared or the patient had received 10 weekly injections.
 A final evaluation was scored by measuring the total progress of each patient during the study.
 Sixty-four patients were treated to completion.
 More than 81% of the interferon-treated extremities were either cured or responded effectively to therapy.
 Only 17% of the placebo-treated lesions responded in this fashion.
 A statistical analysis of these data confirms the effectiveness of intralesional interferon therapy.
 The average number of interferon injections until cure was 5.9 +/- 1.7.
 No adverse effects were observed.
 The applications of interferon in patients with epidermodysplasia verruciformis and flat warts were also studied.
 Intralesional interferon beta was, to a certain degree, effective for benign lesions of epidermodysplasia verruciformis, but systemic treatments were not effective.
 Subcutaneous interferon beta was, in an uncontrolled study, effective in 45% of patients with flat warts.
",16
2774,"Atlantoaxial stabilization in rheumatoid arthritis.
 Atlantoaxial subluxation in patients with rheumatoid arthritis is common.
 Operative stabilization is clearly indicated when signs and symptoms of spinal cord compression occur.
 However, many recommend early operative fusion before evidence of appreciable neural compression occurs because 1) the myelopathy in these patients may be irreversible; 2) the overall prognosis is poor once symptoms of cord compression are present; and 3) the risk of sudden death associated with atlantoaxial subluxation is increased even in asymptomatic patients.
 The authors believe that rheumatoid arthritis patients in relatively good health without advanced multisystem disease and less than 65 years of age should be considered for operative stabilization if mobile atlantoaxial subluxation is greater than 6 mm.
 Seventeen patients with severe rheumatoid arthritis and atlantoaxial subluxation treated with a posterior arthrodesis are presented.
 A new method of fusion, devised by the senior author (V.K.H.S.), was utilized in all cases.
 Indications for operative therapy in these patients included evidence of spinal cord compression in 11 patients (65%) and mobile atlantoaxial subluxation greater than 6 mm but no signs or symptoms of cord compression in six patients (35%).
 Thirteen patients developed a stable osseous fusion, two patients a well-aligned fibrous union, one patient a malaligned fibrous union, and one patient died prior to evaluation of fusion stability.
 The details of the operative technique and management strategies are presented.
 Several technical advantages of this method of fusion make this approach particularly useful in patients with rheumatoid arthritis.
 Because of multisystem involvement of this disease, a high rate of osseous fusion is often difficult to achieve.
",16
2775,"Scar revision and camouflage.
 The successful revision and camouflage of facial scars is as much an art as a science, and the best teacher is continued experience; however, common sense, a broad knowledge of available options, technical ability, and patience are all necessary if one chooses to practice in this challenging field.
 Patients with facial scars are vulnerable in a way that few others are, and it is the responsibility of the facial plastic surgeon to evaluate these patients properly and realistically, to prepare them for a process that may involve multiple procedures, and to see them through this process with all the expertise and compassion possible.
 If this is done, the rewards to the patient and to the surgeon can be immeasurable.
",16
2776,"Autoantibody to Th ribonucleoprotein (nucleolar 7-2 RNA protein particle) in patients with systemic sclerosis.
 We studied sera of 371 consecutive new patients with systemic sclerosis (SSc; scleroderma) who were first evaluated during 1984-1988.
 All sera were tested for antinuclear antibodies by immunofluorescence staining using HEp-2 cells as substrate.
 We excluded 219 sera showing dark nucleoli and screened for antibodies to Th in the remaining 152 sera by immunoprecipitation of a 32P-labeled HeLa cell extract.
 Fifteen (4.0%) of 371 sera were anti-Th+.
 Anti-Th antibodies were present in 14 (8.4%) of 167 SSc patients with limited cutaneous involvement, in 1 of 167 with diffuse cutaneous involvement, and in 0 of 37 with SSc overlap syndrome.
 Among 244 controls with other connective tissue diseases, anti-Th was detected in only 3 patients, all having primary Raynaud's phenomenon of less than 2 years duration.
 In the subgroup with SSc with limited cutaneous involvement, the 14 anti-Th+ patients had a significantly greater frequency of puffy fingers, small bowel involvement, and hypothyroidism, and a significantly lower frequency of arthralgia and/or arthritis.
 Their cumulative survival rate from the time of onset of symptoms was lower than that for anti-Th- patients (78% versus 91% at 10 years), primarily due to 3 deaths from pulmonary arterial hypertension (2 from primary pulmonary hypertension and 1 from pulmonary hypertension secondary to pulmonary interstitial fibrosis).
 Serum anti-Th antibodies are present almost exclusively in patients with SSc with limited cutaneous involvement or in those with primary Raynaud's phenomenon whose disease may evolve to SSc with limited cutaneous involvement, and these antibodies may identify those patients who are at greater risk for reduced survival.
",16
2777,"Increased expression of type VI collagen genes in systemic sclerosis.
 The expression of type VI collagen genes in affected skin from patients with systemic sclerosis (SSc) was examined by in situ hybridizations with a human alpha 2(VI) collagen sequence-specific complementary DNA.
 Five patients with diffuse, rapidly progressive SSc of recent onset (less than 12 months) were studied.
 The results showed increased expression of alpha 2(VI) collagen messenger RNA transcripts in the skin of scleroderma patients compared with that in the skin of normal subjects.
 These findings indicate that alterations in the expression of type VI collagen genes, similar to those previously described for types I and III collagen, are present in the affected skin of SSc patients.
 These alterations may result in excessive tissue accumulation of type VI collagen and may play a role in the progressive skin induration and sclerosis that are prominent features of SSc.
",16
2778,"Increased expression of intercellular adhesion molecule 1 on the fibroblasts of scleroderma patients.
 The surface expression of intercellular adhesion molecule 1 (ICAM-1) and class I and class II major histocompatibility complex molecules on cultured dermal fibroblasts from 7 scleroderma patients and 6 control donors was compared.
 Scleroderma fibroblast lines contained 41.0 +/- 3.0% (mean +/- SEM) cells with high levels of ICAM-1 expression (ICAM-1-high), whereas 26.9 +/- 1.5% of control fibroblasts were ICAM-1-high (P = 0.0003).
 There were no differences in the expression of class I and class II molecules.
 ICAM-1-high and ICAM-1-low fibroblasts produced equal amounts of total protein and procollagen.
 The increase in the number of ICAM-1-high fibroblasts in scleroderma patients may facilitate T cell activation and lymphokine production, and thus indirectly contribute to the fibrotic process.
",16
2779,"Association of HLA-Dw16 with rheumatoid arthritis in Yakima Indians. Further evidence for the ""shared epitope"" hypothesis.
 Rheumatoid arthritis (RA) is prevalent in Yakima Indians, a Native American tribe.
 HLA-DR4, the HLA specificity commonly associated with RA in Caucasians, is rare among the Yakima.
 Using a specific oligonucleotide probe that recognizes DR4 nucleotide sequences associated with RA, a rare HLA-Dw16 gene was identified in 83% of Yakima patients with RA and in 60% of Yakima control subjects.
 This shared sequence encodes a discrete class II epitope that is highly correlated with RA in both DR4 positive and DR4 negative individuals.
",16
2780,"Identification of a platelet dense granule membrane protein that is deficient in a patient with the Hermansky-Pudlak syndrome.
 Monoclonal antibodies were raised after injecting mice with isolated human dense granules.
 Several of these monoclonals were found to recognize a 40-Kd dense granule membrane protein.
 Western blot and immunofluorescent analysis confirmed the dense-granule specificity.
 After thrombin activation, the protein was found in patches on the external platelet membrane.
 By Western blot and slot blot analysis, the protein was found to be markedly deficient in a patient with the Hermansky-Pudlak syndrome.
 Studies of neutrophils and endothelial cells show the presence of immunologically related granule-membrane protein(s).
 Western blots using four anti-synaptophysin antibodies and three antibodies to the platelet 40-Kd protein suggest that the protein may share some homology with, but is not identical to, the synaptosomal membrane protein synaptophysin.
",16
2781,"The transverse anatomy of androgenic alopecia.
 Twenty-five biopsy specimens from the balding frontal scalp of five patients were studied.
 Processing included vertical and transverse (horizontal) sectioning, toluidine blue and hematoxylin and eosin staining, and fixed and frozen sectioning.
 Findings included decreased hair density, increased numbers of vellus hairs, and alteration of the normal follicular architecture.
 Transverse frozen sectioning with toluidine blue staining appeared to be a rapid and reliable tool for studying androgenic alopecia.
",16
2782,"Urticaria: clinical efficacy of cetirizine in comparison with hydroxyzine and placebo.
 Chronic urticaria is a problem for both physician and patient.
 In an effort to avoid the risks associated with corticosteroid treatment, many first-generation H1-receptor antagonists have been tried and found to induce undesirable levels of sedation when given in amounts sufficient to control urticaria.
 Cetirizine, a pharmacologically active oxidized metabolite of hydroxyzine, was developed to provide selective H1-receptor inhibition without depression of the central nervous system.
 In a 4-week, multicenter, double-blind, placebo-controlled safety and efficacy study, cetirizine, in a once-a-day dose (5 to 20 mg), was equivalent in efficacy to hydroxyzine in divided doses (25 to 75 mg/day).
 The incidence of somnolence in the cetirizine group was not significantly different from that of the placebo group.
 However, in the hydroxyzine group, the incidence of somnolence was significantly higher than that in the placebo group (p = 0.001).
 The results of this study demonstrate that cetirizine has a greater safety margin over the older parent drug hydroxyzine.
",16
2783,"Langerhans cells but not monocytes are capable of antigen presentation in vitro in corticosteroid contact hypersensitivity.
 Corticosteroids suppress delayed-type hypersensitivity (DTH) reactions in vivo and impair lymphoid cell functions in vitro.
 In contact hypersensitivity (CHS) to corticosteroids, however, the corticosteroids are capable of inducing DTH responses in vivo.
 The present study examined the capacity of corticosteroids to induce in vitro proliferation of T lymphocytes from patients with CHS to corticosteroids.
 With peripheral blood mononuclear adherent cells as antigen-presenting cells (APC) and hydrocortisone-17-butyrate (H-17-B) as hapten, no proliferation responses were detected of T lymphocytes from patients with CHS to H-17-B.
 However, when epidermal Langerhans cells (LC) were used as APC, weak proliferation responses were observed.
",16
2784,"Validation of Sickness Impact Profile and Psoriasis Disability Index in Psoriasis.
 A prospective cross-sectional questionnaire study of 32 patients with psoriasis was carried out in order to validate the use of the Sickness Impact Profile (SIP) in psoriasis and compare its sensitivity with the Psoriasis Disability Index (PDI).
 Overall PDI scores, but not overall SIP scores, correlated well with PASI scores (P less than 0.05).
 There was good correlation between the PDI and overall SIP scores (P less than 0.01).
 Psychosocial factors are more severely impaired than physical activities in patients with psoriasis.
 It is now possible to directly compare the disability experienced by psoriatic patients with that experienced by patients suffering from other systemic diseases, using the SIP.
 The PDI is an appropriate method to give a rapid overall measure of psoriasis disability.
",16
2785,"Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris [published erratum appears in Lancet 1991 Apr 20;337(8747):988] 
 The therapeutic efficacy and tolerability of calcipotriol ointment and betamethasone valerate ointment in psoriasis were compared in a multicentre, prospective, randomised, double-blind, right/left trial.
 345 inpatients and outpatients with psoriasis vulgaris of symmetrical distribution were treated twice daily for 6 weeks with calcipotriol ointment 50 micrograms/g and betamethasone ointment 0.1% randomly assigned to opposite sides of the body.
 The main outcome measures--the psoriasis area and severity index (PASI), the investigators' assessments of erythema, thickness, and scaling, and the patients' own assessments of the overall response to treatment--were sought at weeks 2, 4, and 6.
 Both treatments significantly reduced the PASI scores and the investigator's assessment scores, but at each visit the PASI score was significantly (p less than 0.001) lower with calcipotriol than with betamethasone.
 At 6 weeks the mean PASI reduction was 68.8% with calcipotriol and 61.4% with betamethasone (95% confidence interval for difference 5.1-9.8, p less than 0.001).
 The scores for erythema, thickness, and scaling were significantly (p less than 0.001) lower with calcipotriol than with betamethasone at the end of treatment.
 The patients considered that 82.1% of calcipotriol-treated sides and 69.3% of betamethasone-treated sides had improved greatly or cleared up by the end of treatment (p less than 0.001).
 57 adverse events were reported by 52 patients (15.1%).
 The most common adverse event, lesional/perilesional skin irritation, was slightly but not significantly (p = 0.12) more common with calcipotriol treatment.
 15 (4.3%) patients were withdrawn from the study, 3 because of local adverse events.
 There were no changes in serum calcium during the study.
 Thus, calcipotriol ointment was superior to betamethasone valerate ointment in psoriasis vulgaris.
 Though long-term results are not yet available, calcipotriol holds great promise as an antipsoriatic agent.
",16
2786,"Keratinocytes as initiators of inflammation 
 Environmental stimuli responsible for inducing cutaneous inflammation include contact allergens and ultraviolet light.
 We postulate that these diverse stimuli trigger a cutaneous inflammatory response by directly inducing epidermal keratinocytes to elaborate specific pro-inflammatory cytokines and adhesion molecules.
 The consequences are activation of dermal microvascular endothelial cells and selective accumulation of specific mononuclear cells in the dermis and epidermis.
 Thus, keratinocytes may act as ""signal transducers"", capable of converting exogenous stimuli into the production of cytokines, adhesion molecules, and chemotactic factors (acting in an autocrine and paracrine fashion) responsible for initiation of ""antigen-independent"" cutaneous inflammation.
 The initiation phase may facilitate or promote an amplification phase with additional production of tumour-necrosis factor alpha and interferon gamma via an ""antigen-dependent"" pathway, and keratinocyte/T cell/antigen-presenting dendritic cellular associations.
 The direct activation of keratinocytes, with their ability to produce the complete repertoire of pro-inflammatory cytokines, can profoundly influence endogenous and recruited immunocompetent cells, thereby providing the critical trigger responsible for the swift and clinically dramatic alterations that occur following contact between the epidermis and a host of ""noxious"" agents.
",16
2787,"Ultrastructural localization of calcium in psoriatic and normal human epidermis.
 With ion capture cytochemistry, we previously demonstrated the distribution of calcium ions in murine epidermis, a pattern consistent with a role for this ion in the regulation of epidermal differentiation.
 Because of the known proliferation and differentiation defects in psoriasis, we compared the calcium distribution of involved vs uninvolved psoriatic lesions and normal human epidermis.
 Whereas normal human and uninvolved psoriatic epidermis revealed increased calcium-containing precipitates in the uppermost stratum granulosum, in contrast the basal layer of psoriatic lesions contained less extracellular calcium, a condition that favored enhanced proliferation.
 Moreover, all psoriatic suprabasal cell layers displayed heavier than normal concentrations of calcium, indicating loss of the normal calcium gradient that programs terminal differentiation.
 This abnormal profile may account for the differentiation defects (eg, parakeratosis) that occur in psoriasis.
 Finally, psoriatic lesions displayed retained ionic Ca in intercellular domains of the upper stratum granulosum with absence of normal intercellular bilayers, findings that may underlie the abnormal desquamation and permeability barrier in psoriasis.
",16
2788,"Papuloerythroderma. Another case of a new disease.
 We describe a case of papuloerythroderma.
 This is a distinctive clinical entity characterized by pruritus, red-brown flat-topped papules exhibiting the ""deck-chair"" sign, eosinophilia, and lymphopenia.
 We propose that the Langerhans cell may have a central role in the pathogenesis of papuloerthroderma and we describe an excellent response to photochemotherapy.
",16
2789,"Newly identified U4/U6 snRNP-binding proteins by serum autoantibodies from a patient with systemic sclerosis.
 We found serum autoantibodies directed against the proteins binding exclusively to U4/U6 of Sm small nuclear ribonucleoprotein particle (snRNP) in serum from a patient (MaS) with systemic sclerosis.
 Their specificity, called anti-MaS, is distinct from that of known antibodies against U snRNP.
 The U4 and U6 small nuclear RNA from a 32P-labeled HeLa cell extract and five proteins with Mr 150,000, 120,000, 80,000, 36,000, and 34,000, in addition to Sm core proteins (B, B', D, E, F, and G) from an [35S] methionine-labeled extract, were immunoprecipitated by anti-MaS in isotonic solution.
 However, the Sm core proteins and U4 and U6 small nuclear RNA were separated from the protein-A-Sepharose facilitated MaS immunoprecipitate by incubation in a solution containing 500 mM NaCl.
 In immunoblots, anti-MaS antibodies reacted with one protein of Mr 150,000 from a HeLa cell nuclear extract that was fractionated by SDS-PAGE and transferred to a nitrocellulose sheet.
 The monospecific immunoaffinity purified antibody eluted from the immunoblot band immunoprecipitated U4 and U6 small nuclear RNA and reblotted the protein with Mr 150,000.
 These data indicate that anti-MaS antibodies recognize at least one antigenic protein that binds exclusively to the U4/U6 snRNP.
",16
2790,"Abnormalities in epidermal lipid metabolism in patients with atopic dermatitis.
 Atopic dermatitis is an inflammatory skin disease characterized by dryness and itch of the skin.
 In this study, we measured the phospholipid content and the fatty acid pattern of lesional and lesion-free epidermal keratome biopsies on 15 patients.
 For comparison, epidermal biopsies were obtained from healthy individuals undergoing plastic surgery.
 The phospholipid content of atopic epidermis was nearly twice as high as in healthy epidermis.
 Monounsaturated fatty acids in the phosphoglycerides were significantly increased (p less than 0.001) and n-6 fatty acids were significantly decreased (p less than 0.001) in lesional atopic epidermis compared to lesion-free epidermis.
 The content of esterified arachidonic acid in phosphatidylcholine from lesional epidermis was only 49% of that found in healthy epidermis (p less than 0.001).
 The content of free arachidonic acid was 47% higher (p less than 0.05), whereas the content of free long-chain saturated fatty acids was decreased by 29% (p less than 0.01), in lesional compared to lesion-free atopic epidermis.
 The disease severity, calculated as an arbitrary index, correlated inversely with the n-6 fatty acid content of lesion-free atopic epidermis (r = -0.89, p less than 0.001).
 Our findings suggest that atopic epidermis is characterized by an increased activity of phospholipase A2 and an incomplete transformation of phospholipids into other lipid classes.
",16
2791,"Effect of retinoic acid on platelet-derived growth factor (PDGF) bioactivity and type-B PDGF receptors in normal and psoriatic human fibroblasts.
 Psoriasis is a common skin disease in which retinoids have beneficial effects.
 It offers a model for the study of benign hyperproliferation with abnormal differentiation.
 The dermis has a prominent role in the appearance of epidermal lesions.
 It is therefore of interest to study the factors that modulate dermal cell proliferation.
 In this study, the role of retinoids in modulating platelet-derived growth factor (PDGF) bioactivity was studied in normal (six subjects) and psoriatic fibroblasts from involved and uninvolved tissues (six patients).
 Retinoic acid treatment (for 4 d at 10(-6) M) of psoriatic fibroblasts significantly increased the chemotactic effect of PDGF in these cells (p less than 0.01 and p less than 0.05, respectively, in involved and uninvolved skin at 20 ng/ml of platelet-derived growth factor as measured in a modified Boyden Chamber Assay).
 In the same way, retinoic acid treatment of psoriatic fibroblasts increased the mitogenicity of platelet-derived growth factor in these cells.
 Retinoic acid treatment has no significant effect on the mitogenic and chemotactic activity of PDGF in normal fibroblasts.
 The binding of the homodimer BB PDGF to its type-B receptor, which mediates the mitogenic and chemotactic effect of PDGF, was not modified by retinoic acid treatment either in psoriatic and/or normal fibroblasts.
 These results suggest that retinoic acid may modulate the PDGF bioactivity in psoriatic fibroblasts not by affecting the binding of this ligand to these cells but by influencing a post-receptor event.
",16
2792,"Characterization of 230-kD bullous pemphigoid antigen associated with the detergent-insoluble fraction of cultured keratinocytes.
 The 230-kD protein identified by antibodies from patients with bullous pemphigoid (BP) has a dual location in cultured normal human epidermal keratinocytes: part in a high-speed supernatant of homogenized cells and part in a particulate fraction, where it is resistant to extraction by non-ionic detergent or mild base.
 Antibodies were affinity purified from the particulate 230-kD BP antigen, which can be extracted in the presence of urea.
 The affinity-purified antibodies bind not only the cytosolic 230-kD protein, showing that it is related, if not identical, to the particulate form, but also produce a discontinuous granular pattern by indirect immunofluorescence in the basement membrane zone of rabbit esophagus.
 In stratifying epidermal cultures, expression of the 230-kD BP antigen is limited to basal cells.
 These data are consistent with 230-kD BP antigen involvement in keratinocyte basal cell interaction with extracellular matrix and indicate that the cultured cell may provide a useful model for analysis of 230-kD BP antigen function.
",16
2793,"The calcium-sensitive epitope of pemphigus foliaceus antigen is present on a murine tryptic fragment and constitutes a major antigenic region for human autoantibodies.
 Recent findings indicate that the pemphigus foliaceus (PF) antigen is involved in epidermal cell adhesion and that characteristic PF lesions result from loss of this function as a consequence of autoantibody binding.
 In the present communication we present data on the epitopes involved in the human autoantibody binding to an immunologically reactive murine tryptic fragment of the PF antigen (tf-PF).
 Immunoprecipitation experiments showed that 39 PF sera, obtained from North American, Colombian, and Brazilian patients recognized only calcium-sensitive epitope(s) on the tf-PF.
 Immunofluorescence blocking experiments showed that preincubation with tf-PF completely blocked the immunofluorescence of 80% of the sera when tested on human skin substrate, and 86% of the sera when tested on murine skin substrate.
 These results show that the calcium-sensitive epitope(s) originally recognized on human PF complex, is (are) present on the murine tf-PF and constitute(s) a major antigenic region for the human PF autoantibodies.
 They also implicate this region of the PF antigen in the pathogenesis of PF as well as in epidermal cell adhesion.
",16
2794,"Reduced neutrophil LTB4 release in atopic dermatitis patients despite normal fatty acid composition.
 Propositions about an abnormal fatty acid metabolism in atopic dermatitis patients prompted us to compare the phospholipid fatty acid composition and LTB4 release of neutrophils from 15 atopic dermatitis patients, as well as the adipose tissue triglyceride fatty acid composition, to that of 15 healthy controls matched by age, gender, and smoking habits.
 We found no differences in the tissue fatty acid composition between the two groups.
 The release of leukotriene B4 from Ca-ionophore-stimulated neutrophils in patients was on the average only 42% (p less than 0.001) of that measured in the control group, despite the very similar arachidonic acid contents of these cells.
 Our study does not support the assumption of an abnormal fatty acid desaturation in atopic dermatitis patients.
 Rather, the capacity to release and/or convert arachidonic acid into leukotrienes in neutrophils appears to be affected by this disease.
",16
2795,"Localization of neutrophil-activating peptide-1/interleukin-8-immunoreactivity in normal and psoriatic skin.
 Various cytokines have in the past been detected in human skin.
 Among these, the neutrophil-activating peptide NAP-1/IL-8 is a potent 8-kD proinflammatory peptide that has been purified from psoriatic scales.
 Its chemotactic activity on human neutrophils, as well as its presence in psoriatic scales, may relate to a role in this disease.
 In the present study, the tissue distribution of the peptide was examined immunohistochemically using two monoclonal antibodies (52E8, 46E5) recently produced and characterized in our laboratory.
 Immunoreactivity was detected in both normal and psoriatic skin, resulting in uniform suprabasal keratinocyte staining in normal skin with 52E8 and of all keratinocytes with 46E5.
 Immunoreactivity in psoriasis correlated to the inflammatory tissue reaction, varying from uniform absence in highly active psoriasis to focally weak staining in plaque type psoriasis.
 Cells of the acrosyringium and hair follicles were always positive and were unaffected by the inflammatory activity.
 Epidermal immunoreactivity detected in this study may be associated with closely related peptides of the IL8 family or with truncated or extended forms of NAP-1/IL-8.
",16
2796,"Characterization of skin-infiltrating lymphocytes in patients with psoriasis.
 In this study, skin-infiltrating cells in psoriasis patients were characterized in biopsies from both involved and uninvolved skin.
 Histologic examination of biopsies showed the presence of both CD4+ and CD8+ T cells and the lack of B lymphocytes.
 Skin biopsies were also placed in tissue culture medium supplemented with human serum, interleukin-2 (IL-2), and irradiated autologous blood lymphocytes.
 T lymphocytes grew from both plaques and univolved skin biopsies and consisted of a heterogeneous population of T-cell subsets.
 The immunophenotypic analysis of cultured cells was comparable to the histologic examination on frozen section, i.e., there was a greater number of CD4/CDw29+ cells than CD8+/CD45+ cells.
 Cultures were tested in the primed lymphocyte test (PLT) and cell-mediated lympholysis (CML) assays.
 All cultures tested demonstrated secondary proliferative but not cytolytic reactivity.
 The PLT results indicate that the cell cultures generated are autoreactive.
 This autoreactivity was found to be directed against non-human leukocyte antigens (HLA), i.e., minor HLA with some restriction to major HLA antigens.
",16
2797,"IgA-binding structures in dermatitis herpetiformis skin are independent of elastic-microfibrillar bundles.
 Dermatitis herpetiformis (DH) is characterized in part by the presence of granular deposits of IgA in the papillary dermis just beneath the dermal-epidermal junction.
 The nature of the structures to which IgA binds in DH skin, however, has not been clearly demonstrated.
 Previous immunoelectron-microscopy studies using the peroxidase-antiperoxidase technique have concluded that the IgA may bind to abnormal elastic microfibrillar bundles.
 Recently, antibodies have been developed against a major component of the elastic microfibril bundles, fibrillin.
 In addition, another dermal matrix protein, hexabrachion, has been characterized and found in normal human skin in a distribution similar to the IgA deposits of DH.
 Utilizing antibodies against fibrillin, hexabrachion, and human IgA and immunoelectronmicroscopy with immunogold staining techniques, we have examined the skin from patients with DH in order to localize the IgA deposits.
 Normal-appearing skin from five patients with DH exhibited electron-dense patches within the dermis, which were not seen in skin from normal subjects.
 These structures were sometimes adjacent to the basement membrane zone, but appeared amorphous and without a well-defined fibrillar structure.
 The electron-dense patches were labeled with anti-human IgA, but not with antibodies to fibrillin or hexabrachion.
 The anti-IgA antibody did not label the normal basement membrane.
 These studies confirm the presence of abnormal electron-dense, amorphous structures in the skin of patients with DH.
 Due to this lack of association with the elastic microfibril bundles and the lack of labeling with antibodies against fibrillin, we suggest that these deposits are distinct from the microfibrillar bundles of elastic tissue and may represent IgA bound to degraded basement membrane or isolated dermal deposits of IgA.
",16
2798,"Expression of basement membrane proteins and interstitial collagens in dermal papillae of human hair follicles.
 The expression of basement membrane molecules and interstitial collagens in human hair follicle mesenchyme was studied by immunohistochemical staining of tissue sections and of cells cultured from dermal papillae.
 Type I and type III collagens were found in the dermal sheath and in the dermal papilla throughout the hair cycle.
 Laminin and type IV collagen were expressed at the outer root sheath basement membrane and in the extracellular matrix of the dermal papilla of anagen and catagen follicles.
 In telogen follicles, where the volume of the dermal papilla extracellular matrix is much reduced, outline staining of dermal papilla cells for laminin and type IV collagen was still apparent.
 Staining for bullous pemphigoid antigen was also seen at the outer root sheath basement membrane extending to the lower tip of the hair bulb.
 In anagen follicles, there was no staining for bullous pemphigoid antigen at the interface between hair bulb epithelium and the dermal papilla and no staining within the dermal papilla.
 However, linear staining for bullous pemphigoid antigen became continuous around hair follicle epithelium during catagen and telogen.
 Cells cultured from human dermal papillae also stained for interstitial collagens, type IV collagen and laminin.
 However, similar results were obtained when cultured dermal fibroblasts were stained with the same antibodies.
 The expression of basement membrane proteins in human dermal papillae resembles that seen in follicles from other mammalian species and suggests that this is relevant to dermal papilla function.
 Cultured dermal papilla cells express a similar pattern of interstitial collagens and basement membrane proteins to those seen in tissue sections but this finding is not specific to dermal papilla cells.
",16
2799,"Cellular localization of interleukin-8 and its inducer, tumor necrosis factor-alpha in psoriasis.
 The importance of immunologic mechanisms in psoriasis has been deduced from the ability of immunosuppressive therapies to ameliorate this common and chronic skin disease.
 Certainly the histology of psoriatic lesions suggests a dialogue between the hyperplastic keratinocytes and infiltrating T lymphocytes and macrophages.
 To begin dissecting the cytokine network involved in the pathophysiology of psoriasis, the location, in both epidermal and dermal compartments, of tumor necrosis factor-alpha, interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha at the protein and/or mRNA levels were identified.
 Tumor necrosis factor-alpha was selected as a potentially key regulatory cytokine, first because it induces cultured keratinocyte interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha production, and second because intercellular adhesion molecule-1 expression by keratinocytes in psoriatic epidermis had been identified previously.
 Using immunohistochemical localization, tumor necrosis factor-alpha was identified in 12 psoriatic lesions as intense and diffuse expression by dermal dendrocytes (macrophages) in the papillary dermis (without significant staining of endothelial cells, mast cells, or dermal Langerhans cells), and focally by keratinocytes and intraepidermal Langerhans cells.
 Functional interaction between the dermal dendrocytes and keratinocytes was suggested by the presence of interleukin-8 expression of suprabasal keratinocytes immediately above the tumor necrosis factor-alpha-positive dermal dendrocytes.
 Interleukin-8 mRNA and transforming growth factor-alpha mRNA were detectable in the epidermal roof of psoriatic lesions, but neither was detectable at the protein or mRNA levels in any normal skin specimens.
 Treatment of cultured human keratinocytes with phorbol ester (which experimentally produces psoriasiform changes on mouse skin) or tumor necrosis factor-alpha also increased interleukin-8 and transforming growth factor-alpha mRNAs.
 Further elucidation of the cellular and molecular basis for the genesis and evolution of psoriasis will provide the framework for a better evaluation of the cause and treatment of this skin disease.
",16
2800,"Monoclonal antibodies detect monocyte/macrophage activation and differentiation antigens and identify functionally distinct subpopulations of human rheumatoid synovial tissue macrophages.
 Monoclonal antibodies (MAbs) to functionally heterogeneous populations of human rheumatoid arthritis (RA) synovial tissue macrophages and lipopolysaccharide (LPS)-activated U937 cells were generated.
 These MAbs were used to characterize macrophages in situ in the synovial pannus and to study relative antigen expression on the surface of cells isolated from the synovium and from normal peripheral blood.
 Monoclonal antibody 3D8, an anti-CD13 MAb, reacts with an antigen expressed on the surface of blood monocytes and is a monocyte activation-related antigen that is upregulated by exposure of monocytes to interferon-gamma (IFN-gamma) and LPS.
 The expression of the 3D8 antigen increases in parallel with MHC class II antigen expression and also is upregulated in culture as monocytes mature to macrophages.
 3D8 antigen is expressed strongly on RA synovial tissue lining cells, which are thought to be composed of macrophages.
 8D7 antigen expression, detected by MAb 8D7, increases on blood monocytes on cellular activation with LPS and interferon-gamma, but in contrast to the 3D8 antigen, does not increase with monocyte maturation in vitro.
 The 8D7 antigen is expressed differentially on density-defined macrophage subpopulations isolated from RA synovial tissue and is expressed more strongly on macrophages that are nonangiogenic than those that are angiogenic.
",16
2801,"Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy.
 Pathologic hoof changes in horses and swine can be normalized by administration of biotin.
 This vitamin has been given orally to women with brittle fingernails or onychoschizia.
 The aim of the study was to test whether the favorable clinical results could be corroborated by scanning electron microscopy.
 We investigated the distal ends of the fingernails from 32 persons.
 They were placed into three groups: group A consisted of 10 control subjects with normal nails, group B comprised eight patients with brittle nails studied before and after biotin treatment, and group C was 14 patients with brittle nails in whom the administration of biotin did not coincide exactly with the initial and terminal clipping of the nails.
 The thickness of the nails in group B increased significantly by 25%.
 In group C, the increase was 7%.
 Splitting of the nails were reduced in groups B and C and the irregular cellular arrangement of the dorsal surface of brittle nails became more regular in all nails of group B and in 8 of 11 nails of group C.
",16
2802,"Lymphocytic infiltrates of the skin in association with cyclosporine therapy.
 Three patients, one of whom has been previously reported, had erythematous papules and nodules of the face and upper part of the chest during cyclosporine therapy for inflammatory skin diseases.
 Histologic examination and DNA analysis (performed in two cases) revealed benign dermal lymphocytic infiltrates.
 In two cases proliferation of only T cells occurred.
 In the third case, both T and B cell populations were expanded and there was vacuolar degeneration of the basal layer of the epidermis and IgG, IgM, and C3 deposition along the dermoepidermal junction.
 These findings may be the result of cyclosporine-induced immune dysregulation.
 The lesions resolved in all patients after therapy was stopped.
",16
2803,"Antibodies to synthetic peptides from Epstein-Barr nuclear antigen-1 in sera of patients with early rheumatoid arthritis and in preillness sera.
 We studied IgG antibody levels to synthetic peptides (p62, E11 and E3) from Epstein-Barr nuclear antigen-1 (EBNA-1) protein sequence in sera of patients with rheumatoid arthritis (RA), in pre-RA and in rheumatoid factor (RF) positive non-RA sera from Finland.
 Anti-E11 and anti-E3 antibody levels were significantly elevated in RA sera, compared with both RF negative and RF positive nonrheumatoid controls.
 The concentrations of anti-E11 and anti-E3 antibodies in the preillness sera were lower than those in RA sera.
 Eight-year followup samples of patients with RA had slightly decreased levels of anti-E3 and anti-E11 antibodies compared with samples taken within 6 months of the disease onset.
 Anti-p62 antibody levels did not differ significantly between any of the groups studied.
 Thus, elevated levels of antibodies to 2 of the glycine containing EBNA-1 peptides were associated with clinical RA.
",16
2804,"Epidermal growth factor receptor of fibroblasts from patients with scleroderma.
 Epidermal growth factor receptor (EGF-R) of fibroblasts from 3 patients with scleroderma (progressive systemic sclerosis, PSS) was studied by radioiodinated-EGF binding assay.
 The binding was 60.9 +/- 4.0% of normal fibroblasts, and the Scatchard plots showed a decrease in the affinity for EGF, not in the number of EGF-R.
 PSS fibroblasts expressed higher levels (1.15-2.45-fold) of RNA for the v-erbB (EGF-R gene).
 All-transretinoic acid (retinoid) had little effect on EGF-R, v-erbB gene expression and the proliferation of PSS fibroblasts.
 These data concerning the abnormality in the EGF-R may all constitute a feature of PSS fibroblasts.
",16
2805,"Reports of erythematous macular skin eruptions associated with diltiazem therapy.
 Diltiazem is a commonly prescribed calcium-channel antagonist for hypertension and ischemic heart disease.
 The incidence of rash associated with diltiazem therapy is reported to be 1.3 percent.
 We describe two patients who developed erythematous, macular skin eruptions, approximately two weeks following institution of diltiazem.
 The skin eruptions resolved after symptomatic treatment and the patients received further therapy with another calcium-channel antagonist.
 Diltiazem-associated skin eruptions are a rare adverse effect; however, the incidence of rash may occur more frequently than reported in postmarketing surveillance studies.
",16
2806,"Cyclosporine in nonpsoriatic dermatoses.
 This article reviews the indications, efficacy, and possible mechanisms of action of cyclosporine in the treatment of nonpsoriatic dermatoses.
 These dermatoses can be categorized according to their responsiveness to cyclosporine therapy as excellent, moderate, variable, and nonresponsive.
 The advantages and disadvantages of cyclosporine are discussed and guidelines are proposed for its use in nonpsoriatic dermatoses.
",16
2807,"Management of patients and side effects during cyclosporine therapy for cutaneous disorders.
 Cyclosporine has been used in the experimental treatment of multiple inflammatory diseases of presumed autoimmune origin, including insulin-dependent diabetes mellitus, uveitis, rheumatoid arthritis, inflammatory bowel diseases, Graves' disease, and myasthenia gravis.
 In dermatology, the drug has been used successfully as primary therapy for psoriasis and psoriatic arthritis, alopecia areata, pyoderma gangrenosum, Behcet's disease, atopic dermatitis, and lichen planus.
 At a dose of 3 to 5 mg/kg per day, cyclosporine is well tolerated by most patients.
 However, because of concerns about its potential short- and long-term side effects, patients who use this drug require close monitoring.
 This review discusses appropriate clinical and laboratory evaluations, common and unusual side effects and their management, drugs that might alter the pharmacokinetics of cyclosporine metabolism, and criteria for dosage adjustments.
",16
2808,"Laboratory monitoring of cyclosporine levels: guidelines for the dermatologist.
 The following guidelines are recommended for laboratory monitoring of circulating levels of cyclosporine in dermatology patients.
 Measurements should be determined as trough levels in whole blood, not plasma or serum.
 The measurements should be performed with an assay that is specific for the parent cyclosporine compound (e.g., a high-performance liquid chromatography method or a specific monoclonal immunoassay).
 The results of nonspecific immunoassays that detect cyclosporine as well as its metabolites are difficult to interpret and cannot readily be compared among different studies or laboratories.
 In psoriasis patients, the circulating concentration of cyclosporine does not correlate reliably with the therapeutic response.
 Some patients may achieve an excellent response with blood levels in the range of 50 ng/ml; others may show little or no response despite blood levels as high as 200 ng/ml.
 In patients with a poor clinical response, monitoring of cyclosporine levels may be useful to confirm that the drug has been taken and may provide an estimate of the degree of absorption and metabolism of the parent compound.
 Because an upper limit of safety for the circulating concentration of cyclosporine has not been clearly defined, one should attempt to achieve a therapeutic response with the lowest possible dose.
 Clinicians must carefully monitor patients for signs of cyclosporine toxicity, regardless of the circulating concentration of the drug.
 Whole blood levels exceeding 250 ng/ml should be avoided.
",16
2809,"Effects of cyclosporine on renal function in psoriasis patients.
 Several prospective studies have documented the effectiveness of oral cyclosporine in the treatment of psoriasis.
 Despite this, the use of cyclosporine has been limited because of concern about the possibility of drug-induced renal dysfunction.
 We review the effects of cyclosporine on renal function.
",16
2810,"Immunity during cyclosporine therapy.
 Cyclosporine is not cytotoxic but it inhibits the production of immunologic memory-building growth factors by CD4+ T lymphocytes.
 It also may have inhibitory effects on the effector phase of certain immune reactions.
 These inhibitory effects are largely reversible and when treatment is stopped, the immune competence of cyclosporine-treated patients returns to normal.
 In contrast, conventional cytotoxic immunosuppressive agents tend to exterminate the lymphocyte clones that are activated during therapy, and such clonal deletions may cause permanent loss of immunologic memory to those antigens because T lymphocytes are not readily restored in adults with involuted thymus.
 Most transplant patients have received cyclosporine in combination with various other immunosuppressive agents, and reports suggest that a combination of this drug and conventional immunosuppressive agents may be associated with increased early appearance of non-Hodgkin's lymphoma and, possibly, endocrine-related tumors.
 An increase in cancers has not been observed in patients treated with cyclosporine alone for such conditions as psoriasis and autoimmune diseases.
 Treatment of adults with cytotoxic immunosuppressive drugs may permanently delete T-lymphocyte clones that are required for control of latent oncogenic viruses or certain malignant cells.
 Because of this, when such patients are treated with cyclosporine, further suppression of T-cell function combined with impairment of cytokine-mediated stimulation of natural killer cells and cytotoxic macrophages may facilitate tumor growth.
 Consequently, it is predicted that if cyclosporine monotherapy is associated with an increased incidence of tumors, it would primarily affect psoriasis patients who are treated with cyclosporine after PUVA or methotrexate therapy.
 Eventually, comparison of cancer incidence in different categories of patients should resolve this issue.
",16
2811,"Interactions of epidermal cells and T cells in inflammatory skin diseases.
 Multiple cell types and their factors and cytokines are involved in regulating the immune response in inflammatory skin diseases.
 Stimulatory and inhibitory factors interact to determine whether the immune response is regulated up or down.
 Normally, stimulatory signals are counteracted by inhibitory signals to prevent an immune reaction from being initiated.
 However, exogenous antigens and irritants or endogenous factors and altered immunogenic self-peptides can upset this balance.
 When that occurs, T cells are activated and an inflammatory skin reaction develops.
 Lymphokines released from such activated T cells can modify the phenotype and function of normal keratinocytes.
 They can induce the expression of adhesion molecules and receptors involved in antigen presentation.
 Furthermore, they can also stimulate keratinocyte proliferation.
 This may be important in development of the hyperplasia seen in inflammatory skin diseases, especially in psoriasis.
 Cytokines released from the activated keratinocytes can both stimulate and attract T cells to the epidermis and thereby continue the ongoing immune reaction.
",16
2812,"Effects of cyclosporine on immunologic mechanisms in psoriasis.
 A major impetus for further investigation of cellular immunologic mechanisms in psoriasis has been the discovery that cyclosporine, a potent immunosuppressive, is highly effective in the treatment of psoriasis.
 Cyclosporine has significant inhibitory effects on the ability of T cells to become activated.
 However, a direct activity of this drug on human keratinocyte signal transduction or growth has been difficult to demonstrate at relevant concentrations.
 Nevertheless, treatment of psoriasis or of 12-O-tetradecanoyl phorbol-13-acetate-treated murine skin with cyclosporine does reverse many epidermal abnormalities that are common to these two systems.
 This suggests that the compound exerts an indirect effect on epidermal keratinocytes in vivo, perhaps through immunocyte inhibition.
 During treatment of psoriasis patients, cyclosporine therapy resulted in selective changes in the numbers and functions of certain antigen-presenting cell subsets (which were distinct from Langerhans cells) and T-cell subsets.
 These changes were accompanied by indirect evidence of decreased T-cell lymphokine release.
 Lesional activity of cyclosporine-treated psoriasis patients was closely correlated with the degree of T-cell activation caused by antigen-presenting cells.
 Cyclosporine inhibition of lymphokine or cytokine release may result in decreased recruitment of non-Langerhans antigen-presenting cells into the epidermis and thus decreased immunoreactivity in the lesion.
",16
2813,"Blistering diseases. Diagnostic help for primary care physicians.
 At presentation, the differential diagnosis of bullous disease may seem difficult.
 However, the diagnosis may be clarified by considering such factors as Nikolsky's sign, age of the patient at onset, and pattern and distribution of blisters.
 Careful review of family, recreational, occupational, and drug histories may also help to identify the cause.
",16
2814,"Rheumatoid arthritis. New developments in treatment.
 If a patient with active rheumatoid arthritis does not obtain significant relief from nonsteroidal anti-inflammatory drugs, prompt institution of disease-modifying antirheumatic drugs (DMARDs) is recommended.
 If one agent fails, another may be tried.
 At present, hydroxychloroquine (Plaquenil) sulfate is one of the most widely used and best tolerated.
 Careful follow-up is essential with all DMARDs, however, because toxic effects may be severe and sometimes unpredictable.
",16
2815,"A mutation in the pro alpha 2(I) gene (COL1A2) for type I procollagen in Ehlers-Danlos syndrome type VII: evidence suggesting that skipping of exon 6 in RNA splicing may be a common cause of the phenotype.
 Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal amounts of normal and shortened pro alpha 2(I) chains of type I procollagen.
 Nuclease S1 probe protection experiments with mRNA demonstrated that the pro alpha 2(I) chains were shortened because of a deletion of most or all of the 54 nucleotides in exon 6, the exon that contains codons for the cleavage site for procollagen N-proteinase.
 Sequencing of genomic clones revealed a single-base mutation that converted the first nucleotide of intron 6 from G to A.
 Therefore, the mutation was a change, in the -GT-consensus splice site, that produced efficient exon skipping.
 Allele-specific oligonucleotide hybridizations demonstrated that the proband's mother, father, and brother did not have the mutation.
 Therefore, the mutation was a sporadic one.
 Analysis of potential 5' splice sites in the 5' end of intron 6 indicated that none had favorable values by the two commonly employed techniques for evaluating such sites.
 The proband is the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base mutation that causes skipping of exon 6 in the splicing of RNA from either the COL1A1 gene or COL1A2 gene.
 No other mutations in the two type I procollagen genes have been found in the syndrome.
 Therefore, such mutations may be a common cause of the phenotype.
 The primers developed should be useful in screening for the same or similar mutations causing the disease.
",16
2816,"Urticaria pigmentosa. Systemic evaluation and successful treatment with topical steroids.
 Nine patients with adult-onset urticaria pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions.
 Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells.
 The bone scan was abnormal in one patient.
 Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients.
 No abnormal gastrointestinal tract roentgenograms were obtained.
 Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters.
 Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients.
 All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks.
 Seven of nine patients treated responded with almost complete resolution of their lesions.
 Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment.
 Only two patients, both of whom used the medication improperly, developed transient abnormalities.
 Slow return of lesions was noted 6 months after completion of therapy.
 Remissions could be lengthened with single weekly applications of topical steroids.
 Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy.
 Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients.
",16
2817,"Intercellular IgA dermatosis of childhood. Selective deposition of monomer IgA1 in the intercellular space of the epidermis.
 We describe a 7-year-old girl with recurrent pruritic vesiculopustular lesions involving the trunk, extremities, face, and oral mucosa.
 Histopathologic examination revealed intraepidermal bullae containing neutrophils and eosinophils, and direct immunofluorescence test showed the deposition of IgA in the intercellular space of the epidermis.
 Circulating IgA anti-intercellular antibodies were also detected by indirect immunofluorescence test.
 Immunofluorescence studies using monoclonal antibodies to human IgA subclasses showed that these IgA antibodies belonged to IgA1.
 Antisera against J chain and secretory component did not show any specific intercellular staining.
 Surface IgA(+)-B cells were transiently increased in the peripheral blood during the active stage of the disease.
 These results indicated the extragut origin of these IgA antibodies.
 Dapsone therapy was shown to be very effective.
",16
2818,"Intralesional bleomycin sulfate therapy for warts. A novel bifurcated needle puncture technique.
 A multiple puncture technique using a bifurcated vaccination needle to introduce bleomycin sulfate (1 U/mL sterile saline solution) into warts resulted in elimination of 92% of a random series of 258 warts after a single treatment.
 Recurrence was not observed during a 6-month follow-up period.
 Six of the 66 patients required two to seven treatments for wart eradication, and four patients requested alternative therapy after initial failure with a single bleomycin treatment.
",16
2819,"Scar revision.
 Different scar revision techniques are compared on similar scars, all on the same patient.
 Comparison of the final results is unique and interesting and provides insight into choosing the ""optimal"" technique for these procedures.
 Historical perspective is provided.
",16
2820,"Transferrin C subtypes in patients with rheumatoid arthritis.
 Transferrin (Tf) subtypes were investigated in 128 patients with rheumatoid arthritis (RA) and the frequencies of TfC subtypes were compared with the results in normal individuals.
 The frequencies of the Tf genes: C1, C2, C3, D1, and D2 were 0.4765, 0.3867, 0.0742, 0.0390 and 0.0234, respectively.
 The frequency of TfC2 gene was significantly higher in these patients (0.3867) compared to the value in the control group (C2 = 0.247).
 The relative risk of RA in association with TfC1C2 type was 2.0, while it was 0.18 in association with TfC1C1 type and the results were statistically significant.
 This paper confirms the significant association between TfC2 and RA.
 Furthermore, it appears from our results that TfC1 homozygous phenotype is protective for the development of RA.
 The results are discussed in the light of earlier suggestions that the TfC2 subtype confers an increased risk of cellular damage by enhancing hydroxyl radical formation, although it is possible that there exists a genetic linkage of Tf variant to some other locus which is influencing susceptibility to RA.
",16
2821,"The prevalence of rheumatoid arthritis in the Sultanate of Oman.
 One thousand nine hundred and twenty-five Omani adults aged 16 and over were studied in a house-to-house survey in representative areas of Oman.
 Seven cases (five female) are described who satisfied the 1987 ARA criteria for rheumatoid arthritis (RA), indicating a prevalence of 3.6 per thousand adults.
 Adjusted for the population structure, the prevalence was 8.4 per thousand adults.
 Complementary data are also presented on cases of RA ascertained by special screening clinics in rural health centres and by hospital rheumatology clinics.
 In all parts of the study, cases of RA were less often seropositive than in European populations which may account for the lower prevalence of erosive disease.
",16
2822,"The development and use of Patient Knowledge Questionnaire in rheumatoid arthritis.
 A multi-choice Patient Knowledge Questionnaire (PKQ) was developed for use with patients with rheumatoid arthritis (RA).
 Test/re-test was used to test its stability (r = 0.81), and Kuder Richardson formula 20 (r = 0.72) for internal consistency.
 Seventy randomly selected RA patients then completed the PKQ in a rheumatology out-patient clinic of a large teaching hospital.
 There was a wide variation in total scores ranging from 3 to 28 out of 30.
 Total scores correlated with years of general education (P less than 0.05) but not with disease duration or age.
 Sixty-two per cent of patients knew that the cause of RA is, as yet, unknown but 27% thought it could be caused by injury and 11% by cold damp weather.
 Fifty-two per cent had no idea why they had blood tests.
 All but four patients were taking some form of medication but there was widespread confusion about disease-modifying drugs and non-steroidal anti-inflammatory drugs (NSAIDs).
 Exercise was reasonably well understood but many patients were unable to differentiate between methods of energy conservation and joint protection.
 This study highlights the need for careful individual knowledge assessment by use of tools such as the PKQ and effective patient education programmes.
",16
2823,"Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha.
 Much of the clinically important pathology associated with IgE-dependent disorders is thought to reflect the actions of the blood-borne leukocytes recruited during these responses.
 To evaluate the extent to which mast cells are responsible for the leukocyte infiltration associated with IgE-dependent cutaneous reactions, we attempted to elicit these responses in normal mice, genetically mast cell-deficient W/Wv mice, and in W/Wv mice selectively repaired of their mast cell deficiency by the intradermal injection of cultured mast cells derived from the congenic normal (+/+) mice.
 We found that the tissue swelling associated with IgE-dependent passive cutaneous anaphylaxis reactions developed rapidly and diminished markedly from 2 to 4 h after antigen challenge, but remained detectable for at least 24 h after elicitation of the responses.
 Infiltration of leukocytes (predominantly neutrophils) also occurred at these sites, but reached maximal levels 6-12 h after antigen challenge, persisted at high levels for 24 h, and largely waned by 48 h.
 Virtually all of the tissue swelling and leukocyte infiltration associated with IgE-dependent cutaneous reactions was mast cell dependent.
 Intradermal injection of 40 U of recombinant murine TNF-alpha (rmTNF-alpha) elicited neutrophil infiltration similar in magnitude and kinetics to that observed after IgE-dependent mast cell degranulation.
 A rabbit anti-rmTNF-alpha (R anti-rmTNF-alpha) antiserum, which was able to inhibit 84% of the neutrophil infiltration observed after i.d.
 injection of rmTNF-alpha, inhibited IgE-, and mast cell-dependent leukocyte infiltration by 47 +/- 7% in three separate experiments.
 These findings indicate that TNF-alpha contributes to mast cell-dependent recruitment of leukocytes during IgE-dependent cutaneous late phase reactions, but suggest that other mast cell-associated mediators probably also contribute to this response.
",16
2824,"Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model.
 The roles of polypeptide growth factors in promoting wound healing and in directing the specificity and sequence of responses of different tissues in wounds are little understood.
 We investigated the influence of four growth factors on the rates of healing of a novel full thickness dermal ulcer placed on an avascular base in the rabbit ear.
 The wound model precludes significant wound contraction and requires new granulation tissue and epithelial cells for healing to originate centripetally.
 5 micrograms (7-31 pmol/mm2) of platelet-derived growth factor-B chain (PDGF-BB), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) applied locally at the time of wounding resulted in a twofold increase in complete reepithelialization of treated wounds (PDGF-BB, P = 0.02 chi square analysis; bFGF, P = 0.04; EGF, P = 0.05); transforming growth factor (TGF)-beta 1 significantly inhibited reepithelialization (P = 0.05).
 Both PDGF-BB and TGF-beta 1 uniquely increased the depth and area of new granulation tissue (P less than 0.005), the influx of fibroblasts, and the deposition of new matrix into wounds.
 Explants from 7-d old PDGF-BB-treated wounds remained metabolically far more active than controls, incorporating 473% more [3H]thymidine into DNA (P = 0.05) and significantly more [3H]leucine and [3H]proline into collagenase-sensitive protein (P = 0.04).
 The results establish that polypeptide growth factors have significant and selective positive influences on healing of full thickness ulcers in the rabbit.
",16
2825,"Identification of two collagen domains within the bullous pemphigoid autoantigen, BP180.
 Bullous pemphigoid (BP) is an autoimmune disease characterized by subepidermal vesicles and the presence of autoantibodies directed against the epidermal basement membrane zone.
 Previous studies have identified two protein components of the hemidesmosome, BP180 and BP230, as the primary antigenic targets of BP autoantibodies.
 We have recently reported the isolation of a 1.0-kb BP180 cDNA.
 Sequence analysis presented in this report reveals that this partial BP180 cDNA encodes two protein domains which have primary structures that are characteristic of the triple helical domains of collagens, i.e., glycine appears at every third position and over one-third of the remaining residues are proline.
 The two collagen domains have lengths of 242 and 30 amino acids and are separated by a noncollagen stretch of 12 amino acids.
 Collagenase digestion of the BP180 cDNA-encoded fusion protein generated a peptide fragment with a size that was consistent with the predicted locations of the collagenase digestion sites.
 A possible physiological function for the collagen domains of the BP180 hemidesmosomal protein may be to form stable interactions with constituents of the extracellular matrix of the cutaneous basement membrane zone.
 Such interactions may provide the molecular framework for the adhesion between the basal keratinocyte and the basal lamina.
",16
2826,"The abraded punch graft for pitted facial scars.
 The abraded punch graft procedure is one in which the surrounding scar area and the graft itself are superficially dermabraded before correction of the defect.
 This alternative procedure has distinct advantages over the standard punch graft and should be considered when contemplating the surgical correction of ""ice pick"" facial scarring.
 Following the normal reparative process, the abraded punch graft heals with a pleasing aesthetic appearance.
",16
2827,"Incisional slit grafting.
 Incisional slit grafting, a new and greatly improved technique in hair transplantation, is described.
 Incisional slit grafting utilizes larger numbers of smaller grafts than does traditional punch grafting.
 No tissue is removed from the recipient bed.
 The vascular supply is conserved, resulting in an increased graft yield.
 The clumping and stalking effect associated with traditional round grafting is eliminated largely, and a more natural frontal hairline is achieved.
",16
2828,"Regional variation in the expression of pemphigus foliaceus, pemphigus erythematosus, and pemphigus vulgaris antigens in human skin.
 The expression of the pemphigus foliaceus (PF), pemphigus erythematosus (PE), and pemphigus vulgaris (PV) antigens in 16 different regions of normal human skin was evaluated by indirect immunofluorescence by using sera with a high titer of PF, PE, and PV antibodies.
 Regional variations were observed in the expression of all these antigens.
 The expression of the PF and PE antigens, as measured by endpoint titer of antibody reactivity, was highest in skin specimens obtained from the upper torso, and lowest in those from the buccal mucosa, lower torso, and scalp.
 This distribution pattern differed from that of PV antigen, whose expression was highest in buccal mucosa and scalp.
 These patterns correlate with, and may provide a partial explanation for, the different distribution of skin lesions in these different forms of pemphigus.
",16
2829,"Glycosaminoglycans production by cultured skin fibroblasts from the Pasini and Cockayne-Touraine forms of dominant dystrophic epidermolysis bullosa.
 Qualitative and quantitative comparisons of glycosaminoglycans e (GAG) production were made on fibroblast lines cultured from the skin of six patients with the Pasini (albopapuloid) form of dominant dystrophic epidermolysis bullosa, six with the non-albopapuloid form (Cockayne-Touraine), eight lines from patients with simplex or recessive dystrophic epidermolysis bullosa and eight lines from normal individuals.
 A reasonable match of donor age and gender, site, and passage number was achieved.
 Contrary to an earlier report, the lines from the Pasini group were unexceptional in the amount of GAG they secreted and the proportions of sulfated and nonsulfated GAG showed no consistent difference from the Cockayne-Touraine or control lines.
 The Pasini lines secreted 77 +/- 18 (SEM) microgram GAG-uronic acid per 10(7) cells and the Cockayne-Touraine lines 81 +/- 12 micrograms at equivalent cells densities.
 Sulfated GAG represented averages of 19 +/- 4+ in Pasini lines, 17 +/- 5% in Cockayne-Touraine, and 14 +/- 3% in controls.
 These findings are consistent with current views of albopapuloid lesions as an unreliable clinical sign in epidermolysis bullosa and bring into question the validity of the Pasini entity.
",16
2830,"Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and captopril-induced pemphigus.
 Pemphigus is an autoimmune blistering disease characterized by circulating autoantibodies directed against the keratinocyte cell surface.
 The two variants, pemphigus foliaceus and pemphigus vulgaris, can be distinguished at the molecular level by immunochemical studies.
 The large majority of patients with pemphigus develop the disease spontaneously; however, there is a small group of patients who develop pemphigus after treatment with certain medications, of which penicillamine and captopril are the best documented.
 Most patients with drug-induced pemphigus have circulating and/or tissue bound epidermal cell surface autoantibodies; however, the molecular specificity of these autoantibodies has not been studied.
 We performed immunoprecipitation studies utilizing extracts of 125I-labeled suction blister epidermis and the sera of three patients with drug-induced pemphigus foliaceus (two due to penicillamine and one due to captopril) and one patient with captopril-induced pemphigus vulgaris.
 We found that the three patients with drug-induced pemphigus foliaceus had circulating autoantibodies that are directed against the pemphigus foliaceus antigen complex and that the one patient with drug-induced pemphigus vulgaris had circulating autoantibodies that are directed against the pemphigus vulgaris antigen complex.
 This study demonstrates that autoantibodies from drug-induced pemphigus patients have the same antigenic specificity, on a molecular level, as do autoantibodies from other pemphigus patients.
",16
2831,"Vaginal birth after cesarean: a meta-analysis of morbidity and mortality.
 The cesarean birth rate has continued to climb despite efforts to counteract it.
 A major reason for this rise is the practice of elective repeat cesarean.
 We conducted a meta-analysis that included 31 studies with a total of 11,417 trials of labor to evaluate the association between birth route after a cesarean and morbidity and mortality for the mother and infant.
 Summary odds ratios were calculated.
 Maternal febrile morbidity was significantly lower after a trial of labor than after an elective repeat cesarean.
 The intended birth route made no difference in the rates of uterine dehiscence or rupture.
 The use of oxytocin, presence of a recurrent indication for the previous cesarean, and presence of an unknown uterine scar were also unassociated with dehiscence or rupture.
 After excluding antepartum deaths, fetuses weighing less than 750 g, and congenital anomalies incompatible with life, we found no difference in perinatal death rates.
 The proportion of 5-minute Apgar scores of 6 or lower was higher after a trial of labor, but we were unable to exclude very low birth weight fetuses or those with congenital anomalies from this analysis.
 Our findings argue for trials of labor for more women after a cesarean birth.
",16
2832,"Distribution of skin-derived antileucoproteases (SKALP) in the marginal zone of the spreading psoriatic lesion.
 Two new elastase inhibitors (SKALP, skin-derived antileucoproteases) were recently described in the lesional skin in psoriasis.
 The present study investigated the distribution of SKALP activity in the marginal zone of spreading psoriatic plaques.
 In a 4-mm zone immediately adjacent to the erythemato-squamous plaques, SKALP activity was slightly increased compared to distant uninvolved skin.
 Within the lesion the anti-elastase activity was pronounced, but was significantly higher in the central zone of the plaque compared to the periphery.
 The appearance of SKALP in the psoriatic lesion appears to be a late event compared to endothelial involvement, intraepidermal accumulation of PMNs, epidermal proliferation and abnormal keratinization.
 This observation lends further support for the hypothesis that the induction of anti-elastase activity is associated with the off-switch of cutaneous inflammation.
",16
2833,"Allergic contact and photocontact dermatitis due to psoralens in patients with psoriasis treated with topical PUVA.
 The incidence and clinical features of allergic contact and/or photocontact dermatitis due to psoralens were examined in 371 patients with psoriasis treated with topical PUVA.
 The psoralen derivatives used in the study were 8-methoxypsoralen (8MOP), 3-carbethoxypsoralen (3CPs), 4,6,4'-trimethylangelicin (TMA) and 7-methyl pyridopsoralen (MPP).
 Of 371 patients treated with 8MOP, three (0.8%) developed an acute dermatitis in the PUVA-treated areas.
 This incidence was significantly lower (P less than 0.01) than that for 3CPs (four of 10 patients) or that for TMA (six of 17 patients).
 None of the seven patients receiving MPP on PUVA had a reaction.
 It was confirmed that these dermatitis reactions were due to contact and/or photocontact allergy to psoralens by several methods that include patch and photopatch tests, photopatch test mapping, determination of the minimal erythema dose (MED) and immunohistochemistry.
",16
2834,"Induction of lesions of dermatitis herpetiformis by autologous serum.
 In the present study various factors which contribute to the initiation of lesions in dermatitis herpetiformis (DH) were examined.
 Thirty-one patients with DH, seven with bullous pemphigoid, two with linear IgA disease and two healthy subjects were studied either before starting treatment or after stopping dapsone for up to 5 days.
 Intradermal inoculation of freshly prepared autologous serum was followed after 18-24 h by the formation of DH-like lesions in 24/31 DH patients.
 The lesions were erythematous papules, often with vesicles and microscopically showed papillary tip microabscesses.
 Serum-induced formation of lesions only occurred in patients with active DH with some spontaneous lesion formation: it did not occur in any of the non-DH controls.
 The formation of lesions was dose-related, declining proportionately with dilution of the serum down to 1/16.
 Plasma prepared by various methods of anticoagulation (heparin, citrate, EDTA) caused lesser reactions, while addition of heparin or epsilon-amino caproic acid (EACA), but not citrate, to serum substantially inhibited the formation of lesions.
 This suggested the responsible factor might be a protease.
 Other vasoactive agents including histamine (1-4 micrograms) and compound 48/80 (1-5 micrograms) caused normal immediate wealing.
 DH-like lesions occurred in only one of 13 subjects challenged with histamine and two of nine challenged with 48/80.
 In all these, autologous serum elicited large vesicular responses.
 There is a factor(s) in serum in DH which can initiate the formation of lesions.
 This factor appears to be activated by clotting and can be inhibited by heparin and EACA, suggesting it may be a protease.
",16
2835,"Erythema elevatum diutinum mimicking porphyria cutanea tarda.
 A case of erythema elevatum diutinum (EED) closely resembling porphyria cutanea tarda (PCT) is reported.
 The initial skin biopsies were suggestive for PCT but porphyrin levels in the urine, stool and plasma were normal.
 A further biopsy from an early cutaneous lesion showed a leucocytoclastic vasculitis with fibrinoid necrosis of the vessel walls.
",16
2836,"Acquired dermal melanocytosis of the face and extremities.
 Four cases of dermal melanocytosis with symmetrical areas of hyperpigmentation involving the face and extremities are reported.
 Light and electron microscopic studies showed changes similar to those seen in naevus of Ota.
",16
2837,"Phosgene (chlorophenyl)hydrazones, strong sensitizers found in yellow sweaters bleached with sodium hypochlorite, defined as causative allergens for contact dermatitis by an experimental screening method in animals [published erratum appears in Contact Dermatitis 1990 Nov;23(5):383]
 12 young men developed allergic contact dermatitis from wearing yellow cotton sweaters.
 We attempted to identify the causative agents by an experimental screening method in animals.
 Guinea pigs were sensitized with an acetone extract of the sweater material, by means of the guinea pig maximization test (GPMT).
 Active ingredients were then separated from the extract, by step-by-step patch test screening of chromatographic fractions in the guinea pigs, and finally analyzed by gas chromatography-mass spectrometry (GC-MS).
 Although there were 2 allergens with important activity (1 in the fraction eluted from the silica gel column with hexane, and 1 in the methanol fraction), the present study is focussed on the fat-soluble allergens in the hexane fraction.
 GC-MS analysis revealed that 4 kinds of phosgene (chlorophenyl)hydrazones (PCPHs) were present in the hexane fraction.
 PCPHs prepared in our laboratory showed strong eliciting activities, not only in the guinea pigs sensitized with the extract, but also in a male volunteer sensitized by exposure to a yellow sweater during irritancy testing.
 Phosgene (2,5-dichlorophenyl)hydrazone, which was the main component among the PCPHs found in the sweater, sensitized guinea pigs even at the 1 ppm level.
 From these results, we conclude that PCPHs were one of the allergens responsible for the cases.
",16
2838,"Patch and prick test study of 593 healthy subjects.
 593 recruits selected by the Military Health Service as being healthy and without a history of present or previous dermatitis, or ocular refraction defects, were patch tested with the GIRDCA (Italian Research Group on Contact and Environmental Dermatitis) standard series.
 Of these, 336 were also patch tested with substances used in the processing and dyeing of textiles and prick tested with 8 major allergens.
 74 (12.5%) reacted to 1 or more substances.
 The most frequent sensitizers were: thimerosal (28 cases), ammoniated mercury (7 cases), phenol-formaldehyde resin (6 cases), parabens, nickel and Disperse Red 17 (4 cases each).
 113 recruits reacted to 1 or more prick test allergens.
 We have demonstrated the importance of establishing such reference values in healthy groups for the correct evaluation of data collected from selected groups.
",16
2839,"Ammoniated mercury ointment: outdated but still in use.
 Although severe mercury-associated side effects, such as poisoning and high irritant and allergic potential, as well as the weak potency of mercury as an antiseptic or antipsoriatic agent, are well-known, topical mercury preparations are still listed in several pharmacopoeias, including that of the United States, UK and several other European countries.
 Thus, topical mercurials are still in use, even though more effective and less toxic drugs are now available.
 We report 2 cases of severe allergic reaction to ammoniated mercury and hope, in agreement with the pertinent literature, to contribute to its removal, and that of most other mercurials, from the therapeutic armamentarium.
",16
2840,"Occupational dermatoses from epoxy resin compounds.
 This study comprises 40 patients with skin disorders from current or previous occupational exposure to epoxy resin compounds (ERC) during 1984-1988.
 ERCs were the 3rd most common cause (32 of 264 cases: 12.1%) of currently relevant allergic contact dermatitis: 23 cases from epoxy resins based on the diglycidyl ether of bisphenol A (DGEBA-ERs), 5 from reactive diluents, 1 from amine hardeners (DETA), and 3 from epoxy acrylates.
 2 cases (0.8%) of irritant contact dermatitis were due to ERCs.
 Methyl hexahydrophthalic anhydride (MHHPA, an epoxy hardener) caused 1 case of contact urticaria.
 Previously relevant occupational allergic contact dermatitis from DGEBA-ERs was detected in 5 cases.
 On patch testing, ERC allergens gave the following positive reactions: epoxy resin of the standard series in 35 cases (4.0% of 870 tested), epoxy reactive diluents in 10 (7.1% of 140), cycloaliphatic epoxy resins in 4 (11.1% of 36), epoxy acrylates in 4 (4.5% of 88), and amine compounds commonly used as epoxy hardeners in 17.
 Despite extensive patch test series, testing with patients' own ERCs remains important.
",16
2841,"Immunodermatology update: the immunologically mediated vesiculobullous diseases.
 Before a specific diagnosis of an immunologically mediated blistering disease can be made, the clinical and histologic features and the results of direct and indirect immunofluorescence studies (with use of multiple substrates in some cases) must be assessed.
 For both subepidermal and intraepidermal groups of blistering diseases, direct immunofluorescence testing of perilesional tissue is critical for diagnosis.
 For these conditions, indirect immunofluorescence testing of serum is important for diagnosis and has a role in management of selected diseases.
 In dermatitis herpetiformis, indirect testing of serum for IgA antiendomysial antibodies is useful for both diagnosis and management.
 Indirect testing of serum for IgG antibodies to intercellular substance is important for diagnosis and, in conjunction with the clinical findings, can be used as a guide for monitoring disease activity in patients with pemphigus.
 Immunoelectron microscopy, immunoprecipitation, and immunoblotting studies have identified the sites of immune deposits and the specific antigens in most of the immunologically mediated bullous diseases.
 From a practical standpoint, however, direct and indirect immunofluorescence testing, in conjunction with clinical and histologic evaluations, is a simple, rapid, and relatively inexpensive tool for diagnosis and management.
",16
2842,"Elemental diet for refractory atopic eczema.
 A total of 37 children with refractory wide-spread atopic eczema were treated with an antigen avoidance regimen comprising hospitalisation, exclusive feeding with an elemental formula for a median duration of 30 days, and measures to reduce exposure to pet and dust mite antigens at home.
 After the initial period of food exclusion, food challenges were performed at intervals of seven days, and the patients followed up for at least 12 months.
 Ten of the children (27%) either failed to respond to the regimen or relapsed within 12 months.
 Improvement in the eczema was seen in 27/37 (73%) patients, by discharge from hospital their disease severity score had fallen to a median of 27% of the pretreatment figure, and only 3/27 required topical corticosteroids.
 There were no clinical or laboratory findings which could be used to predict the outcome.
 Drawbacks to the regimen were prolonged hospitalisation (median 70 days), a fall in body weight and serum albumin concentration, and a risk of anaphylactic shock (4/37 cases).
 A strict antigen avoidance regimen may be associated with improvement of atopic eczema where conventional treatments have failed.
",16
2843,"Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody.
 The effect of treatment with a monoclonal antibody against the CD4 antigen present on T helper cells was studied in 10 patients with severe intractable rheumatoid arthritis.
 In an open trial, monoclonal antibody 16H5 was infused at a dosage of 0.3 mg/kg of body weight on 7 consecutive days.
 Studies of the kinetics demonstrated a drastic depletion of CD4+ cells, to as low as 25 cells/microliters, 1 hour after the first infusion.
 The subsequent recovery of the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and after the full 7-day treatment cycle there was a significant reduction of the number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02).
 There was a reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks.
 Lymphocyte transformation assays demonstrated significantly reduced reactivity in 5 of the 9 patients who completed the 7-day course, whereas 4 individuals exhibited an unexpected elevation in the T cell response to mitogens and common antigens.
 Parallel laboratory studies showed a significant decrease in the erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a reduction in C-reactive protein levels, in 7 of the 9 patients.
 Clinically, there was a significant reduction in the Ritchie articular index (P less than 0.05) and in the number of swollen joints (P less than 0.04).
 Adverse effects were urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and chills with fever, suggestive of a lymphokine release syndrome, in another 2 patients.
 Only low levels of human anti-mouse immunoglobulin antibodies developed (not exceeding 1.7 mg/liter).
 It was therefore possible to repeat the treatment cycle, achieving still better efficacy, in 4 of the patients (reductions in the Ritchie index and the number of swollen joints P less than 0.02).
 Our findings indicate that treatment with monoclonal antibodies against the CD4 antigen leads to immunomodulation which results in clinical benefits, at least during initial observation periods (up to 6 months postinfusion).
 However, it remains to be determined whether long-term remission can be induced with this therapeutic approach.
 The use of immunosuppressive therapies or repeated antibody treatments will have to be considered.
",16
2844,"Clinical correlations with serum C1q levels in patients with rheumatoid arthritis.
 Previous studies have suggested that serum C1q levels measured during the first 5 years of rheumatoid arthritis (RA) may be predictive of the extent of subsequent joint damage.
 To further evaluate the clinical significance of this marker in RA, levels of C1q were measured by radial immunodiffusion in serum samples from 107 well-characterized patients with RA.
 Mean levels of C1q were higher in patients with a disease duration less than or equal to 5 years (173 micrograms/ml) than in patients with a disease duration greater than 5 years (148 micrograms/ml) (P = 0.032).
 Serum C1q levels were correlated with total joint counts and activities of daily living scores, but no correlation was observed with erythrocyte sedimentation rates or with radiographic scores.
 The results suggest that C1q may be a useful early marker of disease activity in patients with RA.
",16
2845,"HLA-D region antigens in patients with rheumatoid arthritis.
 We studied the distribution of HLA-D region antigens in 2 groups of rheumatoid arthritis (RA) patients: those with mild, nonprogressive disease, and those with severe disease.
 The results demonstrate that DR4 was significantly increased in both RA patient populations.
 The frequencies of DR1 and DR4-associated DQw7 alleles, however, were different in these 2 groups of patients.
 DR1 was significantly increased only in patients with mild RA, and DR4-associated DQw7 was significantly increased only in patients with severe disease.
 The results of the present study, together with previous data from our laboratory and from other investigators on the incidence of HLA-D region antigens in RA, suggest that both DR and DQ (A and B) genes may be important in conferring susceptibility to RA; DR in the mild forms of the disease, and DQ in severe RA.
",16
2846,"The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study.
 We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose [18FDG]).
 Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio.
 These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.
",16
2847,"A double-blind gastroscopic evaluation of the effects of etodolac and naproxen on the gastrointestinal mucosa of rheumatic patients.
 The aim of this clinical, endoscopical study was to evaluate the therapeutic efficacy and the gastric tolerability of etodolac, a new anti-inflammatory, non-steroidal drug, compared with naproxen.
 The study was conducted on 48 patients suffering from rheumatoid arthritis.
 44 of whom completed the trial.
 After an initial oesophagogastroduodenoscopy to exclude the presence of gastric mucosal lesions, patients were randomly allocated to double-blind treatment with either etodolac 200 mg b.i.d.
 or naproxen 500 mg b.i.d.
 for a period of 4 weeks.
 Endoscopic control followed this treatment period.
 Both drugs proved effective in relieving clinical symptoms, without a statistically significant difference.
 Gastric mucosal lesions were observed in 15% of etodolac-treated patients and in 46% of patients treated with naproxen (P less than 0.05) (95% CI 0.01-0.60).
 Painful dyspepsia was observed in 15% of patients treated with etodolac vs.
 38% of patients on naproxen therapy.
 This study demonstrates that etodolac is at least as active as naproxen in relieving rheumatic symptoms, and its administration results in a significantly lower degree of gastric damage.
",16
2848,"Selective in vivo removal of rheumatoid factor by an extracorporeal treatment device in rheumatoid arthritis patients 
 A prospective phase II trial was conducted to assess the feasibility, tolerance, and efficacy of a device designed for selective removal of rheumatoid factor from the plasma of rheumatoid arthritis patients.
 The device contained terpolymer hydrogel-coated plates with chemically attached, aggregated human immunoglobulin G, and it operated as an immunoaffinity column.
 Sixty-one patients aged 25 to 73 underwent weekly plasmapheresis treatments (the primary therapy phase).
 During the trial, patients continued current rheumatoid arthritis medications without dose adjustments.
 All patients received two to six treatments (primary therapy).
 Responding patients were eligible to continue apheresis treatment every 2 to 6 weeks (maintenance therapy).
 No serious, untoward side effects were noted in the course of this study; of 640 treatments, only 2 (in different patients) were aborted, one because of complaints of dizziness and angioedema and the other because of chest tightness and shortness of breath.
 Except for a significant (p less than 0.05) decrease in serum iron, no significant changes in complete blood count, serum electrolytes, renal and hepatic function tests, or serum C3 and C4 were noted.
 Although the trial was not designed to determine clinical efficacy, patients noted less morning stiffness, longer time to onset of fatigue, and improved global pain assessment (p less than 0.004); significant objective improvements were noted in joint pain, tenderness, swelling, and the number of affected joints (p less than 0.001).
 One-half of the treated patients had at least a 50 percent improvement in objective measures of antirheumatic activity.
",16
2849,"Computed tomography and ultrasonography of the adrenal glands in paracoccidioidomycosis. Comparison with cortisol and aldosterone responses to ACTH stimulation.
 Fifteen patients with proven disseminated paracoccidioidomycosis (PCM) had computed tomography (CT) and ultrasonography (US) performed to evaluate the form, shape, density and size of their adrenal glands.
 Plasma and urinary cortisol were determined and adrenal reserve assessed by measuring the cortisol and aldosterone responses to synthetic ACTH.
 The adrenal CT showed unilateral lesions in two cases and bilateral in another four.
 The US study showed more frequent alterations, unilateral in seven and bilateral in three subjects.
 Combining both methods increased the sensitivity to 85% of the cases.
 All patients had normal plasma cortisol concentrations and normal or increased urinary cortisol excretion.
 Plasma aldosterone concentration was also normal except in one patient with hypokalemia.
 Seven patients showed diminished cortisol responses, five had subnormal aldosterone responses and in five plasma aldosterone concentration increased more than normally after stimulation by ACTH.
 There was an incidence of limited adrenal reserve in 53% of the patients on ACTH stimulation.
 No correlation was evident between the disorders in adrenal steroid responses to ACTH and changes in morphology revealed by CT and/or US.
",16
2850,"The new genetics and its relevance to orthopedics.
 The recent advances in genetics have practical importance for patients with orthopedic problems.
 Specific genes are being isolated, mapped to chromosomes, and defined.
 Surgical specimens can be used for genetic studies to define specific genetic abnormalities.
 Making specific genetic diagnoses is important for appropriate care of the patient and the family.
",16
2851,"Winning the battle, losing the war? Another editorial about rheumatoid arthritis.
 Major advances in the therapy of RA will likely require future scientific breakthroughs in the understanding of pathophysiology.
 That is not to suggest that clinical investigations should be put on hold while the entire focus of research shifts to the laboratory bench.
 Clinical studies of very early RA, including early treatment interventions, would appear to be of major importance.
 However, better characterization of the early clinical course and identification of pathologic markers of progressive disease are needed before formal randomized treatment studies of early disease can be initiated.
 The entire role of aggressive management, particularly with combination chemotherapy, at any stage of RA is in desperate need of answers.
 In clinical practice it would appear that combination chemotherapy is widely used, often as a last resort in treatment resistant patients who have failed conventional therapies.
 The published clinical studies would seem to support, but certainly not prove, a valuable potential role for combination chemotherapy in this setting.
 Moreover, the studies seem to indicate some increased risk of drug toxicities, the limitations of which are not readily apparent for most combinations.
 Based on the successes observed in these patients that are very difficult to treat, the possibility of a more fundamental role of combination chemotherapy in treatment of the disease has been advocated.
 These questions need to be resolved by well designed, randomized controlled trials.
 There is an urgent need to do the trials soon before combination chemotherapy gains an even stronger foothold in therapy.
",16
2852,"Seronegative rheumatoid arthritis: a clinical study with HLA typing.
 We examined both clinically and by determining HLA-A, -B, -C and -DR antigens 50 patients thought to have seronegative erosive polyarticular rheumatoid arthritis (RA) in Finland and the USSR.
 All the patients fulfilled at least 4 of the 1987 ARA criteria for RA.
 According to HLA typing and clinical findings, of which a part was collected by followup, the patients fell into 5 groups: HLA-B27 related diseases, putative psoriatic arthritis, putative juvenile chronic polyarthritis, and seropositive and seronegative RA.
 Our results indicate that most of the patients with seronegative RA had some other disease.
 In the remaining cases the presence of rheumatoid factors had not been examined adequately, especially at the early phase of disease.
 The classification of erosive seronegative polyarticular patients is discussed.
",16
2853,"Phenotypic markers of lymphocyte and mononuclear phagocyte activation within rheumatoid nodules.
 We investigated rheumatoid subcutaneous nodules using monoclonal antibodies recognizing functional determinants on mononuclear phagocytes (Mph) and lymphocytes.
 Mph at the center of rheumatoid nodules showed strong expression of the leukocyte intergrins CR3 and p150,95 which would be consistent with the presence of a central chemotactic stimulus.
 Mph expression of FcR1, a gamma interferon regulated molecule, was decreased in 5/13 cases despite strong expression of MHC class II.
 There was a variable unstructured infiltrate of T lymphocytes, a majority of which were CD8 positive.
 Lymphocytes showed increased MHC class II expression but interleukin 2 receptor expression was low.
 We discerned no relationship between the number, distribution or phenotype of the T cell infiltrate and the phenotype of the predominant Mph population.
",16
2854,"Administration of folinic acid after low dose methotrexate in patients with rheumatoid arthritis.
 Folinic acid (leucovorin) supplementation has been suggested as a possible means of treating the short term side effects that occur with low dose methotrexate (MTX).
 However, it has not been established whether leucovorin will abrogate the antiarthritic effect of MTX.
 We entered 20 patients with rheumatoid arthritis treated with MTX into a 48 week randomized, double blind, crossover trial of folinic acid vs placebo.
 The dose of folinic acid was equal to the dose of MTX and it was given orally 4 h following the single, weekly MTX administration.
 Under these conditions, leucovorin did not decrease the therapeutic effect of MTX.
 While the incidence of stomatitis and gastrointestinal toxicity were lower during leucovorin treatment, our study lacked sufficient power to establish a statistically significant difference.
",16
2855,"Hypophospholipasemia A2 in systemic sclerosis.
 Phospholipase A2 (PLA2), total and pancreatic, were quantitated in 91 sera of patients with systemic sclerosis (SSc).
 The mean total PLA2 of 216 +/- 161 U/ml (SD) was significantly lower (p less than 0.001) than in controls (317 +/- 128 U/ml).
 In 55 of 91 patients (60%) PLA2 was more than 1 SD and in 6 (7%) more than 2 SD below the normal mean.
 Serum pancreatic PLA2 was also significantly lower in SSc.
 The prevalence of low serum total PLA2 was significantly greater (p less than 0.001) than in healthy adults, or in patients with rheumatoid arthritis, systemic lupus erythematosus or vasculitis.
 Repeat assays of PLA2 activity in 10 patients with SSc documented persistence of low PLA2.
 Among 76 patients with SSc with complete clinical and laboratory assessment, there were 48 with low and 28 with normal (or slightly elevated) PLA2.
 These 2 groups showed no differences in disease manifestation or therapy.
 The group with low serum PLA2 had lower erythrocyte sedimentation rates (p less than 0.0005) and lower neutrophil (p less than 0.05) and monocyte counts (p less than 0.025) in the peripheral blood.
 The finding of low serum PLA2 activity adds to the spectrum of arachidonic acid pathway abnormalities associated with SSc, and may in part be related to the paucity of inflammatory changes observed in this disease.
",16
2856,"Childhood bullous pemphigoid. Clinical and immunologic features, treatment, and prognosis.
 A 2 1/2-month-old female infant presented with multiple tense bullae on the hands and feet.
 Analysis of biopsy specimens confirmed our clinical impression of childhood bullous pemphigoid.
 Confirmatory data included type IV collagen mapping of the basement membrane zone, a readily available technique that helps distinguish childhood bullous pemphigoid from childhood epidermolysis bullosa acquisita.
 To our knowledge, our patient is the youngest described with childhood bullous pemphigoid, and we use this opportunity to review the literature and examine the clinical and immunologic features, treatment, and prognosis of this rare childhood immunobullous disorder.
",16
2857,"Coexistence of pemphigus foliaceus and bullous pemphigoid. Demonstration of autoantibodies that bind to both the pemphigus foliaceus antigen complex and the bullous pemphigoid antigen.
 Pemphigus and bullous pemphigoid are autoimmune blistering diseases of the skin characterized by circulating autoantibodies directed against the keratinocyte cell surface and the epidermal basement membrane zone, respectively.
 The coexistence of pemphigus and bullous pemphigoid is very uncommon.
 We describe a patient with pemphigus foliaceus who later developed bullous pemphigoid and show, by means of immunoprecipitation studies utilizing both cultured keratinocytes and suction blister epidermis, that our patient had circulating autoantibodies directed against both the pemphigus foliaceus antigen complex and the bullous pemphigoid antigen.
 This report is the first to demonstrate the coexistence of pemphigus foliaceus and bullous pemphigoid at the molecular level.
",16
2858,"Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. A consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry.
 Inherited epidermolysis bullosa encompasses a number of diseases, with the common finding of blister formation after minor mechanical trauma to the skin.
 In some forms significant, if not eventually fatal, extracutaneous disease activity may occur.
 In recent years application of newer technologies has contributed substantially to an overall understanding of this collection of inherited diseases.
 Concurrently, many new phenotypes have been recognized, in part the result of ongoing prospective patient registries in the United States and abroad.
 Unfortunately, this has resulted in a massive literature that may appear to be confounded by seemingly excessive or arbitrary subdivision of epidermolysis bullosa variants.
 With these concerns in mind a subcommittee was established by the National Epidermolysis Bullosa Registry to summarize the current literature and to make recommendations as to the best clinical and laboratory criteria for the practical diagnosis and subclassification of patients with inherited epidermolysis bullosa.
",16
2859,"Allergic contact dermatitis to two antioxidants in latex gloves: 4,4'-thiobis(6-tert-butyl-meta-cresol) (Lowinox 44S36) and butylhydroxyanisole. Allergen alternatives for glove-allergic patients.
 Allergic contact dermatitis developed on the hands and/or face of two patients after exposure to latex examination gloves.
 Both patients were patch test negative to the usual rubber allergens, but both had a positive patch test reaction to 4,4'-thiobis(6-tert-butyl-m-cresol) (Lowinox 44S36).
 Patient 2 was also patch test positive to butylhydroxyanisole.
 The patients were tested with other gloves, to find gloves that they could safely use.
 Glove manufacturers were queried to ascertain the occurrence of Lowinox 44S36 and butylhydroxyanisole in different brands of latex and vinyl examination gloves.
 A list of gloves and their associated allergens was generated and is provided to assist dermatologists in helping patients choose gloves free of specific allergens.
",16
2860,"Pathogenesis of onychoschizia (lamellar dystrophy).
 Onychoschizia or lamellar dystrophy of the nails is common, especially in adult women, but little information is available about its cause.
 Most theories involve environmental factors, but supportive experimental data are scarce.
 Therefore we studied the in vitro nail changes produced by several organic solvents, detergents, water, other polar materials, and both acidic and basic solutions.
 Challenged and control fingernail clippings were examined grossly, microscopically, and by scanning electron microscopy at regular intervals.
 There was a progressive increase in severity with prolonged wetting and drying.
 By 3 weeks, scanning electron microscopy demonstrated unattached individual cells in empty spaces in which separation was more prominent.
 Basic solutions caused some softening, but layering (peeling) was seen only after repeated hydration and dehydration.
 Although other factors may influence onychoschizia, the typical changes can be produced in normal nails after a 21-day challenge of repeated exposure to water followed by dehydration.
 These findings suggest a probable cause for the condition and a logical approach to management.
",16
2861,"Immune sensitization against epidermal antigens in polymorphous light eruption.
 To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons.
 Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin.
 An epidermal cell suspension, skin homogenate, or both were prepared from each specimen.
 Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension.
 Cell proliferation was assessed by 3H-thymidine incorporation assay.
 The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls.
 However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate.
 Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells.
 This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.
",16
2862,"Propylene glycol dermatitis.
 Propylene glycol is a commonly used vehicle for topical preparations.
 Although it is well suited for this purpose, it is capable of producing both primary irritant skin reactions and allergic sensitization.
 The literature on propylene glycol is reviewed, with particular attention to the nature of these adverse cutaneous effects.
 Guidelines for patients sensitive to propylene glycol are discussed.
",16
2863,"Persistent light reaction to hexachlorophene.
 The first patient with what appears to be persistent light reaction caused by hexachlorophene alone is reported.
 Persistent light reaction may occur in patients with milder degrees of photosensitivity, and appropriate photopatch testing should be performed.
",16
2864,"Hereditary lactate dehydrogenase M-subunit deficiency: lactate dehydrogenase activity in skin lesions and in hair follicles.
 A 16-year-old Japanese girl had desquamating erythematosquamous lesions mostly on the extensor surface of the extremities.
 The lesions were worse in summer.
 The patient also had a mild muscle pain after strenuous exercise.
 Her paternal and maternal grandfathers are cousins.
 An analysis of lactic acid dehydrogenase (LDH) isozymes in her serum revealed a single peak of LDH1.
 Analysis of LDH isozymes of erythrocytes demonstrated a complete lack of LDH M-subunit in the patient and a substantial lack in the parents.
 The epidermis of the diseased skin and scalp hair follicles of the patient were virtually devoid of LDH activity.
",16
2865,"Hereditary deficiency of C5 in association with discoid lupus erythematosus.
 A 29-year-old woman with discoid lupus erythematosus had undetectable classic pathway complement activity.
 Hypocomplementemia was due to selective deficiency of C5.
 One of her children was also deficient.
 To our knowledge this is the first documented case of an association between discoid lupus erythematosus and C5 deficiency.
",16
2866,"Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein 
 In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus.
 The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees.
 Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively).
 In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e.
 T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable.
 The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both.
 Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals.
 If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.
",16
2867,"When to suspect connective tissue disease.
 When a connective tissue disease is suspected, physical and historical data should be collected to build a case for a clinical syndrome.
 Negative serologic results may be helpful; positive ones must be used with awareness of their limitations.
 If a diagnosis is not clinically evident or serologically confirmed, observation may be preferable to overdiagnosis and unnecessary treatment.
 If the syndrome is atypical, physicians should look for evidence of clinical overlap and reevaluate regularly with an open mind.
",16
2868,"PUVA therapy.
 PUVA is an acronym for psoralen plus ultraviolet-A radiation.
 This form of photochemical therapy is commonly used in the treatment of psoriasis and vitiligo, but it is also beneficial in other dermatologic diseases.
 An understanding of psoralen's mechanism of action and the unique properties of the various psoralen preparations is important in ensuring optimal results with this therapy.
",16
2869,"Community screening for hypercholesterolemia.
 This study focused on a cholesterol screening and education program conducted in Scottsdale, Arizona, to determine the prevalence of hypercholesterolemia among the volunteer participants, and whether such a program motivates lifestyle changes and physician follow-up.
 The study also examined whether participants used the program to monitor known hypercholesterolemia.
 During the 6-month program, 1228 individuals were screened.
 Of these, 29% had a previous history of elevated cholesterol and 5% were on cholesterol-lowering medication.
 Of the group with no previous history of hypercholesterolemia, 41% had cholesterol levels higher than 5.17 mmol/L (200 mg/dL) and 10% had levels higher than 6.21 mmol/L (240 mg/dL).
 A subgroup of 120 persons with levels higher than 6.21 mmol/L (240 mg/dL) were contacted 4 to 6 months after the screening.
 Most of this group reported improvement in diet and exercise patterns, and 58% had consulted a physician.
 These results suggest that people with known hypercholesterolemia are using community screening programs to monitor their own cholesterol levels, and that such programs identity new high-risk individuals.
 Program participants appear to change diet and exercise patterns and to seek physician follow-up.
",17
2870,"Hospitalization experience of Navajo subjects with type II diabetes and matched controls: an historical cohort study.
 Using an historical cohort study design with a 12 year follow-up, we found that 77 Navajo adults with type II diabetes mellitus were hospitalized at a rate of 335 hospitalizations per 1000 patient years compared to a rate of 167 hospitalizations per 1000 patient years for 77 age, sex, and residence matched non-diabetic controls, yielding a risk ratio of 2.0.
 Using matched pairs analysis (sign test), the observed difference in number of hospital admissions is statistically significant (z = 2.30, p less than 0.05).
 The average duration of hospitalization, however, was not statistically different in matched pairs analysis (z = 0.95, p greater than 0.05).
 The 136 excess hospitalizations of the diabetic subjects included 45 admissions for poor metabolic control of diabetes, 50 excess admissions for infectious disease, and 26 excess admissions for conditions of the heart, eye, kidney, or non-traumatic amputation.
 In multivariate analyses, variables found to be associated with greater hospitalization experience among the 77 diabetic subjects in the 12 years follow-up period included older age at entry to the study, poorer metabolic control early in the study period, and presence of diabetic complications.
",17
2871,"Body mass index and 15-year mortality in a cohort of black men and women.
 The association between body mass index (BMI) and mortality was investigated in 2453 black male (aged 30-79 years) and 2731 black female (aged 40-79 years) members of the Kaiser Foundation Health Plan.
 During a 15-year follow-up 393 male and 283 female deaths were identified.
 Analyses were conducted separately in a lower and an upper range of BMI (as well as over the entire range), to isolate separate effects of low weight and high weight on mortality.
 Particular attention was also paid to potential bias from cigarette smoking and antecedent illness.
 Cox regression analyses showed that over the entire range of BMI the adjusted BMI-mortality association was significantly J-shaped for the men and essentially flat for the women.
 The inverse association between BMI and mortality in the lower range of BMI was statistically significant for the men; the adjusted relative hazard increasing from the 10th to the 50th percentile of BMI was 0.76 (95% confidence interval [CI] 0.59-0.98).
 The positive association between BMI and mortality in the upper range of BMI was highly statistically significant for the men; the adjusted relative hazard increasing from the 50th to the 90th percentile of BMI was 1.37 (95% CI 1.14-1.63).
 Whether controlled by multivariate analysis, by excluding the first 5 years of follow-up from the analyses, or by analyzing the BMI-mortality association in smoking-specific and/or illness-specific subgroups, smoking and antecedent illness did not have much impact on the BMI-mortality association, in either sex.
 The general observations on the BMI-mortality association are similar to findings in some white cohorts.
",17
2872,"Effects of excess dietary tyrosine on cholesterol, bile acid metabolism and mixed-function oxidase system in rats.
 Excess dietary tyrosine (12%) caused hypercholesterolemia in male Wistar rats and significantly increased cytochrome P-450 and b5 contents.
 Bile flow and biliary output of total bile acids were significantly increased in rats fed this diet.
 Biliary output of cholesterol was not significantly altered, whereas that of taurocholic acid was significantly increased.
 Excess dietary tyrosine significantly decreased the fecal excretion of neutral steroids, whereas total steroid excretion was not significantly changed.
 The present results indicate that excess dietary tyrosine causes hypercholesterolemia without modifying the fecal total steroid excretion, thus supporting our previous hypothesis that stimulated synthesis of cholesterol is a main reason why excess dietary tyrosine leads to hypercholesterolemia.
",17
2873,"Effect of vitamin C depletion on serum cholesterol and lipoprotein levels in ODS (od/od) rats unable to synthesize ascorbic acid.
 The effect of ascorbic acid deficiency on serum and liver cholesterol, phospholipid and triglyceride levels, serum lipoprotein levels and serum lipoprotein cholesterol levels were examined in male rats with a hereditary defect in ascorbic acid synthesis (ODS rats).
 Male homozygotes (od/od) and male rats of their parent strain (+/+) were each divided into four treatment groups and were fed vitamin C-deficient or vitamin C-replete diets containing either 0 or 0.5% cholesterol.
 During the 3-wk feeding-period the ODS (od/od) rats fed the vitamin C-deficient diet gradually decreased food intake, resulting in a lower body weight than that of od/od rats given ascorbic acid.
 The serum cholesterol level was significantly higher in the vitamin C-deficient od/od rats fed the cholesterol diet, and it tended to be higher in those fed the control (0% cholesterol) diet, whereas the liver lipid levels remained unchanged relative to those in od/od rats fed the vitamin C-replete diet.
 The serum very low density lipoprotein and high density lipoprotein (HDL) cholesterol levels were lower in od/od rats fed the vitamin C-deficient diet without cholesterol, but intermediate density lipoprotein and low density lipoprotein cholesterol levels were markedly higher in the vitamin C-deficient od/od rats than in od/od rats given ascorbic acid, regardless of dietary cholesterol level.
 The ratio of HDL2 cholesterol to HDL3 cholesterol was also higher in the vitamin C-deficient od/od rats.
 The parent strain of the od/od rats (+/+) showed no change due to vitamin C deficiency.
 These results suggest that vitamin C deficiency delays low density lipoprotein metabolism and produces hypercholesterolemia in male od/od rats.
",17
2874,"Ascorbic acid effects on vitamin D hormone metabolism and binding in guinea pigs.
 Ascorbic acid deficiency in guinea pigs fed a vitamin D-replete diet caused a moderate reduction of Ca level in serum and bone; 25-hydroxy-cholecalciferol or 25-hydroxyergocalciferol (25-OHD) serum concentration tended to decline; renal 25-hydroxycholecalciferol-1-hydroxylase (1-OHase) activity decreased 50%; and 25-hydroxycholecalciferol-24-hydroxylase activity increased 1.6-fold.
 Chromatin 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] receptor concentration in the intestinal mucosa decreased 20-30%, and the percentage of occupied receptors decreased from 12-15% to 6-8%.
 Receptor affinity for 1,25-(OH)2D3 did not change (Kd = 0.24-0.26 nmol/L, Kd2 = 0.06-0.10 nmol/L), but the cooperativity coefficient decreased from 1.7 to 1.4.
 Vitamin C deficiency potentiated effects of vitamin D deprivation and impaired a restorative action of vitamin D.
 It was accompanied by a marked delay in the elevation of 25-OHD concentration in serum as well as decreased 1-OHase activity in kidneys and a lower concentration of occupied 1,25-(OH)2D3 receptors in the intestinal mucosa.
 The data demonstrate a critical role for ascorbic acid in vitamin D metabolism and binding.
",17
2875,"Vitamin A deficiency decreases natural killer cell activity and interferon production in rats.
 We examined the effect of vitamin A deficiency on natural killer (NK) cell activity and interferon (IFN) production.
 Rats were weaned at 16 or 21 d of age onto semisynthetic diets containing either 0 or 4 micrograms retinol/g diet.
 At the time of study, retinol-depleted rats had serum vitamin A concentrations less than 7% of those of pair-fed controls.
 In two studies, rats exhibited no external signs of retinol deficiency, but with further depletion some symptoms were observed.
 Splenic NK cell activity against chromium-51-labeled YAC-1 cells was significantly decreased in vitamin A-depleted rats (22-80% of values for control rats, depending on the degree of retinol deficiency), regardless of the ratio of effector to target cells used.
 When vitamin A-depleted rats were repleted orally with retinol, NK cell activity was consistently normalized.
 To understand the possible mechanisms involved in decreasing NK cell activity, we investigated IFN production by concanavalin A-stimulated spleen cells from vitamin A-depleted, from repleted and from control animals.
 IFN titers were significantly decreased (22-33% of values for control rats) in supernatants of spleen cell cultures of the vitamin A-depleted rats.
 Repletion with vitamin A resulted in IFN activities ranging from 80 to 130% of controls.
 Adding alpha/beta IFN in vitro to the spleen cells of vitamin A-depleted animals increased their NK cell activity.
 The number of spleen cells reacting with a monoclonal antibody specific for rat NK cells was slightly lower in retinol-depleted rats, but not enough to account for the differences in NK cell and IFN activities.
 These data suggest that vitamin A deficiency affect the nonspecific arm of the immune system, possibly by altering the functional capacity of cells to produce lymphokines needed for the generation of an appropriate cytolytic response.
",17
2876,"Differential effects of alpha and beta adrenergic blockade on glucose and lactate metabolism during acute stress.
 In this study we examined the role of alpha and beta blockade on glucose and lactate metabolism during the acute stress of insulin-induced hypoglycemia.
 Three groups of conscious dogs with chronically fitted catheters in the femoral artery and in the femoral, portal, and hepatic veins were studied after an 18-hr fast.
 After a 1-hr basal period, hypoglycemia was induced with insulin infusion at 5 mU/kg.min for 3 hr.
 Group 1 received no other treatment.
 Groups 2 and 3 received, respectively, phentolamine (8 micrograms/kg.min) and propranolol (4 micrograms/kg.min) beginning 30 minutes before and throughout the experimental period.
 Despite similar hyperinsulinemia, plasma glucose dropped in Group 1 (from 115 +/- 10 to 40 +/- 3 mg/dl) and in Group 2 (from 110 +/- 4 to 60 +/- 3 mg/dl) but in Group 3 it was maintained at 45 +/- 4 mg/dl by exogenous glucose infusion at a rate of 2.2 +/- 0.4 mg/kg.min.
 Hepatic glucose production increased 50 +/- 13%, 127 +/- 30%, and 55 +/- 30% in Groups 1, 2, and 3, respectively, within 60 minutes and was 56 +/- 19%, 55 +/- 17%, and -0.04 +/- 12% during the last hour of the experiment.
 Glucose utilization did not change in Groups 1 and 2 but it increased in Group 3.
 Plasma lactate increased in Group 1 (from 850 +/- 190 to 1,980 +/- 450 mumol/L) and in Group 2 (985 +/- 180 to 4,785 +/- 500 mumol/L), while in Group 3 there was an early rise (to 695 +/- 120 mumol/L) within 30 minutes that gradually dropped to near basal.
",17
2877,"Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus 
 BACKGROUND.
 The value of routine measurements of glycosylated hemoglobin (hemoglobin A1c) in the care of patients with diabetes mellitus is uncertain.
 We undertook this study to determine whether knowledge of hemoglobin A1c values would result in improved metabolic control in a group of patients with insulin-dependent diabetes mellitus (IDDM).
 METHODS.
 We randomly assigned 240 patients with IDDM to one of two groups that were comparable in age, sex, duration of diabetes, and initial hemoglobin A1c levels.
 The patients were followed for a year, and the hemoglobin A1c concentration was measured at three-month intervals.
 The hemoglobin A1c values were used in assessing glycemic control and modifying therapy in one of the two groups.
 In the other, care givers were not aware of the hemoglobin A1c levels and relied on blood or urine glucose measurements to monitor treatment.
 RESULTS.
 Among the 222 patients still being followed after one year, the mean hemoglobin A1c value decreased significantly--from 10.1 to 9.5 percent (P less than 0.005)--in the group whose hemoglobin A1c level was monitored (n = 115), whereas the initial and one-year values in the control group (n = 107) were 10.0 and 10.1 percent, respectively.
 The proportion of patients with poor control, defined as those having a hemoglobin A1c value above 10.0 percent, decreased from 46 to 30 percent (P less than 0.01) in the group whose hemoglobin A1c level was monitored but did not change significantly (45 to 50 percent) in the control group.
 The patients in the group whose hemoglobin A1c level was monitored were seen and their insulin regimens changed more often, but they were hospitalized for acute care of their diabetes less often than those in the control group.
 A similar decrease in hemoglobin A1c values occurred in the control group in the following year, when their care givers knew their hemoglobin A1c values.
 CONCLUSIONS.
 Regular measurements of hemoglobin A1c lead to changes in diabetes treatment and improvement of metabolic control, indicated by a lowering of hemoglobin A1c values.
",17
2878,"A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes.
 BACKGROUND.
 The presence of cytoplasmic islet-cell autoantibodies has been recognized as a risk factor for the development of diabetes mellitus in relatives of patients with insulin-dependent diabetes mellitus (IDDM), but the magnitude of the risk is unknown, as is the influence of other factors, such as age, sex, and race.
 METHODS.
 From 1979 through 1989, we studied 4015 initially nondiabetic relatives of 1590 probands with IDDM to determine the risk of IDDM according to the presence and titer of autoantibodies, as well as other factors.
 RESULTS.
 Of the 4015 nondiabetic relatives, 125 (3.1 percent) had islet-cell antibodies in their initial serum samples, and 40 contracted IDDM.
 Islet-cell antibodies were most frequent (4.3 percent) in relatives who were under 20 years of age (P = 0.001) and in those (4.8 percent) from families with more than one affected member (a multiplex pedigree) (P = 0.003).
 Independent risk factors for the development of diabetes in the relatives included age of less than 10 years at the time of the initial study (P = 0.001), membership in a multiplex pedigree (P = 0.02), and a positive test for islet-cell antibodies in the initial serum sample (P = 0.0001).
 Twenty-seven of the relatives in whom diabetes developed (67.5 percent) had positive tests for islet-cell antibodies before the diagnosis of IDDM, giving a relative risk of IDDM of 68 (95 percent confidence interval, 34 to 134) for antibody-positive relatives.
 Islet-cell-antibody titers of 20 Juvenile Diabetes Foundation units or higher were associated with an increasing risk of diabetes.
 CONCLUSIONS.
 Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves.
",17
2879,"Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation.
 BACKGROUND AND METHODS.
 The plasma cholesteryl-ester transfer protein (CETP) catalyzes the transfer of cholesteryl esters from high-density lipoprotein (HDL) to other lipoproteins.
 We recently described a Japanese family with increased HDL levels and CETP deficiency due to a splicing defect of the CETP gene.
 To assess the frequency and phenotype of this condition, we screened 11 additional families with high HDL levels by means of a radioimmunoassay for CETP and DNA analysis.
 RESULTS.
 We found the same CETP gene mutation in four families from three different regions of Japan.
 Analysis of restriction-fragment-length polymorphisms of the mutant CETP allele showed that all probands were homozygous for the identical haplotype.
 Family members homozygous for CETP deficiency (n = 10) had moderate hypercholesterolemia (mean total cholesterol level [+/- SD], 7.01 +/- 0.83 mmol per liter), markedly increased levels of HDL cholesterol (4.24 +/- 1.01 mmol per liter) and apolipoprotein A-I, and decreased levels of low-density lipoprotein cholesterol (1.99 +/- 0.80 mmol per liter) and apolipoprotein B.
 Members heterozygous for the deficiency (n = 20), whose CETP levels were in the lower part of the normal range, had moderately increased levels of HDL cholesterol and apolipoprotein A-I and an increased ratio of HDL subclass 2 to HDL subclass 3, as compared with unaffected family members (1.5 +/- 0.8 vs.
 0.7 +/- 0.4).
 CETP deficiency was not found in six unrelated subjects with elevated HDL cholesterol levels who were from different parts of the United States.
 CONCLUSIONS.
 CETP deficiency appears to be a frequent cause of increased HDL levels in the population of Japan, possibly because of a founder effect.
 The results that we observed in heterozygotes suggest that CETP normally plays a part in the regulation of levels of HDL subclass 2.
 There was no evidence of premature atherosclerosis in the families with CETP deficiency.
 In fact, the lipoprotein profile of persons with CETP deficiency is potentially antiatherogenic and may be associated with an increased life span.
",17
2880,"Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.
 The presence of an amino acid other than aspartic acid at position 57 of the HLA-DQ beta chain (non-Asp-57) is highly associated with susceptibility to insulin-dependent diabetes mellitus (IDDM), whereas an aspartic acid at this position (Asp-57) appears to confer resistance to the disease.
 We hypothesize that the 30-fold difference in IDDM incidence across racial groups and countries is related to variability in the frequency of these alleles.
 Diabetic and nondiabetic individuals were evaluated in five populations, including those at low, moderate, and high risk.
 HLA-DQ beta genotype distributions among the IDDM case groups were markedly different (P less than 0.001), as were those among nondiabetic controls (P less than 0.001).
 Non-Asp-57 alleles were significantly associated with IDDM in all areas; population-specific odds ratios for non-Asp-57 homozygotes relative to Asp-57 homozygotes ranged from 14 to 111.
 Relative risk information from the case-control study and population incidence data were combined to estimate genotype-specific incidence rates for the Allegheny County, PA, Caucasians.
 These rates were used to predict the overall incidence rates in the remaining populations, which were within the 95% confidence intervals of the actual rates established from incidence registries.
 These results are consistent with the hypothesis that population variation in the distribution of non-Asp-57 alleles may explain much of the geographic variation in IDDM incidence.
",17
2881,"Defect in thermoregulation in malnutrition reversed by weight gain. Physiological mechanisms and clinical importance.
 Previous studies in infants and in the elderly have shown that a low body weight is associated with a defect in thermoregulation and an increased risk of hypothermia.
 In the present study, thermoregulatory responses to a cooling stimulus were measured in 10 young and middle-aged patients who lost at least 10 per cent of their body weight during illness.
 Investigations were performed before and after restoration of body weight (mean weight gain 7.2 kg, SE 1.2 kg, p less than 0.001).
 The cooling stimulus was provided by a special suit perfused with water at 28 degrees C and then at 23 degrees C.
 Before weight gain, there was no increase in metabolic rate in response to cooling, despite a fall in core temperature.
 Following weight gain, the thermogenic response to cooling was restored towards normal.
 Peripheral vasoconstriction, the principal mechanism for heat conservation, was similar before and after weight gain.
 The thermogenic response to an infusion of adrenaline (25 ng/kg/min) was not abolished by weight loss, suggesting that the defect in cold-induced thermogenesis following weight loss is due to a change in central control mechanisms of thermoregulation, and not to tissue unresponsiveness.
 The phenomenon of abnormal thermoregulation following weight loss and the return to normal with subsequent weight gain may be clinically important, particularly in the elderly, since quite small falls in core temperature may impair both neuromuscular coordination and cerebral function.
",17
2882,"Genetic defects in lipoprotein metabolism. Elevation of atherogenic lipoproteins caused by impaired catabolism.
 Certain proteins (called apolipoproteins B and E) on the surface of lipoprotein particles are responsible for mediating the binding of cholesterol-rich particles to specific lipoprotein receptors on the surface of cells and represent a major pathway controlling blood cholesterol levels.
 Three important disorders of lipoprotein metabolism, which provide insights into the molecular mechanisms responsible for the elevation of specific atherogenic lipoproteins, are the following: (1) Type III hyperlipoproteinemia results from specific mutations in apolipoprotein E that prevent the normal binding of chylomicron remnants and very-low-density lipoprotein remnants to lipoprotein receptors.
 Patients with this disorder who have elevated levels of these remnant lipoproteins develop atherosclerosis.
 (2) Familial defective apolipoprotein B-100 results from a single amino acid substitution in apolipoprotein B that prevents low-density lipoprotein from binding normally to the low-density lipoprotein receptor and elevates plasma cholesterol levels.
 (3) Familial hypercholesterolemia, which results in elevated levels of plasma low-density lipoprotein and premature atherosclerosis, is caused by a variety of mutations in the low-density lipoprotein receptor that interfere with the normal binding of lipoproteins to this receptor.
 These observations not only provide insights into the mechanisms responsible for normal lipoprotein metabolism, but also highlight the potential role of specific lipoproteins in atherogenesis.
",17
2883,"Fatal hypernatremia from exogenous salt intake: report of a case and review of the literature [published erratum appears in Mayo Clin Proc 1991 Apr;66(4):439] 
 Hypernatremia is a common electrolyte disturbance, most often caused by volume depletion.
 Hypernatremia due to sodium excess occurs less frequently, and fatal hypernatremia solely from ingestion of table salt is rare.
 We describe a 41-year-old man who had seizures and hypernatremia after ingestion of a supersaturated salt water solution intended for gargling.
 He had consumed approximately a third cup of table salt (approximately 70 to 90 g of salt or 1,200 to 1,500 meq of sodium).
 His initial serum sodium concentration was 209 meq/liter.
 Hypotonic fluid therapy was given to provide free water and to correct the hypernatremia gradually.
 Our patient, however, failed to recover from the initial insult and died 3 days later.
 Review of the literature revealed 10 adult and 20 pediatric cases of hypernatremia attributable to exogenous intake of salt.
 The type of therapy (fluid or peritoneal dialysis), the type of fluid used, and the rate of correction of hypernatremia did not influence survival.
 The age of the patient and the initial serum sodium concentration were the most important prognostic indicators.
 Both very young patients and those with lesser degrees of hypernatremia had a better rate of survival than did other patients.
 In addition, our review illustrates the surprisingly small amount of salt that can cause severe hypernatremia and the danger of using salt or saline as an emetic.
",17
2884,"Molecular basis of different forms of metachromatic leukodystrophy 
 BACKGROUND.
 Metachromatic leukodystrophy is an autosomal recessive inherited lysosomal storage disorder caused by a deficiency of arylsulfatase A.
 Three forms of the disease can be distinguished according to severity and the age at onset: late infantile (1 to 2 years), juvenile (3 to 16), and adult (greater than 16).
 METHODS AND RESULTS.
 To understand the molecular basis of the different forms of the disease, we analyzed arylsulfatase A alleles associated with metachromatic leukodystrophy.
 Two alleles (termed I and A) were identified and accounted for about half of all arylsulfatase A alleles among 68 patients with metachromatic leukodystrophy whom we examined.
 Sufficient information was available for 66 of the patients to allow classification of their disease.
 Of the six instances of homozygosity for allele I, all were associated with the late-infantile form of the disease; of the eight instances of homozygosity for allele A, five were associated with the adult form and three with the juvenile form.
 When both alleles were present, the juvenile form resulted (seven of seven instances).
 Heterozygosity for allele I (with the other allele unknown) is usually associated with late-infantile disease, and heterozygosity for allele A with a later onset of the disease.
 The clinical variability can be explained by the different levels of residual arylsulfatase A activity associated with these genotypes.
 CONCLUSIONS.
 Like many lysosomal storage disorders, metachromatic leukodystrophy shows clinical heterogeneity that seems to reflect genetic heterogeneity.
 One of the known alleles (allele I) is associated with earlier and more severe disease than the other (allele A).
",17
2885,"Effect of chronic alcohol administration on transketolase in the brain and the liver of rats.
 To estimate the nutritional and the pathological states in thiamin-deficiency-related diseases, especially Wernicke-Korsakoff syndrome, we studied the relationship among transketolase activity, transketolase concentration, and thiamin phosphate esters in rats chronically fed alcohol.
 In the brain of alcohol-fed rats, the enzyme activity and concentration decreased although there was no positive correlation between the two.
 On the contrary, transketolase activity in the liver correlated positively with concentration, and both transketolase activity and concentration were decreased in the thiamin-deficient groups.
 These findings suggest that transketolase in the brain may be different from that in the liver and that the alteration of the enzyme activity in the brain may be based on the conformational change of the protein molecule caused by chronic alcohol administration.
",17
2886,"Influence of breakfasts with different nutrient contents on glucose, C peptide, insulin, glucagon, triglycerides, and GIP in non-insulin-dependent diabetics.
 To examine the influence of coingestion of fat and protein in a mixed meal on carbohydrate metabolism, subjects with non-insulin-dependent diabetes mellitus (NIDDM) received three different breakfasts varying in the amount of fat and protein (group 1) or only in the amount of fat (group 2).
 Compared with the changes after a standard breakfast, insulin increased after the protein-rich meal and decreased after the fat-rich meal in group 1.
 Glucose and gastric inhibitory polypeptide (GIP) remained constant.
 In contrast, only GIP showed a significant increase after a high-fat meal in group 2.
 Thus, in NIDDM subjects, glucose and insulin responses to different mixed meals do not appear to be exclusively mediated by GIP.
 Protein was confirmed as a potent stimulator of insulin secretion.
 Other factors, such as an altered beta-cell response in diabetics to GIP or other incretions, must be considered to explain the reported results.
",17
2887,"Protein metabolism in obesity: effects of body fat distribution and hyperinsulinemia on leucine turnover.
 To examine whether moderate obesity and differences in body fat distribution are associated with abnormalities of protein metabolism, leucine turnover was measured in three groups of age-matched premenopausal women.
 Ten upper-body-obese (UB Ob), 10 lower-body-obese (LB Ob), and 10 nonobese (Non Ob) women were studied in an overnight postabsorptive condition (basal) and again during an infusion of low physiologic amounts of insulin (insulin clamp).
 Results showed that basal leucine carbon flux was greater (P less than 0.05) in UB Ob and LB Ob women than in Non Ob women (2.96 +/- 0.08 vs 3.14 +/- 0.16 vs 2.68 +/- 0.08 mumol.kg lean body mass-1.min-1, respectively; mean +/- SEM).
 Leucine carbon flux was not suppressed during the insulin-clamp study in UB Ob women but was in the LB Ob and Non Ob women.
 We conclude that moderate obesity is associated with increased proteolysis and that insulin's antiproteolytic actions are impaired in upper-body obesity.
 These findings could have implications for future studies of and treatment of obesity.
",17
2888,"Effect of trestatin, an amylase inhibitor, incorporated into bread, on glycemic responses in normal and diabetic patients.
 The effect of incorporating the pancreatic alpha-amylase inhibitor trestatin into bread on postprandial plasma glucose and insulin excursions was tested in healthy volunteers and non-insulin-dependent diabetic patients.
 At both dose levels of trestatin (3 and 6 mg/75 g starch) the peak values of plasma glucose and insulin were reduced markedly (compared with placebo) after the ingestion of 75 g starch in the form of bread.
 In healthy control subjects as well as in diabetic patients, trestatin produced significantly lower insulin excretions but also significant reductions in incremental plasma glucose areas in a dose-dependent fashion.
 It is concluded that it is technologically feasible to incorporate trestatin into starchy foods without loss of activity or impairment of taste.
 Furthermore, the positive effect of trestatin on glycemic and insulinemic responses in diabetics and the lack of serious side effects offer a great potential in the dietary treatment of diabetic patients.
",17
2889,"Percent body fat in obese white females predicted by anthropometric measurements.
 The percent body fat (PBF) and 15 anthropometric measurements were measured in 221 obese white females randomly assigned to validation and cross-validation groups.
 Two new anthropometric equations for the prediction of the percent of body fat were generated by multiple regression.
 Equation 1 includes the residual lung volume (RV) as a factor and had a correlation coefficient (r) of 0.85 and a standard error of the estimate (SEE) of 3.9%.
 Equation 2 does not include the RV and has an r of 0.82 and an SEE of 4.3%.
 Both equations were more precise than two previous widely used equations.
 In a subgroup of 37 subjects who underwent weight loss, equation 1 gave a more precise estimate of the change in PBF.
 We conclude that the new equations permit a better prediction of the PBF in obese white females.
",17
2890,"Vitreous fluorophotometry in insulin-dependent diabetes mellitus. Correlation with microalbuminuria and diastolic blood pressure.
 Vitreous fluorophotometry was performed on 240 eyes of 120 young subjects who had insulin-dependent diabetes mellitus (type I) and various grades of retinopathy.
 The concentration of fluorescein was measured in the anterior chamber and posterior vitreous 1 hour after intravenous injection of fluorescein.
 There was a significant association (P less than .001) between the grade of retinopathy and the level of posterior vitreous leakage.
 The amount of posterior vitreous leakage in each eye also had a significant association with borderline elevation of diastolic blood pressure.
 Subjects with excessive posterior vitreous leakage had significantly higher levels of urinary microalbumin excretion.
 In a multiple linear regression analysis for posterior vitreous leakage, retinal grade consistently entered the model at a significant level (P less than or equal to .00001 to .003).
 Blood pressure also entered the model for posterior vitreous leakage at a significant level for retinal grades of the right and left eyes and of the worst eye.
 These results demonstrate an association between leakage of retinal and renal vessels, possibly linked at least in part to elevation in diastolic blood pressure.
",17
2891,"Incidence and etiology of hyponatremia in an intensive care unit.
 To evaluate the incidence and causes of hyponatremia in intensive care unit (ICU) patients, retrospective and prospective studies were done.
 Hyponatremia was defined as a serum sodium concentration equal to or less than 134 mmol/l (134 mEq/l).
 Prospectively, 29.6% of patients displayed hyponatremia.
 Relevant data were obtained in twelve patients.
 Two patients did not have serum hypoosmolality.
 In the ten patients with serum hypoosmolality, urine osmolality was not maximally dilute and urine sodium concentration was greater than 30 mmol/l (30 mEq/l) suggesting inappropriate antidiuretic hormone secretion (SIADH).
 However, three patients exhibited suppressed ADH levels despite absence of maximal urinary dilution.
 The data suggest that hyponatremia is common in ICU patients and that renal diluting defects are frequent.
 Therefore, hypotonic fluid should be administered cautiously.
",17
2892,"Rational ordering of electrolytes in the emergency department.
 STUDY OBJECTIVE: To validate the predictive abilities of a retrospectively developed set of clinical criteria for detecting clinically significant electrolyte abnormalities, using a different patient population.
 DESIGN: Cross-sectional study.
 SETTING: The emergency department of a busy public hospital.
 TYPE OF PARTICIPANTS: Nine hundred eighty-two patients on whom the emergency physician ordered serum electrolytes.
 INTERVENTIONS: The predictive properties of ten clinical criteria were evaluated; these included poor oral intake, vomiting, chronic hypertension, taking a diuretic, recent seizure, muscle weakness, age of 65 years or more, alcoholism, abnormal mental status, and recent history of electrolyte abnormality.
 MEASUREMENTS AND MAIN RESULTS: Seven hundred thirty patients (74.3%) had one or more electrolytes outside of the laboratory normal range, but only 143 (14.6%) had clinically significant electrolyte abnormalities.
 The clinical criteria predicted 135 of the clinically significant electrolyte abnormalities (sensitivity, 94.4%).
 When the eight ""false-negative"" cases were reviewed, none of the electrolyte abnormalities affected patient outcome.
 Implementation of the criteria would have avoided unnecessary testing in 233 patients (23.7%).
 CONCLUSION: Although no set of clinical criteria can eliminate the need for clinical judgment, use of a set of clinical criteria could substantially decrease electrolyte ordering without compromising patient care.
",17
2893,"Pediatrics residents' attitudes about insulin-dependent diabetes mellitus and children with diabetes.
 Nationwide, pediatricians provide a substantial portion of the health care of children with diabetes.
 Their beliefs and attitudes about diabetes and children with the illness have an important influence on their treatment decisions.
 The attitudes and beliefs of a 1988 sample of pediatrics residents were compared with data from a 1987 national survey of practicing pediatricians' beliefs and attitudes about children with insulin-dependent diabetes mellitus and about the disease itself.
 Pediatrics residents in their second and third years of training were considerably more negative about diabetes and diabetic children than were either the members of the national sample of practicing pediatricians or the residents' first-year colleagues.
",17
2894,"Endothelin and increased contractility in adult rat ventricular myocytes. Role of intracellular alkalosis induced by activation of the protein kinase C-dependent Na(+)-H+ exchanger.
 Endothelin, a 21-amino acid vasoactive peptide, is among the most potent positively inotropic agents yet described in mammalian heart.
 Having demonstrated that endothelin's inotropic effect is due, in part, to an apparent sensitization of cardiac myofilaments to intracellular calcium, we determined whether this could be due to a rise in intracellular pH (pHi).
 In isolated adult rat ventricular cells loaded with the H(+)-selective fluorescent probe BCECF, 100 pM endothelin increased contractile amplitude to 190 +/- 26% of baseline and pHi by 0.08 +/- 0.02 (n = 8), whereas 1 nM endothelin increased pHi by 0.13 +/- 0.03 with little further increase in contractility.
 Amiloride (10(-4)M) prevented the increase in pHi in response to endothelin and reduced the inotropic response by 45%, although the inotropic effect could be readily restored by subsequent NH4Cl-induced alkalinization.
 Similarly, inhibitors of protein kinase C (H-7 and sphingosine) diminished or abolished the rise in pHi after endothelin superfusion while causing a decline in its inotropic effect comparable with that observed with amiloride.
 Pretreatment with pertussis toxin, which we have demonstrated results in complete ADP-ribosylation of the alpha-subunits of Go and Gi GTP-binding proteins and abolition of endothelin's positive inotropic effect, only partially reduced the intracellular alkalinization induced by the peptide, suggesting a complex signal transduction mechanism.
 Thus, the positive inotropic action of endothelin is due in part to stimulation of the sarcolemmal Na(+)-H+ exchanger by a protein kinase C-mediated pathway, resulting in a rise in pHi and sensitization of cardiac myofilaments to intracellular Ca2+.
",17
2895,"Mechanical alternans during acidosis in ferret heart muscle.
 Acidosis leads to mechanical alternans (i.e., alternation of large and small contractions) in ferret papillary muscles.
 This alternation in the size of the contraction is paralleled by alternation in the size of the intracellular Ca2+ transient (monitored using the photoprotein aequorin).
 In isolated myocytes, the large contraction is accompanied by a prolonged action potential.
 Mechanical alternans also can be induced by acidosis in isolated myocytes during a train of voltage-clamp pulses.
 Thus, it appears unlikely that the mechanical alternans is secondary to changes in action potential duration; it is more likely that the observed changes in action potential duration are secondary to changes in the size of the Ca2+ transient.
 The observation that a Ca2(+)-activated inward current also shows alternation during mechanical alternans provides a possible mechanism for the link between Ca2+ and action potential duration.
 The alternation in the size of the Ca2+ transient may be secondary to the slowed mechanical restitution observed in papillary muscles during acidosis.
 This also could explain the observation that decreasing stimulation rate can abolish the alternans.
",17
2896,"Effect of captopril on glucose concentration. Possible role of augmented postprandial forearm blood flow.
 The goal of this study was to evaluate the effects of captopril on plasma glucose concentration.
 The daily profiles of the plasma glucose levels were determined in 12 non-insulin-dependent diabetic normotensive subjects, treated with or without captopril at a dose of 25 mg 3 times/day.
 Forearm blood flow was also measured by strain-gauge plethysmography.
 Administration of captopril improved the daily profile of the plasma glucose level.
 Postprandial forearm blood flow was also augmented 2 h after a meal.
 These results suggest that angiotensin-converting enzyme inhibitors may improve glucose metabolism in diabetic subjects, possibly through enhancement of blood flow to skeletal muscle.
",17
2897,"Self-care predictors of metabolic control in NIDDM patients.
 The objective of this study was to evaluate whether the relationship between self-care behavior and metabolic control is comparable in patients with non-insulin-dependent diabetes mellitus (NIDDM) on insulin and not on insulin.
 We studied 84 NIDDM patients hospitalized for an elective admission in Washington University's Model Demonstration Unit.
 At admission, patients reported the frequency of exercise, blood glucose monitoring, and meal skipping for the previous 2 wk.
 Metabolic control over the previous 8-12 wk was determined from glycosylated hemoglobin assays.
 In cross-sectional analysis controlling for patient sociodemographic and health characteristics, glycosylated hemoglobin levels were positively related to meal skipping (P = 0.0008) and negatively related to the frequency of blood glucose monitoring (P = 0.0025).
 Self-care behaviors explained 26% of the variance in glycosylated hemoglobin levels in NIDDM patients.
 Multivariate modeling demonstrated no significant interaction effects between insulin treatment and self-care on metabolic control.
 In conclusion, these findings support the clinical significance of self-care activities for metabolic control in NIDDM patients, particularly meal skipping and blood glucose monitoring.
",17
2898,"Theoretical and baseline considerations for diet and weight control of diabetes among blacks.
 This article outlines theoretical considerations for diet and weight control of non-insulin-dependent diabetes mellitus (NIDDM) and identifies factors that may be of particular importance in influencing the success of diet and weight control of NIDDM in the Black population.
 Long-term adherence to dietary or weight-control regimens requires that the patient evaluate and restructure established eating and physical activity patterns.
 With the use of the social action theory as a conceptual framework, this complex behavioral change task can be understood as a function of the interplay of various self-regulatory mechanisms.
 These mechanisms are influenced by the person's capabilities for making changes, his/her physical condition and general health status, the physical and social environmental context, and the person's material and social resources.
 Many of these factors may differ for Blacks and Whites in a direction that suggests a lesser potential for effective diet and weight-loss therapy among Black NIDDM patients.
 For example, compared with Whites, Blacks are more likely to have limited incomes, low educational attainment, ambivalence about weight control, multiple health problems, and high-fat high-sodium low-fiber diets or food preferences.
 However, some evidence suggests that state-of-the-art counseling approaches can be as effective for Blacks as for Whites.
 The challenge is to adapt the types of approaches suggested by the social action theory for culturally appropriate and cost-effective delivery in Black community health-care settings.
",17
2899,"Exercise in therapy and prevention of type II diabetes. Implications for blacks.
 The rationale for the use of exercise in the treatment of type II (non-insulin-dependent) diabetes and its special implications for Blacks are reviewed herein.
 When performed on a regular basis, exercise may improve glycemic control and improve several risk factors for coronary heart disease including hypertriglyceridemia, hypertension, and hyperinsulinemia.
 In addition, it may be a useful adjunct to diet in producing weight loss.
 The metabolic benefits of exercise in part appear to be related to its ability to enhance insulin sensitivity.
 Benefits are short lived after discontinuing exercise.
 Because of problems with compliance and concurrent medical problems, many patients with type II diabetes are not good candidates for an exercise-diet program.
 For this reason, the optimum target population may be people at risk for type II diabetes and premature atherosclerosis.
 Such a population might include the offspring of patients with these disorders and individuals with impaired glucose tolerance, hyperinsulinemia, gestational diabetes, and/or an android pattern of fat distribution.
 Type II diabetes is more common in Blacks than in the general population.
 In most instances, it is associated with cardiovascular risk factors benefited by exercise.
 Despite this, there are no available studies regarding the effects of regular exercise in Blacks with type II diabetes or those at risk for it.
",17
2900,"Cross-sectional analysis of renal function in black Americans with NIDDM.
 Our objective was to define glomerular filtration rate (GFR) and renal plasma flow (RPF) in Black Americans with non-insulin-dependent diabetes mellitus (NIDDM).
 This was a cross-sectional study of 71 Black NIDDM patients with diagnosed diabetes duration from 1 mo to 21 yr.
 Hyperglycemia was regulated and stabilized before patients were entered into the study.
 GFR and RPF were determined by the clearance of [125I]iothalamate and 131I-labeled hippuran, respectively, with a constant-infusion technique and four urine collection periods.
 Hyperfiltration, as defined by a GFR of greater than 140 ml.min-1.1.73 m-2, was found in 7 of 20 patients (35%) with newly diagnosed (less than 2 yr duration) NIDDM.
 The percentage of patients with hyperfiltration decreased with increasing duration of diagnosed diabetes.
 Decreasing GFR and RPF occurred with increasing duration of diagnosed diabetes.
 In conclusion, renal hemodynamic changes in Black Americans with NIDDM are similar to those known to occur in White populations with IDDM.
",17
2901,"Effect of exercise and obesity on skeletal muscle amino acid uptake.
 The genetically obese Zucker rat has a reduced capacity to deposit dietary protein in skeletal muscle.
 To determine whether amino acid uptake by muscle of obese Zucker rats is impaired, soleus strip (SOL) and epitrochlearis (EPI) muscles from 10-wk-old lean and obese Zucker rats were studied in vitro by use of [14C]alpha-aminoisobutyric acid (AIB).
 Muscles from fasted rats were incubated under basal conditions at rest or after a 1-h treadmill run at 8% grade.
 To equate total work completed, lean and obese rats ran at 27 and 20 m/min, respectively.
 Muscles were pinned at resting length, preincubated for 30 min at 37 degrees C in Krebs-Ringer bicarbonate buffer containing 5 mM glucose under 95% O2-5% CO2, and then incubated up to 3 h in Krebs-Ringer bicarbonate with 0.5 mM AIB, [14C]AIB, and [3H]inulin as a marker of extracellular fluid.
 Basal AIB uptake in EPI and SOL from obese rats was significantly reduced by 40 and 30% (P less than 0.01), respectively, compared with lean rats.
 For both lean and obese rats, exercise increased (P less than 0.05) basal AIB uptake in EPI and SOL, but the relative increases were greater in the obese rats (EPI 54% and SOL 71% vs.
 EPI 32% and SOL 37%).
 These results demonstrate that genetically obese Zucker rats have reduced basal skeletal muscle amino acid uptake and suggest that physical inactivity may partially contribute to this defect.
",17
2902,"Regulation of forearm lipolysis in different types of obesity. In vivo evidence for adipocyte heterogeneity.
 Forearm and systemic adipose tissue free fatty acid (FFA) release was measured in eight nonobese, six lower-body obese, and eight upper-body obese women under basal, hyperinsulinemic, and hypoinsulinemic conditions to determine whether forearm fat is regulated in a similar manner as whole body fat.
 Results: Adipose tissue palmitate release was greater from forearm than whole body (5.97 +/- 0.75 vs.
 3.84 +/- 0.34 mumol.kg fat-1.min-1, respectively, P less than 0.005, n = 22 subjects).
 Systemic palmitate release, relative to fat mass, was significantly (P less than 0.01) greater in nonobese than upper-body obese, and upper-body obese than lower-body obese women, and forearm adipose tissue palmitate release followed the same pattern.
 Hyperinsulinemia suppressed systemic and forearm lipolysis to similar degrees, however, hypoinsulinemia consistently increased systemic palmitate flux without increasing forearm palmitate release.
 These results confirm the heterogeneity of adipose tissue in an in vivo model and emphasize the need to consider which adipose tissue depots are responsible for the differences in systemic FFA flux in obese and nonobese humans.
",17
2903,"Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels.
 The present experiments were undertaken to examine the hypothesis that glucose-induced increased de novo synthesis of 1,2-diacyl-sn-glycerol (which has been observed in a number of different tissues, including retinal capillary endothelial cells exposed to elevated glucose levels in vitro) and associated activation of protein kinase C may play a role in mediating glucose-induced vascular functional changes.
 We report here that twice daily instillation of 30 mM glucose over 10 d in a rat skin chamber granulation tissue model induces approximately a 2.7-fold increase in diacylglycerol (DAG) levels (versus tissues exposed to 5 mM glucose) in association with marked increases in vascular clearance of albumin and blood flow.
 The glucose-induced increase in DAG levels as well as the vascular functional changes are prevented by addition of 3 mM pyruvate.
 Pharmacological activation of protein kinase C with the phorbol ester TPA in the presence of 5 mM glucose increases microvascular albumin clearance and blood flow, and similar effects are observed with 1-monoolein (MOG), a pharmacological inhibitor of the catabolism of endogenous DAG.
 A pharmacological inhibitor of protein kinase C (staurosporine) greatly attenuates the rise in microvascular albumin clearance (but not the rise in blood flow) induced by glucose or by MOG.
 These findings are compatible with the hypothesis that elevated concentrations of glucose increase tissue DAG content via de novo synthesis, resulting in protein kinase C activation, and that these biochemical events are among the factors that generate the increased microvascular albumin clearance.
",17
2904,"Anderson's disease: genetic exclusion of the apolipoprotein-B gene in two families.
 Anderson's disease is a recessive disorder characterized by intestinal fat malabsorption, absence of postprandial chylomicrons, and reduced levels of cholesterol, triglycerides, and apoproteins B, AI, and C.
 We have studied two families with, respectively, three and two children with Anderson's disease.
 Intestinal apo-B and apo-AIV mRNAs from two Anderson's patients were normal in size but their concentration was decreased fivefold compared with controls.
 After DNA digestion with seven restriction enzymes, restriction fragment length polymorphisms of apo-B gene did not show conclusive information except for Xba1, which revealed a lack of cosegregation between the restriction fragment length polymorphism and the Anderson's phenotype.
 Linkage analysis was performed using the polymorphism of the apo-B gene 3'minisatellite.
 Genomic DNA from parents and children was amplified by polymerase chain reaction using oligonucleotide primers flanking the apo-B gene 3'hypervariable locus.
 In both families each child inherited different apo-B alleles from at least one parent.
 According to the recessive mode of transmission of the disease, our results are incompatible with the involvement of the apo-B gene.
 More likely a posttranslational defect or a mutation in another gene encoding a protein essential for lipoprotein assembly or secretion may be involved.
",17
2905,"Treating serum lipid abnormalities in high-priority patients.
 Normalization of serum lipid levels should be initiated as soon as possible in patients with myocardial, cerebrovascular, or peripheral vascular disease.
 Clinical trials indicate that coronary artery disease and overall mortality rates can be reduced and atherosclerosis stabilized or reversed by lipid-lowering therapy.
 Treatment should lower low-density lipoprotein cholesterol levels to 130 mg/dL or less and total triglyceride levels to 150 mg/dL or less and increase high-density lipoprotein cholesterol levels to at least 52 mg/dL in men and 66 mg/dL in women.
 Nonlipid coronary risk factors should be eliminated when possible.
 Lipid-lowering therapy may consist of dietary modification and drug treatment with colestipol hydrochloride (Colestid), cholestyramine (Cholybar, Questran), lovastatin (Mevacor), gemfibrozil (Lopid), and nicotinic acid (Nicolar).
",17
2906,"A myo-inositol pool utilized for phosphatidylinositol synthesis is depleted in sciatic nerve from rats with streptozotocin-induced diabetes.
 Peripheral nerve from experimentally diabetic rats exhibits lowered levels of myo-inositol (MI) and decreased incorporation of [3H]MI into phosphatidylinositol (PI).
 There are indications that diminished PI turnover may be causally related to reduced Na+,K(+)-ATPase activity in diabetic nerve.
 We have investigated whether a metabolic compartment of MI that is essential for PI synthesis is decreased in this tissue.
 Sciatic nerve segments from streptozotocin-induced diabetic and age-matched normal rats were incubated in vitro with either 32Pi or [3H]cytidine in the presence of propranolol.
 This cationic amphiphilic agent redirected nerve phospholipid metabolism to produce enhanced 32P incorporation into PI and decreased labeling of phosphatidylcholine and phosphatidyl-ethanolamine.
 The accumulation of phosphatidyl CMP (CMP-PA) was also demonstrated by chromatographic and enzymatic means.
 The incorporation of [3H]cytidine into CMP-PA in normal nerve increased up to 15-fold when 0.6 mM propranolol was present.
 In diabetic nerve, the liponucleotide incorporated 2- to 3-fold more isotope and was more readily labeled at lower drug concentrations as compared to normal nerve.
 The buildup of [3H]CMP-PA was reduced in a dose-dependent manner in the presence of MI in the incubation medium at concentrations up to 3 mM.
 However, if MI was added after liponucleotide accumulation, preformed CMP-PA could not be utilized for PI synthesis.
 The difference in liponucleotide labeling between normal and diabetic nerve was nearly abolished at 0.3 mM medium MI, a concentration much less than the level of cyclitol in the tissue.
 These results strongly suggest the presence in nerve of a pool of MI that is not in equilibrium with the bulk of nerve MI and that is preferentially used for PI synthesis.
 This metabolic compartment is depleted in diabetic nerve but can be readily replenished by exogenous MI and may correspond to the MI pool that has been proposed to be required for the turnover of a portion of tissue PI involved in maintenance of normal Na+,K(+)-ATPase activity.
",17
2907,"Evidence that down-regulation of beta-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia.
 Non-insulin-dependent diabetes mellitus (NIDDM) is attributed to a failure of pancreatic beta cells to maintain insulin secretion at a level sufficient to compensate for underlying insulin resistance.
 In the ZDF rat, a model of NIDDM that closely resembles the human syndrome, we have previously reported profound underexpression of GLUT-2, the high-Km facilitative glucose transporter expressed by beta cells of normal animals.
 Here we report that islets of diabetic rats exhibit a marked decrease in the volume of GLUT-2-positive beta cells and a reduction at the electron-microscopic level in the number of GLUT-2-immunoreactive sites per unit of beta-cell plasma membrane.
 The deficiency of GLUT-2 cannot be induced in normal beta cells by in vivo or in vitro exposure to high levels of glucose nor can it be prevented in beta cells of prediabetic ZDF rats by elimination of hyperglycemia.
 We conclude that this dearth of immunodetectable GLUT-2 in NIDDM is not secondary to hyperglycemia and therefore that it may well play a causal role in the development of hyperglycemia.
",17
2908,"Vitamin E and neurologic deficits.
 Over the past decade it has become apparent that vitamin E is an essential nutrient for maintaining the structural and functional integrity of the developing human nervous system, skeletal muscle, and the retina.
 The clinical and histologic resemblance of the human neuromuscular disorder associated with chronic fat and vitamin E malabsorption to that observed in experimental vitamin E-deficient animal models is striking.
 Because of chronic malabsorption of vitamin E, children with CF, chronic cholestasis, abetalipoproteinemia, and short bowel syndrome are at risk for the development of neurologic deficits caused by vitamin E deficiency.
 Correction of the vitamin E deficiency state prevents, reverses, or, at least, stabilizes the neurologic dysfunction in susceptible individuals.
 Advances in stable isotope technology permit study of the hepatic discrimination among the various stereoisomers and forms of vitamin E.
 Investigations into the cause of the primary form of vitamin E deficiency, the isolated vitamin E deficiency syndrome, promise to delineate the normal physiologic processes involved in absorption, transport, and tissue delivery of vitamin E.
 Studies in progress are addressing the optimal route and form of vitamin E therapy to be used in each predisposing condition.
 One major task remaining is to better define the mechanism by which vitamin E deficiency leads to neurologic injury.
",17
2909,"Localization of the Aland Island eye disease locus to the pericentromeric region of the X chromosome by linkage analysis.
 Aland Island eye disease (AIED) is an X-chromosomal disorder characterized by reduced visual acuity, progressive axial myopia, regular astigmatism, latent nystagmus, foveal hypoplasia, defective dark adaptation, and fundus hypopigmentation.
 The syndrome was originally reported in 1964 in a family on the Aland Islands.
 To determine the localization of the AIED gene, linkage studies were performed in this family.
 total of 37 polymorphisms, covering loci on the entire X chromosome, were used.
 By two-point analysis the strongest evidence for linkage was obtained between AIED and DXS255 (maximum lod score [Zmax] 4.92 at maximum recombination fraction [theta max] .00).
 Marker loci DXS106, DXS159, and DXS1 also showed no recombination with AIED.
 Other positive lod scores at theta max .00 were obtained with markers localized in the XY homologous region in Xq13-q21, but the numbers of informative meioses were small.
 Multilocus linkage analysis indicated that the most probable location of AIED is in the pericentromeric region between DXS7 and DXS72.
 These results rule out localizations of AIED more distal on Xp that have been proposed by others.
 Our data do not exclude the possibility that AIED and incomplete congenital stationary night blindness are caused by mutations in the same gene.
 This question should be resolved by careful clinical comparison of the disorders and ultimately by the molecular dissection of the genes themselves.
",17
2910,"Hyperlipidemia after organ transplantation.
 Hyperlipidemia, long recognized as a difficult and common problem following organ transplantation, may be the underlying cause of the accelerated atherosclerosis observed in heart transplant recipients and children with renal transplants.
 In addition, hyperlipidemia may play a role in late renal graft loss.
 The cause of post-transplant hyperlipidemia is unclear.
 In patients treated with azathioprine and prednisone, hypertriglyceridemia is the commonest finding and probably results from an increased consumption of calories from carbohydrate and fat following resolution of uremia, in conjunction with glucose intolerance secondary to steroid administration.
 In patients treated with cyclosporine, hypercholesterolemia is the most common form of hyperlipidemia.
 Cyclosporine is a lipophilic drug that is transported in the plasma, largely in association with lipoproteins, and may require the low-density lipoprotein (LDL) receptor for internalization into cells.
 Hypercholesterolemia may result from interference with the basic cholesterol feedback mechanism via the LDL receptor.
 In addition, cyclosporine affects bile acid synthesis and worsens glucose tolerance, both factors that may promote hyperlipidemia.
 The first therapeutic approach to hyperlipidemia in the transplant recipient is dietary calorie-fat restriction and supplementation with soluble fiber.
 Ongoing clinical trials of the available pharmacologic lipid-lowering agents are addressing the safety and efficacy of these agents in the setting of immunosuppression; until that time, they should be used cautiously and in low doses.
",17
2911,"Schizophrenia and fatal self-induced water intoxication with appropriately-diluted urine.
 A 31-year-old woman with untreated chronic schizophrenia developed extreme polydipsia which rapidly led to coma and death due to cerebral edema.
 Hyponatremia (120 mEq/liter) and serum hypo-osmolality (260 mOsm/kg) were associated with marked polyuria (up to 1850 ml/hour) and appropriately low urinary osmolality (90 mOsm/kg) which responded to treatment.
 This case and few qualifying previous reports which are reviewed support the possibility that pure self-induced water intoxication with no major contribution of inadequate release of antidiuretic hormone may occur, and that extreme polydipsia can sometimes overwhelm normal renal diluting capacity in psychotic patients.
",17
2912,"Hyperosmolar states.
 The composition of the extracellular fluid (ECF) must remain stable for cells to function properly.
 In normal individuals vasopressin and thirst zealously maintain the total ECF concentration, or osmolality, within a narrow range.
 Disruption of these regulatory mechanisms or rapid addition of solute to the ECF can lead to hyperosmolality.
 The serious neurologic symptoms that accompany many forms of hyperosmolality can be explained by understanding the physiologic response of cells to the osmotic stress.
 This review describes the physiology, pathophysiology, differential diagnosis, and therapy of hyperosmolar states.
",17
2913,"Hypokalemia before induction of anesthesia and prevention by beta 2 adrenoceptor antagonism.
 We have observed that serum potassium levels measured immediately before induction of anesthesia (""preinduction K+"") are often lower than those measured 1-3 days preoperatively (""preoperative K+"").
 The purpose of this investigation was to determine, in two studies, the magnitude of this difference and to elucidate the mechanism by which this occurs.
 In the first study, preinduction K+ (3.6 +/- 0.4 mEq/L, mean +/- SD) was significantly lower than K+ levels measured during routine preoperative testing (4.4 +/- 0.4 mEq/L, n = 47, P less than 0.001).
 Twenty-three patients (49%) had preinduction K+ levels that were considered hypokalemic (less than or equal to 3.5 mEq/L), but 22 of these 23 patients had normal preoperative K+ levels.
 The second study tested the hypothesis that preinduction decreases in serum K+ are mediated by beta 2-adrenergic receptors.
 Preinduction K+ changes were determined in patients given a single preoperative dose of propranolol (beta 1/beta 2-antagonist), atenolol (beta 1-antagonist), or no beta-blocker (control).
 The difference between preoperative and preinduction serum K+ in patients receiving propranolol (0.1 +/- 0.4 mEq/L) was significantly attenuated (P less than 0.02) compared with the difference in control subjects (0.5 +/- 0.4 mEq/L), but was not significantly different from controls in patients pretreated with atenolol (0.3 +/- 0.4 mEq/L).
 These results demonstrate that serum K+ levels measured intraoperatively just before anesthetic induction are consistently and significantly less than those measured 1-3 days preoperatively.
 The ability of propranolol but not atenolol to block this change suggests that the acute decrease in K+ levels was due to beta 2-adrenergic receptor stimulation.
",17
2914,"The role of alpha 1-adrenoceptors in adrenaline-induced hyperkalaemia.
 The hyperkalaemic action of adrenaline was investigated in 44 anaesthetized domestic pigs.
 Plasma and epicardial concentrations of K+ were measured, in the latter case with an ion-selective electrode.
 Adrenaline 10 micrograms kg-1 caused a rapid increase in the plasma concentration of K+ from 4.2 to 5.9 mmol litre-1.
 The magnitude and the time course of epicardial concentration of K+ were similar.
 Alpha-adrenoceptor block with either phentolamine 5 mg kg-1 (non-selective block) or prazosin 0.1 mg kg-1 (selective alpha 1-adrenoceptor block) abolished the hyperkalaemic effect of adrenaline in the plasma and on the epicardium.
 The alpha 1-adrenoceptor agonist phenylephrine increased the K+ concentration, but the alpha 2-adrenoceptor agonist UK 14.304 did not cause any change in concentration.
 These results suggest that the hyperkalaemia induced by adrenaline occurs in the interstitial fluid of the myocardium and is mediated by alpha 1-adrenoceptors.
 These findings may be important in patients at risk of hyperkalaemia, with implications, for example, in the use of suxamethonium during induction of anaesthesia.
",17
2915,"Free protein S levels are elevated in familial C4b-binding protein deficiency.
 In plasma, 40% of the protein S is free and functions as a cofactor for the anticoagulant effects of activated protein C.
 The remaining 60% of protein S is complexed to C4b-binding protein and is functionally inactive.
 A family with hereditary C4b binding protein deficiency has been identified with C4b-binding protein levels in an affected father and daughter of 37 micrograms/mL and 23 micrograms/mL, respectively; these values are significantly below the normal range for this protein of 180 micrograms/mL +/- 44 micrograms/mL (mean +/- 2 SD).
 The total protein S (free + bound) is normal in these individuals (23.2 micrograms/mL and 17.8 micrograms/mL, respectively; normal 19.1 micrograms/mL +/- 6.0 micrograms/mL).
 The free protein S levels are markedly increased at 22.5 micrograms/mL and 17.4 micrograms/mL, respectively (normal 5.9 micrograms/mL +/- 2.4 micrograms/mL).
 This experiment of nature shows that total protein S levels in plasma are not affected by the absence of C4b-binding protein and that chronic elevation of free protein S is not associated with increased hemorrhagic tendencies.
",17
2916,"Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man.
 We have examined the mechanisms underlying reduced circulating GH concentrations in the obese human.
 Computer-assisted (deconvolution) analysis was used to determine endogenous GH secretory and clearance rates quantitatively from entire 24-h plasma GH concentration profiles.
 These analyses revealed that the half-life (t 1/2) of endogenous GH was significantly shorter in obese (11.7 +/- 1.6 min) than in normal weight subjects (15.5 +/- 0.81 min; P less than 0.01).
 The accelerated blood disposal rate of GH was not due to decreased circulating concentrations of GH-binding protein, since the latter were similar in obese (25 +/- 1.0%) and normal weight (24 +/- 2.3%) men.
 However, obese men had significantly fewer GH secretory bursts (3.2 +/- 0.53 vs.
 9.7 +/- 0.67/day; P less than 0.01).
 Among the rare GH secretory bursts that occurred in obese subjects, there were significantly prolonged mean intersecretory burst intervals (282 +/- 65 vs.
 131 +/- 11 min; P less than 0.05).
 The resultant daily GH production rate in obese men was reduced to one fourth that in normal weight individuals.
 Both GH secretion rate and burst frequency were negatively correlated with the degree of obesity (ponderal index).
 The decreases in GH burst frequency and half-life were specific, since GH secretory pulse amplitude (maximal rate of GH release), the mass of GH released per burst, and the duration of computer-resolved GH secretory bursts were not different in obese and normal weight men.
 We conclude that obese men harbor a double defect in GH dynamics involving both GH secretion and clearance, and that the severity of the GH secretory deficiency is proportionate to the degree of obesity.
",17
2917,"Influence of thiamin supplementation on the health and general well-being of an elderly Irish population with marginal thiamin deficiency [published erratum appears in J Gerontol 1991 Sep;46(5):M180]
 The effect of thiamin supplementation on the health and general well-being of 80 randomly selected healthy elderly Irish women, from a population with marginal thiamin deficiency, was studied.
 Key variables affecting thiamin status were controlled.
 Weekly dietary intakes, subjective feelings, and activity assessments were measured during a 4-week baseline and 6-week double blind treatment period.
 Clinical assessments were performed during the last week of each period.
 For treatment, subjects were randomly assigned to either thiamin (10 mg daily) or placebo groups.
 Compared to baseline and placebo supplemented values, thiamin-supplemented women experienced significantly increased appetite, energy intake, body weight and general well-being, and decreased fatigue.
 Thiamin supplementation also tended to reduce daytime sleep time, improve sleep patterns, and increase activity.
 These data suggest that evaluation of thiamin status is indicated when nonspecific conditions such as anorexia, weight loss, fatigue, depression, and sleep disorders are present in elderly persons.
",17
2918,"Abnormal arginine vasopressin response to cigarette smoking and metoclopramide (but not to insulin-induced hypoglycemia) in elderly subjects.
 Aging is known to reduce arginine vasopressin (AVP) response to volumetric stimulations and to increase AVP responses to osmotic stimuli and to administration of metoclopramide (MCP).
 In order to gain a better insight into the effect of age on AVP secretion, we evaluated AVP responses to cigarette smoking, MCP, and insulin-induced hypoglycemia in 30 male subjects aged 22-81 and divided into 3 groups by age.
 Basal AVP concentrations were similar in all groups.
 The AVP response during the insulin tolerance test had a similar pattern and magnitude (2.5-fold increase) in all groups.
 AVP responses to MCP and cigarette smoking were similar in the two younger groups, with plasma AVP levels increased 2 times by MCP and 2.5 times by cigarette smoking.
 In contrast, both MCP- and cigarette smoking-induced AVP rises were significantly higher in the oldest group, where plasma AVP concentrations increased 2.5 times after MCP and 3.25 times after smoking.
 When data of the MCP and cigarette smoking tests were combined, regression analyses showed a significant positive correlation between AVP peak responses to MCP and cigarette smoking in the oldest subjects.
 These data show that elderly humans have increased AVP responses not only to MCP but also to cigarette smoking, suggesting a common disorder for both alterations.
 In contrast, the lack of age-related changes in AVP response during the insulin tolerance test demonstrates that the mechanism underlying the AVP response to hypoglycemia is not affected by aging.
",17
2919,"The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid.
 Over a 1-year period, we examined 42 consecutive patients with low serum cobalamin levels detected by primary screening test (S-protein binder, RIA).
 In 31 patients (74%) clinical cobalamin deficiency was confirmed, whereas the remaining 11 patients (26%) were characterized clinically as non-cobalamin deficient.
 The serum methylmalonic acid level was higher than 0.34 mumol l-1 (3 SD above the mean in normal controls) in 30 of the 31 clinically characterized cobalamin-deficient subjects, and below this level in 10 of the 11 non-deficient patients.
 We conclude that the serum methylmalonic acid assay provides an appropriate means of discrimination between cobalamin deficiency and non-cobalamin deficiency (efficiency = 0.95), and we recommend that the assay be adopted as the standard test for diagnosis of tissue cobalamin deficiency.
",17
2920,"Drug related admissions to a cardiology department; frequency and avoidability.
 Three hundred and sixty-six consecutive patients admitted to a department of cardiology were evaluated for drug events as a cause of admission.
 The drug events considered were adverse drug reactions (ADR) and dose-related therapeutic failures (DTF).
 'Definite' or 'probable' drug events accounted for 15 admissions (4.1%, 95% confidence limits 2.3-6.7%), of which eleven were ADR and four were DTF.
 With the inclusion of six 'possible' drug events, the rate of drug-related hospitalizations (DRH) was 5.7%.
 DRHs were characterized by a preponderance of acute admissions and elderly patients.
 Hypokalaemia (less than 3.5 mM) was observed in 27 (16%) patients receiving diuretics, and could be related to four cases of arrhythmias (two 'probable' and two 'possible' ADR).
 The average serum potassium level was similar in diuretic treated patients with or without drugs to counteract hypokalaemia, irrespective of the drugs chosen.
 Among the 15 'definite'/'probable' DRHs, five were considered to be due to an error in prescription, and a further five cases were judged to have been avoidable had appropriate measures been taken by prescribing physicians.
 A DRH educational intervention programme should primarily deal with non-compliance or with prescription of diuretics or digoxin, since these problems constitute the majority of cases of DRH.
 No specific group of doctors could be targeted as responsible for DRH, avoidable or not.
",17
2921,"Lowering the cost of lowering the cholesterol: a formulary policy for lovastatin 
 OBJECTIVES: To describe a medical center policy designed to contain the cost of using the lipid-lowering drug lovastatin in a primary care setting, to examine the effect of the policy on cost containment, and to examine physician acceptance of the policy.
 SETTING: A Veterans Affairs medical center.
 INTERVENTIONS: The policy made lovastatin available to physicians when failure of therapy with diet and two first-line drugs was documented on an order form.
 The form also contained educational information including prices and recommended niacin as the drug treatment of first choice for most patients.
 DESIGN: To evaluate the effect of the policy, lipid-lowering drug use at the medical center was compared with that at a similar center that did not restrict lovastatin use, and with lipid-lowering drug use in the United States as a whole.
 A written questionnaire was used to survey physician reaction to the policy.
 RESULTS: The use of lovastatin as a percentage of total lipid-lowering drug use at the center with the lovastatin policy was one-fourth that at the other center or nationwide, and the use of niacin was four times greater (p less than 0.0001).
 The estimated savings in drug costs to the center with the lovastatin policy due to these differences was more than $30,000 per year.
 In the survey of physicians affected by the policy (n = 78, response rate = 100%), less than one-fourth viewed it unfavorably, and 90% favored this policy over restricting the drug to a subspecialty clinic.
 CONCLUSION: The authors' experience indicates that a formulary policy that permits limited use of an expensive drug in a primary care setting can contain costs in a way that is acceptable to physicians.
 A policy of this type could be useful to the increasing number of health care provider organizations that cover the cost of outpatient medications.
",17
2922,"Lovastatin therapy for cholesterol ester storage disease in two sisters.
 We administered lovastatin to two sisters, aged 4 and 17 years, who had cholesterol ester storage disease, an autosomal recessive disorder manifested by hypercholesterolemia and hypertriglyceridemia.
 The drug, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was taken orally for 6 months.
 Serum lipid concentrations were determined monthly.
 Computed tomography of the liver was performed before and during therapy to evaluate liver fat content.
 The younger sister had liver biopsies before and after 6 months of lovastatin therapy to assess hepatic cholesterol stores.
 Both patients had marked decreases in serum levels of cholesterol, triglycerides, and low-density lipoprotein-cholesterol; high-density lipoprotein-cholesterol levels increased.
 Computed tomography during treatment demonstrated a significant increase in linear attenuation, suggesting a decreased liver fat content.
 Liver tissue obtained 6 months after lovastatin therapy was initiated had 13% less esterified cholesterol than the liver sample obtained before treatment.
 We conclude that lovastatin may be effective in treating children with cholesterol ester storage disease.
",17
2923,"Estimates of metabolic rate in obese and nonobese adolescents.
 To evaluate the validity of equations for the calculation of basal metabolic rate, we compared measured metabolic rates in a population that included obese and nonobese adolescents with metabolic rates calculated from five equations commonly used to estimate metabolic rate.
 Of the available options, neither the Mayo Clinic nomogram nor the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) equations produced estimates that differed significantly from measured values.
 In a second cohort of severely obese adolescent girls, the FAO/WHO/UNU equation that included both height and weight provided the most accurate estimate of metabolic rate.
 Because of their simplicity, we recommend use of the FAO/WHO/UNU equations to estimate metabolic rate in adolescent populations (boys: BMR = 17.5 weight (kg) + 651; girls: BMR = 12.2 weight (kg) + 746).
 However, when obese cohorts are studied, the FAO/WHO/UNU equation that includes both weight and height predicts metabolic rate most accurately (boys: BMR = 16.6 weight (kg) + 77 height (m) + 572; girls: BMR = 7.4 weight (kg) + 482 height (m) + 217).
",17
2924,"Nephron site responsible for the reduced kaliuretic response to mineralocorticoids during hypokalemia in rats.
 Rats with hypokalemia induced by eating a low-K diet have a diminished kaliuretic response to mineralocorticoids.
 The purpose of this study was to determine if this was the due to a lower rate of net secretion of K in the cortical collecting duct (CCD) and/or an enhanced rate of reabsorption of K in the medullary collecting duct (MCD).
 Secondary active secretion of K in the CCD raises the [K] in the lumen as compared to the plasma [TF/P)K).
 If the (TF/P)K is greater than 1, there was secondary active secretion of K in this nephron segment.
 The (TF/P)K in the CCD was measured by microcatheterization of the collecting duct.
 Three groups of rats were studied: rats on a low-K diet with and without the acute administration of DOCA, and rats on a normal-K diet treated with DOCA on a chronic basis.
 Rats on the low-K diet had a (TF/P)K of 0.8 +/- 0.11; this value did not rise to values significantly greater than 1 after the acute administration of DOCA (1.4 +/- 0.35).
 In contrast, chronic administration of DOCA to rats fed a normal-K diet did result in a (TF/P)K which was significantly greater than unity (3.1 +/- 0.39).
 The degree of hypokalemia was not significantly different in these rats.
 The absolute and fractional reabsorption of K in the MCD was not different in the rats on the low-K diet with or without DOCA.
 We conclude that the nephron segment which is responsible for the reduced kaliuretic response to mineralocorticoids is the CCD.
",17
2925,"Effects of chronic alcohol intake on carbohydrate and lipid metabolism in subjects with type II (non-insulin-dependent) diabetes.
 PURPOSE: To study the effects of chronic alcohol intake on carbohydrate and lipid metabolism in subjects with non-insulin-dependent (type II) diabetes (NIDDM).
 To also evaluate the effect of alcohol withdrawal on metabolic control.
 PATIENTS AND METHODS: The study group consisted of 46 alcohol-consuming patients with NIDDM (NIDDM-B group), 35 non-alcohol-consuming patients with NIDDM (NIDDM group), and 40 normal control subjects.
 All patients were admitted to the hospital.
 Carbohydrate and lipid metabolism was assessed in these individuals immediately on admission to the hospital and during the following days.
 RESULTS: In the NIDDM-B group, blood alcohol (ethyl alcohol) concentration was very low.
 However, chronic alcohol intake was associated with higher fasting and postprandial glucose concentrations and higher hemoglobin A1c.
 No significant differences were found in C-peptide levels.
 Moreover, higher concentrations of 3-hydroxybutyrate and free fatty acids were observed in the NIDDM-B group than in the NIDDM group.
 No differences were found in triglyceride concentrations, acid-base patterns, or electrolyte levels.
 The metabolic effects of alcohol completely waned after 3 days of complete withdrawal.
 CONCLUSION: Chronic alcohol intake causes deterioration in metabolic control of persons with NIDDM.
 The effects induced by alcohol are completely reversed after a few days of withdrawal.
 Strict metabolic assessment is necessary when alcohol is an important constituent of the diet.
",17
2926,"Inspiratory muscle performance and pulmonary function changes in insulin-dependent diabetes mellitus.
 The study examined pulmonary function parameters of 36 patients with insulin-dependent diabetes mellitus and analyzed their inspiratory muscle performance.
 The control group consisted of 40 healthy reference persons of a sex ratio, age, height, and weight distribution similar to those of the patients.
 The pulmonary function test included the measurement of the lung volumes and the maximal expiratory flow-volume curves.
 The values of maximal sniff esophageal (Pes) and transdiaphragmatic pressures (Pdi) were used as parameters for global inspiratory muscle strength and diaphragm strength, respectively.
 The 12-s maximum voluntary ventilation (MVV) test supplied the parameter of inspiratory muscle endurance.
 The diabetic patients showed a highly significant decreased value for their inspiratory vital capacity (VCin) compared with that of the control subjects (4.75 +/- 0.84 versus 5.36 +/- 1.37 L; p less than 0.01).
 Inspiratory muscle performance in the diabetic patients was also restricted.
 Sniff Pes was significantly lower in the diabetic group (p less than 0.05); sniff Pdi (p less than 0.01) and MVV (p less than 0.05) were also low.
 The results did not correlate with either the duration of diabetes or the quality of metabolic control measured by glycosylated hemoglobin concentration.
 The reduction of VCin in diabetic patients may have been caused partly by the reduced capacity of the inspiratory muscles.
",17
2927,"Evaluation of albumin loss during low-density lipoprotein apheresis.
 Because the reduced plasma oncotic pressure from hypoproteinemia causes hyperlipidemia, serum albumin levels should be maintained during low-density lipoprotein (LDL) apheresis.
 The amount of albumin loss was evaluated in seven patients with familial hypercholesterolemia during LDL apheresis in which columns packed with dextran sulfate-cellulose beads were used as a selective adsorbent of LDL.
 Serum albumin level significantly decreased from 4.3 +/- 0.3 (mean +/- SD) g/dl to 3.6 +/- 0.2 g/dl.
 The albumin loss was assessed by two different methods: 1) radioimmunoassay of microalbumin content in the discarded fluid, and 2) measurement of changes in plasma albumin reserve.
 The albumin losses during one apheresis session were 3.7 +/- 2.9 g and 8.3 +/- 5.7 g, respectively, depending upon which of two different methods was used.
 There was a significant correlation between these two methods (r = 0.84, p less than 0.02).
 The amount of albumin loss during apheresis was estimated to be between 4.1% and 9.1% of total plasma albumin reserve, and more than half of the decreased serum albumin level appeared to be attributable to dilution due to the electrolyte solution used for priming of the extracorporeal circuit.
",17
2928,"Diabetes-associated impairment of hepatic insulin receptor tyrosine kinase activity: a study of mechanisms.
 Insulin receptor tyrosine kinase activity solubilized from liver of control and streptozotocin diabetic rats was studied using histone H2b and poly-Glu-Tyr (4:1) as phosphoacceptors.
 Both substrates inhibited autophosphorylation and exogenous kinase activity when added before, but not after, receptor activation with ATP.
 When H2b was added before ATP, insulin stimulated exogenous kinase activity of diabetic-derived receptors was significantly higher (approximately 50%) than control values at low H2b concentrations, but significantly lower (approximately 50%) than control values at high H2b concentrations, suggesting a decrease in the apparent Km and maximal velocity of the diabetic receptor tyrosine kinase toward H2b.
 When receptors were allowed to maximally autophosphorylate before the addition of H2b, the maximal H2b kinase activity of diabetic-derived receptors was only approximately 25% lower than that of controls.
 These effects were not attributable to altered ATP kinetics.
 Insulin receptor kinase activity toward the substrate poly-Glu-Tyr (4:1) was unaltered by insulinopenic diabetes.
 Insulin receptor alpha-beta dimers were not detectable in either control or diabetic-derived preparations.
 We conclude that the impairment of hepatic insulin receptor kinase activity associated with insulinopenic diabetes reflects a decreased ability to maximally activate, which is enhanced when the receptor is activated in the presence of some substrates, e.g.
 H2b.
 Impaired signalling by the diabetic-derived receptor appears to be dependent on the type of substrate and its concentration.
",17
2929,"The hypothalamic-pituitary axis of streptozotocin-induced diabetic female rats is not normalized by estradiol replacement.
 Studies in diabetic rats have found abnormalities at the hypothalamic, pituitary, and/or ovarian level but have not controlled for changes in estrogen levels induced by diabetes.
 The purpose of this investigation was to study the effect of diabetes on the hypothalamic-pituitary axis in ovariectomized rats treated with estradiol (E2).
 Ovariectomized 60 day old female rats were assigned to control (C, n = 42), diabetic (D, n = 47) or insulin-treated diabetic (DI, n = 16) groups.
 Diabetes was induced with an injection of streptozotocin in the D and DI groups.
 In the C, D, and DI groups, estrogen was replaced by implanting blank, 5 micrograms or 20 micrograms E2 pellets sc.
 Pituitary LH responsiveness to GnRH was assessed in C and D animals.
 Anterior hypothalamic and midhypothalamic concentrations of proGnRH and GnRH, pituitary LH and FSH and serum levels of LH, and E2 were measured by RIA.
 Anterior hypothalamic proGnRH concentrations were decreased in diabetic rats treated with 5 micrograms E2 compared to 5 micrograms E2 control animals (P less than 0.05).
 Midhypothalamic GnRH concentrations were also reduced in D vs.
 C animals despite comparable estrogen therapy (P less than 0.004).
 GnRH-stimulated LH levels were greater in E2-treated diabetic females than in similarly treated control rats (P less than 0.001).
 D and DI animals were more sensitive than controls to the inhibitory effect of estrogen on basal LH levels.
 Pituitary LH and FSH content was lower in 20 micrograms E2-replaced animals but was not influenced by the diabetic state.
 These data demonstrate a diabetes-induced decrease in hypothalamic proGnRH and GnRH concentration which is not corrected with E2 replacement.
 The hyper-responsiveness of the diabetic rat pituitary to GnRH also suggests a chronic lack of GnRH stimulation from the hypothalamus but a continued ability of the pituitary to respond to GnRH.
",17
2930,"Long-term studies of mental health after the Greenville gastric bypass operation for morbid obesity.
 From February 1, 1980, to May 1, 1989, 462 patients underwent the Greenville gastric bypass at the East Carolina University School of Medicine.
 The operation effectively maintained satisfactory weight loss after 9 years (mean weight preoperatively, 293 lbs; at 24 months, 179 lbs; at 96 months, 194 lbs).
 The gastric bypass favorably affected non-insulin-dependent diabetes, hypertension, and physical and role functioning.
 In the most recent 157 patients, our studies were extended to study the effects of the gastric bypass on mental health.
 The significant improvements in mental health indices that were observed 6 and 12 months after surgery eroded by the end of 2 years.
 This return of the mental health indices to the preoperative status, plus the late occurrence of 3 suicides and 2 deaths from alcohol abuse among the total 462 patients, suggest that long-term follow-up and continued emotional support are essential ingredients for successful bariatric surgery.
",17
2931,"Human isophane or lente insulin? A double blind crossover trial in insulin dependent diabetes mellitus.
 Fifty two children with insulin dependent diabetes mellitus were randomised to receive human isophane or lente insulin preparations in combination with soluble insulin in a double blind trial.
 Patients were seen every two months, and crossed over after four months of treatment.
 Control assessed by glycated haemoglobin was significantly lower in children on human isophane insulin, but fasting blood glucose and fructosamine concentrations and the number of episodes of hypoglycaemia were similar on both regimens.
 In five children on twice daily insulin regimens, insulin profiles throughout a 24 hour period demonstrated greater variability on lente compared with isophane insulin despite identically administered insulin doses.
 A questionnaire completed at the end of the study showed that two thirds of the children and/or their parents preferred the isophane insulin, and they gave perceived improvement of metabolic control as the major reason for their choice.
",17
2932,"Comparison of non-mydriatic retinal photography with ophthalmoscopy in 2159 patients: mobile retinal camera study 
 OBJECTIVE--To determine whether non-mydriatic Polaroid retinal photography was comparable to ophthalmoscopy with mydriasis in routine clinic screening for early, treatable diabetic retinopathy.
 DESIGN--Prospective study of ophthalmoscopic findings according to retinal camera screening and ophthalmoscopy and outcome of referral to ophthalmologist.
 SETTING--Outpatient diabetic clinics of three teaching hospitals and three district general hospitals.
 PATIENTS--2159 Adults selected randomly from the diabetic clinics, excluding only those registered as blind or those in wheelchairs and unable to enter the screening vehicle.
 MAIN OUTCOME MEASURES--Numbers of patients and eyes correctly identified by each technique as requiring referral with potentially treatable retinopathy (new vessel formation and maculopathy) and congruence in numbers of microaneurysms, haemorrhages, and exudates reported.
 RESULTS--Camera screening missed two cases of new vessel formation and did not identify a further 12 but indicated a need for referral.
 Ophthalmoscopy missed five cases of new vessel formation and indicated a need for referral in another four for other reasons.
 Maculopathy was reported in 147 eyes with camera screening alone and 95 eyes by ophthalmoscopy only (chi 2 = 11.2; p less than 0.001), in 66 and 29 of which respectively maculopathy was subsequently confirmed.
 Overall, 38 eyes received laser treatment for maculopathy after detection by camera screening compared with 17 after ophthalmoscopic detection (chi 2 = 8.0; p less than 0.01).
 Camera screening underestimated numbers of microaneurysms (chi 2 = 12.9; p less than 0.001) and haemorrhages (chi 2 = 7.4; p less than 0.01) and ophthalmoscopy underestimated hard exudates (chi 2 = 48.2; p less than 0.001).
 CONCLUSIONS--Non-mydriatic Polaroid retinal photography is at least as good as ophthalmoscopy with mydriasis in routine diabetic clinics in identifying new vessel formation and absence of retinopathy and is significantly better in detecting exudative maculopathy.
",17
2933,"D-xylose absorption test. Urine or blood?
 The D-xylose absorption test has been used during the last four decades for evaluation of malabsorption in the small intestine.
 However, some disagreement still exists about the recommended method of performing this test: the 1-hr blood test, the 5-hr urine test, or both.
 We evaluated the test by performing 125 combined blood and urine tests in 111 patients.
 Normal xylose absorption was recorded in both blood and urine in 71 tests (group A, 56.8%).
 Abnormal test results in both blood and urine were recorded in 29 patients (group B, 23.2%).
 Only one patient had a pathological blood value and normal xylose excretion in the urine.
 Twenty-four patients (group D, 19.2%) had normal 1-hr blood xylose (greater than 25 mg/100 ml) with abnormal 5-hr urine xylose (less than 4.5 g/5 hr).
 Fat and/or bile salt malabsorption were documented in 21 patients (87.5%) of this group using stool fat analysis and the [14C]cholylglycine breath test.
 These data suggest that in adults the 5-hr urine collection more accurately reflects intestinal absorption in comparison with the 1-hr blood value.
",17
2934,"BMY 30047: a novel topically active retinoid with low local and systemic toxicity.
 In the treatment of various dermatological disorders, topically applied retinoids have potential therapeutic use with the advantage of improved localized activity and lower toxicity over systemically administered retinoids.
 However, most retinoids cause a significant degree of local irritation.
 In the present study, the ability to produce local activity with low local irritation potential was evaluated with a novel retinoic acid derivative.
 BMY 30047 (11-cis, 13-cis-12-hydroxymethylretinoic acid delta-lactone) is one of a series of retinoic acid derivatives in which the carboxyl function of the polar end was modified with the aim of achieving reduced local irritation and systemic toxicity while retaining the local therapeutic effect.
 BMY 30047 was evaluated and compared with all-trans retinoic acid for topical retinoid activity in several preclinical assay systems, including the utricle reduction assay in rhino mice, 12-o-tetradecanoylphorbol 13-acetate ester-stimulated ornithine decarboxylase induction in hairless mice and the UV light-induced photodamaged skin model in hairless mice.
 BMY 30047 was assessed for retinoid-type side effects by evaluating the skin irritation potential in rabbits after repeated topical application, and hypervitaminosis A-inducing potential in mice after i.p.
 injection.
 BMY 30047 demonstrated significant topical retinoid activity in several in vivo models with less skin irritation potential relative to the most used clinical concentrations of all-trans retinoic acid.
 BMY 30047 also showed very little systemic activity and did not produce any evidence of hypervitaminosis A syndrome at systemic doses 20 times greater than the no-effect dose of all-trans retinoic acid.
",17
2935,"Metabolic alterations following continent urinary diversion through colonic segments.
 This study examined acid-base metabolism in patients with continent colonic urinary diversions and compared them to a control population.
 Diverted patients demonstrated mild acidosis and a urinary acidification defect.
 Ammonium chloride loading failed to demonstrate any major differences in the ability of these patients to handle an acute acid challenge.
 Continent colonic urinary diversions do not appear to create significant acid-base changes in patients with normal hepatic and renal function.
",17
2936,"Urinary bladder function 6 months after the onset of diabetes in the spontaneously diabetic BB rat.
 Urinary bladder function was examined in the spontaneously diabetic BB rat six months after the onset of diabetes.
 Diabetes caused significant decreases in rat weight and increases in bladder body weights and in vivo bladder capacities compared to age-matched controls, but no changes in the weights of bladder bases.
 The absolute contractile responses of urinary bladder body and base strips to nerve stimulation, carbachol, 5-hydroxytryptamine, ATP, phenylephrine, and KCl were unaltered by diabetes.
 However, when the data were corrected for tissue mass, there were slight but not significant decreases in contractile responses of strips from diabetic rats.
 There were increases in total muscarinic receptor numbers and calcium channel binding sites in bladder bodies from BB rats as a result of the increases in tissue mass.
 The data indicate that the six month-diabetic BB rat differs from the streptozotocin-diabetic rat in the sensitivity of the urinary bladder to the complications of diabetes, probably as a result of the insulin treatment required to keep BB rats alive.
",17
2937,"Comparison of the accuracy of glucose reflectance meters in pregnant insulin-dependent diabetics.
 Home monitoring of blood glucose by reflectance meters has been shown to be accurate in the nonpregnant diabetic and is currently used for outpatient glucose control in the pregnant diabetic as well.
 Beckman ASTRA glucose results from samples collected into sodium fluoride were used as the standard for this study.
 Comparisons were then made to four glucose reflectance meters: Accu-Check II, One Touch, DiaScan S, and ExacTech.
 Although the reflectance meters appeared to be useful for assessing blood glucose trends in the pregnant diabetic, the results obtained from these meters would be unacceptable in the laboratory setting.
 Unfortunately, because of the erratic combination of proportional and constant bias, correction factors are not easily ascertained.
 Laboratories and physicians should reconsider the use of these reflectance meters for inpatient evaluation and general population screening of pregnant women.
",17
2938,"Pharmacokinetics of ranitidine in morbidly obese women.
 The pharmacokinetics of a single dose of ranitidine 50 mg iv were determined in ten normal-weight and ten morbidly obese (greater than 90 percent ideal body weight) age-matched female subjects.
 No significant difference between normal and obese subjects was found in ranitidine peak serum concentration, volume of distribution, clearance, and elimination rate constant.
 Ranitidine volume of distribution and clearance were significantly smaller in the obese subjects per kilogram of total body weight (1.45 vs.
 0.80 L/kg and 0.59 vs.
 0.33 L/h/kg, respectively; p less than 0.001) but not when normalized to ideal body weight (1.65 vs.
 1.45 L/kg and 0.68 vs.
 0.59 L/h/kg).
 We conclude that obese patients receiving ranitidine therapy should be treated with standard dosages or dosages based on ideal body weight.
",17
2939,"Plasma lecithin-cholesterol acyltransferase activity and plasma lipoprotein composition and concentrations in kwashiorkor [published erratum appears in Am J Clin Nutr 1991 Sep;54(3):590]
 Plasma lecithin-cholesterol acyltransferase (LCAT) activity, lipoprotein composition, and lipoprotein concentrations were measured in 21 children with kwashiorkor before (day 1), during (day 10), and after treatment (day 30).
 Day 1 LCAT activity (78.2 mumol.L-1.h-1) was decreased with respect to day 10 (139.2 mumol.L-1.h-1, P less than 0.001) and day 30 (108.0 mumol.L-1.h-1, P = 0.08).
 Plasma total cholesterol (TC), cholesterol ester (CE), and lipoprotein CEs (VLDL, IDL, LDL, and HDL) were reduced relative to days 10 and 30 (P less than 0.001).
 Before treatment HDL composition was abnormal.
 On days 1, 10, and 30, the respective mean HDL-apolipoprotein A-I (apo A-I) concentrations were 23.33, 39.66, and 36.08 mumol/L.
 LDL-apo B concentrations were 0.40, 0.68, and 0.56 mumol/L (P less than 0.01, days 10 and 30 vs day 1).
 LDL particles on day 1 were decreased in number, depleted of CE, and laden with triacylglycerol and surface lipids.
 LCAT activity on day 1 correlated with LDL-CE linoleate (P less than 0.05, r = 0.48).
 Reduced plasma LCAT activity is an important factor related to abnormalities in lipoprotein composition and concentrations.
",17
2940,"Preprandial blood glucose values and glycemic responses in insulin-dependent diabetes mellitus at constant insulinemia.
 The influence of preprandial blood glucose (PPBG) concentration on glycemic responses was studied in seven subjects with insulin-dependent diabetes who, by means of the artificial pancreas, had achieved PPBG concentrations of 6, 9, and 17 mmol/L.
 A test meal of 50 g parboiled rice was given at the three different occasions and a constant insulin infusion was provided during the observation periods.
 The mean postprandial-blood-glucose-response area (above basal) differed significantly at the three blood glucose concentrations of 6, 9, and 17 mmol/L, reaching 1371, 621, and 179 mmol/L x 240 min, respectively (P less than 0.01).
 A negative correlation between the PPBG concentrations and the glycemic responses to the test meal was found (r = 0.94; P less than 0.001).
 The fasting insulin concentration at a PPBG concentration of 17 mmol/L was lower than at a PPBG concentration of 6 and 9 mmol/L.
 In conclusion, the glycemic responses to a carbohydrate meal are inversely correlated to the PPBG concentration in insulin-dependent diabetic subjects.
",17
2941,"Permanent muscle weakness in familial hypokalaemic periodic paralysis. Clinical, radiological and pathological aspects.
 Myopathy accompanying familial hypokalaemic periodic paralysis (HPP) is much less well documented than the paralytic attacks from which the disease derives its name.
 Eleven affected members of a large kinship with HPP were studied clinically and radiologically for the presence of myopathy.
 In 4 patients muscle biopsies were also performed and in 1 of them the histological findings obtained at autopsy were compared with the CT scans of various muscles.
 In another patient not previously biopsied, the specimens of both amputated legs were examined histologically.
 The age of the studied individuals ranged from 33 to 74 yrs.
 The 4 youngest patients showed no clinical signs of myopathy.
 However, in 2 of them CT scans demonstrated discrete hypodense lesions in the leg muscles, whereas in the other 2, muscle biopsies showed a vacuolar myopathy.
 The other 7 patients, all older than 50 yrs, presented both clinical and CT evidence of myopathy of proximal and distal muscles ranging from very mild to very severe, males being slightly more affected than females.
 In all 11 patients a mean CT grading was made that was based on the abnormalities found in the different muscle groups.
 The myopathy appeared to be unrelated to the history of paralytic attacks, but a strong correlation was found between age and mean CT grading.
 It was concluded that HPP is a myopathy with permanent muscle weakness of late onset in all the patients.
 The expression of the paralytic attacks is variable.
",17
2942,"Treatment of NIDDM with insulin agonists or substitutes.
 Non-insulin-dependent diabetes mellitus (NIDDM) is a common disorder occurring in 3-6% of adults in most western populations.
 In the United States, 29% of patients with diabetes take insulin; of these, 76% have NIDDM.
 Insulin therapy is usually required at some time in NIDDM.
 Insulin therapy improves the abnormalities of NIDDM (reduced beta-cell function, increased hepatic glucose production, reduced peripheral glucose disposal, lipid abnormalities).
 Insulin and sulfonylurea agents have comparable effects on mild forms of NIDDM, but for more severe forms, insulin is usually superior.
 Combination insulin-sulfonylurea treatment may improve the response to sulfonylureas, although long-term well-controlled trials have not been conducted.
 Short-term insulin treatment may restore response to sulfonylureas.
 Other promising treatments (human proinsulin, nasal insulin, somatostatin) have not shown any advantage over conventional insulin therapy.
 Insulin causes hypoglycemia and peripheral hyperinsulinemia.
 The hazards of hyperinsulinemia, e.g., weight gain and hypoglycemia, have been overstated, and questions about its atherogenic effects remain to be resolved.
 The effect of glycemic control on macro- and microvascular complications has not been established; however, maintaining fasting blood glucose levels of less than 6.7 mM may protect against progression of retinopathy, neuropathy, and nephropathy and reduce the severity of ischemic stroke.
 Dosage algorithms generally use intermediate- or long-acting insulin to control basal glycemia, with regular insulin added before meals if needed to control postprandial glycemia.
 Effective therapy depends on the patient being informed, cooperative, and willing to self-monitor blood glucose.
 Insulin treatment intermittency increases the risk for immune complications (resistance and allergy).
 Overall, patients with NIDDM can benefit from insulin therapy.
",17
2943,"Insulin use in NIDDM.
 The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein.
 Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function.
 These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality.
 Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms.
 In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin.
 A key goal of insulin therapy is to normalize the fasting plasma glucose level.
 In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime.
 Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control.
 In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both.
 However, long-term benefits from such combination therapy remain to be demonstrated conclusively.
 Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain.
 Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia.
 Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial.
 A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension.
 Although potential mechanisms for an atherogenic action of insulin exist, current evidence does not prove cause and effect and does not warrant withholding insulin therapy (or compromising on dosage) when it is needed.
",17
2944,"Intensive insulin therapy for treatment of type I diabetes.
 Intensive insulin therapy is best defined as a comprehensive system of diabetes management with the patient and management team as partners.
 The system is directed at improvement of glycemia and patient well-being.
 Glycemic targets should be individually defined.
 Frequent self-monitoring of blood glucose, probably at least four times per day, is essential for meticulous control.
 The benefits include improved psychosocial functioning and the potential of lessening the risks of chronic complications of diabetes.
 The risks relate to problems associated with hypoglycemia, which are increased if meticulous glycemic control is sought.
 One of the important elements of intensive therapy is a multiple-component insulin program designed to provide effective insulinemia coinciding with each major meal and continuous basal insulinemia throughout the 24-h day.
 This may be achieved with continuous subcutaneous insulin infusion (CSII) or multiple injections with various insulin regimens, although CSII may offer real advantages in terms of the pharmacokinetics of insulin delivery.
 Other pharmacokinetic issues to be considered involve selection of injection sites, timing of premeal insulin, and mixing insulins.
 Many studies have shown that, albeit with effort, excellent glycemic control can be achieved by various intensive insulin-therapy regimens.
 The implementation of a program of intensive therapy involves patient self-management in terms of altering insulin dosages, food intake, and/or activity in an attempt to achieve the target level of glycemia selected.
 In motivated patients willing to embark on such a course of therapy, intensive insulin therapy can be worthwhile.
 It should be considered for all patients with type I (insulin-dependent) diabetes mellitus.
",17
2945,"Retinoic acid is able to reinitiate spermatogenesis in vitamin A-deficient rats and high replicate doses support the full development of spermatogenic cells.
 The effect of various doses of retinoic acid (RA) on the seminiferous epithelium in vitamin A-deficient rats has been studied.
 Although it was generally thought that RA was not able to reinitiate spermatogenesis in vitamin A-deficient rats, one injection of 5 mg RA strongly stimulated the proliferative activity of A-spermatogonia within 24 h, as evidenced by a 7-fold increase in the number of bromodeoxyuridine-labeled A-spermatogonia.
 Ten days after RA administration, B-spermatogonia or preleptotene spermatocytes were seen in most of the seminiferous tubules.
 After 15 days, zygotene spermatocytes were present.
 Hence, RA is able to induce a massive and synchronized development of A-spermatogonia into spermatocytes.
 When RA was given once, combined with a RA-containing diet, only few of the zygotene spermatocytes present on day 15 were able to develop into pachytene spermatocytes, which did not develop into spermatids.
 In subsequent epithelial cycles new B-spermatogonia and spermatocytes were formed, although in lower numbers than during the first cycle after RA injection.
 When RA was given once a week, the formation of B-spermatogonia and preleptotene spermatocytes continued at a higher level.
 Also, more pachytene spermatocytes were formed, some of which were able to develop into spermatids.
 Finally, when RA was injected twice a week, even more pachytene spermatocytes and round spermatids were found after 36 days, and after 49 days elongated spermatids were found in all animals.
 It is concluded that RA, similar to retinol, is able to induce synchronous proliferation and differentiation of A-spermatogonia.
 When repeated injections are given, RA is able to support the full development of spermatogenic cells into elongated spermatids.
",17
2946,"Failure of insulin-like growth factor-I (IGF-I) infusion to promote growth in protein-restricted rats despite normalization of serum IGF-I concentrations.
 Dietary protein restriction in young rats induces GH resistance characterized by growth arrest and low serum insulin-like growth factor-I (IGF-I) concentrations.
 To determine whether the low serum IGF-I concentrations are responsible for the stunted growth, we infused 4-week-old protein-restricted rats with recombinant human IGF-I (300 micrograms/day) or rat GH (200 micrograms/100 g body wt/day) by osmotic minipump for 1 week.
 Despite the normalization of serum IGF-I concentrations by IGF-I infusion, carcass growth was not stimulated.
 In contrast, growth of the spleen and kidney was enhanced (+45% and +28%, respectively).
 Serum IGF-binding protein 3 (IGFBP-3), the principal carrier of IGF-I in the serum at this age, is decreased by 34% in protein-restricted animals and restored to normal by IGF-I infusion.
 Contrary to the selective effects of IGF-I on growth of protein-restricted rats, well nourished hypophysectomized rats infused with 150 micrograms/day recombinant human IGF-I showed a significant growth response, including carcass and organ growth and normalization of IGFBP-3 values.
 These responses indicate that our IGF-I preparation and mode of delivery were effective.
 We conclude that: 1) dietary protein restriction causes organ-specific resistance to the growth-promoting properties of exogenous IGF-I; 2) IGF-I mediates the stimulatory effects of growth hormone on IGFBP-3 synthesis; and 3) the absence of carcass growth in the presence of normal serum IGF-I concentrations during infusion of IGF-I suggests that the growth arrest that accompanies protein restriction is mediated in part by resistance to IGF-I.
",17
2947,"Pituitary insulin-like growth factor-I content and gene expression in the streptozotocin-diabetic rat: evidence for tissue-specific regulation.
 Insulinopenic diabetes mellitus in the rat is associated with reduced circulating levels of insulin-like growth factor-I (IGF-I), resulting primarily from decreased IGF-I synthesis in liver and extrahepatic sites.
 Plasma GH levels in these animals are also suppressed, with loss of episodic secretion and decreased pituitary synthesis.
 Intrapituitary IGF-I has been postulated to exert local autocrine/paracrine negative feedback regulation on GH synthesis and secretion.
 The present studies were designed to examine regulation of pituitary IGF-I peptide content and gene expression in insulinopenic streptozotocin (STZ)-diabetic rats compared to that in liver and testis.
 Serum IGF-I levels were reduced by 86% in STZ-diabetic rats together with reduction of IGF-I content in liver (53%) and testis (74%; all P less than 0.001 vs.
 control).
 Concomitantly, liver and testicular IGF-I mRNA levels were reduced by 90% (P less than 0.001 vs.
 control).
 Insulin treatment restored IGF-I peptide levels in serum, liver, and testis toward normal, with a partial but significant increase in liver IGF-I mRNA.
 In contrast, pituitary IFG-I peptide content increased by 69% in STZ-diabetic rats (P less than 0.001 vs.
 control), with no change in IGF-I gene expression.
 Insulin treatment completely reversed the rise of pituitary IGF-I peptide content.
 These results demonstrate a novel discordance in the regulation of IGF-I gene expression and peptide content between pituitary and other tissues in STZ-induced diabetic rats.
 Elevated IGF-I levels in the pituitaries of these animals may partly explain the suppressed GH synthesis and secretion seen in STZ-diabetic rats and provide further evidence for a potential autocrine or paracrine role of pituitary IGF-I in GH regulation.
",17
2948,"Cerebrospinal fluid losses through ventricular catheters leading to hyponatremia in two children.
 I have presented two cases of patients with hyponatremia due to excessive cerebrospinal fluid losses from ventricular drains.
 The possibility of such losses exists whether the drain is used to treat hydrocephalus or to monitor intracranial pressure.
 I find normal saline (sodium concentration = 154 mEq/L) to be an appropriate fluid to replace ongoing losses of cerebrospinal fluid from a ventricular drain and currently start such replacement therapy (mL for mL) when the drain is placed.
",17
2949,"Effects on serum lipids of adding instant oats to usual American diets.
 This study was designed as a test of the serum lipid response and dietary adaptation to recommended daily inclusion of instant oats in an otherwise regular diet.
 Hypercholesterolemic adults were randomly assigned to a control or intervention group.
 Participants in the intervention group were given packages of instant oats and requested to eat two servings per day (approximately two ounces dry weight), substituting the oats for other carbohydrate foods in order to maintain baseline calorie intake and keep weight stable.
 Serum lipids were measured in blood collected by venipuncture at baseline, four weeks, and eight weeks.
 Baseline mean total cholesterol (TC) levels were 6.56 mmol/L and 6.39 mmol/L for intervention and control groups, respectively.
 After eight weeks, mean serum total cholesterol of the intervention group was lower by -0.40 mmol/L, and mean net difference in TC between the two groups was 0.32 mmol/L (95% CI: 0.09, 0.54).
 Low-density lipoprotein-cholesterol was similarly reduced with mean net difference of 0.25 mmol/L (95% CI: 0.02, 0.48) between the two groups.
 Mean soluble fiber intake increased along with slight self-imposed reductions in mean total fat, saturated fat, and dietary cholesterol intake in the intervention group.
 Neither group changed mean body weight.
 Daily inclusion of two ounces of oats appeared to facilitate reduction of serum total cholesterol and LDL-C in these hyperlipidemic individuals.
",17
2950,"Microcirculation and hemorheology in NIDDM patients.
 The authors studied 10 patients with non-insulin-dependent diabetes mellitus and 5 controls matched for age, sex, blood lipids, and smoking habit.
 The two groups were also comparable for hemorheologic characteristics as evaluated by viscosimetry on whole blood, plasma and serum, erythrocyte filtration and aggregation.
 The microcirculation was studied in the subjects of both groups by microalbuminuria determination, retinal fluorangiography, and capillaroscopic examination of the bulbar conjunctive and nail folds.
 None of the patients presented microalbuminuria values higher than the upper limit of normal (20mg/24h).
 Fluoroangiographic alterations were observed in 4 patients, and all 10 presented capillaroscopic alterations at the bulbar conjunctiva (microaneurysms, erythrocyte aggregates) and nail folds (more frequently of the fingers than toes).
 Similar alterations were detected in controls.
 Thus these abnormalities seem independent of hemorheologic values.
",17
2951,"Putative mechanisms of the impairment of endothelium-dependent relaxation of the aorta with atheromatous plaque in heritable hyperlipidemic rabbits.
 Attenuation of acetylcholine-induced endothelium-dependent relaxation of thoracic aortas excised from Watanabe heritable hyperlipidemic (WHHL) rabbits linearly correlated with the percent area coated with atheromatous plaque.
 To elucidate mechanisms related to this reduced endothelium-dependent relaxation in the presence of atherosclerosis, the acetylcholine-induced release of endothelium-derived relaxing factor (EDRF) was assessed functionally as a percent relaxation of the precontracted detector strips obtained from the tunica media beneath the intact intima or the atheromatous plaque in the same aortic ring preparation.
 Relaxations of the normal detectors to effluents containing EDRF of thoracic aortas during stimulation by acetylcholine (3 x 10(-6) M) in heterozygous and homozygous WHHL rabbits were 73 +/- 5% and 59 +/- 9% (p less than 0.01) of the phenylephrine-induced precontraction, respectively.
 Relaxations of the atherosclerotic detectors to effluents (EDRF) through the aortas during stimulation by acetylcholine (3 x 10(-6) M) in heterozygous and homozygous WHHL rabbits were 16 +/- 4% and 14 +/- 5%, respectively--values significantly smaller than those seen in the normal detectors.
 When superoxide dismutase was added to the perfusate of the donors from homozygous and heterozygous WHHL rabbits, atherosclerotic detectors relaxed by effluents stimulated by acetylcholine to 73% and 65% (p less than 0.01 versus before the addition of superoxide dismutase) of the normal detector, respectively.
 Relaxations induced by sodium nitroprusside as well as the contractions by acetylcholine, phenylephrine, and KCl (118 mM) were comparable in detector strips from the normal and atherosclerotic portions.
 Thus, not only is the amount of EDRF released by acetylcholine reduced in the presence of atherosclerosis, the tunica media beneath the atheromatous plaque is also to some extent responsible for the superoxide-induced inactivation of EDRF.
",17
2952,"Enhancing blood glucose awareness in adolescents and young adults with IDDM.
 OBJECTIVE: To determine the effectiveness of an intervention program designed to improve blood glucose awareness.
 RESEARCH DESIGN AND METHODS: Eight young-adult outpatients (mean age 22 yr) and six adolescent inpatients (mean age 14.5 yr) with insulin-dependent diabetes mellitus participated in the intervention program.
 Nine adolescent inpatients (mean age 13.9 yr) served as an untreated comparison group.
 One adult outpatient with unreliable data was removed.
 Before treatment, each patient completed a minimum of 40 blood glucose estimations, blood glucose tests, and symptom-rating checklists.
 Symptoms of hypo- or hyperglycemia were identified for each patient.
 The three-session intervention focused on internal (e.g., personal symptoms) and external (e.g., timing and amount of insulin, food, and exercise) cues that could be used to enhance blood glucose awareness.
 At postintervention, patients completed a minimum of 40 additional blood glucose estimates and tests.
 Comparison subjects completed the pre-postassessments but did not receive the intervention.
 RESULTS: Blood glucose estimation accuracy was evaluated with error grid analysis.
 All estimated-actual blood glucose values were plotted into one of five zones: accurate estimates (zone A), benign errors (zone B), and clinically dangerous errors (zones C, D, and E).
 An overall accuracy index (AI) was calculated by subtracting the summed percentage of clinically dangerous estimates (zones C, D, and E) from the percentage of accurate estimates (zone A).
 At study entry, the adolescent inpatients' mean AI of 7% was significantly poorer than the 32% mean AI exhibited by the outpatient young-adult sample (P less than 0.02).
 At postintervention, the adolescents' mean AI improved to 30% (P less than 0.02) and the young adults' mean outpatient AI improved to 45% (P less than 0.06).
 The treated sample as a whole exhibited increased sensitivity to both hypo- (P less than 0.005) and hyperglycemia (P less than 0.05).
 Similar improvements did not occur in the untreated comparison sample.
 CONCLUSIONS: Adolescents may exhibit poorer blood glucose awareness than adults.
 Although this intervention program improved blood glucose awareness in both adolescent and adult patients, postintervention blood glucose estimation accuracy remained far from ideal.
",17
2953,"Racial differences in metabolic control of children and adolescents with type I diabetes mellitus.
 OBJECTIVE: This study evaluated racial differences in the metabolic control of children and adolescents with insulin-dependent (type I) diabetes mellitus and examined the interactive effects of race with age and sex.
 RESEARCH DESIGN AND METHODS: Data on several demographic and clinical variables were obtained for 102 black and 108 white children, including the percentage of total HbA1, age, age at diagnosis, duration of diabetes, pubertal status, insulin dose (U.kg-1.day-1), body mass index, number of clinic visits kept and missed, number of hospitalizations for diabetic ketoacidosis (DKA) for the year, and socioeconomic status (SES).
 RESULTS: Black children had higher insulin dosages (P less than 0.05) and lower SESs (P less than 0.001) than white children.
 HbA1 was higher in black than white children (P less than 0.01) after statistically adjusting for the effects of insulin dose, diabetes duration, and SES.
 With HbA1-based criteria, more black than white children were in poor and fewer in good metabolic control (P less than 0.001).
 Older children (greater than or equal to 13 yr) had higher HbA1 levels than younger (less than 13 yr) children (P less than 0.002), but there were no differences in HbA1 between males and females nor were there interactive effects of race, sex, and age-group.
 Black children were hospitalized for DKA more frequently than white children (P less than 0.04).
 More black than white children missed clinic visits (P less than 0.01), but they did not differ in number of visits kept.
 CONCLUSIONS: Black youths with type I diabetes mellitus are in poorer metabolic control than white youths.
",17
2954,"Demonstration of insulin transformation products in insulin vials by high-performance liquid chromatography.
 OBJECTIVE: To assess the importance of temperature, light, agitation, and regular withdrawal of insulin on the rates of appearance of three groups of insulin transformation products (ITPs) in vials of human and beef soluble insulin.
 RESEARCH DESIGN AND METHODS: Twelve insulin-treated patients (6 receiving human soluble insulin, 6 receiving beef soluble insulin) participated in the study.
 Reverse-phase high-performance liquid chromatography was used to measure ITP in serial samples from vials stored in various laboratory environments or issued to patients.
 Vials in the laboratory were analyzed on nine occasions over 26 wk; those issued to patients were analyzed weekly.
 RESULTS: Results were expressed as rates of change (% total protein/wk).
 Except for human insulin stored at 4 degrees C, sampling did not accelerate transformation.
 Storage at higher temperatures caused more rapid transformation to all ITP groups, and human insulin was more susceptible than beef insulin.
 Exposure to light accelerated transformation mainly to group 3 ITP.
 Fibrillation occurred in beef but not human insulin carried in a shirt pocket.
 Results from patients' vials were consistent with reported storage conditions.
 CONCLUSIONS: All three ITP groups form in human and beef soluble insulin.
 Their rate of production is a function of temperature and light exposure.
 Differences between the two insulins were probably due to differences in formulation.
 Patients should be discouraged from hoarding vials and storing insulin in direct sunlight.
 One or more ITPs could contribute to the residual immunogenicity of modern insulin preparations.
",17
2955,"International evaluation of cause-specific mortality and IDDM. Diabetes Epidemiology Research International Mortality Study Group.
 OBJECTIVE: A cross-cultural study was completed to evaluate differences in mortality patterns in four population cohorts in Japan; Israel; Allegheny County, Pennsylvania; and Finland.
 RESEARCH DESIGN AND METHODS: Cases were diagnosed between 1 January 1965 and 31 December 1979.
 Mortality was determined as of 1 January 1985.
 There were 147 deaths occurring in the 8212 insulin-dependent diabetes mellitus (IDDM) patients in the four countries.
 A standardized protocol for assessing causes of death (cause-specific mortality) was developed; in this article, we report the causes.
 RESULTS: Major overall mortality differences by country appeared, with IDDM subjects in Japan much more likely to die than in the other countries.
 In Japan, the elevated mortality was the result of acute diabetes-related complications and kidney disease.
 For all countries, mortality from acute diabetes-related complications accounted for a surprisingly high percentage of deaths (greater than 25% in each country).
 A larger percentage of cases in Finland died as a result of suicide than for the other three countries.
 CONCLUSIONS: The results suggest that there are major cross-country differences in cause-specific mortality and that much of the premature mortality associated with diabetes is potentially preventable.
",17
2956,"Superiority of radiobinding assay over ELISA for detection of IAAs in newly diagnosed type I diabetic children.
 OBJECTIVE: Liquid- or solid-phase assays have been used for insulin autoantibody (IAA) determination, and the method of IAA measurement has not been standardized.
 RESEARCH DESIGN AND METHODS: IAAs were determined by radiobinding assay (RBA) and enzyme-linked immunosorbent assay (ELISA) in two large age-matched groups of nondiabetic and newly diagnosed insulin-dependent (type I) diabetic children.
 RESULTS: Positivity for IAA by RBA (greater than or equal to nondiabetic mean + 3SD) was 2 of 178 (1.1%) and 55 of 173 (32%) in nondiabetic and diabetic children, respectively.
 Prevalence of IAA by RBA was significantly higher in the youngest age-group (63% between 0-4 yr).
 Positivity for IAA by ELISA was 1 of 178 (0.6%) and 8 of 169 (4.7%) in nondiabetic and diabetic children, respectively.
 Concordance rates between both assays were 0 of 3 (0%) in control subjects and 5 of 58 (8.6%) in diabetic children.
 CONCLUSIONS: We conclude that RBA is more appropriate than ELISA for IAA detection at the onset of the disease.
 In addition, because available data suggest that IAAs detected by RBA only are high-affinity antibodies, it is tempting to speculate that IAAs reflect a mature immune reaction against endogenous insulin.
",17
2957,"Vitamin E reduction of protein glycosylation in diabetes. New prospect for prevention of diabetic complications?
 OBJECTIVE: This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E.
 RESEARCH DESIGN AND METHODS: Two groups of 10 insulin-requiring diabetic patients, matched for duration of disease and metabolic control, received daily vitamin E supplementation of 1200 and 600 mg, respectively, for 2 mo.
 A third group of 10 diabetic patients, matched for duration of disease and metabolic control, served as the control group and received placebo.
 Fasting plasma glucose, mean daily plasma glucose, fasting labile HbA1, and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment.
 In addition, hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients.
 RESULTS: Glycemic indices did not show any significant changes during the study, whereas fasting labile HbA, and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration.
 Stable HbA1 decreased after 2 mo.
 Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment, whereas a significant reduction in mean labile HbA1 incremental area was found after vitamin E supplementation.
 A significant difference was also found in both fasting and incremental labile HbA1 levels, stable HbA1, and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E; the diabetic patients who received the higher dose of vitamin E showed the greater reduction.
 No significant changes in these parameters were observed in diabetic patients on placebo administration.
 CONCLUSIONS: These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation, the first step of the Maillard reaction.
 Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications.
",17
2958,"Archaeology of NIDDM. Excavation of the ""thrifty"" genotype.
 Since the 1940s, numerous cases of non-insulin-dependent diabetes mellitus (NIDDM) have been observed in certain American Indian populations.
 Extremely high prevalence rates of NIDDM occur most strikingly in several tribes of Paleo-Indians, whose ancestors migrated to North America greater than 11,000 yr ago.
 Archaeological evidence from that period indicates that certain groups of Paleo-Indians maintained an arctic-like hunter-gatherer life-style in an area in temperate North America ranging from Wyoming to Arizona.
 This life-style featured a reliance on unpredictable big game species as a major food source.
 However, at this time, big game species were becoming extinct.
 It is hypothesized that those Paleo-Indians who relied on big game as a food source developed a ""thrifty"" genotype that allowed a selective advantage during the periods of fasting that occurred between big game kills.
 It also is hypothesized that this thrifty genotype in these Indians may contribute to NIDDM when a sedentary life-style is adopted and food sources are constant.
 Because insulin resistance in muscle is a major feature of NIDDM, it is possible that insulin resistance per se is the phenotypic expression of the thrifty genotype.
",17
2959,"Banting lecture 1990. Beta-cells in type II diabetes mellitus.
 In 1960, immunoassays of insulin first demonstrated significant quantities of circulating hormone in non-insulin-dependent (type II) diabetes and for 30 yr have fostered debate as to whether a beta-cell abnormality plays an etiological role in this syndrome.
 Early efforts to determine the adequacy of islet beta-cell function showed that obesity and its associated insulin resistance were major confounding variables.
 Subsequently, it was recognized that glucose not only directly regulated insulin synthesis and secretion but moderated all other islet signals, including other substrates, hormones, and neural factors.
 When both obesity and glucose are taken into account, it becomes clear that patients with fasting hyperglycemia all have abnormal islet function.
 Type II diabetes is characterized by a defect in first-phase or acute glucose-induced insulin secretion and a deficiency in the ability of glucose to potentiate other islet nonglucose beta-cell secretagogues.
 The resulting hyperglycemia compensates for the defective glucose potentiation and maintains nearly normal basal insulin levels and insulin responses to nonglucose secretagogues but does not correct the defect in first-phase glucose-induced insulin release.
 Before the development of fasting hyperglycemia, only first-phase glucose-induced insulin secretion is obviously defective.
 This is because progressive islet failure is matched by rising glucose levels to maintain basal and second-phase insulin output.
 The relationship between islet function and fasting plasma glucose is steeply curvilinear, so that there is a 75% loss of beta-cell function by the time the diagnostic level of 140 mg/dl is exceeded.
 This new steady state is characterized by glucose overproduction and inefficient utilization.
 Insulin resistance is also present in most patients and contributes to the hyperglycemia by augmenting the glucose levels needed for compensation.
 Decompensation and absolute hypoinsulinemia occur when the renal threshold for glucose is exceeded and prevents further elevation of circulating glucose.
 The etiology of the islet beta-cell lesion is not known, but a hypothesis based on basal hyperproinsulinemia and islet amyloid deposits in the pancreas of type II diabetes is reviewed.
 The recent discovery of the islet amyloid polypeptide (IAPP) or amylin, which is the major constituent of islet amyloid deposits, is integrated into this hypothesis.
 It is suggested that pro-IAPP and proinsulin processing and mature peptide secretion normally occur together and that abnormal processing, secondary to or in conjunction with defects in hormone secretion, lead to progressive accumulation of intracellular IAPP and pro-IAPP, which in cats, monkeys, and humans form intracellular fibrils and amyloid deposits with a loss of beta-cell mass.(ABSTRACT TRUNCATED AT 400 WORDS).
",17
2960,"Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans.
 To test the hypothesis that hypoglycemia itself causes reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia, we measured those responses during clamped hypoglycemia (2.8 mM) on consecutive mornings on two occasions, with interval afternoon (1400-1600) hypoglycemia (3 mM) on one occasion and interval afternoon euglycemia (5 mM) on the other, in nine nondiabetic humans.
 None of the measured responses were reduced by interval euglycemia.
 In contrast, plasma epinephrine (P less than 0.005), glucagon (P less than 0.005), pancreatic polypeptide (P less than 0.01), cortisol (P less than 0.02), and total (P less than 0.001), neurogenic (P less than 0.001) and neuroglycopenic (P less than 0.05) symptom responses to morning hypoglycemia were reduced after interval afternoon hypoglycemia.
 Thus, a single episode of hypoglycemia caused a generalized reduction of the neuroendocrine and symptomatic responses to subsequent hypoglycemia, a finding that may be important to the pathogenesis of iatrogenic hypoglycemia in insulin-dependent diabetes mellitus.
",17
2961,"Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin.
 In islets from adult rats injected with streptozocin during the neonatal period, the oxidative and secretory responses to D-glucose are more severely affected than those evoked by L-leucine.
 A possible explanation for such a preferential defect was sought by comparing the rate of aerobic glycolysis, taken as the sum of D-[3,4-14C]glucose conversion to labeled CO2, pyruvate, and amino acid, with the total glycolytic flux, as judged from the conversion of D-[5-3H]glucose to 3H2O.
 A preferential impairment of aerobic relative to total glycolysis was found in islets from diabetic rats incubated at either low or high D-glucose concentration.
 This coincided in islet mitochondria of diabetic rats with a severe decrease in both the basal (no-Ca2+) generation of 3H2O from L-[2-3H]glycerol-3-phosphate and the Ca2(+)-induced increment in [3H]glycerophosphate detritiation.
 The mitochondria of diabetic rats were also less efficient than those of control animals in generating 14CO2 from [1-14C]-2-ketoglutarate.
 The diabetes-induced alteration of 2-ketoglutarate dehydrogenase in islet mitochondria was less marked, however, than that of the FAD-linked glycerophosphate dehydrogenase and was not associated with any change in responsiveness to Ca2+.
 Sonicated islet mitochondria of diabetic rats displayed normal to slightly elevated glutamate dehydrogenase activity.
 We propose, therefore, that the preferential impairment of the oxidative and secretory responses of islet cells to D-glucose in this experimental model of diabetes may be at least partly attributable to an altered transfer of reducing equivalents into the mitochondria as mediated by the glycerol phosphate shuttle.
",17
2962,"Effects of PP-56 and vitamin E on platelet hyperaggregability, fatty acid abnormalities, and clinical manifestations in streptozocin-induced diabetic rats.
 The effects of vitamin E and D-myo-inositol 1,2,6-trisphosphate (PP-56) were investigated in long-term studies in streptozocin-induced diabetic rats fed a purified diet with 33% lipids and a polyunsaturated-to -saturated fatty acid ratio of 1.
 A supplement of vitamin E decreased plasma triglycerides, platelet lipid biosynthesis, some of the delta 6- and delta 5-desaturase abnormalities, and urine ketone bodies but did not affect the response of platelets to aggregation.
 PP-56 completely normalized the platelet reactivity to ADP and thrombin.
 This was accompanied by normalization of platelet lipid biosynthesis and diabetes-induced abnormalities in delta 6- and delta 5-desaturases.
 PP-56 treatment also reduced the mortality rate and to a certain extent urinary ketone bodies.
 The protective effect of PP-56 on platelet aggregation and mortality rate were dose related.
 PP-56, a molecule derived from phytic acid, seems to exert potent protective effects on some of the manifestations associated with diabetes in rats.
",17
2963,"Insulin-receptor cDNA sequence in NIDDM patient homozygous for insulin-receptor gene RFLP.
 Resistance to insulin action is a well-established feature of non-insulin-dependent diabetes mellitus (NIDDM) and is believed to contribute to the etiology of this condition.
 A strong genetic contribution to the etiology of NIDDM exists, and we previously identified an insulin-receptor gene restriction-fragment-length polymorphism (RFLP) associated with the NIDDM phenotype.
 In an attempt to elucidate whether structural defects in the insulin receptor could be a primary cause of insulin resistance in NIDDM, we analyzed the insulin-receptor cDNA sequence in a subject with NIDDM who is also homozygous for this RFLP.
 The insulin-receptor cDNA was sequenced with the polymerase chain reaction (PCR).
 mRNA from transformed lymphocytes was reverse transcribed and amplified with five overlapping sets of primers that span the coding sequence of both alpha- and beta-subunits.
 No difference was found in the predicted amino acid sequence of the subject's insulin receptor compared with the normal insulin receptor.
 At nucleotide positions 831 and 2247, the subject is heterozygous for silent nucleotide polymorphisms that do not affect the amino acid sequence.
 Exon 11 encodes a 12-amino acid insert in the alpha-subunit, which, due to alternate splicing, is not expressed in lymphocyte insulin-receptor mRNA.
 Consequently, exon 11 was amplified from genomic DNA by PCR; the sequence of exon 11 was found to be normal.
 In addition, when this patient's transformed lymphocytes were maintained in culture, no abnormalities in insulin binding were observed.
 We conclude that the insulin resistance seen in this NIDDM subject is not due to a structural alteration in the insulin receptor itself.
",17
2964,"Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patient with insulin resistance and NIDDM.
 Although non-insulin-dependent diabetes mellitus (NIDDM) is associated with defects in insulin action, the molecular basis of this resistance is unknown.
 We studied fibroblasts from a markedly insulin-resistant patient with NIDDM but without acanthosis nigricans.
 Her fibroblasts were resistant to insulin when alpha-aminoisobutyric acid uptake was measured.
 Fibroblasts from this patient demonstrated normal insulin-receptor content as measured by both insulin-receptor radioimmunoassay and by Scatchard analysis.
 However, when compared with nondiabetic control subjects, insulin-receptor kinase assays of wheat-germ-purified receptors prepared from her fibroblasts showed very low basal and no insulin-stimulated tyrosine kinase activity.
 The insulin receptor was then removed from the wheat-germ fraction by monoclonal antibody affinity chromatography.
 This insulin-receptor-deficient fraction inhibited both basal and insulin-stimulated tyrosine kinase activity of highly purified insulin receptors.
 When the specificity of this inhibition was tested, less inhibition was seen with insulinlike growth factor I-receptor tyrosine kinase, and even less inhibition was seen with the proto-oncogene p60c-src tyrosine kinase.
 Thus, these studies indicate that fibroblasts from an insulin-resistant patient with NIDDM produce a relatively specific glycoprotein inhibitor of insulin-receptor tyrosine kinase.
 Therefore, these studies raise the possibility that this inhibitor may play an important role in the insulin resistance seen in this patient.
",17
2965,"Effects of glucagon on free fatty acid metabolism in humans.
 To determine whether physiological changes in plasma glucagon concentrations are important in regulating basal adipose tissue lipolysis, FFA flux ([1-14C]palmitate) was measured in response to increases and decreases in plasma glucagon.
 Eight volunteers with insulin-dependent diabetes mellitus (IDDM) and nine healthy nondiabetic volunteers were studied using the pancreatic clamp technique to control plasma insulin, GH, and glucagon concentrations at desired levels.
 Palmitate flux at the chosen euglucagonemic hormone infusion rates was similar to baseline values (1.73 +/- 0.12 vs.
 1.75 +/- 0.23 and 1.35 +/- 0.18 vs.
 1.35 +/- 0.16 mumol/kg.min, respectively, in IDDM and nondiabetic subjects).
 No significant changes in palmitate flux occurred in response to glucagon withdrawal or mild (nondiabetic volunteers) or high physiological (IDDM volunteers) hyperglucagonemia.
 Thus, under conditions of normal FFA availability, changes in plasma glucagon concentrations within the physiological range have little or no effect on adipose tissue lipolysis.
",17
2966,"Acute changes in serum osteocalcin during induced hypocalcemia in humans.
 Although levels of serum osteocalcin are thought to be an indicator of osteoblastic activity and bone formation, there is little information regarding the acute effects of changes in calcium or PTH levels on circulating osteocalcin concentrations.
 To study the effect of stepwise decreases in ionized calcium (CaI) on osteocalcin levels, we infused six normal subjects with citrate for four 30-min intervals using two different protocols.
 One protocol (pulse infusion) used alternating rates of infusion and resulted in rapid stepwise decrements in serum CaI.
 The second protocol (continuous infusion) used constant intermediate rates of citrate infusion and produced slower decrements in CaI, but with similar changes in magnitude.
 We monitored serum CaI, intact PTH, and osteocalcin concentrations during the course of these infusions.
 During each step of the pulse infusion the osteocalcin responses to changes in CaI in general were parallel to the changes in PTH (r = 0.462; P = 0.02) and were inversely correlated to CaI (r = -0.562; P = 0.003).
 The osteocalcin concentrations at the end of each 30-min period were higher than at the beginning of that period; over the total 120 min, osteocalcin levels rose from 3.46 +/- 0.63 to 6.88 +/- 1.08 micrograms/L (P less than 0.05).
 In contrast, during the first two periods of the continuous infusion, osteocalcin concentrations changed slightly.
 Only during the last two periods of the continuous infusion did osteocalcin respond in a manner characteristic of that observed with the pulse infusion.
 These data indicate that osteocalcin concentrations in the circulation may be acutely regulated by calcium and/or PTH.
",17
2967,"Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes.
 To define the spontaneous diurnal variations in glucose regulation during fasting in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11 patients with untreated diabetes and 7 matched control subjects studied during a 24-h period.
 The rates of insulin secretion were derived from the concentrations of C-peptide by deconvolution using a two-compartment mathematical model for C-peptide distribution and metabolism.
 In both groups of subjects, despite continued fasting, glucose levels stopped declining in the evening and subsequently rose throughout the night to reach a morning maximum.
 Elevated levels persisted until noon.
 The morning glucose maximum corresponded to a relative increase of 23.8 +/- 5.5% above the evening nadir in NIDDM patients and 13.2 +/- 4.6% in nondiabetic subjects (P less than 0.05).
 In NIDDM patients, insulin levels and insulin secretion rates did not parallel the nocturnal glucose changes.
 In contrast, in control subjects, this nocturnal glucose rise coincided with a similar increase in insulin secretion rates.
 Cortisol concentrations in patients with NIDDM were higher than those in control subjects throughout the study period (P less than 0.001) and rose earlier in the evening than in control subjects, thus failing to demonstrate the normal nocturnal suppression.
 In both groups of subjects, the nighttime glucose elevation was temporally and quantitatively correlated with the circadian cortisol rise.
 GH secretion was increased in the evening and nighttime periods compared to the daytime values, and in NIDDM patients, but not in control subjects, the size of the morning glucose elevation was directly related to the magnitude of this increase in GH secretion (r = 0.88; P less than 0.01).
 Glucagon concentrations were similar in both groups of subjects and remained essentially constant throughout the study period.
 We hypothesize that the nocturnal glucose rise that occurs during fasting represents a normal diurnal variation in the set-point of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.
",17
2968,"Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine.
 We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration.
 In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group.
 Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen.
 All integrated incremental responses after intravenous arginine were identical in the two groups.
 After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group.
 The gel filtration analysis showed that arginine stimulated the secretion of pancreatic glucagon (PG 33-61), major proglucagon fragment (PG 72-158) and probably GLP-1 (PG 72-107 amide) in both groups, whereas oral glucose stimulated the secretion of glicentin (PG 1-69) and intestinal GLP-1 (PG 78-107 amide), an insulinotropic hormone.
 The elevated levels of immunoreactive GLP-1 in diabetics in the fasting state were mainly due to an increased concentration of major proglucagon fragment.
",17
2969,"Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes.
 Nitric oxide (an endothelium-derived relaxing factor) induces smooth muscle relaxation and is an important mediator in the regulation of vascular tone.
 Advanced glycosylation end products, the glucose-derived moieties that form nonenzymatically and accumulate on long-lived tissue proteins, have been implicated in many of the complications of diabetes and normal aging.
 We demonstrate that advanced glycosylation products quench nitric oxide activity in vitro and in vivo.
 Acceleration of the advanced glycosylation process in vivo results in a time-dependent impairment in endothelium-dependent relaxation.
 Inhibition of advanced glycosylation with aminoguanidine prevents nitric oxide quenching, and ameliorates the vasodilatory impairment.
 These results implicate advanced glycosylation products as important modulators of nitric oxide activity and endothelium-dependent relaxation.
",17
2970,"Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression.
 Evidence is emerging for a direct role of glucose, independent of changes in insulin, in the regulation of cellular glucose transport and glucose utilization in vivo.
 In this study we investigate potential cellular and molecular mechanisms for this regulatory effect of glucose by determining how normalization of glycemia without insulin therapy in diabetic rats influences 3-O-methylglucose transport and the expression and translocation of two genetically distinct species of glucose transporters (GTs) in adipose cells.
 These results are compared with alterations in glucose disposal in vivo measured by euglycemic clamp.
 In rats rendered diabetic by 90% pancreatectomy, insulin-stimulated glucose transport in adipose cells is decreased 50% in parallel with reduced insulin-mediated glucose disposal in vivo.
 Levels of adipose/muscle GTs measured by immunoblotting are decreased in adipose cell subcellular membrane fractions, as are the corresponding mRNA levels assessed by Northern blotting of total adipose cell RNA.
 Normalization of blood glucose in diabetic rats with phlorizin, which impairs renal tubular glucose reabsorption and thus enhances glucose excretion, restores insulin-stimulated glucose transport in adipose cells and insulin-mediated glucose disposal in vivo.
 Importantly, levels of the adipose/muscle GT protein remain 43% reduced in the low-density microsomes in the basal state and 46% reduced in the plasma membranes in the insulin-stimulated state.
 Adipose/muscle GT mRNA levels remain approximately 50% depressed.
 Levels of the HepG2/brain GT protein and mRNA are unaltered by diabetes or phlorizin treatment.
 Thus, changes in ambient glucose independent of changes in ambient insulin can regulate the glucose transport response to insulin in isolated adipose cells and changes in responsiveness parallel alterations in glucose uptake in vivo.
 Since this effect can occur without alteration in the expression of the two species of glucose transporters present in adipose cells or in their translocation to the plasma membrane in response to insulin, it may result from changes in GT functional activity.
",17
2971,"Role of increased cytosolic free calcium in the pathogenesis of rabbit proximal tubule cell injury and protection by glycine or acidosis.
 To assess the role of increased cytosolic free calcium (Caf) in the pathogenesis of acute proximal tubule cell injury and the protection afforded by exposure to reduced medium pH or treatment with glycine, fura-2-loaded tubules were studied in suspension and singly in a superfusion system.
 The Ca2+ ionophore, ionomycin, increased Caf to micromolar levels and rapidly produced lethal cell injury as indicated by loss of lactate dehydrogenase to the medium by suspended tubules and accelerated leak of fura and failure to exclude Trypan blue by superfused tubules.
 Decreasing medium Ca2+ to 100 nM prevented the ionomycin-induced increases of Caf and the injury.
 Reducing medium pH from 7.4 to 6.9 or adding 2 mM glycine to the medium also prevented the cell death, but did not prevent the increase of Caf to micromolar levels.
 Cells treated with 1799, an uncoupler of oxidative phosphorylation which produced severe adenosine triphosphate (ATP) depletion, did not develop increases of Caf until just before loss of viability.
 Preventing these increases of Caf with 100 nM Ca2+ medium did not protect 1799-treated cells.
 Reduced pH and glycine protected 1799-treated cells without ameliorating the increases of Caf.
 These data demonstrate the toxic potential of increased Caf in the proximal tubule and show that Caf does sharply increase prior to loss of viability in an ATP depletion model of injury, but this increase does not necessarily contribute to the outcome.
 The potent protective actions of decreased pH and glycine allow the cells to sustain increases of Caf to micromolar levels in spite of severe, accompanying cellular ATP depletion without developing lethal cell injury.
",17
2972,"A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus.
 To elucidate the molecular mechanism of familial central diabetes insipidus (FDI), we sequenced the arginine vasopressin-neurophysin II (AVP-NPII) gene in 2 patients belonging to a pedigree that is consistent with an autosomal dominant mode of inheritance.
 10 patients with idiopathic central diabetes insipidus (IDI) and 5 normals were also studied.
 The AVP-NPII gene, locating on chromosome 20, consists of three exons that encode putative signal peptide, AVP, NPII, and glycoprotein.
 Using polymerase chain reaction, fragments including the promoter region and all coding regions were amplified from genomic DNA and subjected to direct sequencing.
 Sequences of 10 patients with IDI were identical with those of normals, while in 2 patients with FDI, a single base substitution was detected in one of two alleles of the AVP-NPII gene, indicating they were heterozygotes for this mutation.
 It was a G----A transition at nucleotide position 1859 in the second exon, resulting in a substitution of Gly for Ser at amino acid position 57 in the NPII moiety.
 It was speculated that the mutated AVP-NPII precursor or the mutated NPII molecule, through their conformational changes, might be responsible for AVP deficiency.
",17
2973,"Nutrition management for individuals with noninsulin-dependent diabetes mellitus in the 1990s: a review by the Diabetes Care and Education dietetic practice group.
 Noninsulin-dependent diabetes mellitus (NIDDM), or Type II diabetes, is characterized by two primary defects: insulin resistance and insulin secretion.
 The two major goals of management of NIDDM are to achieve near normal metabolic control and to prevent/delay the microvascular and macrovascular complications of diabetes.
 Nutrition, exercise, and, if necessary, medication are the three primary treatment modalities used in NIDDM.
 Treatment regimens need to be individualized and developed with consideration for diabetes management goals and quality-of-life issues.
 Lean individuals with NIDDM should be encouraged to maintain their body weight and modify food composition and eating pattern to minimize glucose excursions.
 The primary treatment goal for an obese individual with NIDDM is weight loss.
 The process of teaching nutrition and meal planning involves developing a cooperative alliance, gathering information, setting realistic goals, intervention, and maintaining change.
 Nutrition intervention involves providing information in stages, beginning with ""survival skill"" information and progressing to in-depth information.
 The dietitian's responsibility is to promote continuity of learning by introducing new ideas and concepts and altering the learning environment.
 Dietitians can expand their role in the 1990s to that of a diabetes educator taking a leadership role to ensure that the individual with NIDDM receives comprehensive and individualized care.
",17
2974,"A dietary education program for hypercholesterolemic children and their parents.
 A parent-child autotutorial dietary education program for 4- to 10-year-old, hypercholesterolemic children and their families was developed and pilot tested.
 The 10-lesson program, designed for weekly use at home, uses a ""talking-book"" approach (audiotapes with accompanying picture booklet) for the child.
 Parents are provided with information on ways to make recommended dietary changes, along with hands-on activities to do with the children.
 To help match the instructional approach to the wide developmental range within the children's age span, materials are divided into three program levels that use different story characters and concept presentations.
 During program development, evaluation by two children (and their parents) for each of the program levels guided the design and refinement of the lessons.
 A pilot test among 22 hypercholesterolemic children (whose treatment was limited to diet modification) revealed that children within the 4- to 10-year age range liked the ""talking-book"" approach and identified positively with the story characters.
 Parents indicated that their materials were clear and helpful.
 Between the baseline and 3-month follow-up visits, the children exhibited a significant increase in knowledge of heart healthy foods, a decrease in total fat consumption that approached significance, and a significant decrease in plasma low-density-lipoprotein cholesterol values.
",17
2975,"Is the recommended daily allowance for vitamin D too low for the homebound elderly?
 A population of sunlight-deprived elderly was studied to determine the daily intake of vitamin D and whether dietary intake was sufficient to maintain a normal vitamin D status.
 Twenty-two subjects over 65 years old with serum creatinine less than 180 mumols/L and confined indoors for more than 6 months were chosen from the community and a nursing home in Southeast Baltimore.
 Three-day food records were obtained along with serum levels of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2 D), and intact parathyroid hormone (PTH).
 The mean daily vitamin D intake was over twofold greater than the adult Recommended Daily Allowance (RDA) of 200 IU.
 The mean 25-OHD level was 40 nmol/L (normal 25-138 nmol/L) with seven patients less than 25 nmol/L.
 Of these participants with 25-OHD values less than 25 nmol/L, the mean vitamin D intake was 467 IU (range 36-1096 IU).
 We conclude that the current RDA seems inadequate for many older individuals who do not get sun exposure.
 This particular population of elderly is at risk to develop vitamin D deficiency and the associated complications.
",17
2976,"The relationship between symptomatic and biochemical hypoglycaemia in insulin-dependent diabetic patients.
 The relationship between symptomatic (subjective feelings) and biochemical (blood glucose concentration less than 3 mmol l-1) hypoglycaemia was studied in 66 randomly selected insulin-dependent diabetic out-patients under normal conditions of daily life with conventional insulin injection regimens.
 The patients (a) collected 7-point diurnal blood glucose profiles at home on three consecutive days and then once weekly for 3 weeks, (b) indicated whether they felt hypoglycaemic at sampling times, and (c) collected extra samples if they felt hypoglycaemic at any time during the study period.
 The weekly frequencies of symptomatic and biochemical hypoglycaemia were 0.99 and 1.75 per patient, respectively.
 Biochemical hypoglycaemia was present in 29% of the symptomatic episodes, and symptomatic hypoglycaemia accompanied 16% of the biochemical episodes.
 Symptomatic hypoglycaemia was experienced at a median blood glucose concentration of 3.4 mmol l-1 (range 1.4-14.9 mmol l-1).
 Fifty per cent of both symptomatic and biochemical episodes occurred before lunch, while the remainder were evenly distributed throughout the day.
 The occurrence of biochemical hypoglycaemia, but not of symptomatic hypoglycaemia, was inversely correlated with HbA1c and median blood glucose concentration.
 Thus symptomatic hypoglycaemia is an unreliable indicator of biochemical hypoglycaemia and of the degree of glycaemic control.
 Blood glucose measurements are a prerequisite for the diagnosis of hypoglycaemia.
",17
2977,"Modulation by dietary vitamin E of I-compounds (putative indigenous DNA modifications) in rat liver and kidney.
 I(indigenous)-compounds are age-related, carcinogen adduct-like, putative indigenous DNA modifications detectable by 32P-postlabeling assay in untreated animals.
 To investigate the origins of these DNA derivatives, we examined the effects of dietary vitamin E, a natural antioxidant, on I-compounds of rat liver and kidney DNA.
 Weanling female Sprague-Dawley rats were fed Draper's diets containing 0, 100, 1000, or 10,000 mg/kg alpha-tocopheryl acetate for 6 mo.
 The DNA from four individual rats of each group was analyzed by a nuclease P1-enhanced version of the 32P-postlabeling assay for DNA adducts.
 The amount of vitamin E in the liver was measured by high performance liquid chromatography.
 Rats fed vitamin E-deficient diet (0 mg/kg) showed identical profiles and similar levels of I-compounds as those fed the 100 mg/kg diet.
 Most I-spots were significantly intensified and one tissue-specific extra spot was found in both liver and kidney DNA of rats fed the 1000 or 10,000 mg/kg vitamin E diet.
 However, one of the five major I-spots detected in the kidney was weaker in the 1000 and 10,000 mg/kg groups than in the 0 and 100 mg/kg groups.
 These results show that formation of most I-compounds was not affected by vitamin E-deficient diet, and that long-term feeding of diet containing high levels of vitamin E may cause metabolic alterations leading to an increased formation of DNA-reactive (potentially mutagenic or carcinogenic) electrophiles.
",17
2978,"Lovastatin efficacy in reducing low-density lipoprotein cholesterol levels on high- vs low-fat diets.
 The effectiveness of lovastatin was compared with both a high-fat vs low-fat diet.
 Hypercholesterolemic subjects were studied under metabolic ward conditions for diet periods of 3 weeks while receiving lovastatin (40 mg/d) or placebo.
 Multiple lipoprotein levels were measured during the final week of each diet period.
 Nineteen subjects completed the study on the high-fat (43% of kilojoules) diet and 16 on the low-fat (25% of kilojoules) diet.
 Lovastatin reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30%, compared with placebo on both diets, with no significant diet-drug interaction.
 High-density lipoprotein cholesterol was raised by 7% to 8% on the diet regimens.
 Addition of lovastatin to the low-fat diet permitted 80% of subjects on this diet, but less than 50% of those on the high-fat diet, to achieve current guidelines.
 Although lovastatin produces a comparable percentage reduction in lipoprotein profiles on either diet, the accompanying low-fat diet remains advisable for additional reduction of low-density lipoprotein cholesterol levels to specified goals.
",17
2979,"Comparative study of a microporous cholestyramine analogue (filicol) and gemfibrozil for treatment of severe primary hypercholesterolemia. Short- and long-term results.
 The hypolipidemic effect of gemfibrozil in severe hypercholesterolemia is not well established.
 Fifty patients with primary hypercholesterolemia (including 18 patients with familial hypercholesterolemia) and stable low-density lipoprotein cholesterol levels greater than 3.90 mmol/L (greater than 150 mg/dL) (6.10 +/- 1.30 [SD] mmol/L; 236 +/- 50 mg/dL) while on a hypolipidemic diet were assigned to treatment for 12 weeks with either 9 g/d of filicol, a microporous cholestyramine analogue, or 1.2 g/d of gemfibrozil in a randomized clinical trial.
 Tolerance was good with both drugs.
 Filicol and gemfibrozil caused similar decrements of total cholesterol (14% for both), low-density lipoprotein cholesterol (20% and 18%, respectively), and apolipoprotein B (16% and 21%, respectively).
 Close to 40% of the patients had decreases of greater than 25% in low-density lipoprotein cholesterol levels with both drugs.
 Gemfibrozil, but not filicol, significantly increased plasma high-density lipoprotein cholesterol (16%) and apolipoprotein A-I (17%) levels and reduced triglyceride levels (35%).
 No loss of efficacy was observed with either drug in subsets of patients who had a good 12-week response rate and had extended therapy for up to 12 months.
 This study demonstrates that gemfibrozil may have a beneficial effect on all aspects of the plasma lipid profile in patients with severe hypercholesterolemia, a clinical situation where it can be used with potential advantages over standard doses of anion-exchange resins.
",17
2980,"Effects of recombinant human macrophage colony-stimulating factor on plasma cholesterol levels.
 Recombinant human macrophage colony-stimulating factor (rhM-CSF) is a hematopoietic growth factor that stimulates the growth, differentiation, proliferation, and activation of cells of the monocyte/macrophage lineage.
 rhM-CSF was administered to rabbits and nonhuman primates to evaluate effects on cholesterol homeostasis.
 Decreases in plasma cholesterol concentrations were observed during rhM-CSF administration.
 The observed mean (+/- SD) decreases over a range of doses in nonhuman primates receiving rhM-CSF by continuous intravenous infusion (CIVI) or intravenous bolus (IVB) injection were approximately 16% +/- 8% and 43% +/- 10%, respectively.
 Low-density lipoprotein (LDL) cholesterol levels decreased 55% +/- 9% from pretreatment baseline values in the animals receiving rhM-CSF by IVB.
 Normocholesterolemic New Zealand white rabbits receiving rhM-CSF over a range of doses by CIVI showed a decrease from baseline in total cholesterol of approximately 28% +/- 17%, with LDL cholesterol levels decreasing by approximately 72% +/- 33%, while high-density lipoprotein levels showed variable changes, including increased values.
 A decrease of 36% +/- 26% in total plasma cholesterol was observed in Watanabe Heritable Hyperlipidemic rabbits receiving rhM-CSF by CIVI for 7 days.
 This decrease was attributable almost entirely to decreases in LDL cholesterol, which fell approximately 34% +/- 24% from baseline.
 Although the mechanism of this cholesterol-lowering effect is unknown, these results strongly suggest that rhM-CSF may provide a novel treatment for hypercholesterolemia and may be useful in investigations into the mechanisms of cholesterol homeostasis and atherogenesis.
",17
2981,"Risk of disability and mortality due to overweight in a Finnish population [published erratum appears in BMJ 1990 Nov 3;301(6759):1027]
 OBJECTIVE--To investigate the effect of overweight on premature mortality and work disability in young and middle aged Finns.
 DESIGN--Prospective cohort study based on data collected in the multiphasic health examinations by the Social Insurance Institution of Finland from 1966 to 1972 and follow up until 1982.
 SETTING--34 Communities throughout Finland.
 SUBJECTS--12,053 Women and 19,076 men who were employed and aged 25-64 at baseline.
 MAIN OUTCOME MEASURES--Mortality and work disability pensions from all and specified causes.
 RESULTS--Body mass index was a weak predictor of death but a strong predictor of early work disability, which increased linearly with body mass index.
 After adjustment for age, geographical region, occupation, and smoking the relative risks of work disability for women and men with a body mass index greater than or equal to 30 kg/m2 were, respectively, 2.0 (95% confidence interval 1.8 to 2.3) and 1.5 (1.3 to 1.7) when compared with those of subjects with body mass index less than 22.5 kg/m2.
 The increased risks were due to an excess of cardiovascular and musculoskeletal diseases but not of mental diseases.
 One fourth of all disability pensions from cardiovascular and musculoskeletal causes in women and half as many in men could be attributed to overweight (body mass index greater than 25 kg/m2) alone.
 CONCLUSIONS--Though modest overweight has little impact on mortality it predicts severe functional impairment.
 A considerable proportion of work disability pensions could probably be prevented by efficient weight control.
",17
2982,"The differential diagnosis of Crigler-Najjar disease, types 1 and 2, by bile pigment analysis.
 Phenobarbital response, bile pigment composition, and the fractional biliary excretion ratio of bilirubin were studied in nine children with Crigler-Najjar disease.
 In five children, serum bilirubin levels decreased during phenobarbital treatment by 26% or more and the pigment composition in bile changed with a decrease in the proportion of unconjugated bilirubin from 33% +/- 12% to 13% +/- 1% and an increase in monoconjugates and diconjugates from 57% +/- 14% and 10% +/- 2%, respectively, to 72% +/- 4% and 16% +/- 3%.
 In four children, serum bilirubin levels did not change significantly during phenobarbital treatment.
 In these patients, bile pigments comprised 91% +/- 10% unconjugated bilirubin, 9% +/- 11% monoconjugates, and 1% +/- 1% diconjugates.
 On the basis of these differences, the former group can be classified as having type 2 Crigler-Najjar disease and the latter, type 1.
 Bile pigment analysis in parents of patients with Crigler-Najjar disease showed an increased proportion of monoconjugates in at least one of the partners in three of four couples tested, despite normal serum bilirubin levels.
 Serum bilirubin levels were about the same in type 1 and 2 patients and amounted to 236 +/- 62 mumol/L and 214 +/- 82 mumol/L, respectively.
 In addition the fractional bilirubin excretion ratio, calculated as the ratio ([bilirubin in bile]/[bilirubin in serum])/([bile acid in bile]/[bile acid in serum]) could not differentiate between these two groups.
 However, there was a 10-fold and 100-fold difference of this ratio between patients with Crigler-Najjar disease and those with Gilbert's syndrome and between patients with Crigler-Najjar disease and controls.
 The fractional bilirubin excretion ratio proved an excellent tool to differentiate between Gilbert's syndrome and Crigler-Najjar disease, whereas Crigler-Najjar disease types 1 and 2 could be differentiated on the basis of bile pigment analysis.
",17
2983,"Hypomagnesemia and the parathyroid hormone-vitamin D endocrine system in children with insulin-dependent diabetes mellitus: effects of magnesium administration.
 Because insulin-dependent diabetes mellitus is associated with altered electrolyte metabolism and a derangement of the parathyroid hormone (PTH)-vitamin D endocrine system, we studied 23 children with diabetes (age 9.4 +/- 2.5 years) and found lower serum values for total and ionized calcium, magnesium, intact PTH, calcitriol, and osteocalcin than in age- and sex-matched control subjects.
 All patients were given magnesium orally (6 mg/kg daily of elemental magnesium) for up to 60 days.
 During treatment, serum magnesium, total and ionized calcium, intact PTH, calcitriol, and osteocalcin concentrations significantly increased, reaching control values.
 After a 3-day low-calcium diet, the patients had a significantly reduced delta-increment of PTH and calcitriol in comparison with values obtained during hypomagnesemia.
 After magnesium repletion, the delta-increments of both PTH and calcitriol, in response to the low-calcium diet, were not significantly different from control values.
 These data suggest that magnesium deficiency plays a pivotal role in altering mineral homeostasis in insulin-dependent diabetes mellitus.
",17
2984,"Diabetic retinopathy: can we modify its course?
 With the exception of panretinal laser photocoagulation, no therapy has been shown to modify the course of diabetic retinopathy.
 Success in developing new therapies for diabetic retinopathy will depend on how well the disease process is understood and on whether interventions can be identified that ameliorate or circumvent critical stages in the development of the disease.
 A model of the disease process is presented to serve as a frame-work on which pieces of the puzzle can be placed and new areas of potential interventional therapy can be conceptualized.
",17
2985,"A history of phlebotomy therapy for hemochromatosis.
 Hemochromatosis was recognized as an iron-storage disease for 50 years before it was proposed to treat it by removing hemoglobin.
 Davis and Arrowsmith are credited with the first report that demonstrated its value.
 Larger series have provided statistically valid evidence of improved quality of life and increased longevity.
 The earlier the disease is discovered, the less risk of morbidity and mortality.
 Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.
",17
2986,"Comparison of stainable liver iron between symptomatic and asymptomatic hemochromatosis homozygotes and their homozygous relatives.
 The authors compared the amount of hepatic parenchymal cell stainable iron in 159 hemochromatosis homozygotes.
 They were separated into four groups.
 Group 1: 59 symptomatic hemochromatosis probands with hemochromatosis (mean age 49 years) who were identified because of symptoms and signs of iron overload.
 Group 2: 38 asymptomatic probands with hemochromatosis (mean age 29 years) identified during population screening studies or during routine health maintenance evaluation.
 Group 3: 47 homozygous relatives (mean age 43 years) of Group 1 probands.
 Group 4: 15 homozygous relatives (mean age 30 years) of Group 2 probands.
 The symptomatic probands (Group 1) were 20 years older and had much more stainable hepatic iron (p less than 0.0001) than the asymptomatic probands (Group 2).
 The homozygous relatives (Group 3) of the symptomatic probands also were older and had much more stainable hepatic iron than the homozygous relatives (Group 4) of asymptomatic probands (p less than 0.0002).
 The results of this study suggest that population screening studies can result in early identification of individuals with hemochromatosis before massive hepatic iron overload occurs and before symptoms of iron overload develop.
",17
2987,"The immunogenetics of hereditary hemochromatosis.
 Hereditary hemochromatosis (HH), an iron overload disease caused by unregulated intestinal iron absorption, is a recessive HLA-linked disease.
 HH is the most common inherited metabolic disorder with one of every 400 to 500 individuals having both genes and being likely to develop the disease.
 Thus, although the product of the hemochromatosis gene is unknown, its mode of inheritance allows HLA-genotyping of the proband and his/her siblings to be highly predictive of the genetic propensity to develop the clinical features of HH.
 In view of the known immunoregulatory properties of iron and its binding proteins, it is important to determine if the high levels of storage iron in HH influence the immunosurveillance network in HH patients and whether that has any clinical relevance.
 We have defined certain alterations of the effector cells of the cellular arm of the immune system and have studied a patient with HH who had specific immune alterations, including delayed cutaneous-type hypersensitivity anergy, and was diagnosed with poorly differentiated adenocarcinoma of the stomach four years after his HH diagnosis.
 Those findings are consistent with the interpretation that in certain clinical situations of elevated body iron stores, the immunoregulatory balance or environment may be tipped in favor of growth and development of cancer cells.
",17
2988,"The immune system in hereditary hemochromatosis: a quantitative and functional assessment of the cellular arm.
 The objective of this investigation was to evaluate certain quantitative and functional characteristics of the effector cells of the cellular arm of the immune system in hereditary hemochromatosis (HH) with respect to treatment status.
 Two observations were consistent with the postulate that the elevated levels of storage iron has in vivo immunoregulatory properties: (1) the absolute number of CD8-positive T cells were significantly elevated in untreated HH patients (n = 7) and reduced in treated patients (n = 7), as compared with controls; and (2) the proliferative response of peripheral blood mononuclear cells from untreated HH patients to mitogens was suboptimal but the response of peripheral blood mononuclear cells (PBM) from treated HH patients was normal.
 Furthermore, immunoglobulin secretion by PBM from treated HH patients as compared to controls was altered.
 Finally, one T effector cell abnormality was unrelated to treatment status in that a subset of mature, non-activated T lymphocytes aberrantly formed thermostable erythrocyte-rosettes (TE-R), a lymphoid surface marker usually expressed on thymocytes or activated T cells.
 Taken together these data define certain immune alterations that are consistent with the interpretation that cellular immunity may be influenced by the high level of storage iron in HH patients.
",17
2989,"Psychosocial factors in maternal phenylketonuria: prevention of unplanned pregnancies.
 BACKGROUND.
 Women with phenylketonuria (PKU) not treated prior to conception can have a pregnancy that results in serious fetal damage.
 In this report, factors associated with preventing unplanned (and hence late treated) pregnancies are described.
 METHODS.
 Subjects included 60 phenylketonuric women and two comparison groups composed of female acquaintances and diabetic women.
 All were interviewed and administered tests of intelligence, general well-being, knowledge, and personality.
 RESULTS.
 Thirty-five percent of the sexually active women with PKU used contraception only sporadically.
 The variables that best predicted reported frequency of birth control use were the extent to which women felt social support to use contraception (r = .64) along with positive attitudes about birth control (r = .66) and knowledge of family planning (r = .43).
 For the comparison groups, a different pattern of variables predicted contraceptive use, with locus of control figuring most prominently for the diabetics (r = .39) and social support for birth control being most important for the acquaintances (r = .46).
 CONCLUSIONS.
 As more girls with PKU enter childbearing ages, there will be an increased need for specific programs that address psychosocial factors in maternal PKU.
",17
2990,"A form of familial hypobetalipoproteinaemia not due to a mutation in the apolipoprotein B gene.
 Familial hypobetalipoproteinaemia (FHBL) is a dominant disorder of lipoprotein metabolism characterized by levels of apolipoprotein B-carrying lipoproteins (VLDL, IDL and LDL) which are 50% of the normal levels in the heterozygotes and almost absent in the homozygotes.
 Several reports have recently shown that the underlying defect in FHBL involves different mutations in the apo B gene which lead to reduced levels of apo B mRNA or to the production of truncated forms of apo B having either a lower synthetic rate or a higher catabolic rate than normal apo B.
 We here present a three-generation family with several FHBL members in which the linkage analysis shows absence of co-segregation between apo B gene alleles and the hypocholesterolaemic phenotype.
 We conclude that a dominantly transmitted mutation in a gene other than that for apo B is responsible for the low plasma cholesterol levels.
",17
2991,"Hypoglycaemic episodes during intensified insulin treatment: increased frequency but no effect on cognitive function.
 Ninety-seven patients with insulin dependent diabetes mellitus (IDDM) were randomized to intensified conventional treatment (ICT, n = 44) or regular treatment (RT, n = 53).
 The mean HbA1c level (+/- SEM) was reduced from 9.5 +/- 0.2% to 7.4 +/- 0.1% in the ICT group (P less than 0.001), and from 9.4 +/- 0.2% to 9.0 +/- 0.2% (P less than 0.01) in the RT group.
 The difference between the groups was significant (P less than 0.001).
 During a period of 3 years, 57% of the ICT patients (95% confidence interval 44-73%) and 23% of the RT patients (95% CI, 11-34%) (P less than 0.001) had at least one episode of serious hypoglycaemia, with the need for third-party assistance or resulting in coma.
 Eighteen of the 32 ICT patients who initially had adrenergic symptoms during hypoglycaemia changed to predominantly neuroglycopenic symptoms.
 This was the case with only 8 of 38 RT patients (P less than 0.01).
 The change in symptoms was related to the increased frequency of serious hypoglycaemia, but neither symptoms nor frequency of hypoglycaemia bor any relationship to insulin dose, body mass index, duration of diabetes or autonomic nerve function.
 The results of several neuropsychological tests did not differ between the groups at baseline, and did not change during the study.
 There were no signs of deteriorating cognitive function in the patients with serious hypoglycaemic episodes.
",17
2992,"Short-term effects of dehydroepiandrosterone treatment in rats on mitochondrial respiration.
 Administration of dehydroepiandrosterone (DHEA) to rats results in alterations in liver and serum factors.
 This study was undertaken to determine the earliest metabolic change(s) associated with DHEA treatment.
 Serum cholesterol, triacylglycerol, glucose, insulin, glucagon, thyroid hormones and hepatic glucose-6-phosphate dehydrogenase activity were, in general, unaltered in obese Zucker rats after 7 d and 24, 12 and 3 h of DHEA treatment.
 Malic enzyme, long-chain fatty acyl-coenzyme A hydrolase and catalase activities and peroxisomal beta-oxidation rates were elevated after 7 d and 24 h in DHEA treatment, but not after 12 h.
 Mitochondrial beta-oxidation was not altered.
 Hepatic mitochondrial state 3 respiration per g liver with glutamate-malate was elevated after 7 d and 24, 12 and 3 h in DHEA-treated rats and was elevated per mg protein except after 7 d.
 Succinate-supported state 3 respiration per g liver was also elevated after 7 d and 24 and 12 h of DHEA treatment.
 Mitochondria from rats treated for 7 d had lower levels of cardiolipin and phosphatidylethanolamine and an increase in phosphatidylcholine.
 Changes in fatty acid composition of these phospholipids occurred after 7 d and 24 h of DHEA treatment.
 In an additional study, rats were treated with DHEA or DHEA plus ethidium bromide for 3 d.
 Ethidium bromide inhibited the increase in mitochondrial protein and respiration associated with DHEA treatment.
 These findings indicate that mitochondrial respiration is the earliest factor affected by DHEA and may be associated with protein synthesis.
",17
2993,"Endotoxin and lipid peroxidation in vivo in selenium- and vitamin E-deficient and -adequate rats.
 The effect of Salmonella typhimurium endotoxin injected intraperitoneally (0.5 mg/kg body weight) on lipid peroxidation in vivo was assessed.
 Peroxidation was monitored by measuring ethane production, an autoxidation product of (n-3) unsaturated fatty acids.
 Weanling rats were fed a selenium- and vitamin E-deficient basal diet or one supplemented with 0.2 mg Se/kg and/or 200 mg vitamin E/kg.
 After 11 to 13 wk of feeding, ethane production was tripled in LPS-treated Se- and vitamin E-deficient rats compared to saline-treated deficient rats.
 In both doubly deficient and adequate rats, LPS increased ethane production, but it did so to a greater extent in Se- and vitamin E-deficient rats.
 Dietary Se or vitamin E supplementation alone significantly reduced ethane production from LPS-treated rats.
 Vitamin E was more protective than Se against LPS-induced lipid peroxidation.
 Escherichia coli and Salmonella minnesota LPS also increased ethane production in Se- and vitamin E-deficient rats.
 These results show that low doses of LPS stimulate lipid peroxidation in vivo in Se- and vitamin E-deficient rats.
",17
2994,"Endotoxin and lipid peroxidation in vitro in selenium- and vitamin E-deficient and -adequate rat tissues.
 The effect of Salmonella typhimurium endotoxin injected intraperitoneally into rats (0.5 mg/kg of body weight) on subsequent lipid peroxidation in vitro was assessed.
 Peroxidation was monitored by measuring ethane production from tissue slices, as well as thiobarbituric acid-reactive substances and conjugated dienes in tissue homogenates.
 Weanling rats were fed a selenium- and vitamin E-deficient basal diet or one supplemented with 0.2 mg of Se/kg of diet and 200 mg of vitamin E/kg.
 After 9 to 16 wk, ethane production and thiobarbituric acid-reactive substances in liver and lung generally were increased by LPS treatment of Se- and vitamin E-deficient rats.
 Conjugated dienes were increased by LPS treatment in liver of Se- and vitamin E-deficient rats, but paradoxically, were higher in Se- and vitamin E-adequate liver tissue.
 Daily injections of 1 g of hydroxyurea/kg of body weight, a cell proliferation inhibitor, for 2 d prior to LPS injection significantly decreased the LPS-induced ethane production in Se- and vitamin E-deficient rat liver and lung.
 These results show that low doses of LPS injected into rats stimulated lipid peroxidation in vitro in Se- and vitamin E-deficient rat liver tissue.
 Hydroxyurea decreased LPS-induced lipid peroxidation in vitro; this suggests that neutrophils or macrophages are involved in LPS-induced lipid peroxidation.
",17
2995,"Effects of dehydration on gastric emptying and gastrointestinal distress while running.
 Gastrointestinal distress is commonly reported by athletes after ingestion of a beverage.
 We speculate that ingestion may be occurring after dehydration has taken place.
 The high prevalence of GI disorders in marathon runners who have lost greater than or equal to 4% body weight supports this theory.
 To test this theory, the effects of dehydration, and dehydration in combination with endurance running, on gastric emptying (GE) and frequency of gastrointestinal (GI) complaints were tested in this experiment.
 A complete cross-over study was designed.
 Sixteen subjects ingested 8 ml.kg BW-1 of a 7% carbohydrate (296 mOsm.kg-1), solution after a euhydration or dehydration regime.
 Dehydration (4% BW loss) was produced by 60% maximal speed running at 30 degrees C or by intermittent sauna exposure at 100 degrees C.
 Euhydration experiments were conducted with a 2 h rest period with water administered at 20 and 40 min.
 Gastric drink volumes were measured every 10 min for 40 min.
 Emptying curves were compared using semi-log transformation of the percentage emptying data and simple linear regression.
 The slope of each line was used as a measure of average GE rate.
 Dehydration-exercise resulted in slower GE than in all other treatments (P less than 0.05).
 ANOVA revealed significant effects of dehydration (P less than 0.05) and exercise (P less than 0.05), these two effects being additive in delaying GE.
 GI complaints were reported by 37.5% of the subjects during dehydration-exercise experiments.
 No GI disturbance was reported in other tests.
",17
2996,"A two-step model for development of non-insulin-dependent diabetes.
 Both insulin resistance and beta-cell dysfunction occur during the development of non-insulin-dependent diabetes mellitus (NIDDM), but controversy exists about which lesion is primary.
 Based on longitudinal studies in the Pima Indians, a population with the world's highest reported prevalence of NIDDM, a two-step model for development of the disease is proposed.
 The first step is transition from normal to impaired glucose tolerance, for which insulin resistance is the main determinant, and the second and later step is worsening from impaired glucose tolerance to diabetes, in which beta-cell dysfunction plays a critical role.
 This hypothesis is consistent with findings from other ethnic groups from many parts of the world.
",17
2997,"Feasibility and effects of a diabetes type II protocol with blood glucose self-monitoring in general practice.
 A diabetes protocol characterized by self-monitoring of blood glucose was introduced in four general practices with the aim of making the frequency of consultations dependent on the metabolic regulation and emphasizing body weight reduction.
 The feasibility of the programme was investigated and the results after 1 year were compared with those of conventional care in four control practices.
 In the experimental practices, 13 patients switched from a medical specialist's to a general practitioner's supervision, 20 remained under supervision of their GP and 33 started self-monitoring.
 The self-monitoring rate, the consultation frequency according to protocol, the low number of dropouts and inadequate referrals and adherence to the therapeutic scheme showed that the protocol was feasible for both the GPs and the patients.
 At the initial assessment, the regulation of the diabetes was worse in patients of the experimental group, compared with those of the control group (mean HbA1 9.7% vs 8.9%; p less than 0.05).
 On average, patients in the experimental group (n = 56) lost 0.4 kg of body weight, whereas those in the control group (n = 73) gained 0.1 kg (n.s.).
 The mean change in HbA1, adjusted for the initial value, was -0.4% in the experimental and +0.5% in the control group (p less than 0.05).
 The results of the protocol can be attributed to a combination of greater participation of the patient, the individualized consultation frequency and the prescription of oral hypoglycaemic agents according to body weight development.
",17
2998,"The influence of simvastatin on adrenal corticosteroid production and urinary mevalonate during adrenocorticotropin stimulation in patients with heterozygous familial hypercholesterolemia.
 The adrenal gland requires a continuous supply of cholesterol for the biosynthesis of adrenal corticosteroids, which can be supplied by low density lipoprotein receptor-mediated uptake or local synthesis.
 The present study examined whether hypolipidemic therapy with a potent HMG CoA reductase inhibitor, simvastatin, compromises the adrenal response to ACTH stimulation in adult patients with heterozygous familial hypercholesterolemia.
 The adrenal response to a 36-h continuous ACTH infusion was determined at baseline and after 2 months of simvastatin treatment (40 mg, twice daily) in eight patients.
 Simvastatin reduced total and low density lipoprotein cholesterol levels by 36% and 45%, respectively.
 The time course of the increase in serum cortisol concentrations with continuous ACTH infusion was the same before and during simvastatin therapy, as were the rates of urinary excretion of free cortisol, 17-hydroxycorticosteroids, and 17-ketosteroids.
 Urinary excretion of mevalonate, which correlates with rates of whole body cholesterol synthesis, decreased from 3.8 +/- 0.42 (+/- SEM) mu,ol/24 h at baseline to 2.75 +/- 0.56 on simvastatin; no significant changes were seen in the urinary mevalonate levels before and after simvastatin therapy during ACTH stimulation.
 We conclude that the hypolipidemic effects of simvastatin in patients with heterozygous familial hypercholesterolemia are paralleled by a decrease in urinary mevalonate, but that the drug does not adversely affect ACTH-stimulated adrenal corticosteroid production.
",17
2999,"Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies.
 Chromogranin-A (CgA) is an acidic soluble protein with a virtually ubiquitous occurrence in normal human neuroendocrine tissues.
 Of the many potential tissue sources of CgA immunoreactivity, which contribute to basal (unstimulated) circulating CgA? To explore this question we studied the effects of selective and nonselective suppression of secretion at several sites within the neuroendocrine system.
 Selective disruption of sympathetic outflow by trimethaphan decreased basal CgA by 25%, suggesting that sympathetic neurons contribute to circulating CgA.
 Plasma CgA in patients with unilateral and bilateral adrenalectomy fell within the range observed in normal subjects, weighing against the adrenal medulla as a major source of basal circulating CgA.
 Selective suppression of a variety of anterior and posterior pituitary cell types decreased plasma levels of the usual resident peptide hormones, but left plasma CgA unperturbed.
 After propranolol treatment, plasma CgA remained unaltered.
 Secretin suppressed plasma PTH and calcitonin, but did not alter plasma CgA levels.
 On the other hand, widespread nonselective suppression of a variety of neuroendocrine secretory cells by somatostatin decreased plasma CgA by 48%.
 Plasma catecholamines were unaltered by somatostatin infusion, suggesting that somatostatin inhibited CgA release from nonsympathoadrenal sources.
 During the infusion of somatostatin, the plasma epinephrine increment in response to insulin-induced hypoglycemia was maintained, and plasma CgA did not fall, nor did it rise after somatostatin cessation.
 Taken together, these findings suggest that somatostatin did not inhibit transport of stimulation-released CgA from the adrenal medulla to the circulation.
 In conclusion, although the adrenal medulla is the major tissue source of CgA immunoreactivity in man, other neuroendocrine sites, including sympathetic axons and multiple endocrine glands, appear to influence the basal circulating concentration of CgA.
",17
3000,"Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass.
 To define the potential role of subclinical vitamin D deficiency in postmenopausal bone loss, we analyzed the levels of circulating 25-hydroxyvitamin D (25OHD) in 539 midwestern caucasian women screened for osteoporosis.
 Low 25OHD (less than 38 nmol/L) was found in 49 subjects (aged 52-77 yr).
 Women with low 25OHD had a reduced vertebral bone density (VBD), assessed by quantitative computed tomography, compared to age-matched controls (P less than 0.001).
 They also had significantly lower levels of serum calcium and phosphate, lower urinary calcium, higher serum alkaline phosphatase, and, in most cases, increased immunoreactive PTH (iPTH) concentrations, suggesting secondary hyperparathyroidism.
 Furthermore, only in the low 25OHD group did VBD correlate directly with 25OHD (r = 0.41; P less than 0.01), and inversely with iPTH (r = -0.47; P less than 0.01).
 Multivariate analyses revealed that iPTH was the major determinant of the observed decrease in VBD.
 Seasonal variations of serum 25OHD were noted only in the control population; in this group the 25OHD levels also correlated with sunlight exposure (r = 0.48; P less than 0.01), as assessed by an outdoor score.
 Thus, vitamin D deficiency develops when both the endogenous and exogenous sources are insufficient and contributes to a reduced bone mass in elderly women.
",17
3001,"HLA antigens in Hungarian patients with idiopathic haemochromatosis.
 Thirteen unrelated patients with idiopathic haemochromatosis (eight men, five women) were studied.
 The diagnosis was based on clinical, biological, and histochemical findings.
 HLA typing was performed in all 13 and in all of their available first degree relatives (n = 31).
 HLA A3 was present in nine of 13 probands (69.2% compared with 18.8% in the group of 53 healthy blood donors and 22.4% in a selected Hungarian population (n = 1910).
 HLA B7 was present in five of 13 probands (38.4% compared with 11.3% and 14.6%).
 An A3B7 antigen association was found in five of 13 patients.
 The A3B7 haplotype was found in three, A2B12 and A2B38 haplotypes were found twice in 10 genotyped probands.
 Pedigree studies showed that there was one unaffected homozygote, 24 heterozygotes, and six non-carriers.
 Extended family and population studies are necessary to establish the prevalence of the gene in Hungary and an association with haplotypes other than A3B7.
",17
3002,"Inpatient and post-discharge course of the malnourished patient.
 A retrospective review of the medical records of 114 malnourished and 106 non-malnourished male veterans assessed the inpatient and 1 year post-discharge dietetic care given for the treatment of malnutrition.
 The malnourished sample consisted of subjects discharged with a protein-energy or protein malnutrition comorbidity.
 Subjects in the diagnosis-matched and age-matched control sample were discharged without a malnutrition comorbidity during the same period.
 Data collected from progress notes included diagnoses, inpatient dietetic feedings and services provided, discharge dietetic care, intervening clinic visits, and rehospitalizations.
 On initial admission, 79% of the diagnoses for the malnourished group fell into five diagnosis categories: neoplasms; respiratory system diseases; digestive system diseases; endocrine, nutritional, and metabolic diseases; and mental disorders (including alcohol-related disorders).
 Malnourished subjects received more specialized feedings and dietetic services than did the controls on initial admission.
 However, the discharge and post-discharge care received by surviving members of both groups was similar.
 Fewer than half the members of either group received post-discharge care.
 Fifty-four malnourished and 54 control patients were hospitalized more than once.
 The findings indicate that levels of inpatient and outpatient dietetic care need to be coordinated to alleviate malnutrition.
",17
3003,"Relationship of obesity and physical fitness to cardiopulmonary and metabolic function in healthy older men.
 The relationship of obesity and physical fitness (VO2max) to cardiopulmonary and metabolic function was examined in 132 healthy obese, nonsmoking men age 45-79.
 Obese men with higher VO2max had lower % body fat and waist-to-hip ratio (WHR) than obese men with low VO2max.
 The obese subjects with high WHR (upper body fat distribution) had higher systolic blood pressure, hyperinsulinemia and impaired glucose tolerance, lower high density lipoprotein cholesterol (HDL-C), and higher triglyceride (TG).
 VO2max (ml/kg FFM.min) was lower in the older men (r = -0.54, p less than .001), and 32% of the variation was accounted for by age and the one-second forced expiratory volume.
 Although pulmonary function was normal, 50% of the variability was predicted by age, height, and VO2max or WHR.
 Glucose tolerance and insulin correlated better with VO2max and indices of body composition than with age, while plasma TG and HDL-C correlated with body composition, not VO2max or age.
 Thus, while age affects the cardiopulmonary and metabolic function of obese older men, physical inactivity, obesity, and an abdominal body fat distribution (increased WHR) contributed significantly to their reductions in physiological function.
",17
3004,"Dependency and eating disorders in female psychiatric inpatients.
 Research indicates that oral dependent and eating-disordered individuals have similar personality traits, attitudes, and behaviors, suggesting that dependency may be a factor in the dynamics of anorexia and bulimia.
 To investigate this issue, we compared the proportions of dependent and food-related percepts in the Rorschach protocols of matched samples of eating-disordered (N = 16), obese (N = 18), and non-eating-disordered, normal-weight female psychiatric inpatients (N = 17).
 Eating-disordered patients reported significantly more dependent Rorschach imagery than did obese or normal-weight control patients, but no difference in the proportion of food-related imagery was found among the three groups.
 These results support the hypothesis that unresolved dependency issues underlie anorexia and bulimia.
",17
3005,"Comparison of the efficacy of Questran Light, a new formulation of cholestyramine powder, to regular Questran in maintaining lowered plasma cholesterol levels.
 Sixty-one men with known hypercholesterolemia (plasma cholesterol greater than 265 mg/dl), most of whom were previous participants in the Coronary Primary Prevention Trial of the U.S.
 Lipid Research Clinic Program, were chosen to take part in this study to test the effectiveness of a new low-calorie (Questran Light) cholestyramine formulation against the proven effectiveness of the currently marketed formulation Questran in maintaining lowered plasma cholesterol levels.
 The study recorded changes in fasting plasma lipids, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and calculated low-density lipoprotein cholesterol.
 After establishing baseline lipid/lipoprotein levels in a 3-week period during which all participants received the currently marketed formulation, the men were randomized into 2 groups, 1 group (n = 31) taking the new Questran Light formulation of 4 g of cholestyramine in 5 g of powder per pack, while the other group (n = 30) continued to take the marketed Questran formulation of 4 g of cholestyramine in 9 g of powder per pack.
 Each group consumed a total of 24 g/day of cholestyramine in 2 divided doses.
 At the end of the maintenance phase of the study there were no statistically significant mean changes in percentage from baseline to end-point lipid/lipoprotein levels within either group, nor were there any significant differences between the Questran Light group or the currently marketed Questran formulation group.
 The new low-calorie cholestyramine formulation appears to be equally as effective in maintaining lowered plasma cholesterol levels as the currently marketed formulation.
",17
3006,"Effect of educational program and interview on adoption of guidelines for the management of neonatal hyperbilirubinemia.
 OBJECTIVES: To determine (a) whether physicians are adhering to the guidelines for the management of neonatal hyperbilirubinemia, (b) what influences their decisions to investigate and treat the condition and (c) the effect of an educational program and clinical recall interview on compliance with the guidelines.
 DESIGN: Retrospective chart audit.
 SETTING: Urban tertiary care hospital.
 PARTICIPANTS: All term neonates who received phototherapy but were not admitted to the neonatal intensive care unit.
 INTERVENTIONS: Educational program and clinical recall interview.
 MEASURES: Charts were reviewed from March to May 1986 (period I, before publication of the guidelines) and from November 1986 to January 1987 (period II, after publication and after the educational program).
 The audits were repeated from April to June 1989 (period III, during the interview phase) and from October to December 1989 (period IV, 6 months after the interviews).
 Two criteria determined the appropriate use of phototherapy: the serum bilirubin level and the postnatal day on which phototherapy was started.
 RESULTS: The proportion of infants receiving phototherapy for whom there were orders for complete blood counts to investigate hyperbilirubinemia increased from 20% in period I to 37% in period IV.
 The frequency of orders to determine the proportion of reticulocytes did not change significantly.
 The number of infants receiving phototherapy decreased over the study periods.
 The proportion receiving phototherapy in accordance with the criteria for the serum bilirubin level increased from 10% to 17% after the educational program (insignificant difference) and to 31% after the interviews (p = 0.02).
 Compliance with the guidelines was greater before the infants were 2 days old than when they were 3 days old or more (p = 0.01).
 Of the 45 physicians who prescribed phototherapy (for 94 infants) during period IV 26 never prescribed in accordance with the guidelines.
 The other 19 prescribed in accordance with the guidelines for 30 of 52 infants.
 Decisions to investigate and treat with phototherapy were affected by clinical and parental factors in addition to the guidelines.
 Two of the 25 physicians interviewed stated that the interview would influence their management of future cases of hyperbilirubinemia.
 CONCLUSION: A clinical recall interview can have a greater impact on changing physician management practices than factual communication on a group basis.
",17
3007,"Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta 
 BACKGROUND.
 Reduced synthesis of endothelium-derived relaxing factor (EDRF) may explain impaired endothelium-dependent vasodilation in hypercholesterolemia.
 Accordingly, we designed studies to determine if endothelium-dependent relaxation in hypercholesterolemic rabbits may be restored by supplying L-arginine, the precursor of EDRF.
 METHODS AND RESULTS.
 Normal or hypercholesterolemic rabbits received intravenous L-arginine (10 mg/kg/min) or vehicle for 70 minutes.
 Subsequently, animals were killed, thoracic aortas were harvested, and vascular rings were studied in vitro.
 Rings were contracted by norepinephrine and relaxed by acetylcholine chloride or sodium nitroprusside.
 Vasorelaxation was quantified by determining the maximal response (expressed as percent relaxation of the contraction) and the ED50 (dose of drug inducing 50% relaxation; expressed as -log M).
 In vessels from hypercholesterolemic animals receiving vehicle, there was a fivefold rightward shift in sensitivity to acetylcholine compared with normal animals (p = 0.05, n = 5 in each group).
 In vessels from hypercholesterolemic animals, L-arginine augmented the maximal response to acetylcholine (83 +/- 16% versus 60 +/- 15%, p = 0.04 versus vehicle) and increased the sensitivity to acetylcholine (ED50 value: 6.7 +/- 0.2 versus 6.2 +/- 0.2, p less than 0.05 versus vehicle).
 Arginine did not affect maximal and EC50 responses to acetylcholine in vessels from normal animals.
 Arginine did not potentiate endothelium-independent responses in either group.
 CONCLUSIONS.
 We conclude that the endothelium-dependent relaxation is normalized in hypercholesterolemic rabbit thoracic aorta by in vivo exposure to L-arginine, the precursor for EDRF.
",17
3008,"Comparison of the effects of hypertonic sucrose and intracellular potassium depletion on growth hormone receptor binding kinetics and down-regulation in IM-9 cells: evidence for a sequential block of receptor--mediated endocytosis.
 To better understand the complex kinetics of human GH (hGH) binding to its receptors, we have further investigated, in IM-9 cultured human lymphocytes, the cellular locus corresponding to the slowly dissociating component of hormone binding, and to the homologous down-regulation of hGH receptors.
 First, we have detailed the biphasic kinetics of dissociation of bound hormone in control cells at 30 C.
 When the association at 30 C was extended from 0.5 to 3 h, the time required for half-dissociation of the fast component was slightly decreased (from 30 to 15 min) but that of the slow component increased considerably (from 6 h to 30 h).
 Concomitantly, the size of the slowly dissociating component increased from 50 to 80% of total.
 This indicates a maturation of bound hormone, from a rapidly to a slowly dissociating pool and, in the latter, an increase in the apparent affinity that may reflect a molecular rearrangement.
 Next, we have compared the effect of two procedures reported to inhibit receptor-mediated endocytosis at the level of coated pits.
 As previously reported, depletion of intracellular K+ abolished the slowly dissociating component and the down-regulation of hGH receptors.
 In contrast, upon incubation with 0.4 M sucrose, which like K+ depletion virtually abrogated hGH internalization, the dissociation kinetics remained non-first order, and the down-regulation of hGH-receptor was only slightly reduced.
 Thus, these procedures appear to block receptor-mediated endocytosis at two successive compartments of the cell surface.
 In conclusion, we propose that some conformational change of hGH-receptor at the cell surface (possibly associated with clustering) may considerably slow down their dissociation and may be sufficient for down-regulation.
",17
3009,"Defective tolerance to the toxic and metabolic effects of interleukin 1.
 The effect on food intake, body weight, and survival of mice given recombinant lipopolysaccharide (LPS), tumor necrosis factor/cachectin (TNF), or interleukin 1 (IL-1) (5 micrograms/mouse, ip, twice daily) was studied.
 All agents induced a rapid reduction of food intake and body weight after 1 day of treatment.
 Unlike TNF and LPS, IL-1 given as two daily administrations of 5 micrograms was lethal within 3 days.
 Mice treated with LPS or TNF rapidly developed tolerance to their anorectic effect, whereas tolerance to IL-1 required a longer time to develop and was not complete.
 We investigated the possible roles of changes in serum corticosterone and glucose in the effects of LPS, TNF and IL-1.
 A single injection of LPS, TNF, or IL-1 markedly increased serum corticosterone levels after 2 h.
 After only 2 days of chronic treatment, mice given LPS or TNF were refractory to induction of serum corticosterone by a subsequent injection of LPS or TNF, but mice given IL-1 for 2 days were still fully responsive to IL-1.
 IL-1, unlike TNF and LPS, induced a marked hypoglycemic response.
 Repeated administration of IL-1 sensitized to its hypoglycemic effect.
 This lack of adaptation to the increase of serum corticosterone and hypoglycemia was also observed when IL-1 was given at lower, nonlethal doses (0.25-1.0 microgram) and for a longer period (up to 8 days).
 The defective tolerance to the metabolic and toxic effects of IL-1 in this experimental model indicates that there are major differences between the in vivo biological responses to IL-1 and TNF.
",17
3010,"Frequency and effects of apolipoprotein E polymorphism in Mexican-American NIDDM subjects.
 We typed 254 non-insulin-dependent diabetic (NIDDM) Mexican Americans living in Starr County, Texas, for the three common apolipoprotein E (apoE) alleles.
 Typing was performed via DNA amplification and Hha I restriction.
 The allele frequencies (epsilon 2 = 0.041, epsilon 3 = 0.860, epsilon 4 = 0.099) were in Hardy-Weinberg equilibrium (chi 2 = 0.60, df = 3) and did not differ from a random sample from the same population (chi 2 = 0.16, df = 2).
 Analysis of variance was used to test for mean differences in lipid, lipoprotein, and glucose levels among apoE types.
 Significant differences among types were detected for low-density lipoprotein cholesterol (LDL-chol; P = 0.042, R2 = 2.6) and beta-lipoprotein cholesterol (P = 0.019, R2 = 3.3) levels.
 Mean LDL-chol in E2/3 individuals was 2.69 mM, E3/3 was 3.26 mM, and E4/3 was 3.36 mM.
 Mean beta-lipoprotein cholesterol in E2/3 individuals was 3.05 mM, E3/3 was 3.64 mM, and E4/3 was 3.67 mM.
 Based on these results, we conclude that the effects of the apoE polymorphism on lipid profiles and glucose levels are the same in NIDDM subjects as in nondiabetic Mexican Americans and other populations.
 Other studies investigating the role of apoE polymorphism in diabetic subjects have found increased triglyceride levels in individuals possessing an epsilon 2-allele and an increased frequency of the epsilon 2-allele in hyperlipidemic diabetic subjects.
 We found no significant difference in mean triglyceride levels among genotypes.
 Possible reasons for this discrepancy are discussed, including DNA- versus protein-typing methods.
",17
3011,"Blunted diuretic and natriuretic responses to central administration of clonidine in streptozocin-induced diabetic rats.
 The purpose of this study was to determine whether diuretic and natriuretic effects are altered in response to intracerebroventricular (ICV) infusion of clonidine in diabetic rats.
 Diabetes was induced in male Sprague-Dawley rats by 65 mg/kg i.p.
 injection of streptozocin, and control rats were injected with vehicle 2 wk before the experiment.
 Blood glucose levels were significantly elevated in the diabetic group (26.3 +/- 1.3 mM) compared with the control group (8.4 +/- 1.6 mM).
 Before and during ICV infusion of clonidine (2 micrograms.kg-1.min-1 for 45 min), urine flow and sodium excretion were measured from intact and denervated kidneys in anesthetized diabetic and control rats.
 The ICV infusion of clonidine significantly increased urine flow in both innervated and denervated kidneys from control rats but not from diabetic rats.
 There was a significant increase in sodium excretion during ICV infusion of clonidine from innervated kidneys of control rats, and denervation abolished this effect.
 In diabetic rats, clonidine failed to promote natriuresis from intact kidneys, and similar to control rats, did not promote natriuresis in denervated kidneys.
 This study demonstrates that 1) the diuretic response to the ICV infusion of clonidine is blunted in diabetic rats, and 2) a natriuretic response to the ICV infusion of clonidine is blunted in innervated kidneys of diabetic rats.
",17
3012,"Changes in hepatic glutathione metabolism in diabetes.
 Glutathione is important in the regulation of the redox state, and a decline in its tissue level has often been considered to be indicative of increased oxidative stress in diabetes.
 In this study of diabetic rats, the level of hepatic glutathione was normal unless food intake was restricted.
 Thus, the previous report of a reduction in hepatic glutathione in diabetes is likely to be the result of food deprivation rather than diabetes alone.
 In contrast to changes characteristic of oxidative stress, the efflux of glutathione in bile from diabetic animals was significantly decreased, whereas hepatic mixed disulfides were unchanged, and the hepatic gamma-glutamyltransferase activity was considerably increased.
 These changes were not reproduced by food deprivation.
 The decrease in biliary excretion of glutathione in diabetes may reflect an attempt to conserve glutathione by activation of the hepatic gamma-glutamyl cycle.
 We conclude that the disturbances of glutathione metabolism in diabetes are not typical of those seen in oxidative stress or food restriction.
",17
3013,"Lack of evidence for improvement in long-term glycemic control by pulsatile insulin infusion in streptozocin-induced diabetic baboon.
 To assess the potential therapeutic use of pulsatile intravenous insulin delivery, five streptozocin-induced diabetic baboons were treated with alternate 3- to 6-wk periods of pulsatile and continuous insulin infusion.
 Time-averaged insulin concentrations were matched during two pulsatile administration periods (P1 and P2) and an intervening period of continuous insulin administration (C).
 There were no significant differences among the overall means of four daily glucose determinations performed during the three periods (P1, 5.7 +/- 1 mM; C, 5.6 +/- 0.9 mM; P2, 5.3 +/- 0.9 mM); the mean M value, a measure of the stability of glycemic control (P1, 4 +/- 1.7; C, 3.9 +/- 1.8; P2, 3.6 +/- 1.5); the percentage of glucose values less than 2.8 mM (P1, 13 +/- 8.5%; C, 14 +/- 12%; P2, 13 +/- 9.1%); or the glycosylated hemoglobin levels determined at the end of the P1 and C (7.5 +/- 3.4 and 6.5 +/- 1.8%, respectively [all values are means +/- SD]).
 Fasting hepatic glucose production was suppressed to a similar degree during pulsatile and continuous insulin infusion (P1, 23 +/- 3 mumol.kg-1.min-1; C, 24 +/- 8 mumol.kg-1.min-1).
 Arterial glucagon levels were similar during pulsatile and continuous insulin infusion, both in the fasting state (84 +/- 29 and 84 +/- 31 ng/L, respectively) and postprandially (30 +/- 14 and 27 +/- 12 ng/L, respectively).
 Pulsatile insulin infusion failed to entrain a corresponding glucagon secretory rhythm.
 These data suggest that the metabolic consequences of long-term pulsatile and continuous insulin infusion in an animal model of human non-insulin-dependent diabetes are comparable.
",17
3014,"Independent effects of youth and poor diabetes control on responses to hypoglycemia in children.
 To evaluate the effects of childhood and poorly controlled insulin-dependent diabetes mellitus (IDDM) on counterregulatory hormone and symptomatic responses to hypoglycemia, we studied 16 nondiabetic children (13 +/- 2 yr), 19 nondiabetic adults (26 +/- 3 yr), and 13 children with IDDM (14 +/- 2 yr, HbA, 15.1 +/- 3.3%) during a gradual reduction in plasma glucose with the glucose-clamp technique.
 Plasma glucose was reduced from approximately 5 to approximately 2.8 mM over 240 min with serial assessment of counterregulatory hormone levels and symptom awareness.
 The plasma glucose level that triggered a sustained rise in plasma epinephrine was consistently higher in nondiabetic children than in adults (3.9 +/- 0.06 vs.
 3.2 +/- 0.06 mM, P less than 0.001).
 Poorly controlled IDDM further elevated the glucose threshold for epinephrine release to normoglycemic levels (4.9 +/- 0.2 mM, P less than 0.001 vs.
 both control groups).
 Age and IDDM also produced an upward shift in the glucose level at which growth hormone release and symptom awareness were initiated.
 In contrast to the effect on glucose thresholds, maximal epinephrine responses and symptom scores were increased only by age and not IDDM (2-fold higher in children).
 We conclude that childhood and poor diabetes control independently contribute to an upward shift in glucose thresholds for counterregulatory hormone release and symptom awareness during mild hypoglycemia.
 Normoglycemic counterregulation may interfere with efforts to control diabetes in young patients.
",17
3015,"Use of X-ray diffraction in study of human diabetic and aging collagen.
 Extensive investigations of the solubility and fluorescence of collagen fibers in diabetes have revealed that there are significant changes in their physical properties.
 These changes are associated with increased cross-link formation.
 We used X-ray diffraction to study these changes in human extensor tendons at a molecular level in relation to both aging and diabetes.
 Our results indicate that diabetes induces significant alterations in the ultrastructure of collagen in the lateral packing of the molecules and the axial structure of the specimen.
 These changes can be induced in normal tendon by incubation in ribose and glucose-6-phosphate but are different from those associated with the normal process of aging.
",17
3016,"Pretranslational suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with non-insulin-dependent diabetes mellitus and obesity.
 A major portion of insulin-mediated glucose uptake occurs via the translocation of GLUT 4 glucose transporter proteins from an intracellular depot to the plasma membrane.
 We have examined gene expression for the GLUT 4 transporter isoform in subcutaneous adipocytes, a classic insulin target cell, to better understand molecular mechanisms causing insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) and obesity.
 In subgroups of lean (body mass index [BMI] = 24 +/- 1) and obese (BMI = 32 +/- 2) controls and in obese NIDDM (BMI = 35 +/- 2) patients, the number of GLUT 4 glucose transporters was measured in total postnuclear and subcellular membrane fractions using specific antibodies on Western blots.
 Relative to lean controls, the cellular content of GLUT 4 was decreased 40% in obesity and 85% in NIDDM in total cellular membranes.
 In obesity, cellular depletion of GLUT 4 primarily involved low density microsomes (LDM), leaving fewer transporters available for insulin-mediated recruitment to the plasma membrane (PM).
 In NIDDM, loss of GLUT 4 was profound in all membrane subfractions, PM, LDM, as well as high density microsomes.
 These observations corresponded with decrements in maximally stimulated glucose transport rates in intact cells.
 To assess mechanisms responsible for depletion of GLUT 4, we quantitated levels of mRNA specifically hybridizing with human GLUT 4 cDNA on Northern blots.
 In obesity, GLUT 4 mRNA was decreased 36% compared with lean controls, and the level was well correlated (r = + 0.77) with the cellular content of GLUT 4 protein over a wide spectrum of body weight.
 GLUT 4 mRNA in adipocytes from NIDDM patients was profoundly reduced by 86% compared with lean controls and by 78% relative to their weight-matched nondiabetic counterparts (whether expressed per RNA, per cell, or for the amount of CHO-B mRNA).
 Interestingly, GLUT 4 mRNA levels in patients with impaired glucose tolerance (BMI = 34 +/- 4) were decreased to the same level as in overt NIDDM.
 We conclude that, in obesity, insulin resistance in adipocytes is due to depletion of GLUT 4 glucose transporters, and that the cellular content of GLUT 4 is determined by the level of encoding mRNA over a wide range of body weight.
 In NIDDM, more profound insulin resistance is caused by a further reduction in GLUT 4 mRNA and protein than is attributable to obesity per se.
 Suppression of GLUT 4 mRNA is observed in patients with impaired glucose tolerance, and therefore, may occur early in the evolution of diabetes.(ABSTRACT TRUNCATED AT 400 WORDS).
",17
3017,"Differential regulation of adipose tissue glucose transporters in genetic obesity (fatty rat). Selective increase in the adipose cell/muscle glucose transporter (GLUT 4) expression.
 Adipocytes from young obese Zucker rats exhibit a hyperresponsive insulin-mediated glucose transport, together with a marked increase in cytochalasin B binding as compared with lean rat adipocytes.
 Here, we examined in these cells the expression of two isoforms of glucose transporter, the erythroid (GLUT 1) and the adipose cell/muscle (GLUT 4) types, in rats aged 16 or 30 d, i.e., before and after the emergence of hyperinsulinemia.
 GLUT 1 protein and mRNA levels were identical in the two genotypes at both ages.
 In contrast, the levels of GLUT 4 protein in obese rat adipocytes were 2.4- and 4.5-fold those of lean littermates at 16 and 30 d of age, respectively, in perfect agreement with the genotype effect on insulin-stimulated glucose transport activity.
 The levels of GLUT 4 mRNA per fat pad were increased 2.3- and 6.2-fold in obese vs.
 lean rats 16- and 30-d-old, indicating a pretranslational level of regulation.
 The obese phenotype was not associated with overexpression of GLUT 4 mRNA in gastrocnemius muscle.
 This work indicates that the fa gene exerts a differential control on the expression of GLUT 1 and GLUT 4 in adipose tissue and provides evidence that independent of hyperinsulinemia, genotype is a major regulatory factor of GLUT 4 expression in this tissue.
",17
3018,"Randomised prospective study of short-term and long-term initial stay in hospital by children with diabetes mellitus.
 To assess how an isolated change in the pattern of care influences outcome of care and hospital use, a randomised prospective 2-year study was done in which 31 of 61 consecutive children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) were admitted to hospital at disease onset for about a week and compared with the other 30 children who were admitted for about 4 weeks.
 Insulin treatment and education about diabetes were similar in the two groups.
 Duration of initial stay in hospital had no effect on metabolic control during the 2 years but time since diagnosis was significant with respect to effect on haemoglobin A1 (p = 0.001), haemoglobin A1c (p = 0.004), and insulin dose (p less than 0.001).
 At 2 years, 45% of the children in the short-term group and 29% in the long-term group were C-peptide positive (p = NS); C-peptide positivity correlated with age.
 A change in the pattern of care of children with IDDM, led to a pronounced decrease in hospital use by this patient group.
 Irrespective of the length of initial stay in hospital, equally good metabolic control was obtained in both groups for 2 years.
",17
3019,"Intensive management of type II diabetes.
 The goals of intensive treatment of type II diabetes are to restore blood glucose levels to normal; correct hyperlipidemia, hypertension, and other cardiovascular risk factors; and prevent hyperinsulinemia.
 Treatment should begin with attempts to reduce weight through diet and exercise.
 In fact, diet and exercise should be stressed as vital components of a diabetic patient's life-style no matter what treatment method is used.
 Drug treatment may consist of a sulfonylurea to increase insulin secretion and improve insulin resistance or of exogenous insulin to achieve glucose control and avoid the dangers of chronic hyperglycemia.
 A combination of the two appears attractive but is still under investigation.
 Control of hypertension is mandatory and may require use of an angiotensin-converting enzyme inhibitor or calcium channel blocker.
 Normalization of serum lipid levels is also important in these patients, and agents that adversely affect glucose levels must be avoided.
",17
3020,"Postheparin lipolytic activity and plasma lipoprotein response to omega-3 polyunsaturated fatty acids in patients with primary hypertriglyceridemia.
 The hypotriglyceridemic action of omega-3 (n-3) fatty acids is attributed primarily to reduction in hepatic triglyceride synthesis and reduced secretion of very-low-density lipoproteins (VLDLs).
 However, increased catabolism of triglyceride-rich lipoproteins was reported and could be due to increased availability of peripheral lipoprotein lipase (LPL) or hepatic lipase (HL).
 In this study plasma lipoproteins and postheparin activities of LPL and HL were determined in 12 patients with primary hypertriglyceridemia before and during isocaloric substitution of omega-3 fatty acids (10 g/d) for 4 wk.
 Omega-3 polyunsaturates resulted in 53% and 61% reductions in plasma triglyceride and VLDL-cholesterol concentrations, respectively (P less than 0.0001).
 However, low-density-lipoprotein (LDL)-cholesterol concentrations increased by 26% (P less than 0.001).
 Activities of postheparin LPL and HL essentially remained the same.
 Thus, in patients with primary hypertriglyceridemia, reduction in plasma triglyceride concentrations and increase in LDL-cholesterol concentrations mediated by omega-3 polyunsaturates seem to occur without an increase in LPL or HL activities.
",17
3021,"Fat absorption in neonates: comparison of long-chain-fatty-acid and triglyceride compositions of formula, feces, and blood.
 We studied malabsorption of fat in neonates who were fed either a lard-modified formula (n = 22, gestational age, 33.6 +/- 3.9 wk) or an unmodified formula (n = 14, gestational age, 34.1 +/- 3.7 wk).
 In both groups fecal lipid consisted almost completely (greater than 90%) of free fatty acids, whose composition was highly correlated with the corresponding formula's fatty acid composition [r = 0.96 (lard modified) and r = 0.99 (standard)].
 Both groups had similar relative amounts and compositions of fecal cholesterol esters and triglycerides.
 Plasma and, to a lesser extent, erythrocyte membrane long-chain-fatty-acid compositions correlated with those of the corresponding formulas.
 We suggest that the extensive intestinal hydrolysis and limited absorption of dietary lipids is, at least partly, due to lipolysis in the colon.
 Appearance of triglycerides in the colon may be due to a rapid small-intestinal passage in relation to small-intestinal lipolysis.
",17
3022,"Lactose maldigestion and milk intolerance in healthy Greek schoolchildren.
 The prevalence of lactose maldigestion in Greek adults is 75% but the age at which the lactase activity starts declining is not known.
 The prevalences of lactose maldigestion and intolerance were investigated in 150 randomly selected Greek children 5-12 y old by using breath-hydrogen analysis after ingestion of lactose (2 g/kg body wt, maximum 50 g) or 0.240 L of milk.
 Prevalence of lactose maldigestion increased with age (y = -7.30 + 6.49x, r = 0.88, P = 0.004), being 29.4% and 80.0% at ages 5 and 12 y, respectively.
 Before testing, the reported prevalences of milk-related symptoms by children with high and low lactose-digestion capacity were 21.1% and 39.7% (chi 2 = 5.96, P = 0.015), respectively.
 However, the corresponding prevalences of lactose intolerance after ingestion of milk were 7.3% and 8.6% (chi 2 = 0.1, P = 0.72) and only three children had a delta H2 greater than or equal to 20 ppm postprandially.
 Although intestinal lactase activity declines before age 5 y and many Greek children report milk-related symptoms, true malabsorption and intolerance of lactose after a glass of milk is rarely seen at this age.
",17
3023,"Brain uptake of glucose in diabetes mellitus: the role of glucose transporters.
 It is not known if the diabetes-related reduction in blood-brain barrier (BBB) transport of glucose is due to a change in the functional capacity of transporters or to an as yet unidentified mechanism occurring at the plasma membrane or cytoplasm.
 To increase our understanding of this problem, the cerebral blood flow, the brain uptake index (BUI) of 3-O-methyl glucose and the concentration of 3H-cytochalasin B binding sites were determined in diabetic rats and diabetic rats treated with insulin.
 The BUI of 3-O-methyl glucose was significantly reduced (less than 0.001) in diabetic rats (32.7 +/- 1.2%) compared to control rats (41.9 +/- 1.0%).
 This change could not be attributed to an alteration in cerebral blood flow or to a non-specific change in BBB permeability.
 Normalization of blood glucose with insulin therapy corrected the BUI measurements in diabetic rats (42.2 +/- 1.4%).
 The level of measurable glucose transporters measured with 3H-cytochalasin B binding assay did not appear to be reduced in the diabetic brain microvessels.
 The data indicate that the reduced brain uptake of glucose in chronic hyperglycemia can occur in the absence of a change in glucose transporter concentration.
",17
3024,"Receptor autoimmunity in endocrine disorders.
 The discovery in 1956 of the long-acting thyroid stimulator of Graves' disease, now known as thyroid-stimulating antibodies, was seminal.
 A new mechanism for disease was revealed that appears applicable to virtually all endocrine systems, involving the growth as well as the function of endocrine cells.
 An endocrine gland may fail through at least three autoimmune mechanisms: destruction, atrophy, and inhibition of function.
 Destruction is probably irreversible but is not usually distinguishable clinically from receptor blockade causing atrophy or from metabolic unresponsiveness.
 The contribution made by receptor autoimmunity to endocrine diseases other than thyroid disease is at present unclear, but with immunologic manipulation it is potentially reversible, improving the replicative capacity of the gland, its metabolic responsiveness, or both.
",18
3025,"Correlation between first- and early third-trimester glucose screening test results.
 One hundred twenty-four normal gravidas had paired first- and early third-trimester (26-32 weeks) 1-hour oral glucose screening tests performed.
 First-trimester oral glucose screening test values correlated significantly with third-trimester glucose screening test results for the entire population, for whites and non-whites, and for normal-weight and obese patients.
 First-trimester oral glucose screening test values at or below 110 mg/dL were seldom associated with third-trimester oral glucose screening test results at or above 135 mg/dL and were not associated with abnormal 3-hour glucose tolerance test (GTT) results.
 Nine of the gravidas (7.3%) were diagnosed with gestational diabetes mellitus during the third trimester, all of whom had first-trimester glucose screening test results above 110 mg/dL.
 The difference in incidence of gestational diabetes mellitus between gravidas having first-trimester glucose screening test results at or below 110 mg/dL (0%) and those having values above 110 mg/dL (16.4%) was highly significant (P less than .0001).
 For patients with first-trimester glucose screening test values at or below 110 mg/dL, third-trimester glucose screening may be unnecessary.
 In contrast, for gravidas having first-trimester glucose screening test results at or above 135 mg/dL, there is a high positive predictive value for elevated repeat glucose screening test results during the early third trimester.
 Patients having elevated first-trimester glucose screening values at or above 140 mg/dL are at particularly high risk for elevated glucose screening test results later in pregnancy and should forego repeat 1-hour third-trimester glucose screening in favor of a direct third-trimester 3-hour GTT.
",18
3026,"Fructosamine compared with a glucose load as a screening test for gestational diabetes.
 Five hundred seven women were screened for gestational diabetes between 20-36 weeks' gestation.
 All received a 100-g glucose (polycose) load at 28 weeks with measurement of plasma glucose 1 hour later.
 Fructosamine levels were measured at 4-week intervals from 20-36 weeks.
 At 36 weeks, a full 100-g 3-hour glucose tolerance test was performed on all subjects.
 Eighteen women were diagnosed as having gestational diabetes.
 The glucose load had a sensitivity of 81% in detection of gestational diabetes, compared with 50% for fructosamine at 36 weeks.
 Fructosamine is not useful as a screening test for gestational diabetes as currently defined.
",18
3027,"Diagnosis and management of precocious puberty.
 The onset of pubertal development before the age of 8 years in girls or 9 years in boys constitutes precocious puberty.
 There are numerous causes of precocious puberty, which can be classified as central or peripheral precocious puberty.
 Central precocious puberty results from premature activation of the hypothalamic-pituitary-gonadal axis and thus presents with physical and hormonal findings similar to those found in normal puberty.
 Peripheral precocious puberty results from extrapituitary gonadotropin secretion or secretion of sex steroids independent of pituitary gonadotropins.
 All types of precocious puberty are characterized by rapid growth and advancement of skeletal age, leading to the paradox of the tall child becoming a short adult as a result of premature epiphyseal fusion.
 Long-acting GnRH agonists afford effective, selective, and reversible therapy of central precocious puberty without significant toxicity.
 GnRH agonists are not effective in managing the premature sexual maturation associated with peripheral precocious puberty, but a number of other agents have been used with some success.
 These agents include testolactone, ketoconazole, and medroxyprogesterone acetate.
 GnRH agonist treatment leads to an increase in predicted final height.
 To determine the true benefit of any of these agents in increasing ultimate height, there is a need for continuing studies in treated cohorts to follow growth patterns until adult stature is achieved.
",18
3028,"Hyperthyroidism in children and adolescents.
 Hyperthyroidism in infants and children usually is caused by Graves' disease; however, several other diseases can also produce hyperthyroidism in these age groups.
 Because the pathophysiology and clinical course of these conditions differ, optimal treatment depends on precise diagnosis.
",18
3029,"The Cushing syndromes.
 The 10 years since this journal's last review of CS have seen extraordinary advances in our understanding of many aspects of its causes, diagnosis, and treatment.
 The spectrum of what are now called the Cushing syndromes has expanded considerably to include CD, multiple sources of ectopic ACTH secretion, and an apparent autoimmune cause.
 Improved assays of ACTH and the availability of CRF have provided new insight into the physiology and pathophysiology of the HPA axis and new tools for diagnosis of CS, especially in combination with selective catheterization and sampling.
 New imaging technology has improved our visualization of pituitary adenomas and has provided powerful methods for identifying tumors ectopically secreting ACTH and primary adrenal tumors.
 Finally, the refinement of transsphenoidal surgery and its success in treating CD have provided a safe and effective therapy for this disease.
 For those occasional patients who require medical therapy, drugs are available that decrease steroid biosynthesis.
 We now have a much better understanding of a fascinating disease process and are able to diagnose and treat it more correctly.
 One is impatient to see which new pieces of this puzzle will fall into place over the next ten years.
",18
3030,"Primary and secondary testicular insufficiency.
 The possibility of testicular insufficiency is a common problem for the pediatric practitioner.
 Presentation varies with the severity of the defect, the developmental age achieved before onset, and the presence of associated other abnormalities.
 Most commonly, primary and secondary testicular insufficiency present at the time of puberty, but the presentation may be at birth or in the early neonatal period.
 Appropriate investigations may uncover the diagnosis at the time and allow intervention later at the appropriate age.
 Secondary testicular failure, although more difficult to diagnose and to differentiate from simple delay of development, offers the possibility of later development of spermatogenesis and the attainment of fertility through the use of gonadotropins or GnRH replacement programs.
 In primary testicular failure, because it implies an intrinsic abnormality of the functioning elements of the testis, spermatogenesis is not inducable by hormonal stimulation.
 Treatment of testicular failure in the neonatal period is unnecessary unless micropenis is associated.
 In the pubertal boy, testosterone replacement is the treatment of choice and should be initiated carefully, taking into consideration the age of the subject, his bone age, and the psychosocial circumstances.
 The goal of therapy is to achieve a normal progression of physical changes of puberty to physical maturity and the normal potential for sexual function.
",18
3031,"Adolescent gynecomastia. Differential diagnosis and management.
 Gynecomastia signifies a transient or permanent disturbance in steroid hormone physiology and occurs when the male breast is exposed to a decreased ratio of androgen to estrogen.
 This article discusses pubertal and pathologic gynecomastia, diagnostic approach, and treatment.
",18
3032,"Disorders of sexual differentiation and development. Psychological aspects.
 Children with abnormalities in sexual differentiation and development can have a smooth course of psychosocial development in spite of the significant risks and challenges they face.
 Chances for a positive emotional outcome are made more likely by the careful handling of these patients at the time of first presentation.
 Parents' unambiguous acceptance of the child's sex of rearing and early surgical intervention to normalize the child's external genital appearance are critical elements in a positive outcome.
 Further, the patterns of behavior documented in the materials reviewed in this article suggest difficulties of immaturity and social development rather than significant psychopathology.
 Parent-child interactions were repeatedly found to be central to the child's emotional well-being, underscoring the need to provide parents with adequate counsel and support.
 These patterns, however, represent findings across groups of patients and cannot predict the emotional, social, or academic functioning of any individual.
 Within all these clinical syndromes there is great individual variation in social, emotional, and physical presentation.
 Finally, rather than minimizing problems, physicians need to educate parents so they can be active advocates for their children in the educational and social arenas.
",18
3033,"Mathematical models of myosin heterodimer formation in the rat heart during thyroid hormone alterations.
 To characterize the mechanisms involved in the formation of the myosin heavy chain (MHC) heterodimer V2 (alpha beta-MHC) and the homodimers V3 (beta beta-MHC) and V1 (alpha alpha-MHC), 82 5-week-old normotensive rats with homogeneous V1 were made hypothyroid with propylthiouracil (0.8%, drinking water), and the proportion of V2, V3, and V1 was determined by pyrophosphate gel electrophoresis in multicellular specimens of the left and right ventricles.
 After the switch from alpha-MHC to beta-MHC, the beta-MHC occurred initially in the form of the heterodimer.
 After 4 and 6 days, V2 was greater (p less than 0.05) than V3.
 At day 8, V2 was smaller than V3, and at day 10, V2 was not statistically different from V3.
 From day 12 onward, V2 was smaller than V3.
 After 21 days, the propylthiouracil treatment was stopped, and the remaining 34 hypothyroid rats were injected with a daily dose of thyroxine (average, 0.1 mg/kg body wt), resulting in a switch from beta-MHC to alpha-MHC.
 After 1 day, V2 still was greater than V1; however, already from day 3 onward, V2 was smaller than V1.
 This characteristic but unexplained heterodimeric and homodimeric organization of the thick filament was analyzed by mathematical models involving probability calculations.
 Two principally different models were established that assume either the exchange of MHC dimers or of single MHC in the thick filament.
 The parameters of the models were estimated by minimization routines using the squared discrepancies between the experimental and predicted isoenzyme populations.
 Based on goodness of fit and crucial model parameters, we concluded that the characteristic organization of the thick filament can be accounted for by an exchange involving predominantly MHC dimers and not single MHC.
 The fact that V2 was lower than expected if formation of heterodimers and homodimers were random was attributed to the preferred homodimerization of 35% of the newly synthesized MHC.
",18
3034,"Disparate effects of colchicine on thyroxine-induced cardiac hypertrophy and adrenoceptor changes.
 Short-term (5 days) administration of L-thyroxine (0.1 mg/kg i.p.
 daily) to adult Sprague-Dawley rats induces a modest degree of cardiac hypertrophy (22% increase in heart weight/body weight ratios) and directionally opposite changes in cardiac adrenoceptors (24% increase in beta-adrenoceptors and 20% decline in alpha 1-adrenoceptors).
 Pretreatment with colchicine did not affect the ability of L-thyroxine to induce cardiac hypertrophy but prevented its effects on both beta- and alpha 1-adrenoceptors.
 These results suggest a selective involvement of microtubules in the action of thyroid hormones on the expression of cardiac adrenoceptor genes.
",18
3035,"Chronic diabetic complications and tissue glycosylation. Relevant concern for diabetes-prone black population.
 A significant segment of the Black population is affected by chronic diabetes, and most of them are subjected to severe cardiovascular, renal, and neurological complications that shorten survival and diminish quality of life.
 One of the important pathogenetic mechanisms under intensive investigation is advanced tissue glycosylation.
 Tissue and cell surface proteins modified nonenzymatically by glucose are shown to be highly active in protein cross-linking and have been implicated in tissue damage.
 Such protein-glucose interactions, called advanced glycosylation end products (AGEs), are processed by macrophages through a high-affinity receptor.
 Coupling of AGE proteins to their AGE receptors results in their degradation and removal and, simultaneously, in synthesis and secretion of pluripotential cytokines such as tumor necrosis factor and interleukin 1.
 This suggests that AGE may act normally as a signal for growth-promoting factor secretion in a coordinated replacement process during tissue remodeling.
 In chronic diabetes, however, where accelerated accumulation of tissue AGE occurs, a disturbance of this balance may lead to several pathological, lytic, and/or proliferative responses like those in the vasculopathy of diabetes.
 Progress has been made with the discovery of aminoguanidine HCl, an AGE inhibitor, which has prevented significant pathology in short-term diabetic animal studies.
",18
3036,"Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism.
 We studied a large population (n = 2575) of unselected ambulatory persons older than 60 years to determine the prevalence of a low serum thyroid-stimulating hormone (TSH) level, ie, of less than 0.1 mU/L using a sensitive assay, a level suggestive of hyperthyroidism in younger adults.
 One hundred one persons (3.9%) had a low serum TSH level.
 About half of them (51/101) were taking thyroid hormone.
 Of the remainder, 44 were not hyperthyroid did not become so during up to 4 years of follow-up.
 Forty-one of the 44 euthyroid persons had a serum thyroxine level of less than 129 nmol/L; repeated testing showed a serum TSH level of more than 0.1 mU/L in the three euthyroid persons with a serum thyroxine level of more than 129 nmol/L.
 Only six were hyperthyroid or became so during the follow-up period; all had a serum thyroxine level of more than 129 nmol/L.
 Routine clinical examination was not a sensitive indicator of hyperthyroidism and did not permit discrimination from euthyroidism.
 A low value of serum TSH alone, while it had high sensitivity and specificity for hyperthyroidism, had a low positive predictive value (12%) for this diagnosis; addition of the thyroxine assay raised the predictive value fivefold to 67%.
 A low value of serum TSH is far more common in older persons than is hyperthyroidism.
 Low values in euthyroid persons are accompanied by a clearly normal serum T4 concentration (less than 129 nmol/L) or by a serum TSH level of more than 0.1 mU/L on repeated testing.
 We recommend measurement of the serum TSH thyroid concentration, using a sensitive assay, as the initial step in testing any older person for possible hyperthyroidism.
 Measurement of the serum T4 concentration or the free T4 index on the same sample would be needed only in the approximately 2% with a serum TSH level of less than 0.1 mU/L; alternatively, the TSH assay in these could be repeated at a later time.
",18
3037,"Nature of altered growth hormone secretion in hyperthyroidism.
 Hyperthyroidism is accompanied by various neuroendocrine regulatory disturbances that affect not only the thyrotropic, but also the gonadotropic, corticotropic, and somatotropic axes.
 To examine the nature of alterations in neuroendocrine control mechanisms that direct the somatotropic axis in hyperthyroidism, we have applied a novel deconvolution technique designed to estimate the number, amplitude, and mass of significant underlying GH secretory events after the influence of GH metabolic clearance has been removed mathematically.
 To this end, blood was sampled at 10-min intervals for 24 h in seven hyperthyroid and seven age-matched euthyroid men.
 The subsequent GH time series were assayed by immunoradiometric assay (sensitivity, 0.08 ng/mL) and submitted to quantitative deconvolution analysis.
 We found that hyperthyroid compared to euthyroid men 1) had significantly more GH secretory bursts per 24 h (viz.
 15 +/- 1.0 vs.
 10 +/- 1.1; P = 0.017); 2) secreted 3 times as much GH per burst (3.7 +/- 0.80 vs.
 1.3 +/- 0.42 ng/mL distribution vol; P = 0.013); 3) achieved a maximal rate of GH secretion in each burst 2.3-fold higher than that in control men (0.14 +/- 0.028 vs.
 0.060 +/- 0.015 ng/mL.min; P = 0.017); and 4) had 3.7-fold higher 24-h endogenous GH production rates (P less than 0.01).
 Neither hyperthyroid nor euthyroid men had significant interburst (tonic) GH secretion.
 We conclude that the somatotropic axis in hyperthyroid men is marked by a higher frequency of spontaneous GH secretory bursts, a higher rate of maximal GH secretion attained per burst, and a larger mass of GH released per burst.
 These neuroregulatory disturbances result in a nearly 4-fold increase in the 24-h production rate of GH in thyrotoxicosis.
",18
3038,"Falsely elevated serum parathyroid hormone levels due to immunoglobulin G in a patient with idiopathic hypoparathyroidism.
 A 73-yr-old patient with idiopathic hypoparathyroidism was admitted to our hospital in May 1981.
 The immunoreactive PTH (iPTH) level determined by RIA using antiserum specific for the C-terminal region of PTH-(65-69) was in the upper normal range (0.6 ng/mL) and over the next 7 yr increased gradually to 6 ng/mL.
 Since iPTH levels determined using other commercial RIA kits remained constantly decreased or in the undetectable range, we studied the mechanism of false elevation of iPTH in this patient.
 The patient's serum contained no binding protein to the tracer ([125I]) [Tyr45] human PTH-(46-84)), nor was any heterophilic antibody to the first [guinea pig immunoglobulin G (IgG)] or the second antibody (goat IgG) detected.
 Consistent with these findings, the dilution curve of the serum was parallel with that of standard bovine PTH-(1-84).
 Gel filtration analysis revealed that the iPTH-like substance was eluted in the void volume (apparent mol wt, greater than 70,000).
 Almost all of the iPTH-like substance was adsorbod by a protein-A-Sepharose column.
 When the IgG fraction purified by protein-A-Sepharose affinity chromatography was applied to an antihuman IgG lambda-Sepharose column, 72% of the iPTH-like substance was detected in the IgG lambda.
 These results suggest that the falsely elevated iPTH in the patient's serum was due to IgGs (mainly IgG lambda), which were cross-reactive with the antiserum highly specific for the C-terminal region of human PTH-(65-69).
",18
3039,"3 alpha-Androstanediol glucuronide in premature and normal pubarche.
 To investigate the role of adrenal androgens in 3 alpha-androstanediol glucuronide (3AG) production in childhood, we compared serum 3AG and androgen levels [dehydroepiandrosterone (DHEA), DHEA sulfate (DS), androstenedione (delta 4-A), and testosterone (T)] in 32 children with premature pubarche due to idiopathic premature adrenarche (IPA; n = 26), partial 21-hydroxylase deficiency (n = 2), or 3 beta-hydroxysteroid dehydrogenase deficiency (n = 4) with those in 36 normal prepubertal (18 males and 18 females) and 22 normal pubertal Tanner II-III subjects (10 males and 12 females).
 Serum 3AG (2.7 +/- 2.0 nmol/L) and all androgen concentrations in children with IPA were significantly higher (P less than 0.05-0.001) than those in normal prepubertal children (3AG, 0.8 +/- 0.5 nmol/L).
 Serum 3AG and androgen levels, except T, in all children with premature pubarche due to 21-hydroxylase deficiency or 3 beta-hydroxysteroid dehydrogenase deficiency were higher than those in the normal prepubertal children.
 Serum 3AG and all androgen levels in normal Tanner II-III male (3AG, 3.8 +/- 1.7 nmol/L) or female (3AG, 1.74 +/- 0.52 nmol/L) subjects were also significantly higher (P less than 0.05-0.001) than those in prepubertal children.
 Serum 3AG, DHEA, DS, and delta 4-A levels in children with IPA were similar to those in normal Tanner II-III females or males, but serum T in children with IPA (0.37 +/- 0.2 nmol/L) was significantly lower (P less than 0.05-0.001) than that in normal pubertal females (0.71 +/- 0.37 nmol/L) or males (4.5 +/- 2.6 nmol/L).
 In the combined group (n = 88), 3AG levels correlated better with serum DS (r = 0.7), DHEA (r = 0.6), and delta 4-A (r = 0.52), than with T (r = 0.31) levels.
 These data suggest that the weak adrenal androgens DS, DHEA, and delta 4-A contribute substantially to 3AG production in premature and normal pubarche.
",18
3040,"Pulsatile thyrotropin release and thyroid function in acromegalics before and during subcutaneous octreotide infusion.
 The pulsatile secretion of TSH was studied in eight patients with active acromegaly before treatment and after 1 month of therapy consisting of the sc infusion of 300 micrograms octreotide/day.
 Mean GH levels decreased from 37.1 +/- 7.2 to 5.2 +/- 1.4 mU/L (P = 0.002).
 Insulin-like growth factor-I levels decreased from 82.9 +/- 8.8 to 37.8 +/- 9.8 nmol/L (P less than 0.01) and normalized in five of the eight patients.
 In one patient TSH levels were undetectable before and during octreotide therapy.
 In the other seven patients, Cluster analysis revealed 11.9 +/- 0.8 pulses/24 h, with a mean pulse width of 81 +/- 4.6 min, a mean pulse height of 1.33 +/- 0.42 mU/L, and a mean pulse increment of 0.36 +/- 0.12 mU/L.
 During octreotide therapy these pulse parameters remained unchanged.
 Pulse height and amplitude increased significantly during the night (i.e.
 from 2000-0800 h) in both untreated and treated patients.
 The acrophase was unchanged by therapy.
 During therapy T3 levels decreased from 2.05 +/- 0.17 nmol/L to 1.44 +/- 0.08 nmol/L (P = 0.001), while rT3 levels increased from 0.14 +/- 0.02 nmol/L to 0.19 +/- 0.03 nmol/L (P less than 0.05).
 Plasma T4 levels remained unchanged.
 From these studies we conclude that the TSH pulse generator is unchanged in active acromegaly and apparently unaffected by chronic octreotide infusions.
",18
3041,"Thyroid function in a healthy elderly population: implications for clinical evaluation.
 Evaluation of thyroid function in elderly people is complex and has generated some controversy about what is normal.
 This study analyzed thyroid function assays in an identified healthy elderly population of 216 subjects.
 Thyroxine, free thyroxine, triiodothyronine, T3 uptake, ""supersensitive"" thyrotropin, and thyroid antibody titers were performed.
 Histories of treatment for thyroid conditions were present in 13.9% (n = 30) of the population, and test results for an additional 4.3% (n = 8) revealed some hypothyroidism.
 These subjects were excluded from statistical analysis.
 Test results revealed significant differences from younger controls as well as skewed distributions for T4, FT4, and TSH.
 There were no significant correlations with increasing age or gender within the elderly population.
 11.8% (n = 21) of the population exhibited elevated TSF levels with normal T4 values, and 23.0% (n = 41) exhibited a titer of one or both thyroid antibodies.
 Current reference ranges for thyroid tests are broad enough to include the range of values seen in the healthy elderly, but some cautions are discussed.
",18
3042,"Assessment of pupillary light reflex latency and darkness adapted pupil size in control subjects and in diabetic patients with and without cardiovascular autonomic neuropathy.
 Increased pupillary light reflex latencies were found more often than a reduced darkness pupil size in diabetic patients with and without abnormal cardiovascular reflexes.
 This finding suggests that parasympathetic pupillary dysfunction precedes sympathetic pupillary denervation in diabetic autonomic neuropathy.
",18
3043,"Parathyroid autotransplantation during thyroid surgery.
 Permanent hypoparathyroidism is one of the most distressing complications of thyroid surgery.
 The incidence of this iatrogenic complication varies between 3 and 25 percent among patients undergoing total thyroidectomy.
 Parathyroid injury may be caused by inadvertent removal of the parathyroids, ligation of the blood supply, or destruction secondary to capsular hematoma.
 Attention to such technical details as identification of the parathyroids, dissection close to the thyroid gland, preservation of the blood supply to the parathyroids, and avoiding manipulation of parathyroids reduces the incidence of temporary and permanent hypoparathyrodism.
 However, if the parathyroids are injured, the best method of preserving their function is by autotransplantation.
 Over the past 7 years we have performed 250 thyroidectomies.
 An attempt was made to identify and preserve parathyroid gland in each case.
 Even during lobectomy procedures, the ipsilateral parathyroids were identified and preserved.
 Whenever any of the parathyroids was devascularized or separated from the surrounding structures, it was autotransplanted into the sternomastoid muscle.
 The sternomastoid was chosen for autotransplantation rather than forearm muscles to avoid an added incision and because selective measurement of parathormone is not essential in this group of patients.
 Prior to autotransplantation, confirmation of the nature of the tissue was made by frozen section of a small portion of the parathyroid gland.
 Parathyroid autotransplantation was performed in 15 instances, even when only one parathyroid was injured.
 Only one member of this group of 15 patients developed temporary hypoparathyroidism, which disappeared after 4 weeks of calcium supplementation.
 The remaining patients had an uncomplicated recovery.
 Autotransplantation of the parathyroid glands should be performed whenever the parathyroid is devascularized or damaged by retraction or hematoma.
 It is essential for every thyroid surgeon to be familiar with the technique of parathyroid autotransplantation.
",18
3044,"Epidermal growth factor induces the functional expression of dopamine receptors in the GH3 cell line.
 GH3 cells are a clonal strain from a rat pituitary tumor that synthesizes and secretes both PRL and GH.
 The peculiarity of these cells is that they do not express receptors for dopamine; thus the hormone release is insensitive to the inhibitory effect of dopamine and D2 receptor agonists.
 Exposure of GH3 cells to epidermal growth factor for 4 consecutive days markedly altered the cell morphology, from a spherical appearance to an elongated flattened shape, and increased the cell size.
 These morphological changes were accompanied by the functional expression of D2 dopamine receptors as shown by the presence of a specific, saturable, and stereoselective high affinity binding for [3H]spiroperidol in epidermal growth factor-treated cells and by the fact that the selective D2 agonist quinpirole recovered the property to inhibit PRL secretion in the cell cultures exposed to the neurotrophic factor.
 The effect of EGF on the functional expression of D2 receptors was dose dependent (EC50 = 8 pM) and reversible.
 These data suggest that EGF elicits major effects on the expression of specific genes leading to the differentiation of GH3 cells into lactotroph-like cells endowed with dopamine D2 receptors.
",18
3045,"Thyroid hormones and 5'-deiodinase in the rat fetus late in gestation: effects of maternal hypothyroidism.
 Having previously observed that T4 and T3 levels in fetal rat brain and brown adipose tissue are clearly higher than expected from their low circulating levels, we have now studied thyroid hormone concentrations and 5'-deiodinase activities (5'D) in several other rat fetal tissues during the last 6 days of gestation (dg), namely 17-22 dg.
 This period comprises the onset of fetal thyroid activity.
 Total thyroidal T4 and T3 contents increased 100- and 400-fold, respectively; T4 concentrations increased 8- to 10-fold in plasma, carcass, lung, and liver, and T3 increased 4.5- to 9-fold, except in plasma and liver, where T3 levels increased less than 2-fold in plasma and 3-fold in liver.
 During this developmental period 5'D activity increased 5- and 10-fold in fetal liver and lung, respectively.
 In fetuses from hypothyroid [thyroidectomized (T)] dams, body weight was lower than in fetuses from normal dams.
 Total thyroidal T4 and T3 contents were initially the same, but decreased markedly in fetuses from T dams by the end of gestation.
 At the earliest fetal ages studied (17-18 dg) T4 and T3 concentrations were lower in carcass, liver, lung, and brain, although near term there were no consistent differences between the fetal tissues from T and control dams, probably because of compensatory stimulation of thyroidal secretion.
 Liver 5'D was decreased by 50% throughout gestation, and lung 5'D activities were lower by the end of gestation.
 Thyroid hormones in placentas from T dams were very low, but increased by the end of gestation because of the contribution by the fetal thyroid.
 Present results describe the ontogenic profiles for thyroid hormone concentrations and 5'D activities during late fetal development; active regulatory mechanisms are already present at this age.
 It has been frequently stated that rat fetuses near term are deficient in thyroid hormones, and that their thyroid hormone economy is independent of maternal thyroid status, but present results show that near term, T4 and T3 concentrations in several tissues reach levels that are 50% or more of those described for adult animals, and that fetal thyroid function is influenced by maternal hypothyroidism.
",18
3046,"Iodine and thyroid disease.
 Iodine is a requisite substrate for the synthesis of the thyroid hormones, the minimum daily requirement being about 50 micrograms.
 An autoregulatory mechanism within the thyroid serves as the first line of defense against fluctuations in the supply of iodine and also permits escape from the inhibition of hormone synthesis that a very large quantity of iodine induces (Wolff-Chaikoff effect and escape therefrom).
 Environmental iodine deficiency continues to be a significant public health problem worldwide, compounded in some geographic regions by the presence of other goitrogens in some staple foods.
 The pathologic consequences of severe iodine deficiency include endemic goiter, endemic cretinism, increased fetal and infant mortality, and an increased prevalence in the community of cognitive and neuromotor disabilities.
 The implementation of an iodization program prevents endemic cretinism and reduces the frequency of the other pathologic consequences of iodine deficiency.
 Iodine excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media.
 The pathologic consequences of iodine excess will ensue only when thyroid autoregulation is defective, in that escape from the Wolff-Chaikoff effect cannot occur, or when autoregulation is absent.
 Defective autoregulation characterizes the fetal and neonatal thyroid, Hashimoto's thyroiditis, radioiodine or surgically treated Graves' hyperthyroidism, the thyroid of patients with cystic fibrosis, and the thyroid that has been exposed to weak inhibitors of the organic binding of iodine.
 In these circumstances, the provision of excess iodine may lead to iodide goiter with or without hypothyroidism.
 Absent autoregulation may be a feature of longstanding multinodular goiter, and the provision of excess iodine in this circumstance may induce thyrotoxicosis (Jod-Basedow disease).
 The pathologic consequences of iodine excess will resolve when the source of iodine has been dissipated.
 In addition to its role in reversing iodine deficiency, iodine is used as adjunctive therapy for hyperthyroidism.
 By inhibiting the proteolytic release of iodothyronines from thyroglobulin, it induces a prompt slowing of thyroid hormone secretion.
 This effect is exploited in the treatment of thyrotoxic crisis or severe thyrocardiac disease.
 Iodine also reduces thyroid cellularity and vascularity and therefore is used in the preparation of the patient for thyroidectomy.
 Finally, by exploiting the failure of escape from the Wolff-Chaikoff effect, iodine may also be used in the early management of radioiodine-treated Graves' hyperthyroidism.
",18
3047,"The problem of the nodular goiter.
 Nodular goiter is a worldwide problem involving millions of persons.
 Endemic goiter, and associated cretinism, is totally preventable by ensuring an adequate dietary iodine intake and eliminating malnutrition and dietary goitrogens.
 Therapy, on the other hand, is difficult in that the goiters often do not regress and the cretinoid changes are irreversible.
 Nonendemic goiter due to autoimmune thyroid disease, genetic defects in thyroid hormone biosynthesis, and environmental goitrogens or neoplasia is not usually preventable.
 The usual therapy, involving TSH suppression by administration of L-thyroxine orally, will frequently bring about regression of early, diffuse goiters but is often ineffective in bringing about regression of large, multinodular goiters.
 In these patients, surgical removal of the goiter may be necessary for alleviation of obstructive symptoms.
 Further research is needed to elucidate the factors involved in the development of these multinodular goiters and to control the autocrine and paracrine factors involved in nodule growth.
",18
3048,"Estimated burden of diabetes mellitus in Manitoba according to health insurance claims: a pilot study.
 OBJECTIVE: To estimate the burden of diabetes mellitus in Manitoba from 1980 to 1984.
 DESIGN: Review of the Manitoba Health Services Commission (MHSC) database.
 The validity of the MHSC data was established through two substudies: one involved self-reports from a survey of elderly Manitobans, and the other involved people with confirmed diabetes enrolled in the provincial diabetes education program.
 SUBJECTS: Sample of 100,000 people stratified by age, sex and MHSC health region: 50,000 were aged 25 to 64 years, and 50,000 were aged 65 or more.
 All MHSC claims containing the ICD-9-CM code for diabetes mellitus or gestational diabetes were identified.
 MAIN RESULTS: Of the sample 7627 people were found to have a diagnosis of diabetes, the annual prevalence being 0.8% among those 25 to 44 years of age, 3.5% among those 45 to 64 and 7.6% among those 65 or older.
 The annual incidence rate among those over 25 years of age was 7.8 per 1000.
 Of the 4556 pregnant women 25 to 44 years old 85 (1.9%) had diabetes; 23 were believed to have gestational diabetes.
 CONCLUSIONS: The incidence and prevalence rates were similar to those determined on the basis of self-reports in Canadian and US national surveys.
 The use of an administrative database such as that of the MHSC will provide key information for planning health services for diabetic patients and will permit the monitoring of long-term trends in the incidence and prevalence of the disease.
",18
3049,"Cardiac sympathetic tone in anaesthetized diabetics.
 To assess cardiac sympathetic nervous function in diabetics, the heart rates attained following a pharmacological dose of intravenous atropine, 23 micrograms.kg-1, were studied under N2O, isoflurane anaesthesia in diabetics (n = 21) and nondiabetics (n = 30).
 Atropine-induced heart rate in diabetics was significantly lower than that in nondiabetics (95 +/- 14 (SD) bpm vs 109 +/- 12 bpm, P less than 0.001) and were closely related to preoperative orthostatic diastolic blood pressure change (r = 0.60, P less than 0.01).
 There was some correlation between the atropine-induced heart rate and preoperative RR-variation in diabetics (r = 0.50, P less than 0.05).
 The findings suggest that cardiac sympathetic function may also be impaired in diabetics with orthostatic hypotension.
",18
3050,"Binding and action of insulin-like growth factor I in pituitary tumor cells.
 Insulin-like growth factor I (IGF-I), a target hormone mediating most of the growth effects of GH, suppresses GH gene expression in a feedback regulatory loop, which may be either endocrine or paracrine in nature.
 Although IGF-I has been shown to directly attenuate GH gene transcription, the relationship of IGF-I binding and action in the somatotroph cell remains unclear.
 Therefore, IGF-I binding and action were compared in two different pituitary cell lines both secreting GH.
 Recombinant human IGF-I attenuated GH secretion in GC cells by up to 70% after 48 h in a dose-dependent manner.
 Surprisingly, IGF-I failed to suppress GH secretion in GH3 cells, a clonally related pituitary cell line.
 Binding studies showed that although the KD for IGF-I was similar in both cell types, GC cells contain 3-fold more IGF-I binding sites compared to GH3 cells, possibly explaining their resistance to IGF-I action.
 Nevertheless, both cell lines possessed abundant and similar binding sites for insulin.
 These results imply that the IGF-I signal for GH gene regulation is receptor-mediated and directly correlated with the number of pituitary IGF-I binding sites.
 Availability of pituitary IGF-I binding sites may therefore be important in determining the level of GH expression by the somatotroph.
",18
3051,"Sexual dimorphism of pancreatic beta-cell degeneration in transgenic mice expressing an insulin-ras hybrid gene.
 The human H-ras oncogene induces cell degeneration and diabetes when expressed in pancreatic beta-cells in transgenic mice.
 The disease develops predominantly in male mice between 5-8 months of age.
 Most transgenic female mice do not manifest this phenotype, even at much greater ages.
 However, ovariectomy induces female beta-cell degeneration similar to that in the males.
 In contrast, castration or the presence of the testicular feminization mutation do not alter the course of the disease in males.
 Treatment of males and ovariectomized females with estrogen prevents the development of diabetes.
 These results suggest that testicular androgens and a functional testosterone receptor are not required for the increased susceptibility of male beta-cells to the effects of the Ras oncoprotein, and that the relative resistance of female beta-cells is mediated by estrogen.
 In addition, a genetic component of female beta-cell resistance to Ras is revealed by crossing the transgenic mice with C3HeB/FeJ mice, which results in a pronounced increase in the incidence of female diabetes.
",18
3052,"Pulsatile luteinizing hormone secretion in normal female mice and in hypogonadal female mice with preoptic area implants.
 Pulsatile LH secretion is driven by GnRH, the hypothalamic hormone that is lacking in the hypogonadal mutant mouse.
 Preoptic area grafts containing GnRH neurons correct many reproductive deficits in hypogonadal mice.
 In this study we evaluated the pattern of LH secretion in hypogonadal female mice with preoptic area grafts (hpg/POA) and in normal female mice.
 Normal females were ovariectomized at 10 weeks of age, and hpg/POA mice were ovariectomized 4 months after graft surgery.
 Three weeks later, all mice received intracardial catheters.
 The next day, sequential blood samples were obtained every 10 min for 4 h from the awake, freely moving mice.
 At ovariectomy, normal and hpg/POA ovarian weights were 8.6 +/- 0.9 and 7.1 +/- 1.2 mg, respectively.
 Significant LH pulses were detected in 9 of 10 normal mice and in 9 of 13 hpg/POA mice.
 Pulse frequency (normal, 0.86 +/- 0.13; hpg/POA, 0.61 +/- 0.13 pulse/h) and interpeak interval (normal, 81.7 +/- 20.3; hpg/POA, 93.2 +/- 24.0 min) were not significantly different (P greater than 0.2), but mean plasma LH levels (normal, 1.07 +/- 0.16 ng/ml; hpg/POA, 0.49 +/- 0.08 ng/ml; P less than 0.005) and mean LH pulse amplitude (normal, 1.92 +/- 0.53; hpg/POA, 0.63 +/- 0.28; P less than 0.05) were significantly lower in the hpg/POA mice.
 The lower mean LH level and LH pulse amplitude in ovariectomized hpg/POA mice are consistent with the inability of most of these mice to show increased LH secretion after castration.
 The findings indicate that preoptic area brain grafts are capable of supporting episodic LH release in the hypogonadal mouse and suggest the presence of a functional GnRH pulse generator in the majority of mice with grafts.
",18
3053,"Riedel's thyroiditis.
 Invasive fibrous (Riedel's) thyroiditis is a rare thyroid condition of unknown origin that may be associated with inflammatory fibrosclerosing processes elsewhere in the body.
 Although the condition is benign and self-limiting, its importance lies in its ability to clinically mimic carcinoma almost completely, necessitating performing an open biopsy to establish the correct diagnosis.
 In a review of over 700 thyroid operations performed at Loma Linda (Calif) University Medical Center in the past 15 years, we encountered only one documented case of Riedel's thyroiditis.
 Our patient presented with a firm thyroid mass, vocal cord paralysis, and symptoms of esophageal compression.
 Surgery was performed to obtain a definitive diagnosis and prevent the possibility of subsequent additional tracheal compression with airway compromise.
 The pathologic findings, as well as the medical and surgical treatment of this condition, are reviewed.
",18
3054,"Lack of effect of isoproterenol on unloaded velocity of sarcomere shortening in rat cardiac trabeculae.
 Several recent reports have indicated that catecholamines may act directly on the crossbridge cycle, independent of intracellular calcium concentration changes.
 The present study investigated the effect of isoproterenol on peak force during twitches at constant sarcomere length and unloaded velocity of sarcomere shortening in isolated right ventricular trabeculae of hearts with V1 or V3 isomyosin obtained from euthyroid and hypothyroid rats, respectively.
 Hypothyroidism was induced by treatment of the rats with propylthiouracil for 6 weeks.
 Electrophoretic analysis showed that the hearts of hypothyroid animals were composed only of V3 isomyosin, whereas the hearts of euthyroid animals were composed predominantly of V1 isomyosin.
 Force development was measured with a silicon strain gauge and sarcomere length with laser diffraction techniques; the shortening velocity was determined from contractions in which sarcomere length was initially held constant followed by a quick release to zero load and a controlled release at zero load.
 Both isometric twitch force and unloaded sarcomere shortening velocity were sigmoidal functions of [Ca2+]o and of the concentration of isoproterenol.
 At optimal [Ca2+]o, unloaded shortening velocity was 40% lower in myocardium of hypothyroid animals than in myocardium of euthyroid animals.
 Isoproterenol increased the sensitivity of isometric twitch force and unloaded shortening velocity to [Ca2+]o in trabeculae from both euthyroid and hypothyroid animals.
 Isoproterenol did not increase unloaded shortening velocity at optimal [Ca2+]o, regardless of the thyroid state.
 From these results we conclude that beta-adrenergic stimulation per se does not accelerate the rate limiting step in the crossbridge cycle that determines unloaded sarcomere shortening velocity in the intact cardiac cell.
",18
3055,"Low growth hormone levels are related to increased body mass index and do not reflect impaired growth in luteinizing hormone-releasing hormone agonist-treated children with precocious puberty.
 To test the hypothesis that GH deficiency might explain the low growth velocity of some LHRH agonist (LHRHa)-treated children with central precocious puberty, we measured stimulated (n = 81) and spontaneous (n = 32) GH levels during or after LHRHa treatment.
 GH stimulation tests in the children who were receiving LHRHa treatment were performed after 2 days of ethinyl estradiol administration.
 Thirty-one of 81 children (38%) who underwent GH stimulation tests had subnormal responses (less than or equal to 7 micrograms/L) to all tests administered (at least 2 stimuli), including 22 of 67 (33%) who had precocious puberty that was idiopathic or associated with hypothalamic hamartoma.
 Eleven of 32 children (34%) who underwent measurement of the mean nighttime spontaneous GH level had levels below the normal range for prepubertal children (less than 1.2 microgram/L).
 Despite the high incidence of subnormal GH levels, there appeared to be no relationship between the GH levels of these children and their growth characteristics.
 The height, growth velocity, bone maturation rate, predicted height, and insulin-like growth factor-I levels were not different between the children with low GH levels and the children with normal GH levels.
 Conversely, the GH levels were not different between the children with subnormal growth rates and the children with normal growth rates.
 Thus, variation in the growth rates of these LHRHa-treated children with central precocious puberty could not be explained by variation in the stimulated or spontaneous secretion of GH.
 In attempting to understand the high incidence of low GH levels in children with precocious puberty, we examined the relationship between GH level and body mass index (BMI).
 Both the stimulated (r = -0.33; P less than 0.002) and the spontaneous (r = -0.61; P less than 0.0002) GH levels were inversely related to BMI.
 Moreover, the children with precocious puberty as a group had significantly elevated BMI [1.2 +/- 0.1 (+/- SE) SD units] compared to normal children of the same age (P less than 0.0001).
 Thus, increased body mass may explain the high incidence of subnormal GH levels in these patients, and normative GH levels adjusted for body mass are needed before it can be concluded that the apparently subnormal GH levels in LHRHa-treated children with precocious puberty are in fact low.
",18
3056,"Serum osteocalcin in patients taking L-thyroxine who have subclinical hyperthyroidism.
 Serum osteocalcin, an index of osteoblastic activity, is increased in hyperthyroidism.
 Serum osteocalcin levels are negatively correlated with bone density in patients with overt hyperthyroidism.
 Osteocalcin levels are also elevated in patients with multinodular goiter and subclinical hyperthyroidism.
 We therefore measured serum osteocalcin levels in patients taking T4 to determine if they correlated with the degree of TSH suppression.
 Despite an upward trend in serum osteocalcin measurements with decreasing TSH concentrations, there was no significant difference in serum osteocalcin among groups of patients with normal (0.5-5.0 mu/L), mildly reduced (0.1-0.5 mU/L), or undetectable serum TSH (less than 0.01 mU/L).
 However, a weak negative correlation was seen between serum TSH and osteocalcin concentrations (r = 0.29, slope = -0.28, P less than 0.05).
 Osteocalcin did not correlate with either serum free T4 or free T3 concentrations.
 Serum PTH concentrations were not different among the three patient groups.
 Our data suggest that osteocalcin is not a useful clinical marker for increased bone turnover in patients with subclinical hyperthyroidism due to T4 therapy.
 However, the trend towards higher osteocalcin levels in patients with suppressed serum TSH values, and the weak negative correlation between serum TSH and osteocalcin are consistent with findings of reduced bone density in these patients.
",18
3057,"Accuracy of portable blood glucose monitoring. Effect of glucose level and prandial state 
 Glucose was determined on capillary and venous blood samples from 274 adult diabetics by three different methodologies: the Glucoscan 2000 and Accu-Check II portable glucose meters (capillary) and the Kodak Ektachem 700 analyzer (venous).
 Both glucose meters correlated significantly with the Ektachem results.
 A significant positive bias was found for the Glucoscan compared with Ektachem, not found with the Accu-Check II.
 The Accu-Check performed better than the Glucoscan at venous plasma glucose levels less than 1 g/L.
 The mean error of Glucoscan determinations was significantly greater and biased positive when the measurement was performed within 4 hours of eating, whereas no such effect was seen with Accu-Check error.
 Multiple regression analysis revealed that the Glucoscan measurement was independently influenced by both venous plasma glucose and prandial state, whereas the Accu-Check II measurement was not dependent on either variable.
 The within-run precision for both glucose meters were comparable.
",18
3058,"Differential expression of basement membrane collagen chains in diabetic nephropathy.
 Diabetic nephropathy is characterized by progressive expansion of mesangial matrix and thickening of the glomerular basement membrane (GBM).
 Kidney tissues from 13 patients with insulin-dependent diabetes mellitus were studied by immunohistochemical techniques for the distribution of three recently described collagen peptides (M28+, M28 [Good-pasture antigen], and Alport antigen) and various components of classical type IV collagen [alpha 1(IV) noncollagenous (NC) globular domain, alpha 2(IV) NC, 7S, triple helix].
 Recently M28 and M28+ were designated as NC monomers of alpha 3(IV) and alpha 4(IV) based on limited amino acid sequencing.
 During the course of the disease, the distribution of the M28 chains and the Alport peptide segregated completely from that of classical type IV collagen.
 In diabetic kidneys, antibodies to the M28 and Alport peptides reacted intensely with the thickened GBM but not with the mesangium.
 In contrast, the reactivity of antibodies to various components of classical type IV collagen was prominent within the expanded mesangial matrix with significant decrease in reactivity in the peripheral capillary wall.
 In hyalinized glomeruli, components of classical type IV collagen virtually disappeared, whereas the M28 and Alport peptides persisted in the collapsed GBM.
 These studies support the view that expansion of the mesangial matrix and thickening of the GBM involve separate and distinct collagen components.
 The differential expression of the M28 and Alport peptides compared with that of classical type IV collagen may be a consequence of differing sites of synthesis (classical type IV collagen from endothelial/mesangial cells and M28 and Alport chains from visceral epithelial cells), independent control mechanisms, and/or differences in degradation.
",18
3059,"Role of thyroid hormone in the development of beta adrenergic control of ornithine decarboxylase in rat heart and kidney.
 The role of thyroid status in the ontogeny of beta adrenergic receptor control of ornithine decarboxylase (ODC) activity was assessed in hearts and kidneys of neonatal rats.
 Hyperthyroidism induced by administration of tri-iodothyronine on postnatal days 1 to 5 caused a reduction in the ability of isoproterenol to stimulate cardiac ODC but subsequently accelerated the onset of the postweaning peak of the response; the latter effect was even more prominent when tri-iodothyronine administration was given on postnatal days 14 to 18.
 Hypothyroidism induced by propylthiouracil administration led to persistent subsensitivity of the cardiac ODC response to beta receptor stimulation.
 Kidney ODC, which does not become subject to beta receptor regulation until after weaning, was resistant to hyperthyroid-induced changes in reactivity, but hypothyroidism still resulted in long-term response deficits.
 These results suggest that thyroid hormone is permissive for normal development of the beta receptor-ODC link, and that the euthyroid state provides the optimal conditions for maturation of this signal transduction mechanism.
 The relative resistance of kidney ODC responses to alterations by hyperthyroidism further indicates that the effects of excess hormone can only be expressed when the receptor-enzyme link is already competent.
 Finally, thyroid status had equivalent effects on the abilities of vasopressin or angiotensin to stimulate ODC, suggesting that the site of thyroid hormone action is at a transduction locus common to several different receptor types.
",18
3060,"Gonadotropin releasing hormones. Clinical applications in gynecology.
 Since the identification and synthesis of gonadotropin releasing hormones (GnRH) 19 years ago, over 2,000 GnRH analogs have been synthesized and evaluated for the treatment of a variety of conditions requiring temporary, reversible suppression or stimulation of gonadotropin secretion.
 Effective stimulation of the gonads requires pulsatile administration of a GnRH agonist, preferably the native decapeptide itself.
 For gonadal suppression, superagonists have proven to be highly effective.
 Intensive studies currently under way promise new and more innovative clinical applications of these compounds.
",18
3061,"Artifactual elevation of thyroid-stimulating hormone.
 A clinically euthyroid patient was found to have a normal serum thyroxine level and an elevated plasma thyrotropin (TSH) level measured by fluoroimmunoassay.
 Thyroid hormone therapy failed to suppress the TSH level.
 The TSH level was unresponsive to thyrotropin-releasing hormone (TRH) administration, alpha-subunits of pituitary glycoproteins were undetectable in her plasma, and imaging of the pituitary-hypothalamic region was normal.
 Measurement of TSH with an assay containing sheep antibody to TSH failed to reveal TSH in the patient's plasma.
 Addition of mouse IgG to the TSH fluoroimmunoassay reduced the patient's TSH to an undetectable level.
 These observations are consistent with a spurious elevation of TSH due to the presence of an anti-mouse antibody.
 Artifactual elevations of TSH have not been identified commonly, but this possibility should be considered when the TSH level is inappropriate for the apparent state of thyroid function.
",18
3062,"Diabetes care in a rural primary health care district where patient education is given high priority. Metabolic evaluation.
 The present population-based study comprises 84% of all known diabetics cared for at a rural primary health care centre.
 Patient education has been given high priority as an integral part of the treatment provided by a specially trained nurse and dietician under the supervision of the general practitioners.
 Most of the patients were under good metabolic control, as reflected by HbA1 (diet-treated, n = 119, 7.3 +/- 1.3%; oral agent-treated, n = 127, 7.8% +/- 1.3%; insulin-treated, n = 110, 8.0 +/- 1.3%; reference range 5.3-7.3%).
 Obvious reasons for any high HbA1 values were found.
",18
3063,"Observer variation in the clinical assessment of the thyroid gland.
 In order to evaluate the reliability of clinical assessment of the thyroid gland, two specialists in endocrinology and two younger doctors independently examined 53 patients twice, and assessed whether they had a diffuse goitre, a multinodular goitre, a solitary nodule or a normal gland.
 In 30% of the patients all four observers were in agreement, whereas in 47% and 23% of the patients, two and three different diagnoses were given, respectively.
 Inter-observer variation was determined and kappa values between -0.04 and 0.54 were found.
 Intra-observer variation was smaller, revealing kappa values between 0.44 and 1.00.
 The present study suggests that clinical assessment of the thyroid gland may lead to misclassification of the type of thyroid disease, and thereby to a less than optimal choice of therapy.
",18
3064,"Postoperative computed tomographic evaluation of patients with large pituitary tumors treated with operative decompression and radiation therapy.
 Thirty consecutive patients who underwent operative decompression and radiation therapy for large sellar and suprasellar pituitary tumors (greater than or equal to 2 cm) were studied in terms of the serial computed tomographic (CT) changes.
 There were 23 men and 7 women.
 The mean age was 49.6 +/- 2.5 years, and the mean follow-up was 45.3 +/- 3.9 months.
 Twenty-eight of the 30 patients had transsphenoidal surgery, and 27 had hormonally inactive tumors.
 Radiation therapy was begun within 1 month of surgery with a mean dose of 4855 +/- 70 cGy.
 Postoperative CT scans were obtained within 1 month of surgery and at 6- to 12-month intervals thereafter.
 Fourteen patients (45%) had no suprasellar tumor visualized in either the early postoperative CT scans or on subsequent scans.
 Eleven patients (35%) had a persistent suprasellar mass during the early postoperative period that resolved on serial CT evaluation.
 The mean time for resolution was 10.4 +/- 1.2 months.
 Six patients (20%) had a persistent suprasellar mass on serial CT evaluation.
 A persistent postoperative mass that subsequently resolved in many of the patients was thought to be caused by the gradual retraction of the postoperative packing and hematoma, as well as the effect of radiation on any residual tumor.
",18
3065,"Is islet amyloid polypeptide a significant factor in pathogenesis or pathophysiology of diabetes?
 Islet amyloid polypeptide (IAPP) or amylin, a recently discovered minor secretory peptide of the beta-cell related to calcitonin gene-related peptide (CGRP), is a constituent of amyloid deposits in the islets of many non-insulin-dependent (type II) diabetic individuals and some elderly nondiabetic subjects.
 IAPP is synthesized as a small precursor at a level of approximately 1% that of insulin and is processed, amidated, stored in beta-granules, and released along with insulin and C-peptide.
 Analysis of its gene (located on chromosome 12) supports an evolutionary relationship to calcitonin and CGRP, peptides with which it shares some biological actions.
 Like CGRP, IAPP antagonizes the action of insulin mainly at the level of muscle glycogen synthesis, but the levels required for this effect seem to be considerably higher than reported circulating levels.
 No evidence for overproduction of IAPP in diabetic subjects has been found thus far, but much more work is necessary to define its normal secretory rates and clearance.
 Other proposed actions of IAPP include serum calcium-lowering effects and smooth muscle relaxation; the latter effect might promote the uptake of insulin into the circulation within the islets.
 Deposition of amyloid is species selective due to structural differences within the central part of the molecule and may be initiated intracellularly in type II diabetes by several mechanisms.
 No differences in the structure of IAPP or its precursor have been found in individuals with maturity-onset diabetes of the young or type II diabetes.
",18
3066,"Newly identified pancreatic protein islet amyloid polypeptide. What is its relationship to diabetes?
 Islet amyloid polypeptide (IAPP) or amylin is a newly identified 37-amino acid COOH-terminal-amidated polypeptide that is the major protein constituent of amyloid deposits in insulinomas and amyloid deposits in pancreatic islets of non-insulin-dependent (type II) diabetic humans and adult diabetic cats.
 IAPP is stored with insulin in beta-cell secretory vesicles and is cosecreted with insulin in response to glucose and several secretagogues.
 IAPP has been demonstrated in normal pancreatic islets of many species, but IAPP-derived amyloid develops commonly in the islets of only a few species (e.g., humans and cats), especially in association with age-related diabetes.
 IAPP from the human and cat inherently contains a short amyloidogenic sequence that is not present in species that do not form islet amyloid.
 Studies in animals indicate that an aberration in the synthesis or processing of IAPP, leading to a local increase in concentration of IAPP in the islet, is also required to facilitate the conversion of IAPP to amyloid.
 The formation of islet amyloid may contribute to the development of type II diabetes by causing disruption of islet cells and by replacement of islets.
 It has also been proposed that an abnormality of IAPP homeostasis underlies the pathogenesis of type II diabetes.
 A significant causal relationship between IAPP and type II diabetes is based on reports that IAPP inhibits glucose-stimulated insulin release by beta-cells and that IAPP inhibits insulin-stimulated rates of glycogen synthesis and glucose uptake by skeletal muscle cells.
",18
3067,"Increased incidence of diabetes mellitus in relation to abdominal adiposity in older women.
 The relationship between body fat distribution, measured by the ratio of waist-to-hip circumferences (WHR), and the 2 year incidence of diabetes mellitus was examined in a cohort of 41,837 women aged 55-69 years.
 The 399 women who reported the new onset of diabetes had a significantly greater mean body mass index (kg/m2) and WHR than non-cases.
 After adjustment for body mass index (BMI), age and education level using multivariate logistic regression, WHR was a significant independent predictor of diabetes in a dose-response fashion.
 Cases were 4.6 times (95% CI = 3.8, 5.6) more likely than non-cases to be in the upper tertile of WHR and 2.2 times (95% CI = 1.8, 2.7) more likely to be in the middle tertile.
 Women in the highest tertiles of both WHR and BMI had a 14.4-fold (95% CI = 9.5, 21.9) higher risk of diabetes than women in the lowest tertiles.
 These results demonstrate that increased abdominal adiposity is a significant independent risk factor for the development of diabetes mellitus in older women.
",18
3068,"Premixed insulins. How do they compare with other insulin preparations?
 With the availability of premixed insulins, physicians and diabetic patients have a wider choice of therapeutic options.
 The premixed preparation now available in the United States consists of 70% NPH insulin and 30% regular insulin.
 The major advantages of premixed insulins are convenience and improved accuracy.
 They are suitable for patients who are too impaired to mix their own insulin dose and for those whose mixed-dose ratio is similar to that of the 70/30 preparation.
",18
3069,"Portable blood glucose meters. Teaching patients how to correctly monitor diabetes.
 Self-monitoring of blood glucose is an important component of treatment in patients with diabetes.
 Recent improvements in glucose meters have made patient self-testing more reliable and less dependent on user technique.
 However, success of the process depends on the training, reassessment, and support of the patient by the healthcare team.
",18
3070,"B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny.
 The circulating lymphocytes of 88 consecutive patients following autologous, conventional, or T-cell depleted bone marrow transplantation were serially analyzed for B-cell surface antigen expression and function.
 In the majority of patients, except for those who developed chronic graft-versus-host disease, the number of circulating CD20+ B cell normalized by the fourth posttransplant month.
 The earliest detectable B cells normally expressed HLA-DR, CD19, surface immunoglobulin (slg), CD21, Leu-8, and lacked expression of CD10 (CALLA).
 In addition, the circulating B cells expressed CD1c, CD38, CD5, and CD23 for the first year following transplant, antigens that are normally expressed on a small percentage of circulating B cells in normal adults, but highly expressed on cord blood B cells.
 Similar to cord blood B cells, patient B cells isolated during the first year following transplant, proliferated normally to Staphylococcus aureus Cowan strain I (SAC), and produced IgM, but minimal or no IgG when stimulated with pokeweed mitogen and SAC, unlike normal adult B cells that produce both.
 The similar phenotype and function of posttransplant and cord blood B cells, and their similar rate of decline in patients and normal children adds further evidence to support the hypothesis that B-cell differentiation posttransplant is recapitulating normal B-cell ontogeny.
",19
3071,"Transmission of HTLV-I by blood transfusion and its prevention by passive immunization in rabbits.
 To determine the minimum volume of blood required to transmit human T-cell leukemia virus type I (HTLV-I), heparinized blood was collected from a virus-infected female rabbit and aliquots of 10, 5, 1, 0.5, 0.1, and 0.01 mL were transfused into groups of two male rabbits each.
 All 10 rabbits transfused with 10 to 0.1 mL and 1 of 2 rabbits transfused with 0.01 mL seroconverted for HTLV-I after 2 to 4 weeks.
 HTLV-I-producing lymphoid cell lines of recipient origin were established from one seroconverted rabbit of each aliquot group.
 To determine the ability of passive immunization to protect against HTLV-I infection, two groups of three rabbits were first transfused with 5 mL of blood from the same virus-infected rabbit and then infused after 24 or 48 hours with 10 mL of HTLV-I immune globulin (77 mg/mL of IgG) prepared from seropositive healthy persons.
 None of the 24-hour immunization group seroconverted for HTLV-I during the observation period of six months; however, all of the 48-hour immunization group became seropositive after 2 to 4 weeks.
 These results indicate that HTLV-I can be transmitted with as little as 0.01 mL of virus-infected blood, and that passive immunization is effective in preventing cell-to-cell infection of HTLV-I when given within 24 hours of transfusion of virus-infected blood.
",19
3072,"Adrenaline and nocturnal asthma.
 OBJECTIVE--To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma.
 DESIGN--Double blind placebo controlled cross-over study.
 In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine.
 In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given.
 PATIENTS--Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study.
 MAIN OUTCOME MEASURES--Peak expiratory flow rate and plasma adrenaline.
 RESULTS--Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine.
 CONCLUSION--A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma.
",19
3073,"Augmentation of monocyte chemotaxis by 1 alpha,25-dihydroxyvitamin D3. Stimulation of defective migration of AIDS patients.
 Preincubation for 20 h with 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) markedly augmented the chemotactic responsiveness of human blood monocytes to the classical chemoattractant, FMLP.
 A modest enhancement of monocyte spontaneous locomotion in the absence of chemoattractants was also observed.
 Maximal increase of monocyte migration was observed after pretreatment with 10(-9) M 1,25(OH)2D3 and was detectable at FMLP concentrations ranging from 10(-10) to 10(-7) M.
 Pretreatment with 1,25(OH)2D3 augmented the number of monocyte high affinity FMLP receptors (1500 +/- 220 and 3800 +/- 300 sites per cell for untreated and 1,25(OH)2D3-pretreated cells, respectively) with no significant changes in Kd values (2 +/- 0.5 nM and 4 +/- 1 nM, for untreated and 1,25(OH)2D3-pretreated monocytes).
 Enhanced chemotaxis was not restricted to FMLP, because 1,25(OH)2D3-treated monocytes showed enhanced migration also in response to activated C components and chemotactic cytokines.
 In agreement with previous observations, monocytes from AIDS patients showed defective migration capacity.
 In vitro exposure to 1,25(OH)2D3 stimulated monocyte migration in all 10 patients examined with considerable quantitative differences among individuals.
 Regulating the responsiveness of mature monocytes to chemo-attractants, 1,25(OH)2D3, produced systemically or in situ by immunocompetent cells, could play a role in the regulation of the recruitment of monocytes at sites of inflammation, cell-mediated immunity, or bone resorption.
 The potential of 1,25(OH)2D3 as a restorative agent under conditions of defective phagocyte recruitment deserves further exploration.
",19
3074,"In vivo effects of anti-IL-4 monoclonal antibody on neonatal induction of tolerance and on an associated autoimmune syndrome.
 The role of IL-4 in the cellular interactions leading to the induction of CTL tolerance to H-2b alloantigens and to the development of a lupus-like autoimmune disease in BALB/c mice after neonatal injection with (C57BL/6 x BALB/c)F1 cells was investigated in vivo by using an anti-IL-4 mAb.
 Treatment of F1 cell-injected BALB/c mice with 15 mg of anti-IL-4 mAb was shown to interfere with tolerance induction, as assessed by the high percentages of H-2b target cell lysis and the very low or undetectable levels of B cell chimerism markers observed in these mice.
 Treatment with 4.5 mg of anti-IL-4 mAb interfered with tolerance induction only in one-third of F1 cell-injected BALB/c mice, but that dose induces specific modulations of the autoimmune manifestations in all mice, leading to the nearly complete prevention of the disease.
 In particular, the production of anti-ssDNA IgG1 and of total IgG1 and IgE antibodies was seriously affected by the treatment, as well as the proliferation and membrane Ia and K expression of F1 donor splenic cells and thymic APC.
 Treatment of F1 cell-injected BALB/c mice between 24 and 48 h of life with 0.5 mg of anti-IL-4 mAb did not interfere with tolerance induction, but had similar effects on the autoimmune syndrome as treatment with 4.5 mg.
 These results suggest that, after F1 cell injection of newborn mice, IL-4 plays an important role in the cellular interactions leading to the induction of tolerance to the corresponding alloantigens and to the development of the associated autoimmune syndrome.
",19
3075,"Loss of epidermal integrity by T cell-mediated attack induces long term local resistance to subsequent attack. II. Thymus dependency in the induction of the resistance.
 Our previous study showed that in cutaneous graft-vs-host disease (GVHD) induced by intradermal injection of autoreactive T cells the epidermal structures spontaneously recovered from the destruction became resistant to the subsequent attempts to induce the cutaneous GVHD and that the resistance correlated well with a 30-fold increase in the number of Thy-1+ epidermal cells (Thy-1+EC).
 We show that the resistance to the cutaneous GVHD was never induced in athymic nude mice and adult thymectomy lethal radiation and bone marrow reconstitution (ATXBM) mice under the same conditions, indicating that the induction of the resistance is dependent on the presence of thymus.
 A great increase in the number of Thy-1+EC was similarly observed in the epidermis of the athymic nude and ATXBM mice that spontaneously recovered from the cutaneous GVHD and that remained susceptible to the induction of the cutaneous GVHD.
 However, the results with B10Thy-1.1----B6 radiation chimeras clearly demonstrate that the vast majority of the increased Thy-1+EC found in the ""susceptible"" epidermis of the ATXBM mice were of donor bone marrow origin and there was no increase in the number of host-derived Thy-1+EC, whereas in the ""resistant"" epidermis of the XBM mice both Thy-1+EC populations were equally increased.
 The overall results indicate that the expansion of Thy-1+EC that mature in the thymus is crucial to the induction of the resistance, although the migration of bone marrow-derived Thy-1+EC precursors to the epidermis occurs quite independently of the presence of thymus.
",19
3076,"Intact antigen receptor-mediated generation of inositol phosphates and increased intracellular calcium in CD4 CD8 T lymphocytes from MRL lpr mice.
 The predominant T lymphocytes that accumulate in the peripheral lymphoid tissues of mice homozygous for the lpr gene bear the phenotype CD3+CD4-CD8-.
 By certain functional criteria these cells would appear to have impaired CD3-mediated signal transduction, in that they do not respond to alloantigen and produce little if any detectable IL-2 or other lymphokines.
 However, the signal pathway appears adequate for achieving other T cell functions, including induction of high affinity IL-2R, and thymic deletion.
 To clarify the basis of this seeming discrepancy, we examined transmembrane signal transduction in T cell subsets of lpr/lpr (lpr) and +/+ mice, as defined by increased [Ca2+]i and the generation of inositol phosphates (InsPs).
 Stimulation of lpr CD4-CD8- cells with anti-CD3 antibody produced prompt and sustained increases in the concentration of [C2+]i and in InsPs.
 Similar responses occurred in mature T cells from lpr and +/+ mice, except for the somewhat slower kinetics of their increased [Ca2+]i.
 In marked distinction to the anti-CD2-mediated response, Con A, even in high doses, could not stimulate any increase of [Ca2+]i in lpr CD4-CD8- cells, and only modest increases in InsPs.
 Mature T cells, whether of lpr or +/+ origin, yielded normal increased [Ca2+]i with Con A.
 The reason for the differences in signal transduction between anti-CD3 and Con A stimulation of lpr CD4-CD8- cells may relate to the absence of surface structures on these immature T cells that are required for activation by Con A but not by anti-CD3.
 The data demonstrate that the CD3 complex in lpr CD4-CD8- T cells can couple to phospholipase C to hydrolyze phosphoinositides.
 These activation properties of lpr CD4-CD8- T cells have interesting functional parallels to thymocytes at the time of thymic selection, as well as tolerance induction of mature T lymphocytes.
",19
3077,"Human severe combined immunodeficiency disease: phenotypic and functional characteristics of peripheral B lymphocytes.
 Human severe combined immunodeficiency disease (SCID) includes an X-chromosome-linked type characterized by a complete absence of mature T cells, hypogammaglobulinemia but normal or elevated number of B cells, suggesting that the disease results from a block in early T cell differentiation.
 It has been shown that B cells from obligate carrier women of this disorder exhibit the preferential use of the nonmutant X chromosome as the active X (as shown for T cells), suggesting that the SCID gene product has a direct effect on B cells as well as on T cells.
 To examine this question, we analyzed the phenotypic and functional characteristics of peripheral B cells from nine infants with SCID.
 We found a constant absence of spontaneously expressed activation Ag on B cell membrane from all SCID patients tested which contrasts with the phenotypic pattern exhibited by age-matched infants whom all cells bearing surface Ig express the 4F2 Ag and to a lesser extent the transferrin receptor.
 Concurrently, B cells from SCID patients have a profound impairment in their responses to stimuli that induce in vitro B cell proliferation and differentiation.
 Although rIL-2 and low-Mr B cell growth factor are potent inducers of proliferation on age-matched infants' B cells, they are poorly efficient in inducing proliferation of anti-mu-activated SCID B cells.
 This impairment is not related to the resting B cell phenotype of SCID B cells as shown by comparison with normal resting B cells.
 Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation.
 These results suggest that the SCID gene defect has a direct effect on B cells and is required during B cell maturation.
",19
3078,"A surgeon's risk of AIDS.
 A probabilistic model is used to estimate the cumulative risk to surgeons from human immunodeficiency virus (HIV).
 Recent data suggest that the probability of infection following percutaneous inoculation is about 1 in 250 cases.
 Several studies suggest that the frequency of percutaneous injury in surgery is at least 1 in 40 cases, for some as high as 1 in 20 cases.
 Assuming that on the average a surgeon will perform 350 operations per year and will practice for 30 years, the cumulative risk of HIV infection will depend on the prevalence of HIV infection in the surgical population.
 For HIV prevalences of 1 in 100 to 1 in 10, the cumulative risk per surgeon ranges from 1 in 100 to 1 in 5, respectively.
 Based on these risk estimates, it is crucial to decrease the frequency of percutaneous injury.
 The case is made for substantial improvements in barrier protection and modification of surgical technique.
",19
3079,"Patterns of food hypersensitivity during sixteen years of double-blind, placebo-controlled food challenges.
 For 16 years the double-blind, placebo-controlled food challenge (DBPCFC) has been used at the National Jewish Center for Immunology and Respiratory Medicine to determine whether adverse reactions to foods do occur in children.
 The objective of these studies was to explore these reproducible adverse reactions and to characterize them.
 Although skin testing was performed on all subjects, a history of an adverse reaction to food and to subsequent DBPCFC were the only criteria for entry into this study.
 Of 480 children studied, 185 (39%) have had positive DBPCFC results.
 In these 480 children, 245 (24%) of 1014 DBPCFCs showed positive results.
 Egg, peanut, and cow milk accounted for 73% of the positive DBPCFC reactions, but many foods produced reactions.
 Skin test results were positive in most children with a positive DBPCFC reaction, but the large number of patients with asymptomatic hypersensitivity limited the accuracy of a positive skin test result alone as a predictor of clinical symptoms during food ingestion.
 Evaluation of results in this large number of children for a prolonged period revealed reproducible patterns of symptoms, timing, and incriminated foods.
 Placebo reactions were rare.
 The procedure was safe.
 Twelve youngsters with a negative DBPCFC result subsequently had positive reactions to open challenges when large amounts of the challenge food were used.
 In each of these cases the reactions were limited to areas of direct contact with the food or could be explained by the larger amount of food ingested during the open challenge.
 Multiple food hypersensitivity has been a rare finding.
 The DBPCFC should be the ""gold standard"" for both research and clinical diagnostic evaluations until it is superseded by methods that have yet to be developed.
",19
3080,"Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.
 Ninety-two children with juvenile rheumatoid arthritis were randomly assigned to treatment in a multicenter, double-blind, 12-week trial designed to compare the efficacy and safety of a liquid formulation of ibuprofen at a dosage of 30 to 40 mg/kg/day versus those of aspirin at a dosage of 60 to 80 mg/kg/day.
 No significant intergroup differences in response rates or in the amount of improvement in articular indexes of disease activity were observed.
 More children treated with aspirin discontinued treatment early because of adverse reactions.
 After this trial, 84 additional patients with juvenile rheumatoid arthritis entered a 24-week, multidose (30, 40, and 50 mg/kg/day), open trial of ibuprofen suspension.
 Favorable response rates for the three groups were similar, and continued improvement was observed throughout the 24-week period.
 A dose-response relationship was observed with respect to adverse reactions of the upper gastrointestinal tract.
 We conclude that ibuprofen suspension is an effective nonsteroidal antiinflammatory drug and that its tolerability in children is acceptable.
",19
3081,"Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis 
 Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy.
 The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours.
 Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or D-penicillamine.
 Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases.
 Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months.
 The range of treatment duration was 8 to 39 months (mean 18.5 months).
 Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts.
 Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively.
 No significant toxic effects were observed.
 Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy.
 We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy.
 Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.
",19
3082,"On the use of laboratory markers as surrogates for clinical endpoints in the evaluation of treatment for HIV infection.
 There are strong ethical and practical reasons for hastening decision-making about the efficacy of new treatments for human immunodeficiency virus (HIV) infection.
 One strategy is to use early markers of disease progression, such as CD4+ lymphocyte levels, as surrogates for ultimate clinical endpoints, such as the development of acquired immune deficiency syndrome (AIDS) or death, in the evaluation of new therapies.
 We used a simple model of transitions among three health states (well; alive but with an adverse marker; and having experienced a definitive clinical endpoint) to examine the extent to which treatment comparisons based on the surrogate endpoint predict ultimate clinical benefits.
 With parameters chosen to model the treatment of HIV infection, computer simulations of clinical trials demonstrated substantial time savings by use of the surrogate endpoint.
 However, reliance on the surrogate led to serious overestimates of ultimate clinical benefit if treatment entailed delayed toxicity or had only transient beneficial effects.
 Likewise, reliance on the surrogate led to serious underestimates of ultimate clinical benefit when the treatment had no effect on the transition from well to the marker state but did reduce the rates of transition from the marker state to the ultimate clinical endpoint and directly from the well state to the ultimate clinical endpoint.
",19
3083,"Immunoadsorbent plasma perfusion in patients with systemic lupus erythematosus 
 Extracorporeal treatment of acute systemic lupus erythematous (SLE) by plasmapheresis has been reported for more than 10 years.
 Risks of plasmapheresis include unselective procedure, an immunoadsorbent plasma perfusion by IM-P column.
 Eight of 10 patients evaluated improved through 3 treatments of a 2-liter perfusion.
 Analysis of proteins removed during plasma perfusion showed a semiselectivity of the IM-P column for circulating immune complexes and anti-dsDNA antibodies.
 After perfusion of 2 liters of plasma, these substances were reduced by about 35-40%, whereas whole protein was lowered by less than 10% and immunoglobulins by about 18%.
 Our results in severe SLE indicate that immunoadsorption having the advantage of lowering side effects by dispensing wih foreign protein substitution.
",19
3084,"Prevalence and concentration of IgM rheumatoid factor in polyarticular onset disease as compared to systemic or pauciarticular onset disease in active juvenile rheumatoid arthritis as measured by ELISA.
 The prevalence and concentration of IgM rheumatoid factor (RF) in children with juvenile rheumatoid arthritis (JRA) and its major disease onset groups remains uncertain.
 In our study enzyme linked immunoabsorbent assay (ELISA) of 68 children with active JRA showed IgM RF in the area of 67% (16/24) of those with polyarticular onset disease, 26% (7/27) of those with systemic onset disease, and 6% (1/17) of those with pauciarticular onset disease.
 The median IgM RF concentration was 50-fold higher in polyarticular disease compared to systemic disease.
 The prevalence of IgM RF in polyarticular disease was greater in those with severe disease (functional classes and 3 and 4), with 90% (9/10) seropositive.
 By agglutination assay, the prevalence of IgM RF in JRA was significantly less than by ELISA, with 33% of the polyarticular group positive for IgM RF, and none of the systemic group positive, Relatively low concentration IgM RF similar to that seen in systemic JRA was also found in high prevalence in the area of children with non-JRA, systemic rheumatic disease (n = 8).
 In summary, our study shows by ELISA that high concentrations of IgM RF are found essentially only in the sera of children with polyarticular onset JRA and especially in those with severe disease.
",19
3085,"Decreased number of peripheral blood CD4 + CD29+ lymphocytes and increased in vitro spontaneous production of anti-DNA antibodies in patients with active systemic lupus erythematosus.
 Flow cytometric 2-color analysis of peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE) showed a reduction of relative and absolute number of CD4+ CD29+ cells compared to matched healthy individuals.
 This abnormality was more marked in patients with active/very active disease.
 Absolute number of CD4+ CD29+ cells was negatively correlated with spontaneous anti-DNA Ig production that we demonstrated to be a laboratory index strongly correlated with a clinical disease activity score.
 A decrease of the percentage of CD8+ CD29+ lymphocytes in patients with active disease was also observed.
",19
3086,"Adult Still's disease: a multicenter survey of Japanese patients.
 A comprehensive survey of Japanese patients with adult Still's disease was made by questionnaire which was sent to major institutions with rheumatology units in Japan.
 Of 146 cases from 32 institutions, 90 were judged to be definitely diagnosed as adult Still's disease.
 The major clinical features in these 90 patients consisted of high fever, polyarthralgia, rash, increased erythrocyte sedimentation rate, negative autoantibodies, leukocytosis, liver dysfunction, and hyperferritinemia.
 The incidence of several features showed significant differences between these cases and previous nonJapanese cases.
",19
3087,"Growth and differentiation of B lymphocytes of patients with juvenile rheumatoid arthritis.
 We studied growth and differentiation of B lymphocytes of patients with juvenile rheumatoid arthritis (JRA) using B cell enriched populations.
 Mitogen stimulation led to similar proportionate increases in proliferation and immunoglobulin (Ig) secretion in cultures of patient and control lymphocytes.
 While there was no increase in proliferation, IgG secretion was increased in the absence of mitogen.
 Nonmitogen activated Ig synthesis could be reduced by replacing culture medium with fresh medium after 16-20 h in culture.
 It was partly reconstituted by addition of recombinant cytokines, interleukin (IL), IL-2, IL-4, or IL-6.
 Our results suggest there may be a population of B circulating B cells in patients with JRA and other rheumatic diseases which is sufficiently mature to differentiate and secrete Ig in response to cytokines alone.
",19
3088,"Clonal analysis of joint fluid T lymphocytes in patients with juvenile rheumatoid arthritis.
 Synovial fluid (SF) lymphocytes from 4 patients with pauciarticular juvenile rheumatoid arthritis (JRA) and 4 patients with polyarticular JRA were examined for their phenotypic and functional characteristics.
 In all 8 patients there was a high proportion of activated SF T cells, together with an increased proportion of CD2+CD3- and the presence of CD3+CD4-CD8-WT31- lymphocytes.
 The functional analysis at the clonal level in 5 patients (427 clones) showed a relevant proportion of cytotoxic T cell clones, which were not confined to typically cytolytic phenotypes, but were also present among CD3+CD4+CD8- cultures.
 Compared to those with pauciarticular JRA, patients with polyarticular disease had a significantly higher proportion of T cell clones with cytotoxic activity.
 Although derived from a limited number of patients, our data suggest a direct involvement of T cells in the pathogenetic mechanisms that originate and maintain the articular damage, and the possibility of different or more pronounced T cell reactivities in the clinically more diffuse JRA types.
",19
3089,"European experience of bone-marrow transplantation for severe combined immunodeficiency.
 The outcome of bone-marrow transplantations (BMT) carried out between 1968 and March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was analysed.
 Recipients of HLA-identical BMTs (70) had a 76% probability of survival (median follow-up 73 months).
 Of the 32 treated since 1983, 97% have been cured (median follow-up 41 months).
 This good prognosis was associated with rapid development of T and B cell function.
 HLA-non-identical, T-cell-depleted, BMT (n = 100) gave significantly lower survival (52%; median follow-up 47 months).
 Factors associated with poor prognosis were the presence of a lung infection before BMT, absence of a protected environment, and use of female donors for male recipients.
 Use of a conditioning regimen significantly increased the frequency of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in more frequent engraftment of donor B lymphocytes and myeloid cells.
 Donor B-cell chimerism was strongly associated with the development of normal B-cell function.
",19
3090,"Measurement of airborne mite antigen in homes of asthmatic children 
 The airborne concentration of major house dust mite antigen Der p1 was measured by low volume sampling (2 litres/min) in the homes of 68 allergic, asthmatic children.
 The presence of detectable airborne antigen was strongly associated with sensitivity to the mite, whereas there was no significant relation between sensitivity and the previously recommended threshold level of 2 micrograms Der p1 per g carpet dust.
 There was a significant association with lower threshold levels in carpet dust (0.5 microgram/g) but at no level was the association as strong as that with air measurements.
 Concentrations of airborne antigen were higher in rooms with wool carpets than in those with synthetic carpets or hard floors, but there was no significant difference between the dust levels of Der p1 in the two carpet types.
 Air sampling is a more appropriate method of assessing antigen exposure than dust sampling for asthmatic patients.
",19
3091,"AIDS and pediatric neurology.
 Human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS, causes a wide spectrum of disease in children owing to its selective tropism for the immune system, nervous system, and perhaps other organs.
 By 1991, there may be as many as 10,000 to 15,000 children with symptomatic HIV-1 infection in the United States.
 This article reviews the current knowledge of the clinical, neuroradiologic, and neuropathologic features of HIV-1-related central nervous system involvement in infants and children with symptomatic HIV infection.
",19
3092,"The scid mutation in mice causes a general defect in DNA repair.
 Mice homozygous for the scid mutation on chromosome 16 have a severe combined immune deficiency as a result of their inability to correctly rearrange their immunoglobulin and T-cell receptor genes.
 In scid mice, when precursors for B and T lymphocytes reach the stage of development requiring expression of these surface receptors, a defective recombinase system aberrantly cuts and rejoins the receptor gene segments greatly reducing the efficiency of producing functional receptors.
 As a result, most scid mice have no detectable B or T lymphocytes.
 We have demonstrated that the scid defect is not specific to lymphocyte development.
 Myeloid cells and fibroblasts from scid mice show a marked increase in sensitivity to ionizing radiation, indicating that the scid mutation leads to an inability to repair DNA damage induced by ionizing radiation as well as interfering with rearrangement of the immunoglobulin and T-cell receptor genes.
",19
3093,"Multiple sclerosis sibling pairs: clustered onset and familial predisposition.
 We evaluated 48 relapsing-remitting multiple sclerosis (R/R MS) sibling pairs derived from 44 families for age and date of onset of MS symptoms, clinical course, and family history of MS.
 Age- and sex-matched R/R MS clinic patients provided a statistical comparison group.
 The age of onset tended to cluster within multiplex families.
 The initial symptom of MS occurred within 5 years of age in 30/48 sibling pairs compared with 16/48 controls.
 A positive family history of MS (other than siblings) was present in 43% of the multiplex families compared with 20% among simplex controls.
 In 1st-, 2nd-, and 3rd-degree relatives who had lived into the age at risk, 22/1,134 family members of multiplex sibling pairs had probable or definite MS compared with 10/1,215 control family members.
 Age of onset clustering in siblings concordant for R/R MS and an increased risk of MS in other family members suggest that factors influencing disease onset may be in part inherited in these kindreds.
",19
3094,"Diffuse CNS involvement in systemic lupus erythematosus: intrathecal synthesis of the 4th component of complement.
 In extracerebral systemic lupus erythematosus (SLE), the complement system plays a prominent pathogenic role, and decreased serum concentration of the 4th component (C4) is a reliable indicator of systemic disease activity.
 In diffuse CNS-SLE, however, the pathogenic role of complement is less clear.
 In 12 patients with active diffuse CNS-SLE presenting with delirium (4), organic personality syndrome (3), or generalized seizures (5), we determined the CSF indexes of the complement components C3, C4, and factor B, and of IgG, IgA, and IgM.
 There was a significant increase of the C4 index in these patients compared with controls and a significantly higher CSF C4 index in patients with an increased IgM index.
 We conclude that intrathecal C4 is being produced in diffuse CNS-SLE.
",19
3095,"IgG subclass concentrations in absolute, partial and transient IgA deficiency in childhood.
 Sixty-seven children with symptomatic IgA deficiency were studied on two separate occasions.
 Eighteen had aIgAd at presentation, and 49 had pIgAd.
 IgA concentrations had risen to the normal range for age in 22.2% of children presenting with aIgAd and 77.6% presenting with pIgAd when restudied at a median interval of 3.2 and 3.0 years, respectively.
 IgG subclass concentrations were measured by enzyme immunoassay in serum samples collected at enrollment from 12 children with aIgAd and 22 children with pIgAd.
 IgG2 and IgG4 concentrations for these 34 children were below the 5th centile for age and sex more frequently than expected (IgG2: chi square 5.8, P less than 0.025; IgG 4: chi square 18.4, P less than 0.0005).
 The prevalence of IgG2 deficiency or IgG4 deficiency did not differ significantly between those with aIgAd and those with pIgAd.
 IgG2 concentrations remained below the 5th centile more frequently than expected when retested in 31 children whose pIgAd had resolved (chi square 4.6, P less than 0.05).
 Children with aIgAd at presentation had IgG1 and IgG2 concentrations above the 95th centile more frequently than expected (IgG1: chi square 19.7, P less than 0.0005; IgG2: chi square 13.5, P less than 0.001) but this was not seen for IgG3 and IgG4 concentrations.
 Children with pIgAd did not have elevated IgG1 or IgG2 concentrations at presentation.
 High IgG1 and IgG2 concentrations in aIgAd may be a compensatory mechanism to afford protection from infection or could be part of a selective secondary response to repeated episodes of infection.
",19
3096,"Nebulized albuterol in acute childhood asthma: comparison of two doses.
 Thirty-three children and adolescents from 5 to 17 years of age with moderate to severe acute asthma were given nebulized albuterol therapy in either a high (0.30 mg/kg body weight) or standard (0.15 mg/kg) dose administered at three hourly intervals in a randomized double-blind study.
 The high-dose hourly regimen resulted in significantly greater improvement in the forced expiratory volume in 1 second (FEV1).
 Furthermore, patients receiving the high dose showed a steady improvement in the FEV1 from the start to the end of the study, whereas FEV1 plateaued after the second dose in the standard-dose group.
 Although a rise in heart rate and a fall in serum potassium level occurred, neither of these changes nor other side effects were different in the two groups.
 The high-dose therapy resulted in much higher serum albuterol levels than the standard dose.
 There was no correlation between the drug levels and side effects or initial and subsequent FEV1.
 It is concluded that occasional hourly high-dose albuterol therapy should be considered for some pediatric patients with acute asthma of moderate severity, especially those who relapse between doses.
",19
3097,"Reactions to iodinated radiographic contrast agents. How to identify and manage patients at risk.
 Systemic adverse reactions to iodinated radiographic contrast material are infrequent but can be dramatic.
 The number of patients experiencing such reactions can be minimized by selecting the most appropriate diagnostic study for each patient and by identifying patients at increased risk.
 Pretreatment with corticosteroids and use of low-osmolality contrast materials can minimize the number of severe reactions in high-risk patients.
",19
3098,"T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis.
 To investigate the function of activated T lymphocytes in autoimmune chronic active hepatitis, 7 of 15 T-cell clones from the peripheral blood of 8 patients were studied.
 These clones showed specificity for liver-membrane antigen with proliferation when stimulated by rabbit liver cell membranes.
 6 of these clones reacted with liver-specific lipoprotein complex, and 1 clone (and 3 subclones) responded to the asialoglycoprotein receptor (ASGPR), both known targets of immune attack in autoimmune chronic active hepatitis.
 2 of these clones stimulated autologous B lymphocytes to produce liver-membrane-specific autoantibodies and antibody to the ASGPR.
 These results suggest that liver-membrane-specific activated T lymphocytes in peripheral blood may be important in the autoimmune attack of chronic active hepatitis.
",19
3099,"Serological and molecular survey for HTLV-I infection in a high-risk Middle Eastern group.
 To define the extent of human T-cell leukaemia virus (HTLV-I) infection among a group of Jewish immigrants to Israel with an increased frequency of adult T-cell leukaemia, various serological and molecular screening methods, including enzyme-linked immunosorbent assay (ELISA) for anti-HTLV-I, ELISA for antibody to recombinant HTLV-I p40tax protein, and molecular detection of infection by polymerase chain reaction (PCR) amplification of HTLV-I proviral DNA from peripheral blood mononuclear cell DNA, were used.
 By HTLV-I ELISA the overall rate of infection was 12% (24 of 208) among immigrants from Khurusan, northeastern Iran; no HTLV-I carriers were detected among 111 unselected Jewish immigrants from other parts of Iran.
 There was unexplained clustering of HTLV-I infection within a cohort of 32 elderly women of similar geographic origin in a home for old people--14 were seropositive by ELISA and 19 of 29 were positive by PCR.
 The findings in this newly identified high-risk population suggest that in addition to ELISA, other screening techniques may be required to detect all carriers in high-risk populations.
",19
3100,"Bronchial hyperresponsiveness in young students of southern China: relation to respiratory symptoms, diagnosed asthma, and risk factors.
 A cross sectional study was carried out to determine the prevalence of bronchial hyperresponsiveness and asthma in 3067 students aged 11-17 years in an urban and a rural area of Guangzhou (Canton), China.
 The methods used included a self administered questionnaire, a histamine bronchial provocation test, and allergen skinprick tests.
 Bronchial hyperresponsiveness was defined as a 20% fall in FEV1 and peak expiratory flow at a provoking dose of histamine (PD20) less than 7.8 mumol on two occasions four weeks apart.
 The response rate was 98.0% and 99.2% in the two areas.
 The prevalence of bronchial hyperresponsiveness was 4.1% and of diagnosed asthma 2.4% in the total population.
 There were no significant differences in prevalence between the urban and the rural area or between boys and girls.
 The 11-12 year group had a higher prevalence of bronchial hyperresponsiveness (7.6%) than the older groups.
 Of the 125 with bronchial hyperresponsiveness, 12.0% were defined as having severe or moderate (PD20 less than 0.8 mumol), 26% mild (0.9-3.2 mumol), and 62% slight bronchial hyperresponsiveness (3.3-7.8 mumol).
 The severity of bronchial hyperresponsiveness was closely related to diagnosed asthma, wheezing, and cough, though half the students with bronchial hyperresponsiveness were symptom free.
 The most common allergens were house dust and house dust mite in the city, and hay dust, pollen, and feathers in the rural area.
 The odds ratios for having respectively slight, mild or moderate, and severe bronchial hyperresponsiveness were 5.9, 21.0, and 30.4 for atopy; 1.9, 1.9, and 7.3 for early respiratory infection; and 3.1, 2.5, and 5.6 for a history of parental asthma.
",19
3101,"Dietary alpha-linolenic acid and immunocompetence in humans.
 We examined the effect of dietary alpha-linolenic acid (ALA) on the indices of immunocompetence in 10 healthy free-living men (age 21-37 y) who consumed all meals at the Western Human Nutrition Research Center for 126 d.
 There was a stabilization period of 14 d at the start when all 10 subjects consumed basal diet (BD) and there were two intervention periods of 56 d each.
 Five of the subjects consumed the basal diet and the other five consumed flax-seed-oil diet (FD) during each intervention period.
 Feeding of FD suppressed the proliferation of peripheral blood mononuclear cells when they were cultured with phytohemagglutinin-P (P = 0.041) and concanavalin A (P = 0.054) and the delayed hypersensitivity response to seven recall antigens (NS).
 Concentrations of immunoglobulins in serum, C3, C4, salivary IgA, the numbers of helper cells, suppressor cells, and total T and B cells in the peripheral blood were not affected by the diets.
",19
3102,"Rice pollen allergy in Taiwan.
 A panel of tests including intracutaneous skin testing (ST), radioallergosorbent test (RAST), immunoblotting and allergen-induced lymphoproliferation was done to study rice pollen allergy in asthmatic children and to characterize the allergens.
 Of the 312 asthmatic patients skin tested, 29 (9.3%) had positive reactions (wheal greater than or equal to 6 mm) to rice pollen extract at a concentration of 10(-5) g/mL and the remaining 283 (90.7%) were negative.
 While eight (34.8%) of the 23 ST-positive patients were also RAST-positive, RAST was negative in all 34 ST-negative patients and 20 normals.
 Immunoblotting revealed three major allergens, with molecular weights of 16 kD, 26 kD, and 32 kD, respectively.
 Interestingly, RAST-positive patients showed IgE responses to most allergens but only a few of them had IgG antibodies, while normal controls had stronger IgG responses to the same allergens, particularly to 32 kD, but none had IgE antibody.
 The preliminary results of rice pollen protein induced-lymphoproliferation were not informative; thus, rice pollen proteins do elicit a specific response in asthmatic children and normals, but its pathogenic role in bronchial asthma needs further study.
",19
3103,"Anaphylaxis to pinon nuts 
 A 21-year-old white male developed life threatening systemic anaphylaxis within seconds of ingesting a small amount of a cookie containing pinon nuts.
 Skin testing, ELISA, and basophil histamine release studies demonstrated pinon nut-specific IgE.
 Electrophoresis of the pinon nut extract demonstrated 30 bands, three of which (in the 66 to 68,000 dalton range) bound IgE in the patient's serum in an immunoblot.
 Ingestion challenge was not performed due to the severity of the patient's reaction.
 Although used for centuries in certain cultures, pinon nuts are now being eaten more frequently in the American diet.
 Physicians should be aware of the potential for anaphylactic reactions following ingestion of this food.
",19
3104,"Bronchial challenge to house dust can induce immediate bronchoconstriction in allergic asthmatic patients.
 The goal of the study was to evaluate whether natural exposure to house dust could elicit immediate bronchoconstriction.
 Two groups of asthmatic patients were studied: 12 asthmatics allergic to house dust mites and seven nonallergic asthmatics.
 The baseline FEV1 was similar in the two groups.
 Each subject was challenged through a nasal mask connected to nebulizer filled with house dust.
 Patients were randomly assigned to inhale dust with high or low Group I allergenic level.
 All allergic patients had an FEV1 drop larger than 20% of the baseline value.
 This drop was maximal at the 30th minute after challenge.
 FEV1 remained unchanged in nonallergic asthmatics.
 Allergic patients challenged with high Group I allergenic house dust (8.4 micrograms/g) had a mean FEV1 drop larger (P less than .01) than those challenged with the low Group I allergenic house dust (0.66 micrograms/g).
 Late asthmatic reactions were found in only two patients who were challenged with the high Group I allergenic house dust.
 These two patients had immediate FEV1 drops greater than 50% of the baseline value.
 Occurrence of symptoms during the test and the drop in FEV1 were correlated (r = .3; P less than .05).
 Natural exposure to house dust can induce immediate bronchial in allergic asthmatics in a dose-dependent manner.
",19
3105,"Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice.
 We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft-versus-host disease to improve survival and cure in leukemia.
 The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution.
 Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98).
 These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment.
",19
3106,"Direct relationship between remission duration in acute myeloid leukemia and cell cycle kinetics: a leukemia intergroup study.
 Cell cycle characteristics including labeling indices (LI), duration of S-phase (Ts), and total cell cycle time (Tc) were determined in 54 standard-risk, newly diagnosed patients with acute myeloid leukemia following an infusion of bromodeoxyuridine.
 Remission induction therapy consisting of cytosine arabinoside and daunomycin was then administered to all patients, followed by three courses of consolidation to those who achieved complete remissions (CR).
 Older patients appeared to have more rapidly cycling cells (P = .003).
 No unique cell cycle characteristics were identified for patients who achieved remission versus those who had resistant disease.
 However, the pretherapy cell cycle characteristics were a strong prognosticator for remission duration.
 CR patients were divided into those whose leukemic cell Tc were above median (A) and below median (B).
 Among 14 B patients, median duration of response was 211 days, and all relapsed by day 600.
 Among 18 A patients, the median has not as yet been reached, with nine patients in continuous complete remission (log rank P = .007, Wilcoxon P = .04).
 We conclude that cell cycle characteristics of leukemic cells play a role in determining remission duration, perhaps because the leukemic cells of the former patients regrow slowly between courses of chemotherapy.
",19
3107,"Combined syngeneic bone marrow transplantation and immunotherapy of a murine B-cell lymphoma: active immunization with tumor-derived idiotypic immunoglobulin.
 Recurrence of the underlying malignancy remains a major cause of treatment failure after autologous bone marrow transplantation (BMT) for patients with lymphoma.
 In this regard, we have developed an immunotherapeutic approach designed to induce resistance against residual tumor cells persisting after BMT.
 Previous studies in the model system of 38C13, a lethal B-cell lymphoma of C3H origin, have shown that active immunization with purified tumor-derived surface immunoglobulin (Id), as a tumor-associated antigen, produces resistance to tumor growth.
 Id immunization of lethally irradiated mice at 3 or 5 weeks after reconstitution with syngeneic bone marrow resulted in significantly prolonged survival after tumor challenge compared with nonspecifically immunized controls.
 Low levels of idiotype-specific antibody were also demonstrated in the sera of specifically immunized mice at this early time, when other functional studies in the literature of immunocompetence after syngeneic reconstitution might have predicted incomplete recovery.
 Immunization of mice before lethal irradiation and syngeneic marrow reconstitution also induced significant resistance to tumor challenge, suggesting the persistence of established host antitumor immunity through total body irradiation.
 These studies demonstrate the feasibility of id immunization in conjunction with bone marrow transplantation.
",19
3108,"The lack of relationship between acetylator phenotype and idiopathic systemic lupus erythematosus in a South-east Asian population: a study of Indians, Malays and Malaysian Chinese.
 An association of idiopathic systemic lupus erythematosus (ISLE) with genetically determined N-acetylation polymorphism has been suspected from previous studies, mainly on Caucasian populations in which there is an approximate incidence of 50% of slow and rapid acetylators.
 The present study is of the incidence of ISLE and acetylator status in a mixed population of Malaysia.
 The results did not support an association between ISLE and acetylator status: the frequencies of slow acetylators in the ISLE patients who were Malaysian Chinese and Malay were 13 and 38% respectively.
 This did not differ significantly from the respective healthy groups (20 and 29%).
 The small number of Indians in the survey did not allow a valid comparison, but the figures did suggest a lack of association between ISLE and acetylator status.
",19
3109,"Quantitative analysis of serum IL-6 and its correlation with increased levels of serum IL-2R in HIV-induced diseases.
 We have devised a luminescence sandwich ELISA for the quantification of IL-6 in both sera and cell culture supernatants, which had a detection limit of 100 fg/ml of test sample.
 By using the luminescence sandwich-ELISA, low but measurable levels of IL-6 (9.5 pg/ml on average) were found in the sera from normal individuals.
 The serum levels of IL-6 were elevated in HIV-seropositive asymptomatic carriers (55.5 pg/ml on average), and the IL-6 levels were correlated with the degree of HIV-induced disease progression (AIDS-related complex 106.8 pg/ml on average and (AIDS 283 pg/ml).
 IL-6 immunoreactivity in the sera of AIDS patients eluted at a 25,000 m.w.
 major peak, which was biologically active and heat-stable, and a 500,000 m.w.
 minor peak in size-exclusion HPLC.
 Interestingly, a significant correlation was observed between the serum IL-6 levels and soluble IL-2R levels.
 In vitro, HIV infection of PHA-activated PBMC led to enhanced release of IL-6 into the culture supernatants.
 Moreover, soluble IL-2R release was markedly increased by adding exogenous IL-6, whereas it was decreased by adding the neutralizing anti-IL-6 mAb to the cultures.
 These results demonstrate that increased IL-6 levels are significantly associated with sIL-2R levels, and suggest a cause of the increased levels of this receptor in patients with HIV infection.
 Furthermore, both serum IL-6 and serum IL-2R levels in HIV infection reflect the stage of the HIV-induced disease.
",19
3110,"Evidence by peptide mapping that the region CD4(81-92) is involved in gp120/CD4 interaction leading to HIV infection and HIV-induced syncytium formation.
 Peptide fragments of the CD4 molecule were compared in their ability to 1) inhibit CD4-dependent HIV-induced cell fusion; 2) inhibit CD4-dependent HIV infection in vitro; and 3) block gp120 envelope glycoprotein binding to CD4.
 Peptides from the region CD4(81-92), although inactive when underivatized, were equipotent inhibitors of CD4-dependent virus infection, cell fusion, and CD4/gp120 binding when derivatized via benzylation and acetylation.
 Peptides of identical chemical composition, but altered sequence and derivatization pattern that blocked gp120 binding to either CD4-positive cells or solubilized CD4, also blocked infection and fusion with similar potencies.
 Those that did not block gp120/CD4 interaction were also inactive in HIV-1 infection and cell fusion assays.
 No other peptide fragments of the CD4 molecule inhibited fusion, infection, or CD4/gp120 interaction.
 The peptide CD4(23-56), derived from a region of CD4 implicated in binding of CD4 antibodies that neutralize HIV infection and cell fusion, had no effect on CD4-dependent cell fusion, HIV-1 infection, or CD4/gp120 binding, but did reverse OKT4A and anti-Leu 3a blockade of gp120 binding to CD4.
 These data provide evidence that the 81-92 region of CD4 is directly involved in gp120 binding leading to CD4-dependent HIV infection and syncytium formation.
 Previous observations with structural mutants of CD4 suggest that the CDR2-homologous region of CD4 is also involved, either directly or indirectly, in binding of gp120 to CD4.
 The CDR2- and CDR3-like domains of CD4 may both contribute to the binding of the HIV envelope necessary for HIV-1 infection and HIV-1-induced cell fusion.
",19
3111,"Immunodominance in the graft-vs-host disease T cell response to minor histocompatibility antigens.
 Immunodominance controls the generation of CTL in the C57BL/6By (B6) anti-BALB.B H-2b-matched strain combination.
 Despite the potential of responding to numerous individual minor histocompatibility (H) Ag on BALB.B APC, the focus of the CTL response is largely specific for only a limited number of target Ag.
 These minor H Ag could be distinguished by their differential expression on a panel of target cells from the CXB recombinant inbred strains, the E, G, I, J, and K (all H-2b), which express different composites of the original BALB minor H Ag.
 A hierarchy was observed in which first-order immunodominant Ag were present on both CXBK and CXBG cells, whereas second-order dominant Ag were found on CXBE, CXBJ, and CXBI cells.
 To test whether immunodominance also plays a role in the development of lethal graft-vs-host disease (GVHD) directed to multiple minor H Ag, B6 T cells were transplanted along with T cell depleted bone marrow, to irradiated (825 rad) recipients of either the BALB.B or CXB recombinant inbred strains.
 The results indicate that a hierarchy of immunodominance does exist in GVHD, but it differs from that predicted from the in vitro CTL studies.
 GVHD was observed in BALB.B, CXBE, CXBI, and CXBJ recipients, but not in CXBG and CXBK recipients.
 Presensitization of B6 donor mice to CXBG or CXBK splenocytes 3 wk before transplant did not significantly increase the overall GVHD potential in the corresponding CXBG or CXBK recipients.
 Evidence for second-order immunodominance was provided by the transfer of CXBE T cells and ATBM to irradiated CXBG and BALB.B recipients with resultant, potent GVHD.
",19
3112,"Human and murine anti-DNA antibodies induce the production of anti-idiotypic antibodies with autoantigen-binding properties (epibodies) through immune-network interactions.
 To examine the potential role of immune-network interactions in the production of lupus autoantibodies, normal NZW rabbit antibody responses were analyzed after immunization with one of the following Ig preparations: human lupus serum anti-dsDNA antibodies, human lupus serum anti-ssDNA antibodies, a mixture of human lupus serum anti-dsDNA and anti-ssDNA antibodies, the MRL-lpr/lpr anti-dsDNA mAb H241, and the MRL-lpr/lpr anti-ssDNA mAb H130.
 Four of five rabbits produced Ig typical of lupus autoantibodies: individual rabbit Ig cross-reacted with multiple autoantigens including nucleic acids, cardiolipin, SmRNP, glomerular extract, laminin, and exogenous Ag.
 Rabbit anti-Id against human anti-dsDNA antibodies were highly specific for dsDNA.
 Notably, in each serum the autoantibody activity was confined to the anti-Id Ig fraction.
 A similar spontaneously occurring Id-anti-Id interaction was also found between anti-ssDNA and anti-dsDNA antibodies isolated from an individual lupus patient.
 These results indicate that lupus autoantibodies which share Ag binding properties with pathogenic Ig, including both cross-reactive and anti-dsDNA antibodies, can induce the production of Ig with similar autoantigen binding properties through immune-network interactions.
 This phenomenon, if unregulated, could lead to the amplification of pathogenic autoantibody production in individuals with systemic lupus.
",19
3113,"Induction of NF-KB during monocyte differentiation by HIV type 1 infection.
 The production of human immunodeficiency virus type 1 (HIV-1) progeny was followed in the U937 promonocytic cell line after stimulation either with retinoic acid or PMA, and in purified human monocytes and macrophages.
 Electrophoretic mobility shift assays and Southwestern blotting experiments were used to detect the binding of cellular transactivation factor NF-KB to the double repeat-KB enhancer sequence located in the long terminal repeat.
 PMA treatment, and not retinoic acid treatment of the U937 cells acts in inducing NF-KB expression in the nuclei.
 In nuclear extracts from monocytes or macrophages, induction of NF-KB occurred only if the cells were previously infected with HIV-1.
 When U937 cells were infected with HIV-1, no induction of NF-KB factor was detected, whereas high level of progeny virions was produced, suggesting that this factor was not required for viral replication.
 These results indicate that in monocytic cell lineage, HIV-1 could mimic some differentiation/activation stimuli allowing nuclear NF-KB expression.
",19
3114,"B cell activation during HIV-1 infection. II. Cell-to-cell interactions and cytokine requirement.
 This study examined the mechanisms underlying the intense activation of HIV-1-specific B cells observed in peripheral blood of HIV-1-infected subjects.
 Spontaneous in vitro synthesis of anti-HIV-1 antibodies, as well as total Ig production, were dramatically reduced by accessory cell, but not T cell removal.
 This fall was counteracted by addition of rIL-6, but not other cytokines, to monocyte-depleted cultures; moreover, antisera against IL-6 suppressed spontaneous anti-HIV-1 antibody synthesis in a dose-dependent manner.
 Although IL-6 apparently sustained HIV-1-specific B cell activation, no increase in serum IL-6 levels was observed; PBMC from seropositive subjects did not produce increased amounts of IL-6 in vitro, compared to seronegative controls, both spontaneously and in the presence of LPS stimulation; finally, no constitutive expression of IL-6 gene could be documented in freshly isolated PBMC.
 These findings indicate that IL-6 may play a central role in HIV-1-specific B cell activation in seropositive patients, and further stress the importance of this cytokine during HIV-1 infection.
",19
3115,"IgE-dependent cytokine production by human peripheral blood mononuclear phagocytes.
 These studies demonstrate the IgE-dependent production of IL-1 beta and TNF-alpha by circulating blood monocytes.
 IL-1 beta production was demonstrated biologically as the stimulation of proliferation of the cloned IL-1-dependent murine T cell line D10.G4.1 in the presence of a submitogenic concentration of PHA.
 In a representative experiment, 3H-thymidine uptake increased from 57826 cpm in the presence of supernatants obtained from unstimulated cells to 200774 cpm with supernatants from monocytes stimulated by IgE/alpha IgE immune complexes.
 By ELISA, IgE complexes increased IL-1 beta production from 0.54 +/- 0.06 ng (per 10(6) monocytes) to 2.60 +/- 0.62 ng (p less than 0.01; mean of eight experiments) and TNF-alpha production from 0.17 +/- 0.10 ng to 3.00 +/- 0.54 ng (p less than 0.01; mean of four experiments).
 No IL-1 alpha secretion was observed.
 RNA hybridization analysis demonstrated that IL-1 beta production represented de novo synthesis of the cytokine.
 Stimulated RNA production was observed after a minimal 1/2-h incubation and was maximal at 2 h.
 The IgE-dependent secretion of these pro-inflammatory cytokines by mononuclear phagocytic cells may contribute to the inflammation characteristic of allergic responses.
",19
3116,"Interferon in the treatment of AIDS-associated Kaposi's sarcoma: the American experience.
 This report is intended to summarize the use of Interferon in the treatment of Kaposi's sarcoma (KS) associated with AIDS.
 The review is basically focused on the trials in the United States, which resulted in approval by the Food & Drug Administration (FDA) of the use of recombinant interferon alpha for the treatment of Kaposi's sarcoma.
",19
3117,"Use of a new CD4-positive HeLa cell clone for direct quantitation of infectious human immunodeficiency virus from blood cells of AIDS patients.
 A new CD4-positive HeLa cell line (clone 1022) with increased sensitivity for human immunodeficiency virus (HIV) isolates derived from AIDS patients could titer infectivity of HIV from most isolates at a level equal to that observed using normal human phytohemagglutinin (PHA)-stimulated lymphocyte cultures.
 By use of this clone with a focal immunoassay (FIA), peripheral blood mononuclear cells (PBMC) producing HIV were detected in 15% of seropositive asymptomatic patients and 23% of AIDS patients at a frequency of 1 in 2 x 10(4) to 3 x 10(6) PBMC.
 HIV detection by primary FIA correlated with low CD4-positive cells counts.
 HIV activation in cocultures with PHA blasts resulted in increasing numbers of cells releasing HIV starting 3-4 days after cocultivation.
 The low incidence of HIV detection by direct FIA compared with the high incidence of HIV isolation after cocultivation with PHA blasts provided quantitative infectivity data suggesting that HIV was in a state of latency or low expression in most PBMC of AIDS patients.
",19
3118,"Iopamidol myelography: morbidity in patients with previous intolerance to iodine derivatives.
 The records of 1005 patients who underwent iopamidol myelography between January and September, 1988, were reviewed.
 In this group, 50 patients had histories suggestive of untoward sequelae associated with iodine intake, contact, or administration.
 The charts of these patients were carefully reviewed, and none of them had any reactions or sequelae suggestive of toxicity or an allergic response after iopamidol myelography.
 It is concluded that, even in patients with a previous history suggestive of intolerance to iodine administration, iopamidol myelography is generally a safe procedure.
",19
3119,"Controlled trial of a home and ambulatory program for asthmatic children.
 Care of asthmatic children is often episodic and more therapeutic than preventive.
 A 2-year randomized, controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures.
 Interventions for the study group during the first year included 3-month clinic visits, education, and home visits by a specially trained research nurse.
 Control subjects continued to receive regular care from a family physician or pediatrician.
 Eight-nine subjects (93%) completed the study.
 Study subjects had less school absenteeism than control subjects (10.7 vs.
 16.0 days, P = .04) and showed significantly better small airway function after 1 year.
 Asthma severity improved in 13 study subjects and worsened in 5.
 The reverse was true for control subjects.
 Study subjects exhibited better metered aerosol technique than control subjects (P = .0005).
 Fewer days were spent in hospital by the study subjects admitted compared with control subjects (3.67 vs 11.2 days, P = .02).
 After 1 year, more study than control families (72.1% vs 33.1%, P = .006) reported that their asthmatic child took responsibility for the asthma management.
 The intervention failed to reduce exposure to secondhand smoke or to household pets.
 There were no significant differences in medical visits, theophylline levels, or records of asthma symptoms.
 One year after discontinuing the intervention, a marked ""washout"" effect was observed.
 Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained.
",19
3120,"Discordant expression of antigens between intraepidermal and intradermal T cells in mycosis fungoides.
 Using immunohistochemical methods, the authors studied the expression of pan-T- and majority-T-cell antigens (CD5, CD2, CD3, TCR-beta, CD7) and T-cell subset antigens (CD4, CD8) in cutaneous T cells in mycosis fungoides (MF) (177 biopsies from 124 patients) and a variety of inflammatory lesions (45 biopsies from 45 patients).
 The authors detected the absence of pan-T- or majority-T-cell antigens, or of both T-cell subset antigens, from T cells in the epidermis but not the dermis in 15 MF biopsies (8%) from 11 MF patients (9%), but in none of the inflammatory skin lesions.
 The opposite picture, characterized by lack of antigen expression by the dermal T cells only, was not seen in any of the MF or inflammatory lesions.
 The absence of antigen expression by epidermal but not dermal T cells, which the authors have termed antigen discordance, was most prevalent for CD5, CD7, and TCR-beta, each being discordant in 6% to 7% of MF cases or patients tested.
 Among the MF biopsies showing antigen discordance, 14 of 15 biospies (93%) from 10 of 11 patients (91%) were discordant for two or more antigens.
 Antigen discordance was not an artifact of treatment, because none of the patients showing discordance was receiving treatment at the time of their initial discordant biopsy.
 The discordance was the only immunophenotypic abnormality detected in 8 of 15 (53%) of the discordant MF biopsies.
 Thus, this antigen discordance was an important diagnostic feature that allowed the immunophenotypic distinction of MF from a variety of inflammatory skin lesions.
",19
3121,"HLA antigens in juvenile arthritis. Pauciarticular and polyarticular juvenile arthritis are immunogenetically distinct.
 Using DNA techniques, we investigated the role of HLA-DR, DQ, and DP alleles in susceptibility to juvenile arthritis (JA).
 We studied 2 groups of patients with JA having a different disease prognosis and course.
 The pauciarticular form is usually benign, while the polyarticular disease frequently leads to joint destruction and disability.
 Persistent pauciarticular disease developed preferentially in patients having HLA-DRw13-Dw18 and DQw6-Dw18, but these antigens did not confer susceptibility in patients whose disease converted to the polyarticular form.
 HLA-DPw2.1 was an additional susceptibility factor for patients with JA of pauciarticular onset.
 In the polyarticular form of JA, HLA-DPw3 was the major factor for susceptibility, giving a relative risk of 10.3 (P less than 0.0001).
 In addition, we found that DRw8.1 and DQw4 were increased, and HLA-DR4 was markedly decreased, in patients with pauciarticular and polyarticular disease.
 These results indicate that in addition to some shared factors, distinct HLA class II alleles are important in pauciarticular or polyarticular JA.
 We conclude that typing with oligonucleotide probes may be useful in predicting the outcome in some children with arthritis.
",19
3122,"Restoration of the DNA binding activity of estrogen receptor in MRL-lpr/lpr mice by a polyamine biosynthesis inhibitor.
 Diverse data link estrogen influences to both the frequency and severity of systemic lupus erythematosus in humans and to murine lupus.
 A fundamental mechanism of action of estrogen involves the interaction of the hormone with its receptor protein, which is then transformed into the DNA binding form.
 We measured the concentration of uterine estrogen receptor and its DNA binding in normal BALB/c mice, lupus-prone MRL-lpr/lpr mice, and MRL-lpr/lpr mice that had been treated with 1% difluoromethylornithine (DFMO).
 Uterine estrogen receptor levels in 20-week-old mice from the 3 groups were not significantly different.
 In contrast, DNA binding activity was significantly higher in BALB/c mice (mean +/- SD 775 +/- 100 fmoles/mg of DNA) than in untreated MRL-lpr/lpr mice (80 +/- 16 fmoles/mg of DNA) (P less than 0.001).
 Treatment with 1% DFMO was associated with an increase in uterine estrogen receptor DNA binding (1,100 +/- 218 fmoles/mg of DNA) in MRL-lpr/lpr mice (P less than 0.001).
 Polyamine levels were 2-6-fold higher in the uterine tissues of untreated MRL-lpr/lpr mice compared with the BALB/c mice and were significantly reduced by DFMO treatment.
 Our results link uterine polyamine production to a dysfunction of the estrogen receptors in MRL-lpr/lpr mice.
 Reduction of the polyamine level by the irreversible inhibition of ornithine decarboxylase with DFMO restores estrogen receptor function.
",19
3123,"Antibody profile of early HTLV-I infection [published erratum appears in Lancet 1990 Dec 22-29;336(8730):1596] 
 To define the antibody profile of early seroconversion in infection with human T-cell lymphotropic virus type I (HTLV-I), consecutive serum samples from 10 subjects presumed to have seroconverted on the basis of the particle agglutination test were studied by three enzyme immunoassays and two confirmatory tests (radioimmunoprecipitation and western blot).
 3 samples positive and 1 sample indeterminate in the confirmatory tests were reactive in one enzyme immunoassay, which used recombinant envelope antigen, but not in the other two enzyme immunoassays.
 2 of 38 particle-agglutination-negative samples had a prozone effect.
 The confirmatory tests identified 8 seroconverters (7 women, 1 man); their serum samples were used to study the antibody reactivity by western blot assays to HTLV-I specific antigens (three recombinant proteins spanning the N-terminal, middle, and C-terminal env glycoprotein gp46; a recombinant transmembrane protein gp21; a recombinant tax protein; and three gag proteins [p28, p24, and p19]).
 All 8 seroconverters had antibody reactivities to the C-terminal region (aminoacid residues 229-308) of gp46 and to gag p19 and p24 when their seroconversion was detected.
",19
3124,"AIDS in the minds of Swedish people: 1986-1989.
 In order to assess changes in knowledge, attitudes and behaviour related to AIDS, annual mail surveys (1986-1989) were sent to random samples of the general public, aged 16-44 years.
 In total, 16,900 individuals were sampled, with an average response rate of 71%.
 Knowledge about the major routes of infection was generally good during the entire study period.
 The fear of unverified infection risks and of contact with HIV-infected people decreased during the period studied, but still remained high in 1989.
 Over the entire period, respondents expressed a strong fear concerning the spread of HIV in the population.
 Although an increasing percentage of respondents reported altered sexual habits as a result of fear of AIDS, overall sexual behaviour did not change sufficiently to reduce the risk of spread of any sexually transmissible disease.
 Progress toward knowledge, attitudes, and behaviour aimed at prevention of transmission of infection and unnecessary fear and counteraction of prejudice was most rapid during the middle of the study period when public debate concerning AIDS was at its peak.
 Knowledge and attitudes did not change during the last year of the study, but, in some respects, reverted to previous levels.
",19
3125,"Complement-mediated enhancement of HIV-1 infection of the monoblastoid cell line U937.
 To assess the role of complement and complement receptors in HIV-1 infection of monocytes and macrophages, we studied the infectivity of HIV-1, isolated from the peripheral blood of a patient with subacute AIDS-related encephalopathy, on the human monoblastoid cell line U937.
 HIV-1 and HIV-1-infected cells were capable of activating the complement system via the classical and the alternative pathways, respectively.
 Low concentrations of HIV-1 were able to infect U937 cells more easily in the presence than in the absence of complement.
 At higher virus concentrations, infectivity was no longer facilitated by the presence of complement.
 Infection of U937 cells was reduced in the presence of any of the monoclonal antibodies (MAbs), OKT4a (anti-CD4), OKM1 (anti-CR3), or M522 (anti-CR3).
 A combination of all three of these MAbs reduced the infection by an even greater amount.
 These data indicate that complement receptors may be a port of entry for complement-coated HIV-1.
",19
3126,"Immunological changes in primary HIV-1 infection.
 Homosexual men with symptomatic primary HIV-1 infection displayed a pronounced lymphopaenia with significantly depressed numbers of CD3+, CD4+ and CD8+ cells and B cells during the first week of illness.
 Subsequently, the CD8+ cell counts rose in parallel with numbers of CD3+ cells, atypical lymphocytes and activated (CD38+ and HLA-Dr+) cells to attain maximal levels about a month following onset of illness.
 In contrast CD4+ and B cell numbers remained low for an extended period of time.
 Early signs of a host response included a transient appearance of interferon-alpha in the blood and raised levels of neopterin and beta 2-microglobulin (beta 2-M).
 Neither CD4+/CD8+ cell ratio nor beta 2-M resumed completely normal values during a follow-up period of 2 years.
 These findings shed some light on pathogenetic events during early HIV-1 infection and suggest that the infection, following the acute symptomatic stage, usually enters a stage of chronic active rather than latent infection.
",19
3127,"Heterosexual transmission of HIV-1 among employees and their spouses at two large businesses in Zaire.
 To better understand the reasons why up to 80% of all HIV-1 infections in Zaire, but less than 5% in North America and Europe, are acquired through heterosexual transmission, and to assess the impact of HIV-1 infection on a large urban African workforce, we enrolled 7068 male employees, 416 female employees and 4548 female spouses of employees at two large Kinshasa businesses (a textile factory and a commercial bank) in a prospective study of HIV-1 infection.
 The HIV-1 seroprevalence rate was higher in male employees (5.8%) and their spouses (5.7%) at the bank than among male employees (2.8%) and their spouses (3.3%) at the textile factory.
 At both businesses HIV-1 seroprevalence was higher among employees in managerial positions (5.0%) than among workers in lower-level positions (3.0%; P less than 0.0001).
 In a multivariate analysis of male employees, receipt of a transfusion, a history of genital ulcer disease, working at the bank, urethritis, or being divorced or separated were independently associated with HIV-1 infection.
 During 1987 and 1988, AIDS was the most common cause of death among recently employed workers, accounting for 20 and 24% of all deaths at the textile factory and the commercial bank, respectively.
 The HIV-1 seroprevalence rate was higher among female workers (7.7%) than among the spouses of male workers (3.9%; P = 0.001).
 In multivariate analysis of the wives of workers, having an HIV-1-seropositive spouse, receipt of a blood transfusion, or a history of genital ulcer disease were independently associated with HIV-1 infection.
",19
3128,"Transition dynamics of HIV disease in a cohort of African prostitutes: a Markov model approach.
 The progression of HIV-related disease from infection to death is represented as a staged Markov model.
 Transitions between stages are considered reversible.
 The model is fitted to data from a cohort of African prostitutes by means of maximum likelihood.
 It appears that the progression to symptomatic disease (Centers for Disease Control stage IV) in this population is considerably more rapid than that reported from studies in Western countries.
",19
3129,"Recreational drug use and sexual behavior change in a cohort of homosexual men. The Multicenter AIDS Cohort Study (MACS).
 The relationship between use of recreational drugs and high-risk (HIV-transmitting) homosexual behavior was examined in the Multicenter AIDS Cohort Study (MACS) population.
 Among the 3916 men who completed both the baseline (1984) and first 6-month follow-up evaluations and were sexually active during the 6 months prior to enrollment, self-reported use of each of 10 classes of recreational drugs in conjunction with sexual activity was analyzed for both cross-sectional and prospective relationships with pattern of sexual behavior using a four-level sexual risk behavior index.
 At baseline, the proportion of men in the highest risk category (unprotected anal exposures with multiple partners) increased from 36 to 85% when men not using any drugs to men using three or more drugs plus volatile nitrites were examined.
 In multivariate logistical analyses, volatile nitrite use was significantly associated with failure to maintain or attain lower sexual risk levels after controlling for the effects of age, educational level and numbers of high-risk partners.
 These results suggest that volatile nitrite use may play an important role in the association between recreational drug use and high-risk sexual behavior among homosexual/bisexual men.
",19
3130,"World Health Organization quality assessment programme on HIV testing.
 A serum panel comprising 19 samples of known (five positives and 14 negatives) but undisclosed HIV-1-antibody content was distributed to 30 national reference laboratories for HIV serology.
 In order to simulate normal circumstances of referral, participants were asked to test the panel for HIV-1-antibody status using their normal procedures.
 Results of testing were returned by 28 participants.
 There were great variations in the number and combinations of tests used.
 The number used ranged from one to five assays per laboratory and none of the 24 laboratories using two or more tests employed the same combination.
 A high average success rate of 99% was seen with the positive samples.
 More errors occurred with the negative samples, with an average of 87% correct negative reports.
 Only four of the 14 negative specimens were reported as negative by all participants.
",19
3131,"Toxicity and efficacy of anti-T-cell ricin toxin A chain immunotoxins in a murine model of established graft-versus-host disease induced across the major histocompatibility barrier.
 Graft-versus-host disease (GVHD) was induced across the murine major histocompatibility complex by injecting C57BL/6 (H-2b) bone marrow and splenocytes into lethally irradiated B10.BR (H-2k) murine recipients.
 An immunotoxin (IT) composed of a pan T-cell monoclonal antibody called anti-Ly1 (the murine homologue to human anti-CD5) was conjugated to ricin toxin A chain (anti-Ly1-RTA) and used to treat recipient mice.
 In vitro, IT was as active as free RTA, bound selectively, and inhibited T-cell proliferation even in the absence of potentiators.
 Mice administered anti-Ly1-RTA in vivo during ongoing GVHD, at a dose of 10 micrograms/d for 5 days, showed lower numbers of splenic Thy1.2+ T cells and significantly improved survival as compared with mice given phosphate-buffered saline (PBS) or irrelevant control RTA IT.
 Protection was transient because GVHD and weight loss occurred when injections ceased.
 Survival could not be enhanced by crosslinking RTA30, a low oligosaccharide-containing fraction of purified RTA.
 Treatment with anti-Ly1-RTA caused a significant elevation in neutrophils, and higher doses were associated with mild hepatotoxicity.
 In contrast, infusion of identical doses and schedules of another pan T-cell immunotoxin, anti-Thy1.2-RTA, caused a significant decrease in lymphocytes, but not neutrophils; a precipitous increase in weight; a decrease in total plasma protein (TPP); and an increase in pleural and peritoneal effusions reminiscent of vascular leak syndrome (VLS).
 Although the toxic effects of anti-Thy1.2-RTA were too severe to show a survival advantage in a GVHD model, histopathologic studies showed a definite anti-GVHD effect.
 The most significant decline in GVHD as compared with the PBS-treated controls was observed in skin, and to a lesser extent, in liver and lung.
 To investigate the cause of IT toxicity, anti-Thy1.2-RTA was administered intraperitoneally to lethally irradiated B10.BR (H-2k) recipients of syngeneic bone marrow.
 These recipients showed the same weight gain, hypoproteinuria, and VLS observed in the GVHD model.
 Death occurred at higher anti-Thy1.2-RTA doses (30 or 50 micrograms/daily injections administered days 8 through 12 posttransplant).
 Anti-Thy1.2-RTA had a negligible effect on renal function, but histologic studies showed patchy dropout of the renal tubules.
 Treatment resulted in pulmonary vascular congestion, but there was no pathologic evidence of liver, brain, or colon toxicity.
 Weight gain was enhanced by irradiation because nonirradiated normal mice did not undergo such a precipitous weight increase.(ABSTRACT TRUNCATED AT 400 WORDS).
",19
3132,"Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides.
 Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides.
 Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks.
 All patients had some clinical improvement, but responses were of relatively short duration.
 Serum levels of chimeric antibody varied as a function of dose.
 At the 80-mg dose level, antibody was readily observed in biopsied skin lesions.
 Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells.
 Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance.
 All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen.
 However, there was marked suppression of the mixed lymphocyte reaction.
 We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.
",19
3133,"The evolving role of etoposide in the management of lymphomas and Hodgkin's disease.
 Etoposide, a derivative of epipodophyllotoxin, is one of the most important new drugs that was introduced into the management of the malignant lymphomas during the past decade.
 A growing number of specific protocols include this useful agent in the management of malignant lymphoma, both at the time of primary treatment and at relapse.
 The broad activity of etoposide across several histologic subtypes of malignant lymphoma and Hodgkin's disease indicates a potential that is only now being fully exploited.
 Used according to optimal doses and schedules, etoposide has single-agent activity that rivals earlier drugs such as the alkylating agents and doxorubicin.
 Functioning as a protein synthesis and topoisomerase II inhibitor, it offers the potential for non-cross-resistant cytotoxicity.
 After a brief comment on the single-agent activity of etoposide, this report will focus on the integration of etoposide into multiagent protocols used in the primary treatment of malignant lymphoma and Hodgkin's disease.
 The specific findings from protocols such as prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide-cytarabine, bleomycin, vincristine, and methotrexate (Pro-MACE-CytaBOM) (US National Cancer Institute [NCI]) and etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) (Vancouver) for the primary treatment of malignant lymphoma, and vinblastine, etoposide, cyclophosphamide, doxorubicin, bleomycin, vincristine, and prednisone (VECABOP) (Vancouver) for the treatment of previously untreated patients with advanced Hodgkin's disease will be discussed.
",19
3134,"Longitudinal study of near fatal asthma.
 The effect of careful follow-up and treatment modification for 45 patients with an admission for NFA has been studied.
 In 24 of 45, inciting events were recognized.
 BDP was used by 14 patients pre-NFA.
 In the mean follow-up of 863 days, there have been no deaths and seven patients have been readmitted with asthma.
 Six of the 45 patients have attained normal FEV1 and PC20H.
 Blunted perception of breathlessness, change in VAS ratio/change in FEV1, was found when first measured, but normalized to be no different than that of other asthmatic subjects as airway responsiveness became milder.
 The CO2 ventilatory responses did not differentiate individual NFA patients from non-NFA asthmatic or normal subjects.
 Comparison of the NFA cohort with the 1985 asthma admission cohort showed that an asthma admission within the last five years was a risk factor for a NFA episode.
",19
3135,"Relationships with AIDS patients: clinical metaphors and preventive bioethics.
 AIDS, more than most diseases, evokes compelling and tragic stories.
 The AIDS epidemic is ""The Plague."" We seek the optimally therapeutic relationship, embodied in the metaphor of the covenant.
 There is a fundamental human possibility of healing through dying.
 ""Death teaches us to live."" We advocate asking AIDS patients the explicit question, ""How do you want me to work with you?"" This can generate conversations that facilitate congruence in relationships.
 A reluctance to talk about uncertainties and limits is a major source of preventable ethical conflict and a major obstacle to fulfillment of the therapeutic possibilities of the doctor-patient relationship.
 The Durable Power of Attorney for Health Care (DPA) can be helpful in facilitating discussions with patients and their families.
 Successful ""preventive bioethics"" is communication that opens for the patient and doctor the broadest possibilities of hearing, understanding, and expressing.
 The doctor as parent, fighter, technician, teacher, and covenanter may be important roles at appropriate moments with a given patient who may be experiencing the disease variably as infectious chaos, brutal enemy, spiritual challenge, or opportunity for growth.
 The context of such communication is a real relationship that includes love, respect, humor, hope, and genuine interest in how this other person lives.
",19
3136,"Interleukin-1 is released at sites of human cutaneous allergic reactions.
 Interleukin-1 (IL-1) promotes cell recruitment and influences allergic mediator release.
 We analyzed histamine, prostaglandin D2, IL-1, and leukocytes accumulating hourly for 12 hours at skin-chamber sites after local ragweed challenge in eight allergic subjects with cutaneous late-phase reactions.
 Ragweed induced a peak of histamine at 1 hour (p less than 0.02), which diminished, and then steadily increased (p less than 0.02).
 Prostaglandin D2 levels peaked by the second hour (p less than 0.02) and then decreased, approaching prechallenge levels by 12 hours.
 Leukocyte infiltration (predominantly neutrophils) was detectable 3 to 4 hours after challenge, although selective enrichment of mononuclear cells, eosinophils, and basophils ws observed at later hours (p less than 0.02).
 IL-1 bioactivity was detected in fluids 10 to 12 hours after challenge but not at control sites (p less than 0.05).
 Analysis of IL-1 beta levels by RIA revealed an initial peak at 1 hour of 0.90 ng/ml (p less than 0.02) and a second elevation of up to 0.75 ng/ml during the later hours (p less than 0.04).
 Ragweed challenge of three nonatopic subjects did not change levels of the above-mentioned mediators or cells.
 Bioactivity in chamber fluids from antigen-challenged sites of atopic subjects was significantly neutralized by an anti-IL-1 beta antiserum, although treatment with anti-IL-1 alpha and anti-IL-1 beta was needed for complete neutralization, IL-1 released locally during cutaneous allergic reactions may contribute to IgE-dependent cutaneous inflammation.
",19
3137,"Alpha- and beta-adrenergic-receptor systems in bronchial asthma and in subjects without asthma: reduced mononuclear cell beta-receptors in bronchial asthma.
 We assessed the adrenergic-receptor system in individuals with bronchial hyperreactivity, beta-Adrenergic receptors on mononuclear cell membranes, alpha-adrenergic receptors on platelet membranes, and the cAMP response in these cell types to different stimuli, including platelet-activating factor (PAF), were determined.
 Studies were assessed in 10 subjects with mild asthma, six methacholine-sensitive subjects without asthma, and 10 normal subjects.
 The density and affinity of beta-receptors and alpha-receptors were determined by Scatchard analysis.
 Our findings were that (1) subjects with asthma had a significantly lower density of beta-receptors compared to normal subjects, (2) subjects with asthma had a significantly lower cAMP response to isoproterenol stimulation compared to the two other groups, (3) in subjects without asthma.
 PAF decreased the basal cAMP level and significantly inhibited the response to isoproterenol stimulation, (4) there was no difference in density and affinity of platelet alpha-receptors or in platelet cAMP responses to stimulation by alpha-agonists among these three groups, and (5) neither cAMP response or beta-receptor density on mononuclear cells were significantly correlated with pulmonary-function tests (FEV/FVC times 100), sensitivity to methacholine, or cold-air inhalation.
 These results suggest that patients with asthma may have a lower isoproterenol cAMP response and decreased density of beta-adrenergic receptors on mononuclear cells in the absence of beta-agonist therapy.
 It is speculated that release of PAF and other mediators secondary to allergen exposure, even in the absence of overt attacks of asthma, may inhibit the response to endogenous or exogenous beta-adrenergic agonists.
",19
3138,"Relationship between the early, late, and rechallenge reaction to nasal challenge with antigen: observations on the role of inflammatory mediators and cells.
 We challenge each of 55 consecutive ragweed (RW)-allergic patients with hay fever and with graded increasing doses of ragweed extract to investigate the frequency and relationship between the early (ER), late (LPR), and rechallenge reactions (RCRs) to nasal challenge.
 We evaluated the nasal response by measuring the levels of histamine, TAME-esterase activity, and kinins in the nasal lavage fluid and by grading symptoms.
 Fifty-one subjects (92.7%) had an ER consisting of a dose-dependent, concommitant increase in both mediators and symptoms.
 The total amount of TAME-esterase activity and kinins generated during ER correlated significantly with specific serum IgE (ssIgE), intradermal skin test (ST) sensitivity, and basophil histamine release (BHR) to antigen E (p less than 0.01 for each).
 Twenty-four (47%) subjects developed a late increase in mediators and 23 (45%) subjects in symptoms.
 None of the four subjects without an ER developed an LPR.
 The levels of the late-appearing mediators were not predicted by ST, ssIgE, or BHR.
 There was a significant but weak association between the intensity of ER and LPR, but there was no significant difference in the IgE antibodies, ST, BHR, and intensity or threshold of ER between dual and early only reactors.
 The number of eosinophils and neutrophils in the LPR lavages increased over the prechallenge baseline, and their numbers correlated (p less than 0.05) with ER kinins (r = 0.46, and 0.37, respectively), ER TAME-esterase activity (r = 0.28 and 0.24, respectively), and in the case of eosinophils, ER histamine (r = 0.29).
",19
3139,"1,25-Dihydroxyvitamin D3 potentiates the decreased response of lymphocytes from atopic subjects to agents that increase intracellular cyclic adenosine monophosphate.
 The inhibitory effect of prostaglandin E2, histamine, isobutylmethylxanthine, and 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) on the mitogenic stimulation of peripheral blood lymphocytes from normal and atopic subjects was studied.
 We found that lymphocytes from atopic patients were less susceptible to inhibition by the three agents that elevate intracellular cyclic adenosine monophosphate (cAMP) concentrations and by the active metabolite of vitamin D (inhibition of 27%, 14%, 12%, and 36% for the atopic patients as compared with 40%, 20%, 22%, and 46% for the normal donors, by the four agents, respectively; p less than 0.02).
 The inhibitory effect of the cAMP-elevating agents was potentiated by the addition of 1,25-(OH)2D3 to the lymphocyte cultures.
 The potentiation was more pronounced on lymphocytes from the atopic donors, increasing their responsiveness to levels comparable to levels of lymphocytes from normal donors.
 The synthetic corticosteroid, dexamethasone, had a similar potentiating effect on the inhibitory action of prostaglandin E2.
 In view of the beneficial action of beta-agonists, phosphodiesterase inhibitors, and corticosteroids in the treatment of allergy, the potentiating effect of 1,25-(OH)2D3 on the action of cAMP-elevating agents may be of therapeutic interest.
",19
3140,"Comparison of the effect of loratadine on the airway and skin responses to histamine, methacholine, and allergen in subjects with asthma.
 Loratadine is a highly selective, long-acting, H1-receptor antagonist.
 In a randomized, double-blind, crossover study, we evaluated the effects of loratadine, 10 and 20 mg, and placebo administered once daily for 3 days on the skin-wheal responses to histamine, the airway responses to inhaled histamine and methacholine, and the skin-wheal and airway responses to allergen in 12 subjects with asthma.
 There was no evidence of a bronchodilator action 3 hours after a third oral dose.
 In the airways, the geometric mean of the provocative concentration of histamine causing a 20% fall in FEV1 after placebo or loratadine, 10 and 20 mg, was 0.68 mg/ml, 2.71 mg/ml (p, not significant), and 5.96 mg/ml (p less than 0.05), respectively.
 The concentration ratios (value after active treatment/value after placebo) for loratadine, 10 and 20 mg, were 5.1 (p less than 0.05) and 13.4 (p less than 0.05).
 Neither dose of loratadine had any significant effect on the methacholine dose-response relationship.
 In the skin, loratadine also displaced the histamine log-concentration response curves to the right with concentration ratios of 4.7 and 6.7, respectively.
 Loratadine, 10 and 20 mg, had no protective effect on the early or late-phase bronchoconstrictor responses to inhaled allergen.
 In the skin, loratadine, 20 mg, significantly inhibited the mean wheal area to allergen.
 Thus, in the dose regimens studied, although loratadine is a moderately potent and selective H1 antagonist in the skin and airways, it failed to attenuate the early and late airway responses to inhaled allergen.
",19
3141,"Altered production of histamine-releasing factor (HRF) activity and responsiveness to HRF after immunotherapy in children with asthma.
 To delineate the working mechanisms of immunotherapy (IT) (hyposensitization), the production of, and responsiveness to, histamine-releasing factor (HRF) was studied in four groups.
 These groups consisted of 32 newly diagnosed children with asthma, 40 good responders and 18 poor responders to IT (older than 2 years), and 15 healthy subjects.
 The results demonstrated (1) peripheral blood mononuclear cells of new patients produced a much greater HRF activity, either spontaneously or after stimulation, than did those of normal subjects, (2) the spontaneous HRF activity decreased significantly in good responders, whereas that of poor responders increased, (3) both the allergen (mite)- and mitogen (phytohemagglutinin [PHA])-stimulated HRF activity was decreased, although decrease was not significant, in good responders, but the activity was not changed in poor responders, (4) the granulocytes of new patients responded to HRF much more vigorously than did granulocytes of normal subjects.
 The responsiveness diminished significantly in both good and poor responders, although the magnitude of decrease was slightly greater in the former, (5) there was a positive correlation between PHA- and mite-stimulated HRF activity, mite-stimulated HRF activity and responsiveness to HRF, and plasma histamine level and responsiveness to HRF in the new patients, and (6) there was an inverse correlation between PHA-stimulated HRF production and responsiveness to HRF in good responders, but the correlation was positive in poor responders.
 Thus, IT is able to suppress the HRF activity, particularly the type of spontaneous synthesis, and responsiveness to HRF in clinically benefitted children with asthma, and this effect may be used to explain, partly, the efficacy of IT in a proportion of allergic patients.
",19
3142,"Allergy to different fish species in cod-allergic children: in vivo and in vitro studies.
 The presence of a positive clinical history and skin test (ST) results for 17 fish species (anchovy, bass, carp, dogfish, eel, gilthead, mackerel, mullet, perch, red mullet, salmon, sardine, sole, tench, toothed gilthead, trout, and tuna) were investigated in 20 children with cod-positive clinical history, ST, and RAST, and in 40 children positive to one or more foods different from cod (cow's milk, chicken egg white, peanut, and tomato).
 In cod-positive children, positive clinical history (60%) and ST (85%) to fish species were more frequent than in cod-negative children (7.5% and 10% respectively).
 In cod-positive children, a high frequency of positive STs to eel (85%) and to bass, dentex, sole, and tuna (55%) was observed.
 Positivity to dogfish (10%) was the least frequent.
 RAST-inhibition experiments suggested the presence of cross-reacting antigen(s) in cod, bass, dentex, eel, sole, and tuna.
 Results of this study demonstrate that cod allergy might be, on the whole, a reliable index of fish allergy, but cod-positive children may perhaps tolerate some other species, which will have to be tested for possible inclusion in their diet.
",19
3143,"Selective desensitization to seminal plasma protein fractions after immunotherapy for postcoital anaphylaxis.
 A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation.
 Systemic reactions (SRs) were prevented by use of condoms.
 Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma.
 The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively.
 Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3.
 A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3.
 The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1.
 On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms.
 There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2.
 IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3.
 At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped.
 The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2.
 Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions.
 Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.
",19
3144,"Cetirizine: antiallergic therapy beyond traditional H1 antihistamines.
 For three decades, traditional H1 antihistamines have been used in the treatment of allergic diseases.
 They are effective in reducing histamine-related symptoms, but the use of such agents has been limited by sedation and anticholinergic side effects.
 These adverse effects are fewer with the recently introduced H1 antihistamines.
 One of these, cetirizine, a human metabolite of hydroxyzine, is characterized by its high selectivity for the H1 receptor site and its reliable and consistent inhibition of histamine-induced allergic reactions.
 It also blocks eosinophil infiltration to the site of allergen-induced cutaneous reactions.
 Cetirizine has proved effective in the treatment of seasonal and perennial allergic rhinitis and urticaria.
 It is excreted primarily by renal mechanisms.
 It is well tolerated by elderly patients.
 Cetirizine has a low rate of penetration of the blood-brain barrier, and it has minimal central nervous system impairment.
 Furthermore, it can be given once a day.
 Cetirizine's low incidence of sedation and anticholinergic side effects contribute to its high profile of safety.
 In this article the characteristics, pharmacology, pharmacokinetics, and mode of action of cetirizine are reviewed.
",19
3145,"AIDS: family physicians' attitudes and experiences 
 A study was developed to examine the current experiences and opinions of a national sample of family physicians with regard to acquired immunodeficiency syndrome (AIDS).
 The survey response rate was 72.5% (757 questionnaires were returned out of a sample of 1044).
 Approximately 47% of respondents have cared for an HIV-infected patients.
 This percentage varied from a low of 31.4% in the Midwest to as high as 56.1% on the East Coast.
 Thirty-two percent of family physicians practicing in communities of fewer than 2500 have dealt with this illness, while 60% of those in communities of greater than 100,000 have done so.
 Seventy-seven percent of respondents are willing to provide care to HIV-infected individuals; 62.9% believe that physicians have a right to refuse to care for a patient because he or she is infected with the AIDS virus.
 Forty percent believe that they would lose patients if it were known that they were caring for an AIDS patient in their office.
 Finally, the vast majority of those surveyed favor required partner notification and would inform the sexual partner of an HIV-positive patient if the patient refused to do so.
",19
3146,"P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil.
 P-glycoprotein is a transmembrane protein thought to function as an efflux pump to detoxify cells.
 It is associated with multidrug resistance in laboratory systems and has recently been found in human tumors associated with in vitro and clinical drug resistance.
 We used an immunohistochemical method employing two monoclonal antibodies, JSB-1 and C-219, to detect expression of P-glycoprotein in lymphoma patients.
 One of 42 newly diagnosed and untreated lymphoma patients (2%) and seven of 11 previously treated and drug-resistant patients (64%) had detectable levels of P-glycoprotein (P less than .001).
 Based on prior reports suggesting that verapamil sensitizes drug-resistant cancer cells to chemotherapy by competitive inhibition of the P-glycoprotein, we tested the efficacy of verapamil as a chemosensitizer in 18 patients with drug-refractory disease.
 All patients had previously failed or relapsed within 3 months of a doxorubicin-vincristine-containing drug regimen.
 Patients received day-1 cyclophosphamide, and 4-day continuous infusion doxorubicin and vincristine and oral dexamethasone (CVAD).
 CVAD was combined with 5-day continuous infusion verapamil given at maximally tolerated dose.
 Overall, 13 of 18 patients (72%) responded to treatment including five complete remissions (CRs; 28%).
 The median duration of response was 200 days and median survival was 242 days.
 The dose-limiting toxicity of the verapamil infusion was temporary cardiac dysfunction including hypotension, congestive heart failure, and cardiac arrhythmia.
 We conclude that the P-glycoprotein is uncommonly expressed in untreated lymphomas and frequently expressed in clinically drug-resistant disease, and that chemotherapy using CVAD plus maximally tolerated doses of verapamil results in a high response rate in patients carefully selected for clinical drug resistance.
",19
3147,"Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial [published erratum appears in J Clin Oncol 1991 Apr;9(4):710]
 One hundred ninety-three patients with stage II, III, or IV follicular large-cell, diffuse large-cell, diffuse mixed, immunoblastic, or diffuse small noncleaved-cell (non-Burkitt's) lymphoma were randomized to receive either cyclophosphamide 650 mg/m2 intravenously (IV), doxorubicin 25 mg/m2 IV, etoposide 120 mg/m2 IV on day 1, mechlorethamine 6 mg/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV on day 8, prednisone 60 mg/m2 orally daily days 1 through 14, procarbazine 100 mg/m2 orally daily days 8 through 14, and methotrexate 500 mg/m2 IV on day 15 with leucovorin 50 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate with cycles repeated every 28 days (ProMACE-MOPP) or same day-1 treatment as ProMACE-MOPP plus cytarabine 300 mg/m2 IV, bleomycin 5 U/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV, and methotrexate 120 mg/m2 IV on day 8, leucovorin 25 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate, and prednisone 60 mg/m2 orally daily days 1 through 14 with cycles repeated every 21 days (ProMACE-CytaBOM).
 Co-trimoxazole two double-strength tablets orally twice daily throughout the period of treatment was added to the ProMACE-CytaBOM regimen when an increased risk of Pneumocystis carinii pneumonia was found in the first 35 patients receiving this combination.
 Median follow-up is 5 years.
 Among the 99 patients treated with ProMACE-MOPP, 73 achieved a complete remission (CR) (74%), 30 complete responders have relapsed (41%), and 45 patients have died (45%), including two (2%) of treatment-related causes.
 Among the 94 patients treated with ProMACE-CytaBOM, 81 achieved a CR (86%), 22 complete responders have relapsed (27%), and 31 patients have died (33%).
 The complete response rate (P2 = .048) and survival (P2 = .046) were significantly higher for patients treated with ProMACE-CytaBOM.
 The mortality of ProMACE-CytaBOM treatment overall was six of 94 patients (6.4%).
 There was no treatment-related mortality among patients treated with prophylactic co-trimoxazole (n = 59).
 ProMACE-CytaBOM combination chemotherapy with co-trimoxazole prophylaxis is a safe and effective treatment for patients with aggressive histology malignant lymphoma and is superior to ProMACE-MOPP.
",19
3148,"Care of the asthmatic oral and maxillofacial surgery patient.
 It is estimated that asthma affects 6 to 9 million people in the United States.
 The nature of this disease makes it a special concern to the oral and maxillofacial surgeon.
 Appropriate management of the asthmatic patient with regard to anesthesia and surgical procedures of the oral and maxillofacial region is discussed.
",19
3149,"Tuftsin deficiency in AIDS.
 Tuftsin is an endogenous tetrapeptide that stimulates phagocytosis and is released from the Fc fragment of IgG by a splenic endocarboxypeptidase.
 Tuftsin activity and splenic function were measured in 21 patients with AIDS, 7 patients with AIDS-related complex (ARC), 22 patients who had undergone splenectomy, and 37 healthy volunteers.
 There was a significant inverse correlation between tuftsin activity and splenic function in all subjects.
 Tuftsin activity was significantly lower in patients with AIDS, ARC, and in those who had undergone splenectomy compared with healthy volunteers.
 Tuftsin deficiency may contribute to the risk of bacterial infection in symptomatic HIV-positive individuals.
",19
3150,"Absence of highly homologous sequence to HTLV-I in Japanese multiple sclerosis.
 We tried to detect HTLV-I-related sequences in Japanese patients with multiple sclerosis with a highly sensitive method that employs the polymerase chain reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis.
 To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding regions.
 Fourteen patients with definite MS, 14 disease controls, 12 normal controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were investigated.
 Results of particle aggregation assay for HTLV-I antibodies were negative in serum from all subjects except for the 3 HAM patients.
 Neither the 14 MS patients nor the 26 controls showed the presence of any highly homologous sequences to HTLV-I.
 We did observe faint signals for gag, pol, and env coding regions only at low stringent hybridization in some MS patients as well as some normal controls.
 The nucleotide sequence analysis of the faint bands was more homologous to major histocompatibility complex molecules than the HTLV-I genome.
",19
3151,"Beta-2-microglobulin concentrations in pediatric human immunodeficiency virus infection.
 Serum concentrations of beta-2-microglobulin (B2-M) were correlated with disease outcome in 40 children infected by the human immunodeficiency virus.
 Serum B2-M serum concentrations below 3.0 mg/100 ml or decreasing concentrations were indicative of a stable disease course but were also noted preterminally in lymphopenic children.
 Of 20 patients with B2-M concentrations above 3.0 mg/liter, 12 had a progressive disease course and 8 remained stable.
 In the latter 8 patients the B2-M values decreased with time.
 Elevated B2-M concentrations were also noted in infants younger than 1 year of age and denoted active human immunodeficiency virus infection.
 B2-M serum concentrations are a useful prognostic marker in human immunodeficiency virus-infected children.
",19
3152,"Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes.
 The circulating T lymphocytes of a female child with recurrent opportunistic infections were normal in number and phenotype but exhibited poor proliferation and decreased synthesis of the T-cell growth factor interleukin (IL) 2 in response to mitogens.
 Recombinant IL-2 fully restored the proliferative responses of her T cells, suggesting that her poor immune function was related to IL-2 deficiency.
 Northern blot analysis of total cellular RNA from the patient's T cells revealed markedly decreased levels of IL-2 mRNA of normal size.
 In addition, mRNA levels of other lymphokines selectively expressed by T cells, which include IL-3, IL-4, and IL-5, were either severely depressed or absent.
 The levels of interferon gamma mRNA were moderately decreased, while those of granulocyte-macrophage colony stimulating factor, a lymphokine the production of which is not restricted to T cells, were unaffected.
 The decreased level of lymphokine mRNA in the patient's T lymphocytes was not from enhanced catabolism but resulted from a diminution in the transcription rate of the affected lymphokine genes.
 Normal transduction via the T-cell receptor/CD3 complex of biochemical signals necessary for the initiation of lymphokine gene transcription indicated that the defect was distal to the membrane signal-transducing apparatus.
 The defect is hypothesized to involve a T-cell-specific trans-acting regulatory factor required for transcription of the affected lymphokine genes.
",19
3153,"Autoimmune preganglionic sympathectomy induced by acetylcholinesterase antibodies.
 Systemic injection of monoclonal antibodies to neural acetylcholinesterase in adult rats caused a syndrome with permanent, complement-mediated destruction of presynaptic fibers in sympathetic ganglia and adrenal medulla.
 Ptosis, hypotension, bradycardia, and postural syncope ensued.
 In sympathetic ganglia, acetylcholinesterase activity disappeared from neuropil but not from nerve cell bodies.
 Choline acetyltransferase activity and ultrastructurally defined synapses were also lost.
 Electrical stimulation of presynaptic fibers to the superior cervical ganglion ceased to evoke end-organ responses.
 On the other hand, direct ganglionic stimulation remained effective, and the postganglionic adrenergic system appeared intact.
 Motor performance and the choline acetyltransferase content of skeletal muscle were preserved, as was parasympathetic (vagal) function.
 This model of selective cholinergic autoimmunity represents another tool for autonomic physiology and may be relevant to the pathogenesis of human dysautonomias.
",19
3154,"Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus 1 is host dependent, rapid, and continuous.
 The principal neutralization epitope of human immunodeficiency virus 1 is localized in the third variable (V3) domain of the external envelope and has been shown to bind isolate-specific antibodies.
 Therefore, the extent of variation within the nucleic acid sequence encoding this epitope was studied in DNA directly obtained from peripheral blood mononuclear cells of six children and their plasma donor.
 This revealed that the quasi-species distribution of sequences obtained after cloning varied from recipient to recipient and that the distance from the donor sequences increased over time.
 V3 nucleotide evolution rates averaged 9.5 x 10(-3) per site per year for silent sites and 11.4 x 10(-3) per site per year for nonsilent sites (vs.
 9.7 and 9.8 x 10(-3) per site per year for a control region 5' adjacent to the V3 region) and, although individual differences were observed, did not correlate with the serum antigen levels or disease progression.
 Sequences of both the epitope coding region itself (V3) and the control region upstream diverted more from the donor sequence among children not progressing to AIDS than among children progressing to AIDS.
 The evolution of V3 sequences is apparently host dependent, rapid, and independent of the level of antigen expression.
",19
3155,"Aggressive non-Hodgkin's lymphomas in AIDS: the University of Colorado experience.
 The authors performed this retrospective study to further investigate the relationship between non-Hodgkin's lymphoma (NHL) and the Acquired Immunodeficiency Syndrome (AIDS).
 From January 1984 through December 1987 all cases of AIDS and NHL diagnosed at the University of Colorado affiliated hospitals were identified and submitted to chart review.
 Twenty-five patients fulfilled criteria for the diagnosis of AIDS and 24 had biopsy-proven NHL, an additional patient met criteria for the diagnosis of primary central nervous system lymphoma and was included in the analysis.
 All patients had known risk factors for the development of AIDS.
 Of the biopsy proven tumors, 23 were categorized as high grade.
 Most patients (68%) presented with stage IV disease and 92% with extra nodal involvement.
 Median survival was 5 months and the cause of death was most often progressive lymphoma and/or opportunistic infections.
 These data are similar to previously published series.
 Clinical trials to evaluate effective treatment are warranted.
",19
3156,"Comparison of median and posterior tibial nerve somatosensory evoked potentials in ambulatory patients with definite multiple sclerosis.
 Somatosensory evoked potentials (SEPs) were recorded for stimulation of both median nerves and both posterior tibial nerves in control subjects and in subjects with multiple sclerosis (MS) of several years' duration, who were ambulatory and not experiencing exacerbation.
 Documentation of peripheral nerve conduction revealed no abnormalities in any of the subjects.
 Centrally, abnormal responses to median and posterior tibial nerve stimulation were found at the spinal level and/or the scalp in nearly all MS patients.
 Using the latency of the initial negativity of scalp SEPs, posterior tibial SEPs were abnormal significantly more often than median SEPs.
 Calculations suggested a significant increase in spinal conduction time.
 The high incidence of abnormal SEPs does not support any substantial physiological recovery in this group of MS patients.
",19
3157,"Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus.
 The pathogenesis of the hematologic abnormalities commonly observed in patients with acquired immunodeficiency syndrome (AIDS) is incompletely understood.
 We report here that in vitro growth of myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells from six patients with AIDS was not significantly different from that of normal human immunodeficiency virus (HIV) seronegative donors: 25.3 +/- 5 CFU-GM per 5 x 10(4) low density marrow cells and 33.5 +/- 5 BFU-E were observed in AIDS patients versus 32.7 +/- 5 CFU-GM and 42.1 +/- 5 BFU-E in controls.
 Furthermore, no HIV-DNA in individual colonies (CFU-GM and BFU-E) could be detected using the polymerase chain reaction (PCR) technique, although HIV-1 DNA was detected in peripheral blood mononuclear cells from the same patients.
 Similarly, normal bone marrow cells exposed in vitro to different isolates of HIV or recombinant purified HIV-1 envelope glycoprotein (gp) 120 did not exhibit any difference in growth of CFU-GM or BFU-E as compared with mock exposed bone marrow cells.
 HIV-1 DNA could not be detected by the PCR technique in individual colonies derived from HIV exposed marrow.
 This study suggests that committed myeloid and erythroid progenitors from AIDS patients are responsive to hematopoietic growth factors in vitro and do not appear to contain HIV-1 DNA.
 Also, HIV or its envelope gp did not alter the growth of hematopoietic progenitor cells in vitro.
 No evidence of HIV infection of progenitor cells could be demonstrated.
 Impaired hematopoiesis in patients with AIDS may not be related to direct effects of HIV on committed progenitor cells.
",19
3158,"Retinoic acid receptors in myeloid leukemia: characterization of receptors in retinoic acid-resistant K-562 cells.
 Although mRNA for the retinoic acid receptor alpha (RAR-alpha) is expressed in many different myeloid leukemias, most of these leukemia cells exhibit little if any phenotypic response when exposed to retinoic acid (RA).
 To determine whether such RA resistance is related to altered RA receptor structure or function, we performed a detailed analysis of nuclear RA receptors in RA-resistant K-562 cells.
 These cells exhibit RA receptors of the same approximate molecular weight and similar kd as those exhibited by the RA-sensitive HL-60 leukemia cell line, but the number of RA receptors in the RA-resistant K-562 cells (80 per cell) is significantly lower than that exhibited by RA-sensitive HL-60 cells (550 per cell).
 Retroviral-mediated transduction of RAR-alpha cDNA into K-562 significantly increased the number of RA receptors to 2,000 per cell.
 These RAR-alpha-transduced K-562 cells, when incubated with RA, exhibit diminished cell proliferation associated with decreased c-myc expression and an accumulation of cells in G0/G1.
 In addition, these RA-treated cells exhibit downregulation of the CD15 surface antigen and a slight increase in hemoglobin production but manifest no other evidence of significant erythroid, megakaryocytic, or myeloid differentiation.
 These results indicate that an elevated number of nuclear RA receptors can be involved in altering proliferation but not necessarily the differentiation of certain RA-treated myeloid leukemia cells.
",19
3159,"Long-term survival in Ki-1 lymphoma.
 Three patients with histologic and immunologic features of Ki-1-positive large cell lymphoma, who experienced long-term survival, are presented.
 These three patients at 2, 28, and 49 years of age had adenopathy; all cases had been initially misdiagnosed as metastatic carcinoma or malignant histiocytosis.
 On subsequent review, they had sinusal and diffuse growth of large pleomorphic cells that were Ber-H2 (Ki-1; CD 30) positive.
 One case marked as a T-cell lymphoma with UCHL1, one case expressed T-cell and B-cell markers, and one case was negative for both T-cell and B-cell markers.
 All patients received chemotherapy, and two received local radiation.
 One patient was not treated until 9 years after initial diagnosis.
 Two patients had several recurrences, but there has been no evidence of lymphoma in any of the three patients for 63 to 301 months; overall survival time has ranged from 14 to 25 years.
 These cases are the longest reported survivors with Ki-1 lymphoma; 5 years was the longest survival time previously reported.
 It also is noteworthy that Ber-H2 and other lymphoid-associated antigens appear to be preserved in formalin-fixed, paraffin-embedded tissues for prolonged periods.
 This may allow retrospective studies to evaluate the natural history of Ki-1 lymphomas, as well as their spontaneous or treatment-induced regression.
",19
3160,"Multiple sclerosis in Australia and New Zealand: are the determinants genetic or environmental? 
 The prevalence of multiple sclerosis (MS) has been recently reported from nine regions of Australia and New Zealand.
 There is a marked variation of prevalence with latitude.
 MS is seven times more common in southern New Zealand than in tropical Queensland.
 On current evidence, it is suggested that in both countries this variation is predominantly due to environmental rather than genetic factors.
",19
3161,"Multiple sclerosis among United Kingdom-born children of immigrants from the Indian subcontinent, Africa and the West Indies 
 Multiple sclerosis (MS) is very uncommon among ethnic Asians in the Indian subcontinent, among Asians and Africans resident in the New Commonwealth countries of Africa and in the West Indies.
 It is also very uncommon among those who have migrated to England from those countries.
 In contrast, the children born in the United Kingdom of Asian, African and West Indian immigrants have, in the age groups available for study, a high prevalence of MS of a similar order to that occurring in the general population of England.
",19
3162,"The use of formal prior directives among patients with HIV-related diseases.
 OBJECTIVE: To examine the knowledge of, counseling about, and use of prior directives among patients with HIV-related disease.
 DESIGN: Cross-sectional survey with personal interviews that was part of the evaluation of a multi-site AIDS Health Services Program.
 SETTING: Outpatient clinics and AIDS community-based organizations.
 PATIENTS/PARTICIPANTS: To be eligible for the survey, subjects had to be at least 18 years of age and enrolled in the AIDS Health Services Program for at least one month.
 1,031 clients were interviewed in nine communities.
 MEASUREMENTS AND MAIN RESULTS: Of those surveyed, 61% had thought a moderate or great amount about naming a proxy for health care decisions.
 The majority (68%) of the patients knew about prior directives, yet only 35% had been counseled and only 28% had a prior directive.
 Of those counseled, physicians had counseled only 11% (38/359).
 Gay/bisexual men were more likely to have been counseled and to have executed a prior directive than were others.
 Counseling was associated with having obtained a prior directive.
 Counseled subjects were 3.5 times more likely to have obtained a prior directive than were those not counseled.
 CONCLUSIONS: A gap exists between subjects' knowledge and implementation of prior directives.
 To help bridge this gap, the authors recommend that physicians not only attend to the technical aspects of patient care, but also determine patient values concerning life-sustaining therapy and counsel patients on prior directives.
",19
3163,"Risk of human immunodeficiency virus (HIV) transmission by blood transfusions before the implementation of HIV-1 antibody screening. The Transfusion Safety Study Group.
 Little information is available regarding the risk of human immunodeficiency virus type 1 (HIV-1) infection for patients transfused before routine anti-HIV-1 screening of blood donors was instituted in March 1985.
 A model was developed for estimating both the proportion and the number of transfusion recipients in the San Francisco Bay area who were infected by HIV-1 during each of the 7 years preceding routine donor screening for anti-HIV-1.
 The model is based on analysis of 1) donation histories of HIV-1-infected donors identified at the regional blood center; 2) HIV-1 seroprevalence estimates for homosexual and bisexual men in San Francisco; and 3) HIV-1 infection and survival rates for recipients traced by the Transfusion Safety Study and Irwin Memorial Blood Centers' Look Back Program.
 The incidence of transfusion-associated HIV-1 infection is estimated to have risen rapidly from the first occurrence in 1978 to a peak in late 1982 of approximately 1.1 percent per transfused unit.
 The decrease after 1982 coincided with the implementation of high-risk donor deferral measures.
 It is estimated that, overall, approximately 2135 transfusion recipients were infected with HIV-1 in the San Francisco region alone.
 This number suggests a higher prevalence of transfusion-associated HIV-1 infection than has been generally recognized and indicates the need for continued tracing of potentially exposed recipients.
 The data also strongly support the effectiveness of early donor education and self-exclusion measures and emphasize the importance of continued research and development in this area.
",19
3164,"Association of psychiatric manifestations with antibodies to ribosomal P proteins in systemic lupus erythematosus.
 PURPOSE: The goal of this study was to determine whether elevated serum levels of antibodies to ribosomal P proteins (anti-P antibodies) are associated with neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE).
 Additional experiments examined characteristics of these antibodies that might be associated with pathogenicity.
 PATIENTS AND METHODS: A large number of serum samples were collected from patients with SLE, control subjects with other rheumatic diseases, and normal individuals.
 At the time serum samples were obtained, patients with SLE were categorized according to the presence of psychosis, depression, and other manifestations of central nervous system (CNS) involvement.
 Serum anti-P antibody activity was quantitated by an enzyme-linked immunosorbent assay utilizing a synthetic peptide corresponding to the major P protein epitope.
 RESULTS: In a group of 79 normal individuals, mean (+/- SE) IgG anti-P activity was 0.01 +/- 0.003 and no individuals had values greater than 3 SD above the mean.
 Similar results were obtained measuring IgM anti-P activity.
 Normal levels were found in all sera from 21 patients with rheumatoid arthritis.
 Of 119 patients demonstrating various patterns of antinuclear and anticytoplasmic antibody activity, elevated anti-P levels were found only in patients with SLE.
 Overall, 19% of 269 patients with SLE demonstrated elevated levels of IgG or IgM anti-P antibodies, including 14% of 187 patients without and 29% of 82 patients with neuropsychiatric manifestations.
 The frequency of positive test results varied greatly depending on the nature of the CNS involvement.
 The frequency in patients with severe depression (n = 8) and psychosis (n = 29) was 88% and 45%, respectively, compared with only 9% in patients with nonpsychiatric neurologic disease (n = 45).
 For the entire SLE group, the odds ratio for the association of anti-P antibodies and severe psychiatric manifestations was 7.63 with a 95% confidence interval of 3.61 to 16.14.
 In a review of 187 patients with SLE originally classified as not having severe psychiatric disease, seven of 10 patients being treated with antidepressant medications had elevated levels of anti-P antibodies.
 In serial studies, the serum level of anti-P antibodies appeared to correlate with the activity of psychiatric disease and did not correlate with the activity of other manifestations of SLE.
 Anti-P antibodies in nearly all patients were IgG and directed primarily to the C-terminal 11 amino acids of the P protein.
 No difference in these characteristics was observed when patients with and without psychiatric manifestations were compared.
 Paired serum and cerebrospinal fluid (CSF) samples were also obtained from eight patients with active neuropsychiatric disease.
 Even when expressed as a fraction of the total IgG present, anti-P activity was markedly lower in CSF than in serum.
 CONCLUSIONS: Elevated levels of autoantibodies to the C-terminal region of ribosomal P proteins appear to be a specific marker for SLE, and are associated with both severe depression and psychosis in this disease.
 This assay is easily reproducible and may help distinguish SLE-induced psychiatric disease from that caused by other processes.
",19
3165,"The effect of inhaled corticosteroids on the maximal degree of airway narrowing to methacholine in asthmatic subjects.
 Airway hyperresponsiveness in asthma is characterized by an increase in sensitivity and in maximal response to airway-narrowing stimuli.
 Long-term therapy with inhaled corticosteroids is known to reduce airway hypersensitivity in asthmatic patients.
 To investigate whether these drugs also reduce the maximal degree of airway narrowing we studied the effects of inhaled budesonide on the maximal response plateau of the dose-response curve to inhaled methacholine in mildly asthmatic patients in whom a raised plateau could be measured.
 Sixteen atopic patients with mild asthma were placed randomly into two parallel treatment groups to receive double-blindly either budesonide (400 micrograms twice daily) or placebo, inhaled via a Turbuhaler, for 4 wk.
 Before treatment, after 2 and 4 wk of treatment, and after 2 and 4 wk of wash-out, complete dose-response curves to methacholine were obtained using a standardized 2-min tidal breathing method.
 The response was measured by FEV1, expressed in % fall from baseline.
 A plateau on the log dose-response curve was considered if three or more data points fell within a 5% response range.
 The maximal response was obtained by averaging the values on the plateau (MFEV1), and the sensitivity was calculated from the provocative concentration of methacholine, causing a 20% fall in FEV1 (PC20).
 After 4 wk of budesonide treatment, mean MFEV1 decreased from 41.6 to 33.7% fall (p = 0.0004).
 The changes in MFEV1 were significantly different between placebo and budesonide (p = 0.03).
 The geometric mean PC20 increased from 3.4 to 6.3 mg/ml (p = 0.02), but the changes in PC20 were not different between the two groups (p = 0.23).
",19
3166,"Morphometry of the airways during late responses to antigen challenge in the rat.
 To quantitate the structural changes in the airways that contribute to the late bronchial response (LR) to antigen challenge we killed six Brown-Norway rats, sensitized to ovalbumin (OA) and challenged by aerosol, during the LR and compared the dimensions of the intraparenchymal airways with those of six control animals.
 Lungs were rapidly frozen with liquid nitrogen and fixed in Carnoy's solution.
 Paraffin sections were stained with hematoxylin-phloxine-saffron.
 At the time of the LR (382 +/- 39 min after OA challenge), RL increased from the baseline value (0.067 +/- 0.034 cm H2O.ml-1.s) by 0.107 +/- 0.03 cm H2O.ml-1.s (p less than 0.05).
 RL did not change significantly in the control rats.
 The lumen size and the wall area of all membranous airways were measured and were corrected for airway size by dividing by the basement membrane length squared (BM2).
 There was no increase in airway wall area in OA-challenged animals.
 However, the lumen of large airways (BM: 2.0 to 2.99 mm) was significantly less for the OA-challenged animals (0.039 +/- 0.0055 mm2) than for the control animals (0.058 +/- 0.0063 mm2; p less than 0.05).
 In six additional rats, the distribution of mast cells (MC) in the bronchial tree was determined.
 Tissues were fixed with Carnoy's solution and stained with a modified May-Grunwald-Giemsa stain.
 There were significantly more MC in the large airways than in medial or small airways.
 We conclude that smooth muscle constriction of large airways and not airway wall edema accounts for the LR in the rat.
 The distribution of the mast cells corresponds closely to the site of bronchoconstriction.
",19
3167,"Methotrexate-induced asthma.
 A patient with rheumatoid arthritis developed pulmonary symptoms and function test abnormalities consistent with asthma during methotrexate therapy.
 Assessments of airway responsiveness to methacholine during therapy revealed airway hyperreactivity that reverted to normal when the methotrexate was stopped.
 An extension of the methotrexate dosage interval from 7 to 10 days resulted in an abolition of the asthma, which remained in remission despite a return to a weekly cycle after a 3-month period of 10-day cycles.
",19
3168,"Prevalence of Mycobacterium avium complex in respiratory specimens from AIDS and non-AIDS patients in a San Francisco hospital.
 Over the past several years there has been a large increase in the recovery of Mycobacterium avium complex (MAC) isolates from respiratory specimens submitted to the clinical laboratory at San Francisco General Hospital (SFGH).
 This increase in MAC recovery correlates with an increase in the number of cases of acquired immunodeficiency syndrome (AIDS) in the community.
 Although it is well known that MAC is often isolated from patients with AIDS, the isolation of MAC from respiratory specimens is often attributed to contamination of the specimen with MAC organisms present in the environment.
 To determine whether the increase in MAC isolates recovered at SFGH was due to an increase in environmental contamination of specimens or to the increase in our AIDS patient population, we conducted a study of the prevalence of MAC in respiratory specimens from AIDS versus non-AIDS patients.
 Results of specimens submitted to the clinical laboratory at SFGH for culture of mycobacteria were reviewed over a 12-yr period, from 1977 through 1988.
 The prevalence of MAC in respiratory specimens from AIDS and non-AIDS patients was determined for 4 yr during this period: the pre-AIDS year 1977; the first year AIDS was reported in San Francisco, 1981; 1984; and 1987.
 In 1977 and 1981 the prevalence of MAC in respiratory specimens was less than or equal to 0.5%, and all MAC isolates were recovered from non-AIDS patients.
 In 1984 the prevalence of MAC in respiratory specimens for AIDS and non-AIDS patients was 6.5 and 0.3%, respectively, and in 1987, 8.8 and 0.3%, respectively.
",19
3169,"Delayed-type hypersensitivity initiation by early-acting cells that are antigen mismatched or MHC incompatible with late-acting, delayed-type hypersensitivity effector T cells.
 The elicitation of delayed-type hypersensitivity (DTH) responses in mice is mediated by the sequential activities of two different Ag-specific, Thy-1+ cells.
 A required early phase of elicitation is due to DTH-initiating Thy-1+ cells that are CD3- and sIg- and produce Ag-specific factors that act like IgE antibodies in that they sensitize the tissues, so that after local challenge with Ag there is release of the vasoactive amine serotonin.
 Released serotonin locally recruits and activates CD4+ Th-1 classical DTH effector T cells that secrete lymphokines that attract and activate a nonspecific perivascular infiltrate of circulating, bone marrow-derived leukocytes.
 The current study used isolated subpopulations of DTH-initiating and DTH-effector T cells to determine whether the two phases of the elicitation of DTH were entirely separate.
 The contact sensitivity model of DTH was used.
 Early-acting DTH-initiating cells, and late-acting DTH-effector T cells were either from oxazolone (OX)-immune or picryl chloride (PCl)-immune CBA or BALB/c donors and were transferred to CBA or BALB/c recipients.
 The results showed that DTH-initiation could be mediated by polyclonal DTH-initiating cells that were Ag mismatched or MHC incompatible with late-acting DTH effector T cells.
 In fact DTH-initiating cells could be both Ag mismatched and MHC incompatible with late-acting T cells.
 In addition, potential interactions between different cell populations were ruled out by showing that DTH-initiation could be mediated by a DTH-initiating clone that was Ag or MHC mismatched with the late-acting DTH-effector T cells.
 Thus, the OX-specific BALB/c clone could initiate DTH for PCl-specific CBA cells in CBA recipients if the recipients were challenged with both OX and PCl, but not when they were challenged with OX or PCl alone.
 We suggest, at least for the elicitation of DTH reactions in mice, that a more comprehensive description of these responses should accommodate the fact that there are early and late phase responses that each begin with Ag specificity and end with non-specific humoral factors.
 Inasmuch as the two Thy-1+ cells of DTH can be of different Ag specificity, this suggests that some forms of delayed and chronic inflammation, might be initiated by an immediate hypersensitivity-like immune reactivity to one set of Ag, and could be prolonged and perpetuated by delayed reactivity to another set of Ag.
",19
3170,"Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells.
 We have recently demonstrated that a single dose (200 J/m2) of UVB radiation abrogates the capacity of mouse epidermal Langerhans cells (LC) or splenic adherent cells (SAC) to present keyhole limpet hemocyanin (KLH) to Ag-specific, MHC-restricted CD4+ Th1 cells.
 In the present study we determined whether such Th1 unresponsiveness represented long-lasting immunologic tolerance.
 To address this question, Th1 were preincubated with KLH-pulsed UVB-LC or UVB-SAC, then isolated and restimulated with unirradiated APC (LC or SAC) plus KLH or with exogenous rIL-2 in the absence of APC.
 Preincubation with KLH and UVB-LC or UVB-SAC rendered Th1 unresponsive to subsequent restimulation with APC and KLH.
 In addition, such Th1 were defective in their autocrine IL-2 production, but could respond normally to exogenous rIL-2, indicating that unresponsiveness was due to functional inactivation and not to cell death.
 Th1 unresponsiveness was Ag-specific, MHC-restricted, and long lasting (greater than 16 days).
 In addition, it appears that Th1 unresponsiveness is not due to the release of soluble suppressor factors from UVB-LC or UVB-SAC because supernatants from such cells had no effect on Th1 proliferation.
 Addition of unirradiated allogeneic SAC during preincubation prevented the induction of unresponsiveness by UVB-LC or UVB-SAC, suggesting that UVB interferes with the capacity of LC or SAC to deliver a costimulatory signal(s) that can be provided by allogeneic SAC.
 We conclude that UVB can convert LC or SAC from immunogenic to tolerogenic APC.
",19
3171,"IL-6 production by human T lymphocytes. Expression in HTLV-1-infected but not in normal T cells.
 IL-6 is an important regulator of humoral and cellular immunity.
 Although this cytokine is produced by diverse cell types, it is not known whether it is produced by T lymphocytes under physiologic conditions or which agents can induce T cell expression of IL-6.
 We analyzed the production of IL-6 by human peripheral blood T cells, human thymocytes, and human T cell lines.
 In pure populations of these cells, stimulated with different combinations of various mitogens and cytokines, IL-6 activity could not be detected.
 Analysis of purified T-alpha beta and T-gamma delta cells showed that neither T cell subset produced IL-6.
 Similarly, IL-6 mRNA was not detected in T cell or thymocyte populations for up to 48 h after stimulation.
 With the use of a PCR assay, IL-6 mRNA in T cells was found to be virtually negligible, and did not change after T cell activation.
 By in situ hybridization it was shown that the cells expressing IL-6 mRNA after mitogen activation of PBMC do not belong to the T cell lineage.
 To analyze whether human T cells express IL-6 in vivo, we examined lymphoid tissues by in situ hybridization.
 In normal human thymus there was no detectable signal for IL-6.
 Tonsils showed only few positive cells within the parenchyma, but strong expression of IL-6 by epithelial cells in crypts.
 In contrast to normal lymph node, which contained only rare cells positive for IL-6, a lymph node from a patient with Castleman's disease showed IL-6 expression in cells occupying the marginal sinus and interfollicular areas.
 Screening of various human T cell lines showed that all cell lines infected with HTLV-1 secrete IL-6 activity and express IL-6 mRNA.
 In addition, in vitro infection of peripheral blood T cells with HTLV-1 induced de novo synthesis and secretion of IL-6.
 Furthermore, IL-6 expression in HTLV-1-infected cells was enhanced by stimulation with IL-1 beta or TNF-alpha.
 In contrast, IL-6 was not detectable in non-infected T cell lines.
 These studies indicate that IL-6 may not be a physiologic product of human T lymphocytes and that infection of T cells with HTLV-1 results in aberrant expression of this cytokine.
",19
3172,"Plasma adenosine deaminase2: a marker for human immunodeficiency virus infection.
 Plasma concentrations of the two isoenzymes of adenosine deaminase (ADA, E.C.
 3.5.4.4), adenosine deaminase1 (ADA1) and adenosine deaminase2 (ADA2), were measured in a cohort of ambulatory patients infected with the human immunodeficiency virus (HIV) and controls.
 A sensitive isoenzyme-specific radioisotopic assay system was developed for these studies.
 Among 22 HIV-infected patients, plasma ADA2 was significantly elevated as compared with 16 control subjects (p less than 0.01) and 6 uninfected subjects having a risk factor for HIV infection (p less than 0.01).
 Plasma ADA2 was not associated with the stage of disease as defined by clinical status (p greater than 0.05) or helper (CD4) lymphocyte count (p greater than 0.05).
 Available evidence suggests that elevated plasma ADA2 could be a useful surrogate marker for HIV infection that occurs early in the disease process.
",19
3173,"The costs of AIDS in Los Angeles.
 This article reports on the findings of a study of medical and non-medical expenditures of persons with acquired immune deficiency syndrome (AIDS) in Los Angeles in 1987 and 1988.
 Sociodemographic and clinical data as well as information on medical and nonmedical expenditures on 36 persons with AIDS were obtained through patient interviews and review of medical bills.
 Persons with AIDS required a mean of 1.6 hospitalizations per year and 17 days of in-hospital care.
 Mean charges for the first 12 months after diagnosis of AIDS were $22,272 for inpatient medical care and $22,850 for outpatient medical care.
 Overall, medical costs averaged $45,122 per patient per year with almost one-third of these costs devoted to outpatient pharmaceuticals, such as AZT and aerosolized pentamidine.
 Mean nonmedical costs of care for volunteer services, counselling, and in-kind assistance were $9,276.
 These results were similar to recently published estimates of medical costs of persons with AIDS.
 However, our data support changing problems of care for PWAs with increased use of outpatient medical care and pharmaceuticals and decreased use of in-hospital resources.
",19
3174,"Epidemiology of pediatric HIV infection.
 Perinatal transmission of human immunodeficiency virus (HIV) continues to increase.
 In 1989 alone, it is estimated that 1750 infected children were born in the United States.
 Although transmission is spreading to areas outside the cities originally most affected, these cities continue to bear the greatest toll.
 Adolescents may be particularly vulnerable to HIV infection; education and counseling are critical for controlling the epidemic in this age group.
",19
3175,"AIDS in the transfusion recipient.
 In summary, the HIV virus was transmitted to approximately 90% of recipients by infectious blood and blood products transfused prior to donor and product testing begun in March 1985.
 Self-elimination of at-risk donors several years prior to testing donor blood helped to reduce the number of infected donations.
 Virtually all contaminated donors are now eliminated.
 The multiply transfused patient developed a stimulated dysregulated immune system due to the numerous antigens and the iron in red cells and plasma.
 This dysregulated immune system has resulted in a variable response to the added exposure of the HIV virus.
 The incubation period and progression to disease have been prolonged and variable.
 Although a small number of patients have progressed as rapidly as other at-risk groups, many continue to do well without therapeutic intervention.
 Natural history of the disease needs continual monitoring to determine the ultimate outcome of these transfusion recipients.
",19
3176,"Antiviral therapy for human immunodeficiency virus infection in children.
 Antiretroviral therapy for children is still at an early stage, although progress is being made slowly.
 Zidovudine administered at 180 mg/m2/dose every 6 hours is the current standard therapy for symptomatic children and those with low CD4 counts.
 This standard is likely to evolve as further testing clarifies the optimal dosage for ZDV in different populations.
 Children on ZDV need to be monitored very closely (at least monthly) for hematologic side effects, which are most common in the more seriously ill children.
 The role of some of the newer antiretrovirals, like ddI and ddC, which are likely to be licensed, has yet to be established.
 They have a different toxicity profile than ZDV and thus may work well in combination with it.
 The issue of peripheral neuropathy and the lack of an easy test to measure it makes using ddC or ddI in young, preverbal children a daunting proposition.
 As with ZDV, the optimum dosage and timing have yet to be fixed for ddC or ddI alone, and even less available are regimens for combination therapy.
 Antiretroviral drugs other than the dideoxynucleosides are less well developed.
 Some, like high-titer antiviral immunoglobulin, involve technology that is already available and thus will be relatively easy to study.
 Others, like the antisense oligomers, are such a new technology that there are many hurdles to be overcome as the agents move from the laboratory to the clinic.
 The goal of agents that work on sites other than reverse transcriptase is a reasonable one, but the work in perfecting such new categories of drug is difficult and slow.
 In the meantime, children with HIV should be symptomatically supported and offered the most effective antiretroviral regimens available.
",19
3177,"Psychosocial aspects of AIDS in children and adolescents [published erratum appears in Pediatr Clin North Am 1991 Jun;38(3):viii]
 The first part of this article addresses the neuropsychiatric aspects of human immunodeficiency virus (HIV) infection in children and adolescents, including developmental delay, depression, and dementia.
 The specific clinical issues of disclosure of diagnosis and discussion of death with a child are examined.
 The second part presents aspects of the impact of AIDS on families, approaches to HIV antibody testing, and therapeutic interventions for the family.
",19
3178,"Laboratory diagnosis of HIV infection.
 Laboratory diagnosis of human immunodeficiency virus (HIV) infection is complicated by absence of data on sensitivity, specificity and predictive value of the various tests as they apply to children.
 The presence of maternal anti-HIV passively transmitted across the placenta also confounds diagnosis.
 The authors review currently available data on the detection of HIV, HIV genome, and HIV gene products, as well as the diagnostic value of detecting serologic and cellular responses to HIV in infants and children.
",19
3179,"Host defense abnormalities associated with HIV infection.
 Infection with human immunodeficiency virus (HIV) impairs immune function.
 Most abnormalities in host defense associated with HIV infection are due to helper T-cell dysfunction.
 Studies defining these abnormalities in the HIV-infected patient have largely been done in adults.
 A more complete understanding of the immunodeficiency that occurs in infants and young children congenitally infected with HIV awaits further study of their immune function and the effect this virus has on the developing immune system.
",19
3180,"Allergenicity of orally administered immunoglobulin preparations in food-allergic children.
 Passive immunization by the oral administration of immunoglobulin preparations derived from bovine milk, chicken egg, and human sera has been proposed as a method for the prevention and treatment of enteric diseases.
 However, the allergenic potential of these proteins may be a factor limiting their widespread use for disease prevention.
 An in vitro study with sera from milk- and egg-allergic children was performed to determine whether these immunoglobulin preparations have allergenic potential.
 Protein extracts of milk, bovine immunoglobulin, egg white, human immune globulin, and five egg yolk antiviral immunoglobulin preparations were bound to nitrocellulose paper.
 These preparations were probed for specific IgE binding with sera from milk- and egg-allergic patients.
 Of 22 milk-hypersensitive patients, 16 had specific IgE binding against the bovine immunoglobulin preparation.
 Of 28 egg-allergic patients 15 had specific IgE binding against one or more of the egg yolk-derived antiviral chicken immunoglobulins.
 Control sera were negative against the milk and egg preparations.
 Western blot analysis confirmed that milk- and egg-allergic patients had IgE-specific antibodies for bovine and chicken immunoglobulin molecules.
 Therefore, the removal of contaminating proteins from milk and egg antibody preparations would be unlikely to eliminate their allergenic potential.
 In contrast, sera from milk- and egg-allergic patients displayed no detectable IgE binding to human immunoglobulin preparations.
 These data indicate that the administration of antibody preparations derived from bovine and chicken sources may lead to severe allergic reactions in milk- or egg-sensitized patients and to sensitization in some nonallergic individuals.
",19
3181,"Fatal reactions to intravenous nonionic contrast material.
 Three cases of fatality related to the use of low-osmolality contrast material (LOCM) are presented.
 LOCM definitely reduces unpleasant side effects and serious reactions, but data are currently insufficient to determine whether the death rate is any different from that associated with high-osmolality contrast agents.
 If the present trend toward universal conversion to LOCM continues, an enormous cost for little, if any, lifesaving benefit may be incurred.
",19
3182,"Prediction of severe adverse reactions to ionic and nonionic contrast media in Japan: evaluation of pretesting. A report from the Japanese Committee on the Safety of Contrast Media.
 In a nationwide prospective study of adverse reactions to intravenous contrast media (CM), the Japanese Committee on the Safety of Contrast Media compared high-osmolar ionic CM with low-osmolar nonionic CM.
 A total of 337,647 cases were analyzed.
 The reliability of pretesting with an intravenous injection of a small amount of CM as a means of predicting severe or fatal reactions was also evaluated.
 The predictive values of the pretest were 1.2% for ionic and 0.0% for nonionic CM, and the sensitivity values were 3.7% and 0.0%, respectively.
 Such low values render this test meaningless for predicting which patients are at risk of a severe adverse reaction.
 A comparison of the incidence of severe adverse reactions between the nonpretested and pretested patients, as well as between the nonpretested and pretested patients with negative results, disclosed no statistically significant differences.
 Also, no beneficial effects of premedication in patients with a positive pretest were proved.
 The authors therefore conclude that pretesting with an intravenous injection of a small amount of CM is not useful in predicting severe reactions to ionic or nonionic CM.
",19
3183,"Multiple sclerosis: specificity of MR for diagnosis.
 The specificity of magnetic resonance (MR) imaging in the diagnosis of multiple sclerosis (MS) has not been measured systematically.
 Conventional MR head images with sagittal localizer and axial multiple-echo sequences with long repetition times were obtained in 92 patients with clinically verified MS (Schumacher criteria), 100 healthy volunteers, 60 subjects with hypertension, and eight patients with dementia.
 Two readers, without the aid of any clinical or demographic information, classified each of the 260 studies as MS or not MS.
 The readers classified the studies again after being supplied with the subjects' ages and sex.
 True-negative and true-positive diagnoses of MS were tabulated.
 The specificity of the MR diagnosis of MS (true-negative results in proportion to all non-MS studies) was 95%-99% with all the control groups included.
 There is a small risk of misinterpreting incidental periventricular white matter foci as plaques of MS in MR studies.
",19
3184,"AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization.
 To investigate the range of pathology shown by acquired immune deficiency syndrome (AIDS)-related lymphomas arising in an epidemiologically well-defined group of patients, all cases of lymphoma recognized in Danish human immunodeficiency virus (HIV)-infected individuals up to the end of 1988 were studied.
 Twenty-seven cases (26 high-grade non-Hodgkin's lymphoma [NHL], 1 Hodgkin's disease) were found, to give a cumulative incidence rate of 8% among Danish AIDS patients.
 Morphologically most NHL patients were classified into two groups: 1) high-grade tumors with a predominant population of immunoblasts, either monomorphic or more often polymorphic with plasmacytic differentiation; 2) Burkitt-type.
 Of 26 NHLs, 22 had a B-cell paraffin-section immunophenotype and 4 were non-B, non-T.
 Epstein-Barr virus (EBV) DNA was demonstrated in tumor cells of 12 of 24 cases (50%) using in situ nucleic acid hybridization with a 35S-labeled probe in paraffin sections.
 Epstein-Barr virus DNA was found in 65% of group 1 and 20% of group 2 tumors.
 This study suggests the existence of two main groups of AIDS-related lymphoma with different pathogeneses.
 First there are immunoblast-rich lesions, which usually are associated with EBV and morphologically resemble lymphomas described in immunosuppressed organ-transplantation patients.
 Second there are Burkitt-type tumors in which EBV sequences are less common and that may be pathogenetically analogous to sporadic Burkitt's lymphoma.
",19
3185,"Fibroblast growth factor gene expression in AIDS-Kaposi's sarcoma detected by in situ hybridization.
 Biopsy samples from five acquired immune deficiency syndrome (AIDS)-Kaposi's sarcomas and one non-AIDS-associated Kaposi's sarcoma were assayed by in situ RNA hybridization onto paraformaldehyde-fixed, paraffin-embedded skin sections for the presence of two fibroblast growth factor gene transcripts, FGFB and FGF5.
 FGF5 gene expression was detected in the characteristic Kaposi's sarcoma spindle-shaped cells in the five samples from human immunodeficiency-positive (HIV+) patients.
 FGFB transcripts were detected in Kaposi's sarcoma cells as well as in epidermis of HIV- and HIV+ patients.
 These results complement the observations about growth factor gene expression done on Kaposi's sarcoma-derived cell lines, which thus appear to be representative of what happens in vivo.
 Furthermore, they demonstrate a contrasting expression pattern of FGF5 and FGFB genes, both involved in the growth factor pathogenic cascade leading to Kaposi's sarcoma.
",19
3186,"Cyclic anaphylaxis associated with menstruation.
 A middle-aged woman developed recurrent episodes of severe life-threatening anaphylaxis.
 All episodes were strikingly associated with the first day of menstrual bleeding.
 Temporary relief was achieved with indomethacin therapy.
 The patient fully recovered following abdominal hysterectomy and salpingoophorectomy.
 The possible role of sex hormones and prostaglandin F2 alpha in the pathogenesis of this problem is discussed.
",19
3187,"Emergency room care of asthmatics: a comparison between Auckland and Toronto.
 We compared emergency room visits for the treatment of asthma in two large downtown teaching hospitals: one in Auckland, New Zealand and one in Toronto, Canada.
 We wished to determine whether the differences in asthma mortality between New Zealand and Canada were reflected in different patterns of emergency room use or physician management.
 Emergency room use during the past decade was enumerated in both hospitals, and charts containing the sole diagnosis of asthma were reviewed in detail for a defined study period in 1986.
 In both Toronto and Auckland, the number of emergency visits for asthma had increased significantly in the past decade (P less than .015 but the rate of rise was significantly higher in Auckland (P less than .05).
 In Auckland, 27% of asthmatics were admitted whereas in Toronto significantly fewer (16%) were admitted (P less than .0005).
 Objective measures of pulmonary function were documented more frequently by emergency room physicians in New Zealand than in Canada (90% versus 48%; P less than .0005).
 Pulmonary function measurement was primarily by peak flow meter in Auckland and most commonly by spirometer in Toronto so that pulmonary function measurements could not be compared directly between centers.
 In both centers, however, admitted patients had significantly lower pulmonary function indices than discharged patients.
 In New Zealand, mean peak flow was 38% of the predicted value among all asthmatics assessed; in Toronto, mean FEV1 was 47% of predicted.
 In Toronto, pulmonary function measurements were most likely to be missing among presumably healthier discharged patients.
 Pulse rate, respiratory rate, and pulsus paradoxus were documented more consistently in Auckland than in Toronto.
",19
3188,"HIV-1 infection in a cohort of haemophilic patients.
 The course of HIV infection in 53 haemophilic patients aged 5-20 years was evaluated by clinical examination and laboratory tests.
 During the evaluation time (median 30 months) two patients died of AIDS and 32 patients (60%) deteriorated when assessed by the Brodt-Helm classification.
 Nineteen patients (37%) had decreased absolute helper cell counts (less than 500 CD4 positive cells/microliters), and 45 patients (87%) had reduced helper cell to lymphocyte ratios (less than 0.35).
 HIV-1 was isolated from peripheral lymphocytes in 29 of 46 patients.
 As the disease progressed the number of positive viral cultures increased.
 Considerable progression of the HIV infection was seen in haemophilic children and adolescents during the median evaluation period of 30 months.
 The transition from symptomless HIV infection to immunodeficiency was easily recognised.
 A lowered ratio of helper cells to lymphocytes seems to be a useful marker of the beginning of the deterioration of the immune system.
",19
3189,"Long term outcome of ventilated asthmatics.
 Over a 25 year period, 31 asthmatic children received artificial ventilation for acute asthma at Alder Hey Children's Hospital on 48 occasions.
 Altogether 47 episodes occurred from 1971-89, with no decline in the number of episodes per year (mean 2.5) over this period.
 Eight children died during intermittent positive pressure ventilation (IPPV), and of the 23 survivors, three further children had subsequently died from asthma.
 Seventeen children were followed up for more than a year after IPPV.
 Sixteen still had symptoms of asthma and over half had symptoms every day.
 Ten cooperated with pulmonary function tests: mean forced expiratory volume in one second was 83% of predicted and geometric mean provocative histamine concentration (PC20) was 2.1 mg/ml.
 Since the follow up study a fourth patient had died from asthma.
 IPPV continues to be required for a small number of asthmatic children each year.
 The survivors remain a high risk group with significant continuing morbidity and mortality.
",19
3190,"Histopathologic features of high-grade non-Hodgkin's lymphomas in acquired immunodeficiency syndrome. The French Study Group of Pathology for Human Immunodeficiency Virus-Associated Tumors.
 High-grade B-cell non-Hodgkin's lymphomas are observed in 5% to 10% of patients with acquired immunodeficiency syndrome.
 To describe their histologic subtypes, a group of pathologists was formed.
 One hundred thirteen cases were reviewed and classified according to the Working Formulation, the updated Kiel classification, and a recent description of morphologic variants of high-grade B-cell non-Hodgkin's lymphoma.
 Three major types of intermediate- or high-grade lymphomas were observed: (1) large-cell or centroblastic mainly polymorphic lymphomas with a component of immunoblasts (35 cases); (2) immunoblastic lymphomas with plasmablastic and plasmacytic features in most cases (33 cases); and (3) small non-cleaved cell Burkitt's or non-Burkitt's lymphoma (41 cases), with 15 cases fitting typical criteria of Burkitt's lymphoma and 26 heterogeneous cases in which the size and shape of the cells and the presence of plasmablastic features varied.
 The most frequent pathologic sites of involvement at presentation were the lymph nodes, gastrointestinal tract, bone marrow, brain, oral cavity, and muscles.
 A comparison between the histologic type and the site of involvement showed that most cases involving lymph nodes, bone marrow, or muscles were small noncleaved cell Burkitt's or non-Burkitt's lymphomas, while those that affected the gastrointestinal tract, brain, and oral cavity were centroblastic or immunoblastic lymphomas with consistent plasmacytic differentiation.
 In 10 cases, previous persistent generalized lymphadenopathy syndrome was present.
 In 13 cases, the lymphomatous proliferation was associated with follicular or diffuse hyperplasia seen on the same lymph node biopsy specimen or in another lymph node.
",19
3191,"Interpretive criteria of the Western blot assay for serodiagnosis of human immunodeficiency virus type 1 infection [published erratum appears in Arch Pathol Lab Med 1991 Aug;115(8):783]
 This project was designed to evaluate different criteria used in the interpretation of the human immunodeficiency virus type 1 (HIV-1) Western blot assay on a group of serum samples blinded to the examiner that were collected from individuals attending three different public health departments in central North Carolina.
 Each individual also completed an anonymous linked questionnaire regarding sociodemographics and risk factors for blood-borne infections.
 All of the Western blot assays for human immunodeficiency virus type 1 were interpreted according to the criteria established at the University of North Carolina Hospitals, Chapel Hill, the Centers for Disease Control, Atlanta, Ga, in association with the Association of State, Territorial, and Public Health Laboratory Directors, Iowa City, Iowa, the American Red Cross, Washington, DC, the Consortium for Retrovirus Serology Standardization, Davis, Calif, and the Food and Drug Administration, Washington, DC.
 The results obtained were grouped as positive, negative, and indeterminate according to each organization's criteria and analyzed in the context of the associated risk factors.
 The results indicate that institutions performing human immunodeficiency virus type 1 Western blot confirmatory testing should adopt the criteria of the Centers for Disease Control and the State, Territorial, and Public Health Laboratory Directors.
",19
3192,"Enhancement of immunoreactivity among lymphoid malignant neoplasms in paraffin-embedded tissues by refixation in zinc sulfate-formalin.
 It has been previously demonstrated that improved cytomorphologic detail can be obtained from tissue blocks initially fixed in 4% formaldehyde solution by means of a ""run-back"" procedure to an aqueous phase of solution, allowing refixation with a protein-precipitating agent, such as zinc sulfate-4% formaldehyde solution.
 Because anecdotal experience with immunostaining such reprocessed tissues had suggested improved results, we performed a prospective trial involving 13 cases to compare the intensity of immunoreactivity before and after such reprocessing.
 In 10 of 13 cases studied with a variety of antibody reagents, we noted a definite improvement of staining, preferentially among those with the weakest original immunoreactivity.
",19
3193,"Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice 
 OBJECTIVE--To compare a peak flow self management plan for asthma with a symptoms only plan.
 DESIGN--Randomisation to one of the self management plans and follow up for a year.
 SETTING--Four partner, rural training practice in Norfolk.
 SUBJECTS--115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic.
 MAIN OUTCOME MEASURES--The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol.
 RESULTS--Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups.
 The results were similar for children and adults.
 The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60).
 The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group.
 CONCLUSIONS--The peak flow meter was not the crucial ingredient in the improved illness of the two groups.
 Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma.
 Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.
",19
3194,"Prominence of slow acetylator phenotype among patients with sulfonamide hypersensitivity reactions.
 Delayed hypersensitivity reactions are among the most severe adverse effects of the sulfonamides in current clinical use.
 These reactions appear to occur because of differences in the metabolism and detoxification of reactive metabolites of the sulfonamides.
 N-Acetylation is a major metabolic pathway for the sulfonamides.
 Slow acetylation phenotype might be a risk factor for the development of these reactions.
 We determined the acetylation phenotype of 21 patients who had suffered hypersensitivity reactions to the sulfonamides.
 There were 11 females and 10 males in the group, with a mean age of 15 years (age range, 1.8 to 50 years).
 Their acetylator phenotype was determined by determining the ratio of urinary caffeine metabolites (1-methylxanthine to 5-amino-6-formylmethyluracil after an oral dose of 50 mg caffeine).
 Nineteen (90%) of the patients were slow acetylators compared to a 55% incidence of slow acetylators in a race-matched control population (p less than 0.008).
 This suggests that a slow acetylator phenotype is a risk factor for the development of sulfonamide hypersensitivity reactions and provides further support for the role of imbalances in genetically determined pathways of metabolism and detoxification of the sulfonamides in the pathogenesis of these reactions.
",19
3195,"Plasma histamine, epinephrine, cortisol, and leukocyte beta-adrenergic receptors in nocturnal asthma.
 Plasma histamine, cortisol, epinephrine, cyclic adenosine monophosphate (cAMP), and leukocyte beta-adrenergic receptors were measured in asthmatic patients with (n = 7) and without (n = 10) nocturnal asthma at 4 PM and 4 AM and compared with those of normal subjects (n = 10).
 A twofold higher plasma histamine concentration was observed at 4 AM compared with 4 PM in all groups, with no change in plasma cortisol, epinephrine, and cAMP concentrations.
 At 4 AM compared with 4 PM, only patients with nocturnal asthma had a significant 33% decrease (p less than 0.05) in mononuclear and polymorphonuclear leukocyte beta-adrenergic receptor density, with no difference in binding affinity in all three groups.
 Polymorphonuclear leukocytes from patients with nocturnal asthma had significantly impaired response to isoproterenol at 4 AM (17% +/- 7.3% SEM increase in cAMP; p less than 0.05) compared with those of patients without nocturnal asthma (69.4% +/- 13.7%) and normal (80.2% +/- 21.3%) subjects.
 A significant change in beta-adrenergic receptor density and function occurs at night in patients with nocturnal asthma.
",19
3196,"Classifications of acute myeloid leukemia.
 A detailed description of the various subtypes of the acute myeloid leukemias is provided.
 The importance of cytochemistry and monoclonal antibodies is discussed.
",19
3197,"Immunophenotyping of acute myeloid leukemia cells.
 This article considers the expression of myeloid cell-associated antigens on both normal and malignant myeloid cells.
 Progress in the use of monoclonal antibodies to myeloid cell surface antigens for the diagnosis, subclassification, and treatment of acute myeloid leukemia is discussed.
 The results of bone marrow purging with monoclonal antibodies to remove leukemia cells for the purpose of autologous bone-marrow transplantation are promising.
",19
3198,"Granulocytic sarcoma.
 Granulocytic sarcoma is a variant presentation of acute myeloblastic leukemia, occurring in extramedullary locations.
 It is uncommon, but it may occur at any site and at any age, which necessitates its inclusion in the differential diagnosis of all undifferentiated tumors.
 Histology, touch-imprint cytology, cytochemistry, immunocytochemistry, electron microscopy, and molecular studies all contribute to the diagnosis.
",19
3199,"Growth regulation of a human mature B cell line, B104, by anti-IgM and anti-IgD antibodies.
 An EBNA- human B lymphoma cell line, B104, was established.
 B104 cells express IgD as well as IgM on their surface, which is thought to be a basic characteristic of mature B cells.
 The growth of B104 cells was inhibited by treatment with a panel of anti-IgM antibodies.
 Cell cycle analyses revealed that the transition of B104 cells from the G2/M to the G0/G1 phase of the cell cycle was markedly inhibited by treatment with anti-IgM antibodies.
 Progression of B104 cells to the M phase of the cell cycle was found to be suppressed in the presence of anti-IgM antibodies.
 In contrast, both the entrance of G0/G1 phase cells into the S phase and the progression of S phase cells to the G2/M phase of the cell cycle did not seem to be inhibited significantly by treatment with anti-IgM antibodies.
 These results indicate that the mechanism of the inhibition of growth of B104 cells by anti-IgM antibodies is blockage of the transition from the G2 to the M phase of the cell cycle.
 In contrast to anti-IgM antibodies, anti-IgD antibodies could not cause growth inhibition of B104 cells at all.
 B cell growth factors such as IL-4 and IL-6 had no effect on the inhibition of growth of B104 cells by anti-IgM antibody.
 IFN-alpha and -beta, which have no B cell growth factor activity, did increase the number of cells that survived the treatment with anti-IgM antibodies.
 B104 is an excellent experimental model for the study of the mechanism of signal transduction through sIg as well as the functional difference between sIgM and sIgD.
",19
3200,"Hyperphosphorylation of CD20 in hairy cells. Alteration by low molecular weight B cell growth factor and IFN-alpha.
 Hairy cell leukemia (HCL) is a B cell tumor affecting the pre-plasma stage of B cell differentiation.
 Hairy cells produce B cell growth factor (BCGF)-related growth factor(s) and we have previously shown that low mol wt (LMW)-BCGF-induced proliferation of hairy cells is inhibited in vitro and in vivo by IFN-alpha.
 We therefore suggested that this effect might contribute to the exquisite sensitivity of HCL to IFN-alpha therapy.
 To elucidate the mechanism involved in the therapeutic effect of IFN-alpha, we have analyzed the pattern of phosphorylated proteins in hairy cells.
 We detected the presence of a hyperphosphorylated protein with a molecular mass of about 35 kDa.
 This protein was identified as the CD20 molecule (B1), which is a structurally unique phosphoprotein exclusively detected on B cells and expressed during most stages of B cell development.
 Incubation of hairy cells with mitogenic concentrations of LMW-BCGF induces an additional increase in CD20 protein phosphorylation.
 In contrast, preincubation of cells with IFN-alpha, but not IFN-gamma, decreases both basal and LMW-BCGF-induced CD20 phosphorylation.
 CD20 phosphorylation in hairy cells is also reduced after in vivo IFN-alpha administration.
 In contrast, in one case of a patient unresponsive to IFN-alpha therapy, CD20 phosphorylation is not altered by in vitro IFN-alpha treatment, whereas LMW-BCGF still elicits CD20 phosphorylation stimulation.
 Our results suggest that IFN-alpha may act in HCL, at least in part, by inhibiting leukemic cell proliferation via regulation of phosphorylation, since CD20 phosphorylation is thought to be associated with cellular proliferation.
 A model involving dysregulation of CD20 is discussed.
",19
3201,"Synergistic action of monoclonal antibodies directed at p55 and p75 chains of the human IL-2-receptor.
 TU27, a mouse IgG1 mAb directed at the p75 chain of the human IL-2R, was analyzed for its ability to interact with IL-2 binding on isolated p75 chains (YT-2C2 cells) and high affinity p55/p75 receptors (human alloreactive T cell clone 4AS), to inhibit IL-2-induced proliferation (4AS cells) and to cooperate with an anti-p55 chain mAb (33B3.1) for inhibiting IL-2 binding and proliferation.
 TU27 and IL-2 bound to the isolated p75 chain expressed by YT-2C2 cells with respective dissociation constants (Kd) of 1.3 and 1 nM.
 They cross-inhibited each other for binding with inhibition constants (Ki) in agreement with their respective Kd values.
 The nature of the interaction was, however, not purely competitive and suggested nonidentical epitopes for the two ligands on the p75 chain.
 On 4AS cells, IL-2 bound with high affinity (Kd = 50 pM) and TU27 with an affinity similar to that found on YT-2C2 cells.
 The binding of TU27 and IL-2 were also mutually exclusive on 4AS cells.
 However, the mechanism of interaction of TU27 with IL-2 was complex since the inhibitory potency of the antibody depended on temperature, antibody preincubation and time of assay.
 Data obtained at 4 degrees C in the presence of suboptimal, tracer-like concentrations of IL-2 indicated that the intrinsic affinity of TU27 for the high affinity configuration was 15-fold lower than for the isolated p75 chain and argued in favor of the affinity-conversion model (as opposed to the preformed complex model) in which p55 and p75 are dissociated in the absence of IL-2.
 At 37 degrees C, TU27 inhibited IL-2 binding only on short time assays (6 min).
 Longer time (30 min) of IL-2 binding resulted in an almost complete disappearance of the effect of TU27, suggesting that internalization of the high affinity p55/p75/IL2 complex enables the cells to escape from the inhibitory effect of TU27.
 In the presence of the 33B3.1 mAb, the interaction of TU27 with IL-2 resembled the one observed on YT-2C2 cells, suggesting that 33B3.1 is able to inhibit the IL-2-induced association of p55 and p75.
 Both antibody were found to synergize on 4AS cells, as a result of a cooperative mechanism in which 33B3.1 blocks the formation of the high affinity complex hence allowing TU27 to bind with higher affinity, and TU27 blocks IL-2 binding to the p75 chain.
 Proliferation studies corroborated the binding experiments.(ABSTRACT TRUNCATED AT 400 WORDS).
",19
3202,"HLA and multiple sclerosis in Italy: a review of the literature.
 HLA antigens of locus A, C, B, DR and DQ were typed in 104 Italian multiple sclerosis patients and in 905 healthy controls; the results have been compared with those published in the Italian literature.
 The Italian studies have been reviewed regarding the ethnic origin of the typed population and the corresponding prevalence of the disease.
 The data suggest a lack of association between A3 and B7 antigens and Italian multiple sclerosis and a relevance of other DR locus antigens (mainly DR4 and DR5), in addition to DR2, in the susceptibility to the disease.
",19
3203,"Wernicke's encephalopathy in two patients with acquired immunodeficiency syndrome.
 Two non-alcoholic homosexual patients with acquired immunodeficiency syndrome (AIDS) are reported who developed acute Wernicke's encephalopathy in the terminal stage of their illness.
 The first patient presented with vascular congestion, minute haemorrhages, proliferation of microglia and of the vessel walls at the predilection sites of the Wernicke-Korsakoff process.
 In the second patient only the mamillary bodies were involved.
 Besides Wernicke's encephalopathy, a primary cerebral immunoblastoma and cerebral toxoplasmosis were found in the first patient, whereas the second showed severe encephalitis with numerous microglial and multinucleated giant cells reacting positively with anti-HIV antibody.
 Just as in the development of Wernicke's encephalopathy in malignant diseases, the catabolic trend of the metabolism of the immunodeficient patients with consecutive thiamine deficiency must be considered the principal pathogenetic mechanism.
",19
3204,"Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. The Groupe d'Etudes des Lymphomes Agressifs 
 The objectives of this study were to determine prognostic factors for response to treatment, freedom-from-relapse (FFR) survival, and overall survival of 737 aggressive malignant lymphoma patients treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, methotrexate with leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH-84) regimen; to construct a prognostic index with factors isolated by multivariate analyses; and to validate this prognostic index with another set of patients.
 Complete response (CR) was reached in 75% of LNH-84 patients, and 30% of them relapsed.
 With a median follow-up of 36 months, median FFR survival and median overall survival were not reached.
 Low serum albumin level, high tumoral mass, weight loss, bone marrow involvement, greater than or equal to 2 extranodal sites, and increased lactic dehydrogenase (LDH) level were associated with a low response rate.
 Advanced stage, increased LDH level, and nonlarge-cell histologic subtypes (diffuse mixed, lymphoblastic, and small non-cleaved) were statistically associated with a high relapse rate and short FFR survival.
 Increased LDH level, low serum albumin level, tumoral mass larger than 10 cm, greater than or equal to 2 extranodal sites, advanced stage, and age older than 65 years were statistically associated with short overall survival.
 Four of these parameters, namely, LDH level, stage, number of extranodal sites, and tumoral mass, were put together to construct a prognostic index.
 This index partitioned LNH-84 patients into three subgroups of good, intermediate, and poor prognosis (P less than .00001): CR rates of 93%, 83%, and 61%; relapse rates of 12%, 25%, and 45%; 3-year FFR survival of 87%, 73%, and 53%, and 3-year survival of 88%, 71%, and 41%, respectively.
 This prognostic index was applied to a test set of patients: 155 patients treated on protocols of the Nebraska Lymphoma Study Group.
 Using this index, these patients had 3-year FFR survival of 70%, 40%, and 22% (P = .0002) and 3-year survival of 79%, 52%, and 31% (P = .005).
 In patients with aggressive lymphomas, this simple prognostic index could distinguish between patients requiring intensive treatment such as autologous bone marrow transplantation in first complete remission and those who could be treated with standard regimens.
",19
3205,"The role of dose intensity in determining outcome in intermediate-grade non-Hodgkin's lymphoma.
 To determine whether the dose intensity of chemotherapeutic regimens correlates with the complete remission rate in adult patients with advanced-stage intermediate-grade lymphoma, reports of comparative trials of therapy were reviewed.
 Reports were identified using MEDLINE, through references from review articles, and through review of selected abstracts.
 Twenty-two studies including 14 randomized and eight cohort trials were analyzed to assess projected dose intensity.
 Four other studies were analyzed to assess the role of received dose intensity.
 Dose intensities were calculated using described methods and correlated with complete remission rates.
 Individual trials were assessed using ""levels of evidence."" A metaanalysis of randomized trials and a cross-trial analysis of all comparative trials using a weighted least squares linear regression were performed.
 Using levels of evidence, support was obtained for the hypothesis that dose intensity correlates with the remission rate from two trials in which dose intensity was ""indirectly"" tested.
 As these studies did not ""directly"" test dose intensity, confounding variables, including those arising from the assumptions made in calculating dose intensity, cannot be excluded.
 Metaanalysis showed a relative probability of achieving complete remission of 1.34 (95% confidence interval, 1.13 to 1.58) favoring the pooled arm of high dose intensity.
 Cross-trial analysis showed a relatively weak association between dose intensity and remission rate (r = .49, P = .0001).
 Two of four reports retrospectively assessing received dose intensity suggested that increased dose intensity is associated with superior remission rates.
 These analyses suggest that dose intensity may correlate with the remission rate in advanced-stage intermediate-grade lymphoma.
 However, properly designed trials directly testing dose intensity have not been performed and are needed to confirm this hypothesis.
",19
3206,"Miller Fisher syndrome in systemic lupus erythematosus.
 We describe the first case of Miller Fisher syndrome, a Guillain Barre variant, complicating systemic lupus erythematosus.
 The symptoms and signs mimicked a brainstem syndrome.
 Despite treatment with high dose gamma globulin, our patient worsened and required mechanical ventilation.
 After plasma exchange, the patient improved.
",19
3207,"Effects of in vitro electrical stimulation on enhancement and suppression of malignant lymphoma cell proliferation.
 The suppression and enhancement of proliferation of mouse EL4 lymphoma cells varied significantly when the cells were electrically stimulated within a narrow range of low-level direct current.
 With the use of platinum electrodes, the suppression characteristics were observed over a narrow range, or window, of direct currents centered at approximately 17 microA.
 Enhancement characteristics were observed over a broad range of low-level direct currents (approximately 0.1 to 10 microA).
 These results indicate that the proliferation of certain eukaryotic cells may be directly controlled by stimulation with low-level direct current.
",19
3208,"Common variable immunodeficiency: the disorder and treatment.
 A case of common variable immunodeficiency, a relatively rare disorder, is presented.
 This case was complicated by the presence of an anti-IgA antibody in the patient's serum and a history of a possible anaphylactic reaction to a prior intravenous infusion of gamma-globulin.
 Common variable immunodeficiency is actually a heterogeneous group of demonstrable immunoglobulin deficiencies that have in common low levels of most immunoglobulin isotypes, the inability to form antibodies to antigen, an absence of gross defects in cell-mediated immunity, and the presence of recurrent bacterial infections.
 The history of immunoglobulin deficiency and its treatment is reviewed.
 Although the primary therapy for common variable immunodeficiency is gamma-globulin replacement, ancillary measures such as early treatment of infections with antibiotics are also important.
 Intravenous gamma-globulin replacement therapy is preferred to intramuscular replacement therapy in these patients because intramuscular doses must be limited in volume to minimize local pain and take 2 to 14 days to achieve maximal blood levels, during which time in situ degradation of up to 50% of the administered dose can occur.
 Five intravenous gamma-globulin preparations are currently available in the United States.
 The potential adverse effects of intravenous gamma-globulin infusion and the precautions currently taken to ensure safety during administration of this product are discussed.
",19
3209,"Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1 [published erratum appears in Science 1991 Jan 4;251(4989):13]
 The principal neutralizing determinant (PND) of human immunodeficiency virus (HIV)-1 resides within the V3 loop of the envelope protein.
 Antibodies elicited by peptides of this region were able to neutralize diverse isolates.
 Serum from one of three animals immunized with the human T cell lymphoma virus (HTLV)-IIIMN PND peptide, RP142, neutralized MN and the sequence-divergent HTLV-IIIB isolate.
 Serum from one of three animals immunized with a 13-amino acid IIIB PND peptide (RP337) also neutralized both of these isolates.
 Characterization of these sera revealed that the cross-neutralizing antibodies bound the amino acid sequence GlyProGlyArgAlaPhe (GPGRAF) that is present in both isolates.
 This sequence is frequently found in the PNDs analyzed in randomly selected HIV-1 isolates.
 Sera from two rabbits immunized with a peptide containing only the GPGRAF residues neutralized divergent isolates, including IIIB and MN.
",19
3210,"Clinical aspects of multiple sclerosis in north-east Scotland with particular reference to its course and prognosis.
 The prognosis and course of multiple sclerosis (MS) and the factors that affect them were assessed in a group of 1055 patients, representing an unselected (epidemiological) sample observed in the north-east (Grampian region) of Scotland for a period ranging between 1 and 60 yrs.
 In 7% the disease began before the age of 20 yrs, in 12% after the age of 50 yrs, and in the remainder onset was between the ages of 20 and 50 yrs.
 The male/female ratio was 1:1.8.
 Mean disease duration in those observed until death (216 patients) was 24.5 yrs, with no significant difference between the sexes.
 Prognosis was assessed either by the interval between onset and death or by the degree of disability over a defined period of time.
 Depending on the length of follow-up, just over one-quarter (26%) to over one-third (36.3%) had a benign course and between 8.0 and 17.7% had a poor prognosis.
 Nearly a third had a remittent (32.8%) or relapsing cumulative (34%) course and 9% had a progressive course from the start.
 Several factors were noted to affect the prognosis.
 Prognosis was significantly better, independent of sex, in those with (1) an early onset (less than 40 yrs of age); (2) retrobulbar neuritis or a brainstem lesion or sensory symptoms alone at onset; (3) short duration of initial symptoms (less than 6 months); (4) a long onset--first relapse interval (greater than 1 yr); (5) a remittent course in the beginning and (6) lack of a family history of MS.
 The factors which predicted a poor prognosis included: (1) a late onset (greater than 40 yrs of age); (2) progressive course from the start; (3) multiple sites of lesions initially, or a cerebellar or spinal cord lesion at the onset; (4) psychiatric or persistent urinary symptoms at the onset or within 10 yrs; (5) persistent initial symptoms (beyond 1 yr); (6) early first relapse (within 6 months); (7) a family history of MS; (8) social class status IV and V; and (9) bilaterally prolonged visual evoked potential (VEP) P100 latency.
 Address in childhood and at the onset of the disease, changes in the CSF and CT brain scan were not of predictive value.
",19
3211,"AIDS in California family medicine. Changing experiences, knowledge, and geographic distribution.
 Information regarding practice patterns specific to acquired immunodeficiency syndrome (AIDS) was obtained in 1988 from 1774 family physicians in California using a mail survey.
 Data were analyzed across the following county groupings: Los Angeles County, other counties in standard metropolitan statistical areas, and counties outside standard metropolitan statistical areas.
 Comparisons were made with the data from a telephone survey conducted in 1986.
 Differences over time were analyzed.
 By 1988, the percentage of physicians treating or referring patients for possible AIDS had more than doubled in counties outside standard metropolitan statistical areas.
 The percentage of physicians reporting one or more diagnosed cases of AIDS had tripled, a finding that suggests the importance of AIDS in family medicine is increasing at a rapid rate.
 In addition, survey results indicate that a majority of those surveyed still lack the AIDS-related knowledge and competency necessary to effectively deal with AIDS.
",19
3212,"Search for retroviral sequences in peripheral blood mononuclear cells and brain tissue of multiple sclerosis patients.
 DNAs from peripheral blood mononuclear cells (PBMCs) of 21 patients with multiple sclerosis (MS), 1 patient with tropical spastic paraparesis (TSP) as well as DNAs from brain and spinal cord of 5 MS cases and 3 controls were examined for human T-cell lymphotropic virus (HTLV)-related sequences by polymerase chain reaction.
 The primers used were derived from the HTLV-I gag, env and tax genes.
 Amplified products were separated on agarose gels, blotted onto nylon membranes and hybridized to specific radiolabelled oligonucleotides.
 The sensitivity of amplification and hybridization was one copy of target DNA in 10(5) cellular genomes.
 None of the specimens was positive for HTLV-I sequences except the TSP probe.
 These negative data are all the more significant because brain material from MS patients was used in these studies.
 Our studies thus fail to support speculations that HTLV-I is involved in the aetiology of multiple sclerosis.
",19
3213,"Brain-stem auditory evoked potentials in multiple sclerosis: the relation to VEP, SEP and CSF immunoglobulins.
 One hundred patients with multiple sclerosis (MS) were analysed retrospectively with respect to investigations of brain-stem auditory evoked potentials (BAEP), pattern reversal visual evoked potentials (VEP), somatosensory evoked potentials (SEP), and cerebrospinal fluid immunoglobulins (CSF-IG).
 BAEP were abnormal in 42% of those with normal VEP and SEP examinations, and in 38% of patients with normal CSF-IG.
 The chance of obtaining at least one abnormal EP was lower in patients with normal CSF-IG than in patients with abnormal CSF.
 When a ""dispersion ratio"" was included in the criteria for BAEP abnormality, the sensitivity increased compared with conventional BAEP criteria.
 We recommend that BAEP should still be included in the EP test battery for patients with suspected MS.
",19
3214,"Vascularized bone marrow transplantation (VBMT): induction of stable mixed T-cell chimerism and transplantation tolerance in unmodified recipients.
 In this preliminary report, our model of VBMT across a semiallogeneic barrier consistently brings about antigen-specific host tolerance with absence of GVHD in the majority of recipients.
 No immunologic or radiologic intervention was utilized.
 These results emphasized a potentially important mechanism for low-level stable mixed lymphoid chimerism (SMLC) in tolerance induction, independent of immune suppressive effects due to irradiation or immunopharmacologic intervention.
",19
3215,"HIV risk behavior reduction following intervention with key opinion leaders of population: an experimental analysis.
 BACKGROUND AND PURPOSE.
 Peer norms influence the adoption of behavior changes to reduce risk for HIV (human immunodeficiency virus) infection.
 By experimentally intervening at a community level to modify risk behavior norms, it may be possible to promote generalized reductions in HIV risk practices within a population.
 METHODS.
 We trained persons reliably identified as popular opinion leaders among gay men in a small city to serve as behavior change endorsers to their peers.
 The opinion leaders acquired social skills for making these endorsements and complied in talking frequently with friends and acquaintances.
 Before and after intervention, we conducted surveys of men patronizing gay clubs in the intervention city and in two matched comparison cities.
 RESULTS.
 In the intervention city, the proportion of men who engaged in any unprotected anal intercourse in a two-month period decreased from 36.9 percent to 27.5 percent (-25 percent from baseline), with a reduction from 27.1 percent to 19.0 percent (-30 percent from baseline) for unprotected receptive anal intercourse.
 Relative to baseline levels, there was a 16 percent increase in condom use during anal intercourse and an 18 percent decrease in the proportion of men with more than one sexual partner.
 Little or no change was observed among men in the comparison cities over the same period of time.
 CONCLUSIONS.
 Interventions that employ peer leaders to endorse change may produce or accelerate population behavior changes to lessen risk for HIV infection.
",19
3216,"Behavioral, health and psychosocial factors and risk for HIV infection among sexually active homosexual men: the Multicenter AIDS Cohort Study.
 We examined whether 644 homosexual men who engaged in receptive anal intercourse were at particularly elevated risk for seroconversion if they also possessed specific behavioral, health or psychosocial vulnerability characteristics.
 Of 11 potential factors examined, heavy drinking, moderate to heavy drug use, and younger age were significantly related to seroconversion.
 These variables were also associated with an increased number of sexual partners, anonymous sex, and failure to use condoms.
",19
3217,"Sexual risk behaviors, AIDS knowledge, and beliefs about AIDS among runaways.
 Sexual risk behaviors, knowledge of acquired immunodeficiency syndrome (AIDS), and beliefs about AIDS prevention were examined among 126 runaways.
 In the previous 3 months, 65 percent of youths had been sexually active.
 Among the sexually active runaways, males reported a median of 2.7 partners and females reported 1.3 partners, and only 18 percent reported consistent condom use.
 Runaways demonstrated moderately high AIDS knowledge and beliefs endorsing AIDS prevention.
 Condom use and abstinence were directly related to beliefs about preventing AIDS.
",19
3218,"Security measures for AIDS and HIV.
 This study describes the measures being taken by AIDS surveillance offices across the country to ensure the security of information regarding patients with AIDS and HIV infection.
 Security measures were evaluated according to the cumulative number of AIDS cases reported, whether partner notification services were provided, and whether HIV seropositive reporting by name was also required.
 This study showed that public health departments have taken extra steps to ensure the security of AIDS and HIV data.
",19
3219,"Anaphylactic anaesthetic reactions. The value of paper radioallergosorbent tests for IgE antibodies to muscle relaxants and thiopentone.
 The three currently available paper radioallergosorbent tests ('suxamethonium', alcuronium and thiopentone) were evaluated.
 'Suxamethonium' radioallergosorbent test (which employs choline conjugated to paper discs) proved to be reliable in the detection of allergy to neuromuscular blockers, which were confirmed as the most common cause of anaphylactic reaction during general anaesthesia.
 Thiopentone radioallergosorbent test may also be useful, and is recommended in conjunction with 'suxamethonium' radioallergosorbent test in the preliminary investigation of reactions.
 Patients with positive 'suxamethonium' radioallergosorbent test usually require further testing, including alcuronium radioallergosorbent test, skin testing with a wide range of drug concentrations or leucocyte histamine release test.
",19
3220,"Allergen-induced asthmatic responses. Relationship between increases in airway responsiveness and increases in circulating eosinophils, basophils, and their progenitors.
 The inflammatory response during allergen-induced asthma was assessed using serial measures of peripheral blood eosinophils (Eo), basophils (B), and Eo/B progenitor cells (Eo/B-CFU).
 A group of 14 stable asthmatic individuals (beta 2-agonists only as needed) had inhalation provocation tests with allergen (18 tests in total) and with diluent.
 Serial blood samples were taken before and 1 and 24 h after the tests; methylcellulose cultures for Eo/B-CFU and granulocyte-macrophage (GM-CFU) were scored at 14 days.
 Circulating Eo, B, and Eo/B-CFU were increased at 24 h after allergen inhalation when this resulted in increased histamine airway responsiveness (n = 13).
 In the 5 subjects with isolated early asthmatic responses the Eo, B, and Eo/B-CFU counts did not change.
 There was no change in the GM-CFU after allergen.
 The ratio change in circulating Eo/B-CFU was negatively correlated with baseline histamine airway responsiveness (r = -0.8, p less than 0.05).
 Four subjects who had an isolated early response and no blood changes to one allergen developed an increase in histamine airway responsiveness and an increase in Eo, B, and Eo/B progenitors after inhalation of a second different allergen.
 The results indicate that in subjects with an allergen-induced increase in histamine airway responsiveness, an inflammatory response occurs that includes an increase in the number of Eo/B progenitors.
 This response, possibly mediated by Eo/B growth and differentiation factors, could lead to the accumulation of these cells in the airway and contribute to the airways inflammation present in asthma.
",19
3221,"Asthma in the elderly. A comparison between patients with recently acquired and long-standing disease.
 To characterize asthma in the elderly, 25 consecutive nonsmoking pulmonary clinic patients over the age of 70 who met the American Thoracic Society criteria for asthma were identified.
 Of these, 12 patients (48%) had developed asthma at an advanced age (greater than 65 yr).
 This group with late-onset asthma had a mean duration of disease of 5.1 +/- 2.5 yr.
 The remaining group with early-onset asthma had a mean duration of illness of 31.4 +/- 14.6 yr.
 On the day of evaluation each patient underwent pulmonary function testing off all medication for at least 12 h.
 These two groups were indistinguishable by symptoms and medication requirements.
 Immediate hypersensitivity skin testing to 43 aeroallergens was uniformly negative in all 25 patients but the histamine control was always positive.
 IgE levels in both groups were not different from those in elderly control subjects.
 Those with early-onset asthma had a greater likelihood of previous allergic disease (p less than 0.001) and a significantly greater degree of airflow obstruction in pre- and postbronchodilator pulmonary function testing (p less than 0.05).
 This study suggests that long-standing asthma may lead to chronic persistent airflow obstruction and thereby mimic chronic bronchitis and emphysema (COPD).
",19
3222,"Inhalation of an alkaline aerosol by subjects with mild asthma does not result in bronchoconstriction.
 Although it is recognized that inhalation of acid aerosols by subjects with asthma can cause bronchoconstriction, the effects of the inhalation of an alkaline aerosol are unknown.
 When supplemental inflatable restraints (automobile air bags) are deployed an alkaline aerosol is released.
 This aerosol is composed of particles of sodium carbonate and sodium bicarbonate with some sodium hydroxide.
 The mass median aerodynamic diameter (MMAD) of the aerosol is approximately 1 micron, and the pH of the aerosol is 9.8 to 10.3.
 A group of 14 volunteer male subjects with mild asthma inhaled increasing concentrations of this aerosol for 20-min periods of mouth-only tidal ventilation.
 Pulmonary function tests were performed at baseline (preexposure), after inhalation of room air alone (control), and after each period of inhalation of the aerosol.
 A total of 5 subjects inhaled aerosols at nominal concentrations of 10, 20, and 40 mg/m3, whereas 11 subjects inhaled aerosols concentrations of approximately 30, 60, and 120 mg/m3.
 The mean changes in FEV1 and specific airways resistance (SRaw) for the 11 subjects who inhaled the higher concentrations (average highest concentration 126.6 +/- 7.5 mg/m3, mean +/- SEM) were -1.4 +/- 1.9 and +17.5 +/- 8.5%, respectively.
 Neither change in lung function was clinically or statistically significant.
 We conclude that the inhalation of relatively high concentrations of this alkaline aerosol by subjects with mild asthma does not result in bronchoconstriction.
",19
3223,"Respiratory membrane permeability and bronchial hyperreactivity in patients with stable asthma. Effects of therapy with inhaled steroids.
 In patients with stable asthma, we assayed plasma proteins in the bronchoalveolar lavage fluid to obtain information on plasma exudation into the airways.
 Fourteen nonsmoking patients with asthma who were in a stable period of their disease and eight nonsmoking healthy volunteers were studied.
 The ratios of the concentrations of albumin, ceruloplasmin (CP), and alpha-2-macroglobulin (A2M) between blood and epithelial lining fluid were calculated (cQalb, cQCP, and cQA2M).
 The cQalb was increased in the patients (Mann-Whitney U test, p less than 0.05).
 In 10 patients the bronchial hyperreactivity was assessed with histamine provocation tests.
 Significant relationships between the cQalb, cQCP, and cQA2M on the one hand and PC15 on the other hand were found (Spearman's rank correlation: r = -0.62, p less than 0.05; r = -0.61, p less than 0.05; r = -0.79, p less than 0.01, respectively).
 Fourteen patients were treated with two inhalations of 200 micrograms glucocorticosteroids per day in a 3-month prospective study.
 Three of them were excluded from further study because of an intercurrent exacerbation of asthmatic symptoms during therapy.
 In the 11 patients with stable asthma, the cQalb and cQA2M decreased after treatment with inhaled steroids (Wilcoxon's matched pairs signed rank test, p less than 0.03).
 Our results show that in patients with stable asthma, there is an increased plasma exudation into the airways, most likely caused by an increased respiratory membrane permeability.
 The plasma exudation correlated with the bronchial hyperreactivity to histamine, and it decreased after corticosteroid therapy.
",19
3224,"Abnormalities in airway smooth muscle in fatal asthma. A comparison between trachea and bronchus.
 Tracheal smooth muscle from seven cases of fatal asthma demonstrated an increased contractile response to histamine, acetylcholine, and electrical stimulation of intrinsic cholinergic nerves; impaired relaxation to isoproterenol, and possibly theophylline, was also evident (1).
 Fourth generation bronchial spirals from the same patients were also studied, and these results were compared with those of the trachea and normal bronchi (n = 5).
 In contrast to trachea, contractile responses in asthmatic bronchi to acetylcholine, histamine, and cholinergic nerve stimulation were similar to those in control bronchi.
 The potency of isoprenaline (IC50) was reduced 9.4-fold (p less than 0.003), similar to trachea (4.5-fold), whereas theophylline responses were normal.
 The discrepant results obtained may reflect differences in the disease process, including rates of postmortem change, at the two anatomic sites.
",19
3225,"Lack of evidence for beta-2 receptor selectivity: a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma.
 In order to investigate the pharmacodynamic selectivity of a number of beta-receptor agonists currently used in asthma, we compared the pulmonary and extrapulmonary effects of repeated inhalations of epinephrine, fenoterol, isoproterenol, and metaproterenol in 12 patients with asthma in a randomized double-blind crossover study.
 The drugs were administered from metered-dose inhalers at 15-min intervals for five doses (total dose, 10 puffs of each compound).
 Measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, plasma potassium, and FEV1 were made 5 min after each dose and 30 min after the final dose.
 Fenoterol and metaproterenol had significantly greater inotropic, electrocardiographic, chronotropic, and hypokalemic effects than did both isoproterenol and epinephrine.
 There was no difference in the bronchodilating effect of metaproterenol, fenoterol, or isoproterenol although these agents caused a significantly greater increase in FEV1 than did epinephrine.
 The concept of increasing beta-2 selectivity for metaproterenol and fenoterol compared with isoproterenol are not supported in the clinical setting.
",19
3226,"IgE-mediated anaphylactic degranulation of isolated human skin mast cells.
 Isolated human skin mast cells (HSMC) were prepared and cultured overnight before functional and electron microscopic studies.
 Mast cell suspensions were examined after stimulation with anti-IgE to produce anaphylactic degranulation or examined in buffer-incubated controls.
 Histamine release was measured in replicate samples.
 Control, isolated HSMC studied by electron microscopy were well preserved and fully granulated.
 Although all granule patterns reported for human mast cells were found, crystal granules were the most prevalent, as is true for HSMC in situ.
 Individual mast cells containing both crystal and scroll granules occurred.
 Lipid bodies were rare, as in HSMC in situ.
 Control, isolated mast cells did not express granule changes associated with either piecemeal degranulation or recovery during wound healing in situ; nor were morphologic changes of anaphylactic degranulation present.
 Spontaneous histamine release was 0% in control samples.
 Anaphylactic degranulation of isolated HSMC was accompanied by 24% maximum histamine release and characteristically showed extrusion of altered, membrane-free granules through multiple pores in the plasma membrane to the exterior of the cell.
 Other morphologic aspects of anaphylactic degranulation, as expressed in isolated human lung mast cells, were also present.
 These events included granule swelling, fusion, alteration of matrix contents, degranulation channel formation, pore formation, and shedding of granules, membranes, and surface processes.
 The ultrastructural morphology of isolated HSMC and their IgE-mediated degranulation shows some differences from similar studies of isolated human lung mast cells and of human lung and gut mast cells in biopsy samples.
 These differences include crystal granules as the predominant granule pattern, minor numbers of lipid bodies, and extrusion of granules during anaphylactic degranulation as characteristic for HSMC.
 By contrast, isolated human lung and gut mast cells have more scroll granules and particle granules, respectively, and more lipid bodies.
 In isolated human lung mast cells, anaphylactic degranulation is almost exclusively an intracellular fusion event characterized by the formation of complex degranulation channels within which altered granule matrix materials solubilize.
 In addition to morphologic differences between mast cells of skin, lung, or gut origin, functional differences have also been reported among mast cells of these organs.
 The ultrastructural morphology of isolated HSMC is identical to that of skin mast cells in biopsy samples, thereby validating the usefulness of this new source of HSMC for correlative functional and morphologic studies.
",19
3227,"Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation.
 The existence of an immunologic antileukemia reaction associated with allogeneic bone marrow transplantation (BMT) is well established.
 However, a similar graft-versus-tumor effect against lymphomas has not been demonstrated.
 We analyzed the results of BMT in 118 consecutive patients with relapsed Hodgkin's disease or aggressive non-Hodgkin's lymphoma.
 The 38 patients less than 50 years of age with HLA-matched donors had allogenic marrow transplants, and the other 80 patients received purged autologous grafts.
 The median age was 26 years in both the allogeneic and the autologous graft recipients.
 The patient's response to conventional salvage therapy before transplant was the only factor that influenced the event-free survival after BMT (P less than .001).
 Both the patient's response to salvage therapy before BMT (P less than .001) and the type of graft (P = .02) significantly influenced the probability of relapse after BMT.
 The actuarial probability of relapse in patients who responded to conventional salvage therapy before BMT was only 18% after allogenic BMT compared with 46% after autologous BMT.
 However, the actuarial probability of event-free survival at 4 years was the same, 47% versus 41%, for patients with responsive lymphomas who received allogeneic and autologous transplants, respectively (P = .8).
 The beneficial antitumor effect of allogeneic BMT was offset by its higher transplant-related mortality (P = .01), largely resulting from graft-versus-host disease.
 Allogeneic BMT appears to induce a clinically significant graft-versus-lymphoma effect.
 The magnitude of this effect is similar to that reported against leukemias.
",19
3228,"Clinical assessment of ankylosing spondylitis: a study of observer variation in spinal measurements.
 Twenty-two measurements repeated non-sequentially on each of 10 patients by five observers were undertaken to determine their reliability for routine clinical use.
 Measurements without significant inter-observer variation or with a coefficient of reliability greater than 0.70 were cervical rotation, cervical lateral flexion, tragus to wall distance, fingertip to floor distance on sagittal and lateral flexion, C7 to iliac crest line distraction and modified Schober index.
 It is concluded that many of the currently used measurements are either statistically unreliable or clinically unhelpful in mild or moderate ankylosing spondylitis.
 The most clinically useful were cervical rotation using a protractor, cervical lateral flexion using a goniometer, thoracolumbar flexion as the C7 to iliac crest line distraction, thoracolumbar lateral flexion as the fingertip to floor distance and the modified Schober index.
",19
3229,"Cytomorphologic, immunocytochemical, and nucleic acid flow cytometric study of 50 lymph nodes by fine-needle aspiration. Comparison with results obtained by subsequent excisional biopsy.
 Fifty patients with clinically suspected or previous diagnosis of lymphoma underwent fine-needle aspiration (FNA) and subsequent excisional biopsy of their lymph nodes.
 Results of cytologic diagnosis made from the direct smears in conjunction with immunocytochemical study of cytospin preparations and nucleic acid flow cytometric study (FCM) were compared with the results obtained from histologic sections, cryostat-immunohistochemical study, and nucleic acid FCM performed on resected lymph nodes.
 This study demonstrates (1) results of immunocytochemical and DNA-FCM analysis of FNA-derived material are comparable in the majority of cases to those obtained from surgical specimens, (2) immunostaining of cytospin preparations for immunoglobulin (Ig) gives less background staining and in certain cases is easier to interpret than when performed on frozen sections, and (3) monotypia in FNA in conjunction with cytomorphologic study is 100% specific for lymphoma, and polytypic staining for Ig does not exclude HD, T-cell lymphoma, or B-cell malignancy focally involving a lymph node.
",19
3230,"Fludarabine therapy in hairy cell leukemia.
 This study evaluated the efficacy of fludarabine, a new adenine nucleoside analogue, in typical and variant forms of hairy cell leukemia (HCL).
 Two patients with HCL and one patient with a variant form of HCL (HCL-variant) with resistant or progressive disease with prior treatments were studied.
 Fludarabine (30 mg/m2) was administered intravenously over 30 minutes daily for 5 days every month.
 Two patients (one with HCL and one with HCL-variant) achieved partial responses; the third patient had a minor response.
 This is the first report of encouraging activity of fludarabine in typical and variant forms of HCL.
 Further experience with fludarabine in these disorders is indicated.
",19
3231,"Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.
 We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages.
 Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients.
 Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation.
 Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size.
 The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24.
 Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages.
 Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine.
 These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates.
",19
3232,"Limited B cell repertoire in severe combined immunodeficient mice engrafted with peripheral blood mononuclear cells derived from immunodeficient or normal humans.
 The ability to engraft human PBMC or fetal tissue immune cells in the severe combined immunodeficient (SCID) mouse has created a need for characterization of these systems and their application to disease models.
 We demonstrate that SCID mice reconstituted with PBMC support the growth and differentiation of a restricted set of B cells.
 Human IgG levels of 1-2 mg/ml (10-20% of normal human serum levels) were routinely achieved in spite of a serum half life of only 12 d.
 Ig levels peaked around 50 d and Ig production was maintained for greater than 100 d.
 The Ig was greater than 85% IgG though some IgM, IgA, IgD, and even IgE could be detected.
 However, the human IgG produced in hu-PBL-SCID mice was pauci-clonal when analyzed by isoelectric focusing and by kappa/lambda light chain usage.
 Using a new polymerase chain reaction based analysis capable of monitoring individual VH family utilization, we found that the engrafted B cells showed skewed and restricted human VH subfamily utilization.
 These parameters were markedly variable among hu-PBL-SCID mice reconstituted from the same donor cell population at both early (21-50 d) and late stages (greater than 100 d).
 Hu-PBL/CVI-SCID mice constructed with cells from patients with common variable immunodeficiency with an in vitro block in terminal B cell differentiation produced human Ig responses that were quantitatively the same as those produced by hu-PBL-SCID mice from normal donors.
 The hu-PBL-SCID system using PBMC appears to lead to growth and Ig production by a small number of B cells and results in a restricted B cell repertoire.
",19
3233,"Effect of a thromboxane A2 receptor antagonist (AA-2414) on bronchial hyperresponsiveness to methacholine in subjects with asthma.
 Bronchial hyperresponsiveness (BHR) to various stimuli is one of the major clinical features of bronchial asthma.
 In this study, the effect of a thromboxane A2 (TXA2) receptor antagonist, AA-2414, on BHR to methacholine was evaluated in 15 patients with asthma.
 The methacholine inhalation test was performed before and after oral administration of AA-2414 for 4 days (20 or 40 mg/day).
 The provocative concentration of methacholine producing a 20% fall in FEV1 (PC20) was measured as an index of BHR.
 There was a significant increase in PC20 (p less than 0.01) from 0.43 (geometric SEM, 1.42) mg/ml to 0.93 (geometric SEM, 1.43) mg/ml after 40 mg/day of AA-2414, whereas baseline values of FVC and FEV1 were not changed by the treatment.
 Twenty milligrams per day of AA-2414 did not alter the PC20 value nor the parameter of baseline pulmonary functions.
 These findings might support our hypothesis that the subthreshold concentration of TXA2 in the bronchial tissues, which has no effect on bronchomotor tone per se, may be involved in BHR in asthma.
 Further studies with more potent and specific TXA2 receptor antagonists are needed to confirm the conclusion.
",19
3234,"Secretion of granule proteins from eosinophils and neutrophils is increased in asthma.
 The activity of eosinophil and neutrophil granulocytes with respect to secretion of granule proteins was studied in 30 patients with asthma and with varying severity of their disease.
 Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase was measured by means of specific radioimmunoassays.
 Eosinophils from patients with asthma released significantly more (p less than 0.001) ECP and EPX after 20 minutes of incubation than cells from control subjects without asthma.
 The release of myeloperoxidase from neutrophils was also somewhat higher (p less than 0.03).
 The serum concentrations of ECP and EPX were also significantly increased (p less than 0.001) in the group with asthma.
 No significant relationships were found between clinical variables and the secretory activity of either eosinophils or neutrophils.
 We conclude that eosinophils and, to some extent, neutrophils from subjects with asthma have an increased propensity to release their granule proteins, which we suggest is a consequence of priming of these cells.
",19
3235,"Food-dependent, exercise-induced anaphylaxis: a study on 11 Japanese cases.
 Eleven patients with food-dependent, exercise-induced anaphylaxis were studied.
 Seven patients experienced anaphylactic symptoms only after eating certain foods, such as shellfish, wheat, and grape before exercise.
 In the remaining four patients, no specific food could be identified, but the act of eating itself predisposed to anaphylaxis.
 Their anaphylactic symptoms were all clearly distinguished from cholinergic urticaria by history.
 Patients who developed anaphylactic symptoms before 20 years of age (N = 7) were atopic themselves or had atopic first-degree relatives.
 Six patients had increased serum IgE levels, and IgE antibodies against the causative food allergens were detected by the skin prick test or RAST in four cases.
 In contrast, patients who developed the symptoms after 30 years of age (N = 4) appeared to have a less atopic background, and IgE levels were within normal range except in one case.
 Three of four patients in the latter group developed symptoms after ingesting food made of wheat followed by exercise.
 All patients were sensitive to wheat as determined by the skin prick test.
 In six of 11 patients, a considerable rise in plasma histamine concentration was observed after exercise challenge with treadmill alone, and food intake followed by exercise induced a further increase in one patient.
",19
3236,"Modern haemophilia treatment: medical improvements and quality of life.
 Adequate replacement therapy in haemophilia has been available for two decades.
 This has led to considerable improvements in the life expectancy and physical status of haemophilia patients.
 A study was conducted to investigate whether this has also led to improvements in quality of life.
 With this aim, information was obtained from 935 Dutch haemophiliacs by mailed questionnaires on relationships, marriage, family life and employment.
 Haemophilia patients were less often married than men in the general population (13% fewer) and had a lower total number of children (30% lower, 17% for those who were married).
 Twenty-two per cent of the patients were not employed and received an income from the disability funds.
 While severity of haemophilia, joint damage and age increased the risk of disability, it was noted that home treatment was associated with a 50% reduction in this risk.
 Remarkably, haemophilia patients did not differ from the general population in their view of the quality of their own health.
 The results of this study show a positive influence of modern haemophilia treatment on quality of life.
 At present, AIDS overshadows all optimistic feelings one may have about this field.
 However, the results described here demonstrate the benefits that can be achieved with adequate replacement therapy, and justify the expectation of further improvements in the near future.
",19
3237,"MRI-guided stereotaxic brain biopsy in neurologically symptomatic AIDS patients.
 Two patients with AIDS-related neurologic dysfunction were evaluated with both computed tomographic (CT) brain scans and magnetic resonance imaging (MRI).
 CT scans were essentially normal in both patients while MRI revealed focal lesions amenable to brain biopsy.
 Using newly developed instrumentation, MRI-guided stereotaxic brain biopsy was performed without complication.
 The benefits and impact of this new technology for the care of neurologically symptomatic AIDS patients is discussed.
",19
3238,"A multicenter proficiency trial of gene amplification (PCR) for the detection of HIV-1.
 The sensitivity and specificity of the polymerase chain reaction (PCR) for the detection of HIV-1 proviral DNA was determined in five laboratories with extensive experience in PCR testing.
 Five panels consisting of 105 HIV-1-seronegative specimens from regularly repeating blood donors with no risk factors for HIV infection and 99 HIV-1-seropositive and culture-positive specimens from a cohort of homosexual/bisexual men were sent under code to each laboratory.
 Amplification procedures and testing algorithms by which specimens were judged positive, negative, or indeterminate varied between laboratories.
 The average sensitivity for the five laboratories was 99.0%, with two laboratories achieving 100%.
 The average specificity was 94.7%, varying between 90.5 and 100%.
 The overall false-positive rate was 1.8%, the false-negative rate was 0.8%, and the indeterminate rate was 1.9%.
 Of 1,005 determinations made by the five laboratories, 32 (3.2%) were misclassifications.
 Most of the classification errors occurred in specimens from uninfected individuals and were distributed among the laboratories in such a way as to indicate laboratory error rather than the inherent reactivity of some samples.
 This emphasizes the need for standardization of PCR testing and caution in interpreting positive PCR reactions in HIV-1-seronegative persons.
",19
3239,"Serial CD4 lymphocyte counts and development of AIDS 
 Low CD4 lymphocyte counts are associated with increased risk of progression to AIDS in human immunodeficiency virus (HIV) infection.
 We investigated the extent to which the timing of progression to AIDS can be explained solely in terms of decline of the CD4 lymphocyte count in 111 haemophiliacs followed for up to 11 years since infection with HIV.
 A median of 10 CD4 lymphocyte counts were made per patient.
 By applying a simple linear model for the decline in CD4 lymphocyte counts over time, we estimated the date of development of AIDS in 96 patients who had at least 5 determinations.
 84% (81 of 96) of patients were correctly classified as to development of AIDS before Jan 1, 1990 (p less than 0.0001), with this model.
 The results suggest that differences in the time at which patients with HIV will progress to AIDS can largely be explained by differences in rates of decline of CD4 lymphocyte counts.
",19
3240,"The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. The Canadian Cooperative Multiple Sclerosis Study Group 
 To find out whether non-specific immunosuppression is beneficial in multiple sclerosis (MS) a randomised, placebo-controlled, single-masked trial was carried out in nine university centres.
 168 patients with clinically or laboratory-supported definite MS in progressive phase (deterioration by at least 1.0 on the expanded disability status scale [EDSS] in the previous year) were randomised to receive intravenous cyclophosphamide and oral prednisone (n = 55); daily oral cyclophosphamide, alternate day prednisone (22 weeks), and weekly plasma exchange (20 weeks) (n = 57); or placebo medications and sham plasma exchange (n = 56).
 All patients were followed for at least 12 months (mean 30.4 months) by a monitoring neurologist, who was aware of treatment allocation, and an evaluating neurologist, who was not.
 The primary analysis was a comparison of rates of treatment failure (worsening of evaluating neurologist's assessment of EDSS by 1.0 or more on two consecutive 6-monthly assessments).
 There were no significant differences among the groups in this primary analysis (19 [35%] treatment failures with cyclophosphamide; 18 [32%] with plasma exchange; 16 [29%] with placebo).
 Nor were there any differences in the proportions improved, stabilised, or worsened at each 6 month assessment or in the mean change in the EDSS at the final assessment (0.81 cyclophosphamide; 0.69 plasma exchange; 0.69 placebo).
 A slight trend favouring the plasma exchange group at 12-24 months of follow-up was not sustained at the final assessment.
 This study fails to confirm previous reports that immunosuppressive treatments result in stabilisation or improvement in progressive MS.
",19
3241,"Unusual amyloid polyneuropathy with predominant lumbosacral nerve roots and plexus involvement.
 We report a 25-year-old patient with a progressive asymmetric peripheral neuropathy of the distal lower limbs.
 Imaging studies showed enlargement of lumbosacral roots, plexus, and proximal sciatic nerve.
 Sacral plexus biopsy revealed amyloidosis associated with endoneurial edema.
 Immunohistochemistry with anti-prealbumin, serum amyloid A, and immunoglobulin light chain antisera failed to label the amyloid.
",19
3242,"A 21-aminosteroid inhibits stimulated monocyte hydrogen peroxide and chemiluminescence measurements from MS patients and controls.
 Monocytes are recruited to active sites of multiple sclerosis (MS) demyelination and may promote local tissue injury by generating an inflammatory response, mediated in part by the production of toxic oxygen metabolites.
 Corticosteroids are frequently and effectively used to ameliorate MS exacerbations, despite inadequate knowledge about the mechanism.
 We assessed the effects of a 21-aminosteroid, U74500A, a new class of steroid derivatives without glucocorticoid or mineralocorticoid effects, on the production of hydrogen peroxide (H2O2) and chemiluminescence by stimulated monocytes harvested from 8 stable MS patients and age- and sex-matched controls.
 H2O2 measurements and chemiluminescence were significantly reduced in both groups by U74500A.
 These results demonstrate that 21-aminosteroids reduce production of toxic oxygen metabolites by monocytes and thus their inflammatory potential, suggesting that these agents may be potentially effective and safe treatment for MS exacerbations.
",19
3243,"Human immunodeficiency virus-infected multinucleated histiocytes in oropharyngeal lymphoid tissues from two asymptomatic patients.
 Human immunodeficiency virus (HIV)-infected multinucleated giant cells previously were detected only in the central nervous system of HIV-positive patients.
 Reported here are the first cases in which such infected cells were observed outside the central nervous system, in the oropharyngeal lymphoid tissues.
 Tonsils and adenoids were removed individually from two asymptomatic homosexual men.
 Follicular hyperplasia and many interfollicular multinucleated giant cells most often in contact with or in close proximity of the mucous membrane were seen.
 The latter were positive for lysozyme, alpha-1 anti-chymotrypsin, OKM1, and S-100 protein in accordance with a histiocytic origin.
 In situ hybridization with an HIV envelope-specific RNA probe demonstrated the presence of viral RNA in these multinucleated giant cells.
 These findings support the role of peripheral histiocytes as a primary virus reservoir early in the disease.
 They also underline the potential role of oropharyngeal tissue as a primary target in some cases.
",19
3244,"Early cellular events in evolving cutaneous delayed hypersensitivity in humans.
 The delayed-type hypersensitivity reaction (DHR) in human skin is prototypic for many inflammatory dermatoses.
 However the cellular events that precede gross lesion formation are unknown.
 In this study, inflammatory cell populations and adhesion molecule expression in early phases of DHR elicited by 2,4-dinitrochlorobenzene were evaluated.
 The first discernible event (at 1 hour) was mast cell degranulation, followed by induction of endothelial leukocyte adhesion molecule (ELAM-1) expression on dermal postcapillary venules at 2 hours.
 Endothelial leukocyte adhesion molecule expression peaked at 24 hours and declined by 48 hours.
 In contrast, endothelial expression of intercellular adhesion molecule-1 (ICAM-1) remained at constitutive levels.
 Intrafollicular T-cell migration occurred independent of ICAM-1 expression and commenced as early as 4 hours after challenge.
 Mature, activated CD4-positive lymphocytes that expressed a helper-inducer/memory phenotype predominated in early lesions.
 These results demonstrate in vivo that mast cell degranulation, ELAM-1 expression, and memory T-cell-follicular interactions are key events in subclinical evolutionary stages of cutaneous DHR.
",19
3245,"Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double-blind, placebo-controlled study 
 OBJECTIVE: To determine the effect of low-dose methotrexate in asthmatic patients on steroid use, asthma symptom scores, pulmonary function, airway reactivity, blood cellular components, and immunoglobulin E levels.
 DESIGN: A randomized, double-blind, parallel, placebo-controlled, 13-week clinical trial with follow-up of patients in an open trial of methotrexate at the conclusion of the double-blind study.
 SETTING: An asthma care outpatient clinic.
 PATIENTS: From February 1988 to March 1990, 19 patients with severe, steroid-dependent asthma were enrolled in the study.
 Two of these patients were excluded from analysis.
 INTERVENTIONS: Patients were administered methotrexate or placebo intramuscularly, to assure complete absorption, once weekly during the 13-week study.
 RESULTS: Patients on methotrexate and placebo both significantly decreased their steroid dose by 39.6% (95% CI, 25.1% to 54.1%, P = 0.001) and 40.2% (CI, 17.9% to 67.4%, P = 0.003), respectively.
 Pulmonary function did not differ significantly between the methotrexate and placebo groups.
 In addition, airway reactivity and symptom scores were unchanged on methotrexate or placebo.
 No significant toxicities were seen during the course of the 13-week blinded study, but one patient on methotrexate and prednisone in the follow-up period developed Pneumocystis carinii pneumonia and died.
 Despite continuing methotrexate for up to 1 year, and increasing methotrexate to 30 mg weekly, no significant benefit of methotrexate on asthma control could be shown.
 CONCLUSION: Our study does not support the use of methotrexate in the treatment of severe asthma.
",19
3246,"Treatment of multiple sclerosis with hyperbaric oxygen. Results of a national registry.
 Three hundred twelve patients were entered into a long-term study of effects of hyperbaric oxygen on multiple sclerosis.
 The protocol called for an initial 20 treatments in either the monoplace or multiplace chamber on a daily basis followed by monthly booster treatments for 2 years.
 One hundred seventy neurologists and 22 institutions provided data for this study.
 There was no control group, but the study was based on Schumacher's postulation that a scientifically valid study to test the efficacy of a new therapy was possible by choosing patients who were definitively diagnosed with multiple sclerosis and following them up for 2 years after the imposed treatment.
 If the overwhelming majority of the subjects failed to get worse over the 2-year observation period, the efficacy of the treatment would be manifest.
 The expanded Kurtzke Disability Status Scale (EDSS) was used to assess the severity of the disease state.
 The dropout rate was high with only 76% (237 of 312 patients) finishing the initial 20 treatments.
 Twenty-two percent (69 of 312) finished 1 year of booster therapy, and 9% (28 of 312) completed 2 years of monthly boosters.
 The mean deterioration on the Kurtzke EDSS score was 0.93 or almost a full step from the beginning of treatment until the last evaluation.
 There was no difference in outcome between those who had the shortest and longest periods of time between onset of symptoms and hyperbaric oxygen treatment.
 Treatment pressure made no difference in outcome.
 Changes in the Kurtzke EDSS score bore no relationship to the use of booster treatment.
 Patients who were reasonably well off at the onset of treatment with initial Kurtzke EDSS scores of 1 or 2 (n = 21) deteriorated by an average of 1.7 Kurtzke points.
 Those patients whose initial Kurtzke EDSS scores were greater than 2 (n = 164) deteriorated on an average of 0.82 points.
 Of interest was that 19.5% (39 of 200) of the patients reported a temporary improvement in bladder function, but improvement was maintained in only 11 patients (5.5%) at 2-year follow-up.
 Fifteen patients (7.5%) indicated long-term worsening.
 There was no significant change in the working status of the patients following hyperbaric oxygen treatment.
 Although this study treated the patients in accordance with protocols reported to produce a benefit in multiple sclerosis, we were unable to substantiate any useful long-term effect of hyperbaric oxygen therapy.
",19
3247,"Prevalence of HIV-1 infection in the Kagera region of Tanzania: a population-based study.
 A population-based survey was carried out in the Kagera region of the United Republic of Tanzania in 1987 to determine the magnitude of HIV-1 infection and to study associated risk factors.
 The region was divided into one urban and three rural zones.
 A multistage cluster sampling technique was adopted.
 Antibodies to HIV-1 were determined by enzyme-linked immunosorbent assay and confirmed by Western blot analysis.
 A total of 2,475 adults (aged 15-54 years) and 1,961 children (aged 0-14 years) was studied.
 The overall prevalence of HIV-1 infection among adults was 9.6%, with a higher prevalence in the urban zone (24.2%) than in the three rural zones (10.0, 4.5 and 0.4%, respectively).
 The corresponding figures for children were 1.3% overall: 3.9% in the urban area and for the rural areas 1.2, 0.8 and 0.0%, respectively.
 The age-specific seroprevalence for adults was highest in the age group 25-34 years.
 The age-standardized sex-specific prevalence was higher among women than men in the urban zone, while it was the same in the rural zones.
 Change of sexual partners among adults was associated with an increased risk of HIV-1 seropositivity.
 Travelling outside the region but within the country was also found to be associated with increased risk of HIV-1 infection but only in the rural population.
",19
3248,"The evolutionary dynamics of HIV-1 quasispecies and the development of immunodeficiency disease.
 This paper presents a theory to explain the development of immunodeficiency disease after a long and variable incubation period of infection with HIV-1.
 Two assumptions are central to the theory: (1) mutation via reverse transcription during viral replication can generate viral strains resistant to neutralization by antibodies specific to earlier mutants in a particular host; (2) the virus can kill the CD4-positive lymphocytes that play a role in mounting an immunological attack directed at the virus.
 The theory is examined via the development of a mathematical model which reveals that an increasing number of antigenically distinct viral strains may overwhelm the immune system of the host.
 As the viral diversity increases beyond a certain level the immune system is unable to suppress the population growth of all the strains simultaneously.
 The intuitive explanation of this pattern of model behaviour lies in the assumption that each virus can kill CD4-positive lymphocytes that are specific to any of the viral strains, but each lymphocyte only directs immunological attack against a single viral strain.
",19
3249,"A cohort study of 89 HIV-1-infected adult patients contaminated by blood products: Bordeaux 1981-1989. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine (GECSA) [published erratum appears in AIDS 1991 Mar;5(3):354]
 A hospital-based surveillance of HIV infection was implemented in the Bordeaux Regional University Hospital (France).
 This reporting system, initiated by the Groupe d'Epidemiologie Clinique du SIDA en Aquitaine, identified and followed-up 89 adult patients with transfusion-associated HIV-1 infection (7.2% of all reported cases).
 Contamination occurred between August 1981 and June 1985 and diagnosis was made between 1985 and 1989.
 By 30 June 1990, 43 patients (48.3%) had full-blown AIDS, and 28 of them had died.
 The mean follow-up period was 66 months (s.d.
 16 months).
 The mean incubation period, i.e.
 The time interval between the contaminating transfusion and the development of full-blown AIDS, was 62 months [median 73 months; 95% confidence interval (CI) 66-82 months].
 Five years after contamination, the cumulative probability of reaching the AIDS stage was 34.2% (95% CI 20.3-49.3%), and the probability of survival was 81.7% (95% CI 72.5-90.0%).
 From this surveillance system we estimate that in south-western France at the end of 1989 the cumulative incidence of transfusion-associated HIV-1 infection was at least 126 cases (45.6 per million inhabitants).
 Although we anticipate an increase in transfusion-associated AIDS cases over the next 5 years, there have been no reports of contamination after 1 August 1985, when systematic screening of HIV antibodies was implemented in French blood banks.
 This confirms the efficacy of screening in countries like France where the risk of contamination through blood products is now minimal.
",19
3250,"Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in de novo acute myeloid leukemia.
 Based on in vitro data suggesting that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is capable of stimulating acute myeloid leukemia (AML) blast cells to become more sensitive to cell-cycle-specific drugs we conducted a phase I/II study in de novo AML patients (pts).
 rhGM-CSF (250 micrograms/m2/d, continuous intravenous infusion) was administered in 18 pts suffering from de novo AML in combination with standard induction chemotherapy (3 + 7 = daunorubicin 45 mg/m2 days 1 through 3, cytosine-arabinoside [Ara-C] 200 mg/m2 continuous infusion days 1 through 7).
 GM-CSF was started 48 or 24 hours before chemotherapy (prephase) in 14 pts.
 In four pts with high white blood cell counts (WBC) rhGM-CSF was started after chemotherapy-induced cell reduction (WBC less than 30,000/mm3).
 During prephase GM-CSF induced an increase in neutrophil and blast cell counts in 13 of 14 and 10 of 14 pts, respectively.
 In vivo recruitment of leukemic cells into drug-sensitive phases of the cell cycle could be demonstrated by multiparameter cell-cycle analyses in peripheral blood (n = 7) and bone marrow (n = 4) specimens.
 On day 14, complete aplasia was evident in 17 of 18 pts.
 GM-CSF was administered until recovery from chemotherapy-induced myelosuppression (absolute neutrophil counts, [ANC] greater than 500/mm3).
 Fifteen pts (83%) achieved complete remission, 12 did so with one cycle.
 A shorter duration of neutropenia was evident in these pts compared with historical controls (n = 39), (ANC greater than 500/mm3, day 22.5 +/- 3.4 v 25.2 +/- 3.7, P less than .05).
 Three pts achieved complete remission after a second cycle (same combination of rhGM-CSF and 3 + 7).
 Two pts died during bone marrow aplasia because of invasive pulmonary aspergillosis.
 Clinical side effects possibly related to GM-CSF, mainly fever, diarrhea, and weight gain were mild and tolerable (World Health Organization toxicity grade less than or equal to 2).
 Together, rhGM-CSF recruits kinetically quiescient AML cells in vivo to enter drug-sensitive phases of the cell cycle and promotes early myeloid recovery from aplasia after exposure to standard induction chemotherapy for AML.
",19
3251,"Expression of the c-fgr and hck protein-tyrosine kinases in acute myeloid leukemic blasts is associated with early commitment and differentiation events in the monocytic and granulocytic lineages.
 Two members of the src proto-oncogene family of intracellular tyrosine kinases, c-fgr and hck, are selectively expressed in differentiated myeloid cells.
 To study the expression of these genes in acute myeloid leukemia (AML) and to determine the specific myeloid lineages and stages of myeloid differentiation at which the expression of these genes is acquired, we used a series of 79 cases of de novo AML as a differentiation model.
 The levels of c-fgr, hck, and c-fms (encoding the colony-stimulating factor-1 receptor) mRNA transcripts were correlated with the presence of specific cell surface antigens and the morphologic and cytochemical features in these AML blasts.
 Relatively undifferentiated leukemic myeloblasts with an HLA-DR, CD34, CD33, CD13+/- cell surface immunophenotype (French-American-British [FAB] M1 or M2) were characterized by a lack of c-fms and c-fgr expression, while low levels of c-fms and c-fgr could be detected in undifferentiated myeloblasts (FAB M1 or M2), which also expressed CD14 at low antigen density.
 The hck transcripts were either undetectable in these cells or were expressed at low levels.
 In contrast, only hck mRNA transcripts could be identified in blasts with progranulocytic morphology (FAB M3), while c-fms, c-fgr, and hck were all expressed at high levels in blasts with differentiated myelomonocytic or monocytic features (FAB M4 and M5).
 No c-fms, c-fgr, or hck transcripts were evident in leukemic cells of the erythroid lineage (FAB M6).
 When undifferentiated leukemic myeloblasts (HLA-DR, CD34, and CD33) were induced to differentiate in vitro to cells with monocytic characteristics, the expression of c-fms, c-fgr, and the CD14 cell surface antigen were induced to high levels, accompanied by the acquisition of hck and CD13 expression.
 In contrast, when HLA-DR, CD34, and CD33 blasts were induced to differentiate in vitro to cells with granulocytic characteristics, only hck and CD13 expression were induced.
 Our data suggest that the acquisition of c-fgr and/or hck expression is associated with early commitment and differentiation events in distinct myeloid lineages.
 Assessment of the expression of these kinases may provide a molecular tool to assign lineage in AML in conjunction with morphology, cytochemistry, and cell surface antigen expression.
",19
3252,"Macrophage colony-stimulating factor (CSF-1) gene expression in human T-lymphocyte clones.
 Macrophage colony stimulating factor (CSF-1) is one of several cytokines that control the differentiation, survival, and proliferation of monocytes and macrophages.
 A set of 11 human T-cell clones, chosen for their phenotypic diversity, were tested for their ability to express CSF-1 mRNA.
 After 5 hours of stimulation with phorbol myristate acetate (PMA) + calcium ionophore (Cal), all T-cell clones expressed a major 4-kb transcript, a less abundant 2-kb transcript, and several other minor species.
 This pattern of expression is typical for CSF-1 mRNAs.
 Furthermore, of the two alloreactive T-cell clones analyzed, only one showed a definitive message for CSF-1 on specific antigenic stimulation, but with delayed kinetics and less efficiency.
 Both conditions of stimulation induced the release of CSF-1 protein by T cells in the culture medium.
 Together, these findings demonstrate for the first time that normal T cells are able to produce CSF-1, previous reports being limited to two cases of tumoral cells of the T-cell lineage.
",19
3253,"Loss of interferon antibodies during prolonged continuous interferon-alpha 2a therapy in hairy cell leukemia.
 Although highly active in hairy cell leukemia (HCL), interferons (IFN) are not curative in this disease; current data indicate that prolonged IFN therapy will be necessary to control disease in the majority of patients.
 We previously observed acquired IFN resistance in association with neutralizing IFN-alpha 2a antibodies in small numbers of patients with HCL.
 This finding suggests that the requisite long-term therapy may be compromised if there is an increasing incidence over time of neutralizing antibodies.
 We performed a follow-up study of IFN antibodies in our patients receiving continuous IFN therapy.
 All 16 patients who were previously antibody negative remained so.
 Surprisingly, all nine patients who previously had non-neutralizing IFN antibodies became antibody negative after a median of 14.5 months.
 Moreover, 3 of 10 patients who had neutralizing antibodies became antibody negative and five had only non-neutralizing antibodies a median of 10 months from the time neutralizing antibody had first been detected.
 Only two patients had persisting neutralizing antibodies.
 Inhibition of neopterin synthesis, inhibition of generation of 2', 5' oligoadenylate synthetase activity, and inability to detect IFN in serum after subcutaneous injection of IFN-alpha 2a was observed only in the one patient tested with neutralizing IFN antibodies confirming that these antibodies have functional significance in vivo.
 We conclude that, although neutralizing IFN antibodies inhibit the effectiveness of IFN in vivo, these antibodies are produced only transiently during long-term therapy.
 The long-term effectiveness of this drug will not likely be affected in most patients by neutralizing antibody.
",19
3254,"Effect of tamoxifen on cell lines displaying the multidrug-resistant phenotype.
 We examined the effect of tamoxifen (Tmx), verapamil, and daunorubicin (DNR) in two cell lines that displayed the multidrug-resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular DNR content.
 In the vinblastine-resistant human lymphoblastic lymphoma cell line CEM-VBL, simultaneous incubation of DNR with Tmx 10 mumol/L or Tmx 50 mumol/L increased intracellular DNR fluorescence in a dose-dependent manner and demonstrated an uptake pattern similar to that seen with DNR and verapamil.
 Similar results were obtained in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+.
 Cellular retention of DNR was also measured in both cell lines and results suggested that continuous exposure of the cells to Tmx resulted in higher intracellular DNR content compared with cells resuspended in fresh medium.
 No effect of Tmx or verapamil was observed in the drug-sensitive parent cell lines CEM or HL-60.
 Clonogenic experiments were then performed to determine whether Tmx was itself inhibitory to cell growth or whether Tmx potentiated DNR cytotoxicity.
 Tmx 10 mumol/L did not significantly inhibit either CEM-VBL or HL-60/RV+ cells after a 3-hour exposure followed by culture in methylcellulose.
 Tmx 50 mumol/L was significantly more inhibitory in both cell lines.
 However, cells that had been incubated with DNR and Tmx 10 mumol/L demonstrated a marked increment in growth inhibition compared with cells that had been incubated with DNR alone or Tmx 10 mumol/L alone.
 Based on the data presented here, we suggest that clinical testing of Tmx and DNR be pursued in the setting where MDR may play a role.
",19
3255,"Rapid simultaneous detection of multiple retroviral DNA sequences using the polymerase chain reaction and capillary DNA chromatography.
 The polymerase chain reaction (PCR) technique is a powerful new tool for amplifying target DNA, thus allowing for sensitive detection of specific nucleic acid sequences.
 One important potential use of PCR involves screening the donated blood supply for transfusion-transmitted viruses.
 Realization of this goal has been limited by (1) the requirement for multiple, discrete PCR reactions to amplify and detect target sequences of more than one virus, and (2) the lack of a rapid, nonhazardous means for specific detection of one or more PCR-amplified products.
 We report the simultaneous amplification of three distinct target sequences without discernable loss in sensitivity toward any single target sequence.
 We also demonstrate very rapid separation and detection of PCR-amplified viral DNA through the use of automated capillary DNA chromatography.
 Amplified DNA peaks were initially identified by scanning the capillary effluent at ultraviolet wavelengths, while discrimination of human immunodeficiency virus type 1 and human T-cell leukemic virus type I PCR-amplified DNA was accomplished through use of virus-specific, fluorescently labeled primers and probes.
 These results indicate progress toward an automated system for screening the blood supply for nucleic acid sequences of multiple pathogens.
",19
3256,"Detection of early human T-cell lymphotropic virus type I antibody patterns during seroconversion among transfusion recipients.
 From a cohort of human T-cell lymphotropic virus type I (HTLV-I) exposed transfusion recipients (N = 71) enrolled in the Jamaican Transfusion Study, 11 were selected for detailed laboratory evaluation.
 All recipients were followed at monthly intervals for 6 months and then bimonthly up to 1 year for evidence of HTLV-I seroconversion.
 Without regard to results on screening assays, pretransfusion and posttransfusion samples were tested with two licensed HTLV-1 whole-virus screening enzyme immunoassays (EIAs), recombinant EIAs for antibody against tax (p40x) and p21e envelope, standard whole virus Western blot (WB), WB enhanced with recombinant p21e, and radioimmunoprecipitation assay (RIPA).
 In the early period posttransfusion, antibody to gag core protein was predominant with anti-p24 generally appearing before anti-p19.
 Recombinant anti-p21e envelope protein, in EIA and WB format, was frequently the earliest envelope reactivity detected, while anti-gp46 in WB and anti-gp61/68 in RIPA system appeared later.
 Anti-tax antibodies appeared later in the time course of seroconversion.
 The whole-virus EIAs were less sensitive than the confirmatory assays.
 The combination of WB and RIPA or WB enhanced with recombinant p21e appeared equally effective in confirming samples as positive by the Public Health Service two gene group confirmatory algorithm.
 However, specificity of this assay approach could not be addressed in this study.
",19
3257,"Reduction of budesonide after a year of increased use: a randomized controlled trial to evaluate whether improvements in airway responsiveness and clinical asthma are maintained.
 We have demonstrated recently that 1 year of regular inhaled budesonide use can produce substantial improvements in airway responsiveness accompanied by significant improvements in clinical asthma severity.
 The present study was designed to evaluate whether these improvements are maintained when the dose of budesonide is reduced.
 At the end of the original study, 28 subjects with asthma, who had been in the active-treatment arm of the study were randomized either to continue taking the dose of budesonide taken in the original study or to have the dose reduced.
 Airway responsiveness to methacholine, bronchodilator requirements, symptoms, and spirometry were assessed after 6 weeks and 3 months.
 During the 3 months, no subject experienced an asthma exacerbation, and there was no evidence of change in airway responsiveness in subjects who had their steroids reduced (provocative concentration causing a 20% drop in FEV1; initial, 2.03 mg/ml; final, 1.91 mg/ml), and this change was not different from change in subjects maintained with a higher dose (initial, 3.02 mg/ml; final, 3.12 mg/ml) (p = 0.39).
 Similarly, there was no evidence of any change in bronchodilator requirements (p = 0.89).
 However, after 3 months of reduced steroid use, there was a small decline in spirometry (FEV1 percent predicted: initial, 84.4%; final, 81.5%), and this change was significantly different from change in subjects in whom steroids were not reduced (initial, 90.2%; final, 90.2%) (p = 0.002).
 At 3 months, symptoms (predominantly sputum production) were also beginning to redevelop in the reduced budesonide group (p = 0.056).
",19
3258,"Environmental exposure to cockroach allergens: analysis with monoclonal antibody-based enzyme immunoassays.
 Quantitative two-site monoclonal antibody (MAb)-based enzyme-linked immunoassays for two cockroach (CR) allergens, Bla g I and Bla g II, have been developed and used to measure allergen levels in house-dust samples.
 Dust collected from the CR-infested homes of two patients with asthma from Charlottesville, Va., demonstrated wide variation in the levels of Bla g I, depending on the location of dust collection.
 Dust from kitchen floors and cabinets contained 50-fold more allergen (mean, 10,755 U/gm of dust) than dust from bedrooms and upholstered furniture (mean, 204 U/gm).
 One hundred forty-five dust samples were collected from the bedrooms and living rooms of 22 children with asthma and 16 control subjects without asthma living in Atlanta, Ga.
 Twenty-seven of the 38 homes (17/22 children with asthma; 10/16 control subjects) had detectable Bla g I (4 to 1340 U/gm of dust).
 Bla g II levels were assayed in 40 kitchen, bedroom, and living room samples from homes in Wilmington, Del.
 Highest levels of Bla g II were detected in kitchen-floor dust (300 U/gm of dust).
 Additionally, approximately 20% of homes with no visual evidence of CR infestation had significant levels of Bla g II in at least one dust sample (greater than 4 U/gm of dust).
 Our results demonstrate that CR may be an occult allergen in homes.
 The kitchen appears to be the primary site of CR-allergen accumulation, but significant CR-allergen levels can also be found at other sites in the home.
 The MAb-based assays can be used for quantitation of environmental exposure to CR allergens.
",19
3259,"Bronchoalveolar lavage fluid mediator levels 5 minutes after allergen challenge in atopic subjects with asthma: relationship to the development of late asthmatic responses.
 Inflammatory mediators have been implicated in the pathogenesis of human asthma and have been demonstrated to increase in bronchoalveolar lavage fluid during the time of the immediate asthmatic response (IAR) after allergen instillation in the lungs.
 However, the relationship of these mediators, measured early to the late asthmatic response (LAR), airway reactivity, and clinical asthma, is unknown.
 In the present study, we evaluated mediator levels in bronchoalveolar lavage fluid before and 5 minutes after allergen challenge from three subject groups: atopic subjects without asthma (N = 7), atopic subjects with asthma and without LAR [-) LAR) (N = 6), and atopic subjects with asthma and with LAR [+) LAR) (N = 6).
 Subjects with asthma were differentiated into subjects with and without LARs based on at least a 15% decrease in FEV1 between 3 to 8 hours postallergen inhalation.
 The mediators, prostaglandin D2 thromboxane B2 leukotriene C4 (LTC4), and histamine, were measured both before and after allergen instillation.
 Baseline prechallenge levels were similar, except in the case of LTC4.
 LTC4 was detectable at baseline significantly more frequently in the atopic subjects with asthma with and without LAR when these subjects were compared to the atopic subjects without asthma (nine of 12 detectable versus one of seven detectable).
 In all groups, significant increases in mediator levels were observed in the groups with asthma postallergen challenge, compared to the atopic subjects without asthma.
 Atopic subjects with asthma and without LAR had significantly higher levels of all four mediators after challenge than atopic subjects with asthma and with LAR and atopic subjects without asthma.
",19
3260,"Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep.
 The effects of inhaled bradykinin (BK), substance P (SP), and neurokinin A (NKA) on pulmonary resistance and airway responsiveness to carbachol were studied in conscious allergic sheep.
 Inhaled BK (20 breaths, 0.1 to 5.0 mg.ml-1) caused dose-dependent increases in pulmonary resistance.
 Neither inhaled SP nor NKA (20 breaths, 0.1 to 1.0 mg.ml-1) produced significant bronchoconstriction in allergic sheep.
 However, the response to SP could be enhanced (p less than 0.05) by pretreatment with the neutral endopeptidase inhibitor, thiorphan (40 breaths, 1 mg.ml-1).
 Sheep that were allergic to Ascaris suum antigen were 5.9 times (p less than 0.05) more sensitive to the constrictor effects of BK than nonallergic sheep.
 BK-induced bronchoconstriction was blocked in a dose-dependent fashion by the BK beta 2-receptor antagonist, NPC 567 (D-arginine[hydroxyproline3,D-phenylalanine7]BK).
 Atropine (0.2 mg.kg-1, intravenously) and nedocromil sodium (1 mg.kg-1 in 3 ml of saline, aerosolized) significantly inhibited the BK-induced bronchoconstriction by 97% and 43%, respectively.
 Chlorpheniramine (2 mg.kg-1, intravenously) had no effect.
 NKA caused a transient increase in airway responsiveness in allergic sheep, producing a mean 1.9-fold leftward shift in dose-response curves to aerosolized carbachol (p less than 0.05).
 This hyperresponsiveness was not evident 24 hours after NKA challenge.
 Neither SP nor BK changed airway responsiveness.
 Thus, in allergic sheep, inhaled BK caused a more pronounced bronchoconstriction than that observed in nonallergic sheep.
 The bronchoconstriction was blocked by a BK-receptor antagonist and appeared to be partially mediated via cholinergic reflexes.
",19
3261,"Comparison of cockroach allergenic activity in whole body and fecal extracts.
 Previous studies have established cockroach allergens as important sensitizing agents in the induction/exacerbation of urban asthma.
 The present investigation compared saline extracts of American cockroach (Periplaneta americana) whole bodies and feces and German cockroach (Blattella germanica) whole bodies and feces as important sources of allergens.
 All extracts were tested before or after gel filtration on Sephadex G-75 columns (fraction 2) as previously described.
 Skin test studies of 69 subjects with asthma with extracts of American or German cockroaches demonstrated a significant correlation of reactivity to whole body and fecal extracts for both species.
 Direct RASTs of 13 sera from cockroach skin test-positive subjects were generally greater to both German whole body extracts (GWBEs) and German fecal extracts (GFEs) as compared to American whole body and fecal extracts.
 There was a good correlation of RAST reactivity to GWBE with GFE.
 RAST inhibition demonstrated that GFE contained most of the allergenic activity present in GWBE.
 These studies demonstrate the allergenic similarities of cockroach whole body and fecal extracts and suggest that cockroach feces are an important sensitizing agent in atopic asthma.
",19
3262,"Analyses of microvascular permeability in response to mediators of immediate hypersensitivity.
 Mediator-induced changes in microvascular permeability were studied in rodent skin.
 To monitor these changes, Evan's blue dye, iodinated rat albumin and IgG, and tritiated neutral dextran molecules having different molecular radii were used.
 After intradermal injections of serotonin, histamine, and bradykinin, the degree of radiolabeled tracer efflux was determined by measuring the extent of blueing and the level of radioactivity in skin biopsy specimens.
 Although the mediators varied in potency on a molar basis (serotonin greater than bradykinin greater than histamine), the efflux resulting from each was similar.
 Furthermore, kinetic studies revealed that each of these vasoactive agents caused a marked but transient increase in macromolecular permeability that lasted less than 30 minutes.
 To determine the pore size created and the effect of charge on the transudation of macromolecules into the interstitium, fractions of neutral [3H]dextrans with a known molecular size (average radii, 12 and 4.4 nm, respectively) were infused either singly or in combination with 125I-labeled rat albumin and/or IgG before intradermal injection of serotonin, histamine, bradykinin, or compound 48/80.
 Regardless of the mediator used, no differences could be demonstrated in macromolecular efflux, as indicated by either the molecular size of the charge of the tracer used.
 Thus, all mediators of immediate hypersensitivity reactions that were studied produce venular gaps greater than 12 nm in addition to displaying similar vasopermeable characteristics.
",19
3263,"Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation.
 Lymphopenia was induced in mice by a single injection of cyclophosphamide.
 IL-7 or a control protein were administered to the mice twice daily and the cellularity and composition of the spleen, lymph node, bone marrow, and thymus were determined at various time points thereafter.
 In comparison to the control cyclophosphamide-treated mice, animals receiving cyclophosphamide and IL-7 had an accelerated regeneration of splenic and lymph node cellularity.
 There was no significant difference in the rate of recovery of the bone marrow and thymus of the control and IL-7-treated mice.
 Assessment of the pre-B cell compartment revealed a dramatic increase in total pre-B cell numbers in the spleen and bone marrow of the IL-7-treated mice as measured by both flow microfluorimetry and a pre-B cell colony-forming assay.
 This was followed in a few days by a significant increase in surface IgM+B cell numbers to levels above normal values in both the spleen and lymph node.
 IL-7 administration to cyclophosphamide-treated mice also resulted in an accelerated recovery of peripheral CD4+ and CD8+ cell numbers in the spleen and lymph node.
 The numbers of CD8+ cells were increased by twofold over normal levels in cyclophosphamide-treated mice receiving IL-7.
 Myeloid recovery was determined in cyclophosphamide treated mice by assessing the numbers of CFU-granulocyte-macrophage and Mac 1+ cells.
 There was no significant difference in myeloid recovery between cyclophosphamide-treated mice receiving IL-7 or control protein.
 These results suggest that administration of IL-7 after chemical-induced lymphopenia may have therapeutic benefits in shortening the period required to achieve normal lymphoid cellularity.
",19
3264,"Direct identification of the putative surface IgM receptor-associated molecule encoded by murine B cell-specific mb-1 gene.
 The B cell-specific mb-1 gene was recently reported to encode a putative surface glycoprotein with CD3-like structural properties.
 Hombach et al.
 suggested and presented evidence to show that this mb-1 gene encodes the 34-kDa membrane glycoprotein (B34 or IgM-alpha) associated with IgMR molecule.
 To identify the mb-1 gene product directly in B cells, affinity-purified MB-1-specific antibody was prepared by immunization of rabbits with synthetic MB-1 oligopeptide.
 Immunoprecipitation in combination with two-dimensional diagonal gel electrophoresis analysis revealed that this antibody detected a B cell-specific surface glycoprotein that is very similar to the IgM-alpha (B34) protein described by Hombach et al.
 However, MB-1 protein exists usually as the monomeric form on the surface of B cells, in contrast to IgM-alpha, which was detected as the dimeric (IgM-alpha/IgM-alpha or IgM-alpha/Ig-beta) protein.
 We also found that MB-1 protein is already expressed on the sIgM- pre-B cell lymphoma, which might suggest an alternative functional role of this B cell-specific MB-1 protein in B cell differentiation.
 The molecular identity of MB-1 protein and IgM-alpha (B34) is discussed.
",19
3265,"The prevalence of allergic bronchopulmonary aspergillosis in patients with asthma, determined by serologic and radiologic criteria in patients at risk.
 Allergic bronchopulmonary aspergillosis, a hitherto uncommon but potentially crippling complication of asthma, occurs at an unknown prevalence in the United States.
 Using both modern serologic criteria complete with a history of asthma and radiologic findings, we were able to make the diagnosis of allergic bronchopulmonary aspergillosis in 28 of 100 consecutive patients with asthma who had immediate cutaneous reactivity to Aspergillus fumigatus and who were seen in an outpatient setting.
 Problems associated with use of less comprehensive criteria for this diagnosis are discussed.
",19
3266,"Major histocompatibility gene products and human immunodeficiency virus infection.
 In the present paper we analyze the role of major histocompatibility gene products, the human leukocyte antigens, in the pathophysiology of the acquired immunodeficiency syndrome.
 No association has been found between human leukocyte antigen (HLA) frequencies and human immunodeficiency virus type 1 (HIV 1) infection, whereas significant associations have been reported in some populations between some HLA haplotypes and the appearance of either opportunistic infections or secondary cancers.
 With regard to the human leukocyte class I antigens, their role as restriction elements in presenting HIV 1 to virus-specific cytotoxic T lymphocytes seems to be established.
 An increase in the serum levels of their soluble forms that correlate with disease stage has also been demonstrated.
 These circulating molecules could interfere with the immune response to HIV 1 and could contribute to the development of the immunodeficiency.
 Antigenic similarities have been detected between human leukocyte class II antigens and HIV 1 envelope proteins.
 These homologies could explain both the presence in some HIV-positive sera of anti-HLA class II antibodies that mediate the lysis of CD4(+)-HLA class II+ T cells and the false-positive reaction of some HIV-negative sera, which contain anti-HLA class II antibodies, in tests for HIV 1 antibodies.
 Reduced levels of some complement factors (the human leukocyte class III antigens) have been detected in HIV-infected subjects.
 These defects could play a role in the progression of the disease and affect both the clearance of HIV 1 and complement-mediated antibody responses.
 The data reported in this review suggest that HLA antigens may be involved in several steps of the immune deficiency of HIV-infected subjects and thus contribute to the pathophysiology of acquired immunodeficiency syndrome.
",19
3267,"Studies with RP 56976 (taxotere): a semisynthetic analogue of taxol.
 RP 56976 (taxotere), a new semisynthetic analogue of taxol, is a potentially important chemotherapeutic agent for the treatment of cancer.
 We report here that this drug is a potent inhibitor of cell replication and, like taxol, promotes the in vitro assembly of stable microtubules in the absence of guanosine triphosphate and induces microtubule-bundle formation in cells.
 Compared with taxol, RP 56976 is slightly more active as a promoter of tubulin polymerization.
 As an inhibitor of cell replication, RP 56976 is 2.5-fold more potent than taxol in J774.2 and P388 cells and at least 5-fold more potent in taxol-resistant cells.
",19
3268,"AIDS and adolescents. How can you help them reduce their risk?
 AIDS in adolescents (0.4% of all cases) is a problem of increasing importance in the United States.
 Infection with the human immunodeficiency virus (HIV) exists in high schools and on university campuses, and it presents a real and immediate threat to teenaged Americans who engage in drug abuse and sexual activity.
 Appropriately targeted educational efforts are needed to limit HIV transmission among adolescents.
 Most adolescents are aware of the high-risk activities that may lead to HIV transmission.
 However, only about one third alter their sexual behavior to avoid AIDS.
 It is important to move beyond imparting knowledge about AIDS transmission and to move toward changing risky behavior.
 Strategies for AIDS risk reduction in adolescents should be implemented now across the country.
 Appropriate support and intervention are urgently needed for adolescents at high risk.
",19
3269,"Human immunodeficiency virus transmission by child sexual abuse.
 During 1987-1989, 14 (14.6%) of the 96 children who tested positive for the human immunodeficiency virus (HIV) and were followed up by the Duke University (Durham, NC) pediatric acquired immunodeficiency syndrome team were confirmed to have been sexually abused.
 Every sexually abused child was evaluated for each of five modes of HIV transmission, and in nine children the pathway was identified.
 Four of the study children acquired HIV from child sexual abuse and in six, abuse was a possible source.
 Transmission by child sexual abuse was the most frequent of the proven modes of acquisition of HIV in this population.
 The other proven modes of acquisition were vertical transmission (n = 3) and HIV-contaminated blood transfusion (n = 2).
 Twelve males were identified (n = 8) or suspected (n = 4) of being perpetrators.
 Three knew themselves to have HIV at the time of an assault and eight were aware that the child had HIV at the time of an assault.
 There was no indication from any child that ""safe sex"" precautions had been observed.
 Children with HIV infection had multiple risk factors for abuse or neglect.
 The sociological descriptors of the lives of the 14 abused children showed multiple known risk factors for sexual abuse that also overlapped with known risk factors for or sequelae of the acquisition of HIV infection.
 These included drug abuse and alcoholism in the home, prostitution of a parent, lack of parenting, poverty, and chronic illness of the child.
 Prevention efforts should recognize that children as well as adults are at risk for sexually transmitted HIV infection.
",19
3270,"Anaphylaxis to annatto dye: a case report.
 Annatto dye is an orange-yellow food coloring extracted from the seeds of the tree Bixa orellana.
 It is commonly used in cheeses, snack foods, beverages, and cereals.
 Previously reported adverse reactions associated with annatto dye have included urticaria and angioedema.
 We present a patient who developed urticaria, angioedema, and severe hypotension within 20 minutes following ingestion of milk and Fiber One cereal, which contained annatto dye.
 Subsequent skin tests to milk, wheat, and corn were negative.
 The patient had a strong positive skin test to annatto dye, while controls had no response.
 The nondialyzable fraction of annatto dye on SDS-PAGE demonstrated two protein staining bands in the range of 50 kD.
 Immunoblotting demonstrated patient IgE-specific for one of these bands, while controls showed no binding.
 Annatto dye may contain contaminating or residual seed proteins to which our patient developed IgE hypersensitivity.
 Annatto dye is a potential rare cause of anaphylaxis.
",19
3271,"Relationships between skin prick test, radioallergosorbent test, and chemiluminescent assays in allergic children.
 The results of skin prick tests (SPT), radioallergosorbent tests (RAST), and multiple chemiluminescent tests (DHS-CLA) to grass mix, parietaria, D.
 farinae, and D.
 pteronyssinus were evaluated in 43 allergic children.
 All CLA tests had valid positive and negative control threads.
 Chemiluminescent assays class 4 matched with RAST class 3 and/or 4 and CLA class 3 with RAST class 2.
 The D.
 farinae, D.
 pteronyssinus, and grass results obtained with CLA, RAST, and SPT were investigated by principal components analysis that showed a good association between different methods of measuring allergenicity.
 The results of the present study confirm that DHS-CLA is an effective ""in vitro"" method for the detection of IgE-allergen specific antibody.
",19
3272,"Clustering of fungal allergen-specific IgE antibody responses in allergic subjects.
 Statistical analysis of specific IgE immune responses to a panel of nine allergens from 2,094 patients demonstrated significant clustering between Aspergillus fumigatus, Alternaria alternata, and Cladosporium herbarum, not explained by crossreactive elements.
 This may represent a linked, high responder status to these fungal antigens in the allergic population.
",19
3273,"Inhaled bronchodilator's in asthma: low or high dose?
 We studied the effect of regular inhalations of low-dose and high-dose fenoterol and low-dose and high-dose combinations of fenoterol and ipratropium bromide in maintenance treatment of 120 adults with moderately severe asthma.
 We used a double-blind, randomized, parallel group design comparing 12 weeks of treatment with four regimens: fenoterol, 100 micrograms/dose; fenoterol, 200 micrograms/dose; fenoterol, 50 micrograms; and ipratropium, 20 micrograms/dose in a single inhaler (Berodual) and fenoterol, 100 micrograms and ipratropium, 40 micrograms/dose in a single inhaler (Duovent).
 During the baseline and active treatment period the patients recorded PEFR in the morning and evening, symptoms and use of a rescue inhaler.
 Changes in twice daily peak expiratory flow rates or asthma symptoms did not show any significant differences among the four treatment regimens during the 12 weeks compared with the baseline period.
 Use of the rescue inhaler did not differ among the four groups during the active treatment.
 The patients' assessment of the efficacy of the active treatment favored the low-dose fenoterol and low-dose combination.
 More side effects were recorded in the high-dose combination group during the first 4 weeks compared with the other groups.
 We conclude that in maintenance therapy of chronic asthma high doses of fenoterol alone or in combination with ipratropium bromide offer no clinical advantage over low doses.
 On the contrary, the low-dose fenoterol and the low-dose combination are better accepted and tolerated by the patients.
",19
3274,"Treatment and career attitudes of prehospital care providers associated with potential exposure to HIV/AIDS.
 Career and treatment attitudes related to potential human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) exposure are reported based on a survey of 1,228 Maryland career and volunteer prehospital care providers trained to provide basic (BLS) and advanced (ALS) life support.
 Sixty-five percent stated potential exposure to HIV/AIDS was a major occupational stressor.
 Ninety-two percent stated they would treat HIV/AIDS patients if protected.
 Given a choice, 38% would avoid providing treatment to HIV/AIDS patients.
 Eighteen percent considered resigning from emergency medical services (EMS) work.
 An attitudinal scale (AIDSTRESS) was developed to evaluate overall treatment and career reactions.
 Respondents with significantly higher (more negative reactions) AIDSTRESS scores were: BLS providers, men, paid providers, personnel with more than 3 years of field experience, those working in urban areas, personnel with no formal education beyond high school, and those who stated that their HIV/AIDS training was inadequate.
 Implications of the findings for quality of care, career decision making, and inservice education are discussed.
",19
3275,"Identification of functionally distinct domains of human granulocyte-macrophage colony-stimulating factor using monoclonal antibodies.
 Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that is required for the survival, growth, and differentiation of hematopoietic progenitor cells.
 Although the primary structure of GM-CSF is known from cDNA cloning, the relationship between structure and function of GM-CSF is not fully understood.
 Fifteen different monoclonal antibodies (MoAbs) to human GM-CSF were generated to map immunologically distinct areas of the molecule.
 Each of the MoAbs was biotinylated and shown by enzyme-linked immunosorbent assay to bind to recombinant GM-CSF that had been affixed to a solid phase.
 Each of the 15 unconjugated MoAbs was then used to compete with each biotinylated MoAb for binding to GM-CSF.
 These cross-blocking studies identified eight distinct epitopes of native GM-CSF.
 Seven of these epitopes were also present in denatured GM-CSF by Western blotting, and four of the epitopes were at least partially conserved on GM-CSF that was reduced in beta-mercaptoethanol.
 MoAbs to four of eight epitopes neutralized both recombinant (glycosylated and nonglycosylated) and natural human GM-CSF in a GM colony-forming unit (CFU-GM) assay and blocked GM-CSF-induced activation of neutrophils.
 For most of the antibodies there was a good correlation between neutralizing activity and the capacity to block binding of 125I-GM-CSF to neutrophils or blasts.
 Non-neutralizing antibodies to one epitope partially blocked binding of 125I-GM-CSF to neutrophils.
 None of the MoAbs neutralized interleukin-3, G-CSF, or M-CSF.
 The locations of seven of the epitopes could be partially mapped with regard to the amino acid structure by determining reactivity to GM-CSF synthetic peptides or to human-mouse chimeric GM-CSFs.
 The neutralizing antibodies were found to map to amino acids 40-77, 78-94, or 110-127.
 Thus, these MoAbs are useful to identify functional domains of GM-CSF and in identifying regions that are likely to be involved in receptor interaction.
",19
3276,"Inhibition of hydroxymethylglutaryl coenzyme A reductase activity induces a paradoxical increase in DNA synthesis in myeloid leukemia cells.
 The effects of competitive inhibition of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase by compactin on the in vitro proliferation of peripheral blood myeloid leukemia cells were studied using the cells from 45 patients with acute myeloid leukemia or chronic myelogenous leukemia in blast phase.
 The cells from 58% of these patients showed a dose-related inhibition of DNA synthesis when incubated with compactin.
 Unexpectedly, cells from 18% of the patients were resistant to the inhibitory effects of compactin on DNA synthesis and responded to the HMG CoA reductase inhibition with an actual increase in the incorporation of 14C-labeled thymidine into DNA.
 Another 18% of the patients studied displayed both inhibition and stimulation of DNA synthesis in a biphasic response depending on the particular concentration of compactin used.
 The maximum enhanced rates of cellular DNA synthesis were observed with lower compactin concentrations (5 x 10(-7) mol/L) than were required for maximum inhibition of DNA synthesis (10(-5) mol/L).
 Leukemia cells displaying a stimulated response to compactin had a significantly lower baseline DNA synthetic rate than did cells that showed an inhibitory response of DNA synthesis to compactin.
 There was no correlation between these cells' varying DNA synthetic response to compactin and measures of baseline HMG CoA reductase activity or acetate conversion to cholesterol.
 Whereas the observation of cellular DNA synthesis stimulation by HMG CoA reductase inhibition has not been observed in other mammalian cells and seems paradoxical, explanations may emerge in light of our growing knowledge concerning the importance of isoprenylation for the function of certain cell regulatory proteins.
",19
3277,"Epstein-Barr virus infection precedes clonal expansion in Burkitt's and acquired immunodeficiency syndrome-associated lymphoma.
 The Epstein-Barr virus (EBV) is associated with distinct forms of human lymphoid malignancies, including the endemic (eBL) and sporadic forms of Burkitt's lymphoma (sBL) and acquired immunodeficiency syndrome-associated non-Hodgkin lymphoma (AIDS-NHL).
 However, whether EBV has a pathogenetic role in these tumors or is a passenger virus has not been conclusively demonstrated.
 One element to distinguish between these two possibilities is to determine whether EBV infection has preceded and, thus, possibly contributed to clonal expansion, or whether infection has occurred after clonal expansion and thus is unlikely to contribute to pathogenesis.
 Toward this end we analyzed the structure of the heterogeneous genomic termini of EBV as markers of clonal infection in a panel of eBL (11 cases), sBL (9 cases), and AIDS-NHL (10 cases) biopsies.
 We show that EBV termini are uniformly clonal in sBL, eBL, and AIDS-NHL, strongly suggesting that EBV infection has preceded and, thus, most likely contributed to clonal expansion in these malignancies.
",19
3278,"Stages I and II diffuse large cell lymphomas: prognostic factors and long-term results with CHOP-bleo and radiotherapy.
 One hundred forty-seven patients with Ann Arbor stages I and II diffuse large cell lymphoma (DLCL) were treated with combination chemotherapy consisting of cyclophosphamide, doxyrubicin, prednisone, and low-dose bleomycin (CHOP-Bleo) and involved-field radiation (IF XRT) between 1974 and 1984.
 A complete remission (CR) was attained by 54 of 57 patients with stage I disease and by 78 of 90 patients with stage II disease.
 Thirty-five patients had relapsing disease that occurred within 3 years in 31.
 The overall 10-year survival rate, counting all deaths, for patients with stage I was 72% as compared with 43% for patients with stage II (P less than .01).
 Determinate survival rates, censoring eight unrelated deaths, were similar to the overall survival rates: 77% and 51%, respectively.
 A multivariate analysis identified three independent prognostic factors: age, tumor extent, and serum lactic dehydrogenase (LDH) level.
 When the combined effect of tumor extent and LDH level were taken into consideration in the analysis, three risk groups for survival were identified.
 The best group, which consists of patients with minimum tumor and normal LDH levels, had a 10-year determinate survival of 79%.
 Patients with extensive tumors and elevated LDH levels had the poorest survival rate of 44%.
 An intermediate-risk group with a determinant survival of 62% was composed of patients with either extensive tumors or elevated LDH levels.
 These differences demonstrate the need to develop different treatment strategies based on risk factors for survival for patients with apparently localized Ann Arbor stages I/II DLCL.
",19
3279,"Individualized aerobic and high intensity training for asthmatic children in an exercise readaptation program. Is training always helpful for better adaptation to exercise?
 In order to define the role of individualized training intensity in a conditioning program for asthmatic children, we have trained seven asthmatics (age = 11.4 +/- 1.8 years) at their ventilatory threshold (VTh) intensity level for a three-month period (aerobic training) and at maximal intensity also for three months (high intensity training).
 VTh is the point at which a nonlinear increase of VE occurs.
 Another group of seven asthmatics (age = 11.4 +/- 1.5) served as control subjects.
 Cardiopulmonary fitness was determined on a cycle ergometer before and after each training session.
 This study demonstrated that aerobic training, correctly adapted to the child's physical ability, induces the following: (1) a rapid and marked cardiovascular fitness increase; and (2) a decrease in VE over a given work range so that VTh is increased.
 This is of great importance because hyperventilation is a major determinant of exercise-induced bronchospasm.
 In contrast, even if high intensity training is well tolerated in an indoor swimming pool, the long-term effects are unsuitable for asthmatic children because the decrease of VTh will involve an increase of hyperventilation, even when exercise is performed at submaximal intensity.
",19
3280,"Combined zidovudine and interferon-alpha treatment in patients with AIDS-associated Kaposi's sarcoma.
 The effectiveness of addition of interferon-alpha (IFN-alpha) to zidovudine in patients with AIDS-associated Kaposi's sarcoma was assessed in a non-randomized, phase II clinical trial.
 Twenty-one patients were treated with oral zidovudine (600 mg daily) and IFN-alpha was increased to 18 MU daily for another 4 weeks.
 Only one of the 20 evaluable patients achieved a partial response at 8 weeks, that lasted for 3 months.
 Despite IFN-alpha dose escalation in six patients, no further responses were seen.
 While myelotoxicity was mild, fatigue was the dose-limiting side-effect that prevented dose escalation in seven eligible patients.
 The combined treatment did not result in a decrease in HIV-Ag.
 In summary, our results indicate that the addition of IFN-alpha to zidovudine in patients with AIDS-associated Kaposi's sarcoma is not an efficacious treatment.
",19
3281,"scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair.
 C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B cell-mediated immunity, apparently as a result of defective V(D)J joining of the immunoglobulin and T-cell receptor gene elements.
 In the present studies, we have defined the tissue, cellular, and molecular basis of another characteristic of these mice: their hypersensitivity to ionizing radiation.
 Bone marrow stem cells, intestinal crypt cells, and epithelial skin cells from scid mice are 2- to 3-fold more sensitive when irradiated in situ than are congenic BALB/c or C.B-17 controls.
 Two independently isolated embryo fibroblastic scid mouse cell lines display similar hypersensitivities to gamma-rays.
 In addition, these cell lines are sensitive to cell killing by bleomycin, which also produces DNA strand breaks, but not by the DNA crosslinking agent mitomycin C or UV irradiation.
 Measurement of the rejoining of gamma-ray-induced DNA double-strand breaks by pulsed-field gel electrophoresis indicates that these animals are defective in this repair system.
 This suggests that the gamma-ray sensitivity of the scid mouse fibroblasts could be the result of reduced repair of DNA double-strand breaks.
 Therefore, a common factor may participate in both the repair of DNA double-strand breaks as well as V(D)J rejoining during lymphocyte development.
 This murine autosomal recessive mutation should prove extremely useful in fundamental studies of radiation-induced DNA damage and repair.
",19
3282,"Very long charge runs in systemic lupus erythematosus-associated autoantigens.
 Systemic lupus erythematosus and other chronic systemic autoimmune diseases are associated with circulating autoantibodies reactive with a limited set of mostly nuclear proteins.
 Using rigorous statistical methods we have identified segments of highly significant charge concentration in the majority of the characteristic nuclear and cytoplasmic autoantigens.
 Extremely long runs of charged residues, including some sequences of greater than 20 consecutive charged residues (purely acidic or mixed basic and acidic), occur in about a third of these proteins, whereas equivalent runs are found in less than 3% of other mammalian proteins.
 The other sequences have less extreme charge clusters, the type and location of which are often conserved between several otherwise nonsimilar antigens.
 We propose that supercharged surfaces render the targeted host proteins strongly immunogenic and that antinuclear antibody profiles might result from chronic exposure to intracellular contents, possibly in conjunction with crossreactive viral products.
 The limited number of potential systemic autoantigens may partly be due to the rarity of requisite charge properties.
",19
3283,"AIDS epidemiology: inconsistencies with human immunodeficiency virus and with infectious disease.
 The newly defined syndrome AIDS includes 25 unrelated parasitic, neoplastic, and noninfectious indicator diseases.
 Based on epidemiological correlations, the syndrome is thought to be due to a new, sexually or parenterally transmitted retrovirus termed human immunodeficiency virus (HIV).
 The following epidemiological data conflict with this hypothesis.
 (i) Noncorrelations exist between HIV and AIDS; for example, the AIDS risks of infected subjects vary greater than 10-fold with their gender or country.
 Abnormal health risks that are never controlled as independent AIDS causes by AIDS statistics, such as drug addiction and hemophilia, correlate directly with an abnormal incidence of AIDS diseases.
 Above all, the AIDS diseases occur in all risk groups in the absence of HIV.
 (ii) American AIDS is incompatible with infectious disease, because it is almost exclusively restricted to males (91%), because if it occurs, then only on average 10 years after transfusion of HIV, because specific AIDS diseases are not transmissible among different risk groups, and because unlike a new infectious disease, AIDS has not spread exponentially since the AIDS test was established and AIDS received its current definition in 1987.
 (iii) Epidemiological evidence indicates that HIV is a long-established, perinatally transmitted retrovirus.
 HIV acts as a marker for American AIDS risks, because it is rare and not transmissible by horizontal contacts other than frequent transfusions, intravenous drugs, and repeated or promiscuous sex.
 It is concluded that American AIDS is not infectious, and suggested that unidentified, mostly noninfectious pathogens cause AIDS.
",19
3284,"Frequency of nonparenteral occupational exposures to blood and body fluids before and after universal precautions training.
 PURPOSE: During annual periods before and after Universal Precautions training, we compared the frequency of health care workers' self-reported cutaneous exposures to blood and various body substances from any patient and from patients presumed infected with human immunodeficiency virus type 1 (HIV-1).
 SUBJECTS AND METHODS: Self-reported cutaneous exposures to blood, sputum, urine, feces, and other body substances were evaluated separately in 559 workers during the first survey and 269 workers during the second.
 RESULTS: Mean annual blood exposures decreased from 35.8 to 18.1, and mean annual exposures to all substances decreased from 77.8 to 40.0 (p less than 0.001 for both determinations).
 Two matched analyses of a subset of 200 participants who completed both surveys had similar results.
 Reported exposures to blood, presumably infectious blood, sputum, presumably infectious sputum, and urine were significantly decreased.
 Participants were tested for antibodies to HIV-1; no participant reporting cutaneous exposures acquired HIV-1 infection.
 The upper bound for the 95% confidence interval for the risk of HIV-1 infection associated with a single cutaneous exposure was 0.04% for blood presumed to contain HIV-1 and 0.02% for any body substance presumed to contain HIV-1.
 CONCLUSIONS: These data suggest that Universal Precautions training significantly decreased but did not eliminate cutaneous exposures to blood and body substances.
 The results further suggest that the risk for HIV-1 infection associated with cutaneous exposures is substantially lower than the risk associated with parenteral exposures.
",19
3285,"Major differences in the dynamics of primary and secondary progressive multiple sclerosis.
 In patients with primary and secondary progressive multiple sclerosis (MS), major differences in the pattern and extent of abnormality on cerebral magnetic resonance imaging (MRI) between the two groups have recently been demonstrated.
 In the present study, 24 patients, matched for age, sex, duration of disease, and disability, had serial gadolinium diethylenetriaminepentaacetic acid-enhanced MRI over a 6-month period.
 The 12 patients in the secondary progressive group had a total of 109 new lesions over this time (18.2 lesions per patient per year) and 87% of these enhanced.
 Enhancement also occurred within and at the edge of preexisting lesions.
 In contrast, only 20 new lesions were seen in the primary progressive group (3.3 lesions per patient per year) and only one of these enhanced.
 There was no difference in the degree of clinical deterioration between the two groups over the 6-month period.
 These findings may indicate a difference in the dynamics of disease activity between the two forms of progressive MS, particularly in relation to the inflammatory component of the lesions, and have important implications for the selection of patients and the monitoring of disease activity in therapeutic trials.
",19
3286,"Correlation of phasic muscle strength and corticomotoneuron conduction time in multiple sclerosis.
 Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis.
 Two tests of manual dexterity of the same hand also were studied: the Purdue pegboard test, and the maximal frequency of a scissors movement of the thumb and index finger.
 The patients had normal strength or minimal weakness of the intrinsic muscles of the hand on clinical examination.
 The mean central motor conduction times for the adductor pollicis muscle for the patients were longer than normal, the peak twitch force of the adductor pollicis muscle evoked by cortical stimulation and the maximum force of a phasic voluntary contraction of the adductor pollicis muscle were smaller than normal.
 There were strong correlations between all these measures.
 Central motor conduction time in the patients was inversely correlated with voluntary phasic force and the twitch force after cortical stimulation.
 That is, the longer the central motor conduction time, the weaker the force.
 Prolonged central motor conduction time is likely to be accompanied by conduction block in corticomotoneuron pathways.
 The correlation of central motor conduction time with voluntary phasic force and the twitch force most likely reflects the degree of conduction block and temporal dispersion rather than delay in conduction per se.
 These results indicate that objective assessments of phasic muscle strength may reveal correlations with central motor conduction time that are not evident on conventional clinical examination which assesses tonic muscle contraction strength.
",19
3287,"Systemic lupus erythematosus in Iceland 1975 through 1984. A nationwide epidemiological study in an unselected population.
 In a nationwide study the 1982 revised ARA criteria were applied for the classification of systemic lupus erythematosus (SLE).
 This unselected group of patients included all cases diagnosed and managed in hospitals, as well as outside hospitals in Iceland over the 10-year period from 1975 to 1984.
 Seventy-six new cases were found, with an incidence of 5.9 and 0.8/100,000 for females and males at risk, respectively.
 The mean age at diagnosis was 46.6 years.
 Twenty-five percent of the patients would have been missed had the study included hospital patients only.
 A clinical pattern different from previous studies was found as illustrated by a low incidence of kidney disease; nephritis was found in 20% of patients.
 Comparison with a former study on SLE in Iceland shows an actual increase in incidence over a period of 10 years.
 The 5 year survival was 84% and the 10 year survival 78%.
",19
3288,"Juvenile systemic lupus erythematosus among Egyptian children.
 A prospective analysis of 30 Egyptian children with systemic lupus erythematosus (SLE) was conducted throughout a 3 year period.
 The average followup period was 13 months.
 The age of onset ranged from 8 to 14 years.
 Most cases presented with more than one of the classical features of the disease.
 However, 23.3% presented primarily with major organ involvement.
 One case presenting with cardiac tamponade is reported in our series.
 The clinical and laboratory manifestations of the disease are presented, though more complete studies are required to confirm any possible differences in these disease manifestations compared with those found in other populations.
 Contrary to the frequently held view, our results suggest that childhood onset SLE is not rare in Africa or at least some parts of the continent.
",19
3289,"Diagnosis of sulfite and aspirin sensitivity.
 In addition to the well-recognized allergic responses of individuals to high mol wt substances, such as pollens, molds, and animal dander, susceptible asthmatics may also experience adverse reactions to low mol wt substances such as sulfites, ASA, and NSAIDs.
 The diagnosis of sulfite and aspirin sensitivity can only be made by appropriately conducted provocative challenge.
 Every precaution should be taken to assure the safety of the patients, since life-threatening reactions can occur.
 A better understanding of the mechanism or mechanisms involved in the adverse reactions to these substances will not only provide information to better diagnose the reaction, but also improve our understanding of the treatment of asthma.
",19
3290,"Using pulmonary function testing in the diagnosis and treatment of asthma.
 Asthmatics have remarkable changes in their pulmonary function in response to numerous external stimuli and internal controls.
 Serial pulmonary function testing in the office, hospital, at home, or the work place allows the objective measurement that is necessary to intelligently diagnose and treat these patients.
 Once the patient and the physician understand how to use the techniques for monitoring the degree of airways obstruction, they become a key in medical management decisions.
",19
3291,"Human growth hormone-variant is a biologically active somatogen and lactogen.
 The human GH-variant (hGH-V) gene, a member of the GH-PRL gene family, is expressed by the placenta during the second and third trimesters of gestation.
 The secreted hGH-V protein differs from pituitary GH (hGH-N) by only 13 amino acids.
 We have previously demonstrated that hGH-V can bind to both somatogen and lactogen cell surface receptors in vitro, but that the ratio of its somatogen to lactogen receptor-binding affinities is substantially higher than that of hGH-N.
 We now characterize the somatogen and lactogen bioactivities of hGH-V and contrast them to the bioactivity of hGH-N.
 Somatogen bioactivity was assayed by stimulation of weight gain in hypophysectomized rats, and lactogen bioactivity was assayed by the mitogenic response of the Nb2 lymphoma cell line.
 While the average increase in rat body weight in response to a fixed concentration of hormone was comparable using either hGH-V or hGH-N, the mitotic response of the lactogen-inducible Nb2 cells was significantly less for hGH-V.
 The comparable somatogen, but lower lactogen, bioactivity of hGH-V relative to hGH-N parallels the previously reported receptor binding profiles of the two hormones and suggests that hGH-V has the potential to perform a unique role during human gestation.
",19
3292,"The sensitized liver represents a rich source of endogenous leukotrienes.
 The ability of livers to produce endogenous leukotrienes after immunological stimulation was tested with organs from rats and guinea pigs.
 Passive sensitization of rats in vivo with monoclonal murine antidinitrophenol-IgE before antigen challenge in the isolated perfused liver system elicited a rapid hepatic production and biliary excretion of leukotrienes as judged by radioimmunoassay after separation of individual leukotrienes by high-performance liquid chromatography.
 Within 10 min after antigen infusion, mainly leukotriene C4, but also leukotriene D4 and N-acetyl-leukotriene E4, appeared in the bile.
 The biliary excretion rate of antigen-induced cysteinyl leukotrienes rose from less than 2 pmol.min-1.(kg body mass)-1 before challenge to about 30 pmol.min-1.(kg body mass)-1 for 20 min before it declined toward prechallenge level.
 Quantitatively similar hepatic production of cysteinyl leukotrienes was elicited in isolated perfused guinea pig livers challenged with ovalbumin after active sensitization of the animals with ovalbumin plus Al(OH)3.
 To exclude extrahepatic contributions to the observed leukotriene production, both passive sensitization with anti-dinitrophenol-IgE and subsequent antigen challenge were performed on isolated rat livers perfused with blood-free medium.
 Such exclusively hepatic sensitization and challenge also resulted in massive production of leukotrienes.
 The biliary excretion rate of cysteinyl leukotrienes amounted to approximately 20 pmol.min-1.(kg body mass)-1 during the 10 to 20 min period after antigen challenge as compared with less than 1 pmol.min-1.(kg body mass)-1 before challenge.
",19
3293,"Transforming growth factor-beta and suppression of humoral immune responses in HIV infection.
 We reported previously that PBMC from HIV+ patients spontaneously release increased levels of TGF beta 1, contributing to defects in cellular immune responses.
 This study defines the implications of TGF beta overexpression for humoral immunity in HIV infection.
 We found that upon Staphylococcus aureus Cowan I (SAC) stimulation of cells from HIV+ donors, B-lymphocyte proliferative responses were decreased.
 This deficiency correlated closely (r = 0.7, P less than 0.001) with increased TGF beta secretion by PBMC from HIV-infected donors.
 Conditioned medium from HIV+ PBMC and purified TGF beta 1 had similar inhibitory effects on SAC- or EBV-induced B-cell proliferation, and B cells from HIV-infected donors were as sensitive to inhibition by TGF beta as cells from normal donors.
 Antibodies to TGF beta 1 neutralized the inhibitory effect of HIV+ culture supernatants on normal B cells and increased low proliferative responses by HIV+ cells.
 Using PWM as stimulus for B cell differentiation, it was shown that activated TGF beta from HIV+ PBMC is able to significantly reduce the induction of immunoglobulins and this effect was also abrogated by anti-TGF beta.
 These studies support the concept that in HIV infection, TGF beta is a potent suppressor, not only of the cellular, but of the humoral immune responses as well.
",19
3294,"An autocrine role for urokinase in phorbol ester-mediated differentiation of myeloid cell lines.
 The human myeloid cell line HL60 secretes urokinase-type plasminogen activator (uPA) and expresses its receptor.
 When stimulated with phorbol myristate acetate (PMA), both secretion of uPA and the expression of its receptor are up-regulated, and these cells differentiate to an adherent phenotype.
 This adhesive response is markedly reduced in the presence of uPA antibodies.
 The PMA response is restored by the addition of native uPA, an amino-terminal fragment of uPA (residues 1-143) devoid of proteolytic activity, or a synthetic peptide (residues 12-32) from the uPA growth factor domain known to mediate receptor binding.
 In contrast, the addition of catalytically active low molecular weight uPA, which is missing the growth factor domain, or a peptide from the catalytic domain (residues 247-266) is ineffective.
 The influence of uPA antibodies on a second marker of macrophage differentiation, cysteine proteinase activity, was also examined.
 Cysteine proteinase activity of HL60 cells is increased in PMA-treated cells after 24 h but it fails to increase in the presence of anti-uPA.
 This increase in cathepsin B-like activity is also restored by exogenous uPA.
 These experiments indicate that an autocrine interaction of the growth factor domain of uPA with its receptor mediates an essential step in PMA-mediated myeloid cell differentiation.
",19
3295,"Binary methods for continuous outcomes: a parametric alternative.
 Often a ""disease"" or ""state of disease"" is defined by a subdomain of a continuous outcome variable.
 For example, the subdomain of diastolic blood pressure greater than 90 mmHg has been used to define hypertension.
 The classical method of estimating the risk (or prevalence) of such defined disease states is to dichotomize the outcome variable according to the cutoff value.
 The standard statistical analysis of such risk of disease then exploits methods developed specifically for binary data, usually based on the binomial distribution.
 We present a method, based on the assumption of a Gaussian (normal) distribution for the continuous outcome, which does not resort to dichotomization.
 Specifically, the estimation of risk and its variance is presented for the one- and two-sample situations, with the latter focusing on risk differences and ratios, and odds ratios.
 The binomial approach applied to the dichotomized data is found to be less efficient than the proposed method by 67% or less.
 The latter is found to be very accurate, even for small sample sizes, although rather sensitive to substitutions of the underlying distribution by thicker tailed distributions.
 Canadian total cholesterol data are used to illustrate the problem.
 For the one-sample case, the approach is illustrated using data from a study of the arterial oxygenation of 20 patients during one-lung anesthesia for thoracic surgery.
 For the two-sample case, data from a prognostic study of the renal function of 87 lupus nephritic patients are used.
",19
3296,"A phase I trial of monoclonal antibody M195 in acute myelogenous leukemia: specific bone marrow targeting and internalization of radionuclide.
 Ten patients with myeloid leukemias were treated in a phase I trial with escalating doses of mouse monoclonal antibody (mAb) M195, reactive with CD33, a glycoprotein found on myeloid leukemia blasts and early hematopoietic progenitor cells but not on normal stem cells.
 M195 was trace-labeled with iodine-131 (131I) to allow detailed pharmacokinetic and dosimetric studies by serial sampling of blood and bone marrow and whole-body gamma-camera imaging.
 Total doses up to 76 mg were administered safely without immediate adverse effects.
 Absorption of M195 onto targets in vivo was demonstrated by biopsy, pharmacology, flow cytometry, and imaging; saturation of available sites occurred at doses greater than or equal to 5 mg/m2.
 The entire bone marrow was specifically and clearly imaged beginning within hours after injection; optimal imaging occurred at the lowest dose.
 Bone marrow biopsies demonstrated significant dose-related uptake of M195 as early as 1 hour after infusion in all patients, with the majority of the dose found in the marrow.
 Tumor regressions were not observed.
 An estimated 0.33 to 1.0 rad/mCi 131I was delivered to the whole body, 1.1 to 6.1 rad/mCi was delivered to the plasma, and up to 34 rad/mCi was delivered to the red marrow compartment.
 131I-M195 was rapidly modulated, with a majority of the bound immunoglobulin G (IgG) being internalized into target cells in vivo.
 These data indicate that whole bone marrow ablative doses of 131I-M195 can be expected.
 The rapid, specific, and quantitative delivery to the bone marrow and the efficient internalization of M195 into target cells in vivo also suggest that the delivery of other isotopes such as auger or alpha emitters, toxins, or other biologically important molecules into either leukemia cells or normal hematopoietic progenitor cells may be feasible.
",19
3297,"Program directors' attitudes towards residents' care of patients who have AIDS.
 OBJECTIVE: To evaluate the educational strategies and experiences of residency programs regarding the training of primary care providers in the care of patients who have AIDS.
 DESIGN: Cross-sectional, self-administered questionnaire survey.
 SETTING: Survey conducted November 1988-April 1989.
 PARTICIPANTS: All 771 non-military U.S.
 internal medicine and family medicine program directors were surveyed; 80% responded.
 INTERVENTIONS: None.
 MEASUREMENTS AND MAIN RESULTS: While 91% of the directors felt that primary care of AIDS patients was an important educational experience and 94% reported that their programs usually had AIDS inpatients, only 16% reported that the majority of trainees cared for AIDS patients in their continuity clinics.
 Even at programs that typically had six or more AIDS inpatients, only 26% of directors reported that most residents had cared for an AIDS patient in their continuity clinics.
 Among the 57% who did not believe or were unsure whether their residents were adequately trained in AIDS ambulatory care, only 38% reported improving resident education in this area to be a high priority.
 Among the 39% who did not encourage residents' assumption of primary care, 60% had at least one of the following concerns: AIDS care too stressful for residents (24%), AIDS care too complicated for generalists (31%), or clinic faculty not qualified to supervise residents' caring for AIDS patients (39%).
 CONCLUSION: Although program directors view education in AIDS ambulatory care as important, most do not believe that residents are adequately trained, many do not encourage residents' assumption of primary care of AIDS patients, and residents usually have not provided such care in their programs.
 Strategies to augment residents' ambulatory experience in AIDS care are needed.
",19
3298,"Pathogenesis and recent therapeutic approaches to graft-versus-host disease.
 Effective prophylaxis of acute GVHD should bring about improved patient survival by decreasing severe infections during the first 3 months after transplantation and reducing the incidence of chronic GVHD while not compromising the quality of hematopoietic engraftment or increasing the incidence of leukemic relapse by impairing the graft-versus-leukemia effect.
 None of the current approaches to prevention of GVHD succeed at meeting these expectations, although postgrafting immunosuppressive therapy comes closest to the ideal.
 The technique of T cell depletion has been very effective in reducing the incidence of GVHD, but conditioning programs must be developed that will be more successful at eliminating host immune and malignant cells.
 It is doubtful that this will be achieved with systemic chemotherapy and total body irradiation.
 Innovative approaches such as the use of monoclonal antibodies, either alone or linked to short-lived radioactive isotopes with short linear energy transfer, promise to result in less toxic but more efficient programs, not only providing better eradication of malignant disease but also ameliorating the problem of graft failure.
 It is conceivable, however, that it will never be possible to kill all leukemic cells with chemoradiotherapy of any form, and the graft-versus-leukemia effect may be essential.
 Perhaps in the future it will be possible to distinguish lymphocytes causing the graft-versus-leukemia effect from those causing GVHD, isolate them, and use them in attempts at therapy.
 In the meantime, postgrafting immunosuppressive drugs are used most frequently to prevent and treat GVHD, and steadily improving survival statistics can be expected.
",19
3299,"Effect of therapeutic plasma concentrations of theophylline on behavior, cognitive processing, and affect in children with asthma [published erratum appears in J Pediatr 1991 Jul;119(1 Pt 1):164]
 A double-blind, randomized, crossover study assessed the effects of theophylline on behavior, mood, and efficiency of cognitive processing.
 Thirty-one children aged 8 to 12 years with moderate asthma were randomly assigned to 10-day theophylline followed by placebo or to placebo followed by theophylline experimental conditions separated by 2-day washout periods.
 Theophylline plasma concentrations and pulmonary function tests were performed throughout the study.
 Cognitive functioning tests and self-report measures were administered at baseline and after each medication phase.
 Behavior ratings were obtained from parents and teachers.
 Parents' and teachers' ratings did not reflect a theophylline effect on attention or activity level; children's self-reports showed no changes in mood, and no statistically significant differences were found on measures of cognitive processing.
 Large individual differences in sensitivity to theophylline effects were present.
 Although most of the children tolerated theophylline well, those already having attentional or achievement problems appeared vulnerable to adverse effects.
 Individual response differences should be a focus of future studies.
",19
3300,"Travel in eastern Europe. Guidelines for patients.
 Some patients need medical preparation and physician counseling before traveling to eastern European countries.
 In addition to baseline immunizations, a measles booster, a polio booster, typhoid vaccination, and immune globulin prophylaxis against hepatitis A may be indicated.
 Advice should also be given regarding air pollution, contaminated food and water, civil unrest, motor vehicle mishaps, and each country's policy on HIV screening.
 Because the level of healthcare may be poor, contact with American or British embassies or consulates is recommended in an emergency.
",19
3301,"Ritual circumcision (Umkhwetha) amongst the Xhosa of the Ciskei.
 The Umkhwetha is an ancient custom of ritual circumcision still practised by the Xhosa people of Southern Africa.
 In 45 consecutive youths who required hospital admission the mortality rate was 9%.
 The complication seen over the years are reviewed and their management discussed.
",20
3302,"Recruitment of mononuclear cells by endothelial cell binding into wounded skin is a selective, time-dependent process with defined molecular interactions.
 Wound healing involves a complex series of interactions between cells in the dermis and epidermis, and important relationships exist between keratinocytes and resident dermal cells.
 Monocytes and lymphocytes secrete cytokines that are capable of stimulating dermal repair and influencing keratinocyte and fibroblast migration and proliferation, although the mechanism by which mononuclear cells are recruited into the wound is unknown.
 We have tested the hypothesis that in wounded skin specialized endothelial cells are induced to mediate peripheral blood mononuclear cell (PBMC) emigration from the vasculature into the dermis.
 For this purpose, partial-thickness wounds made with a keratome on the backs of domestic pigs were excised 0 to 9, 12, 15, and 21 d after wounding.
 The biopsies were then tested for the capacity to adhere selectively to PBMC.
 The results indicated that PBMC overlaid onto sections of wounds from day 4 to 15 adhered selectively to dermal endothelium, with two distinct peaks of adherence observed on day 7 and day 12.
 In contrast, PBMC did not adhere to the tissue sections when overlaid onto frozen sections of normal skin or 0-, 1-, 2-, 3-, and 21-d-old wounded skin.
 Additional studies on the binding properties of PBMC subsets revealed that monocytes adhered maximally at day 7, whereas T cells adhered optimally at day 12 post-wounding.
 Furthermore, the adhesion process was energy and magnesium dependent but not calcium dependent and involved surface protein and carbohydrate moieties on PBMC surface.
 Pre-treatment of PBMC with monoclonal antibodies against the LFA-1 adhesive receptors inhibited the binding by greater than 80%, suggesting that LFA-1 adhesive receptors play an important role in the binding process.
 These studies provide evidence that the recruitment of monocytes and lymphocytes into wounds is an active, dynamic, and regulated process mediated at least in part by specific adhesive interactions between mononuclear leukocytes and dermal endothelial cells.
",20
3303,"Comparison of functional recovery after nonsurgical and surgical treatment of condylar fractures.
 This article evaluates 16 cases of condylar fracture treated surgically, comparing them with the 20 cases treated nonsurgically, with a 2-year follow-up.
 Although severely displaced and luxated fractures were involved in the surgical group with rigid internal fixation, satisfactory postoperative function and occlusion were achieved at the same level as in the nonsurgical group, without severe complications.
",20
3304,"Effects of long-term administration of haloperidol on electrophysiologic properties of rat mesencephalic neurons.
 Haloperidol (1.5-1.7 mg/kg/day) was administered to rats via their drinking water for periods of either 4 weeks or 13 to 14 months, after which the animals were withdrawn from the neuroleptic for 1 or 2 weeks, respectively.
 Rats given haloperidol for 13 to 14 months exhibited significantly more perioral dyskinesias than controls.
 Single-unit extracellular recordings were obtained from the substantia nigra and ventral tegmental area in subjects under urethane anesthesia.
 After 1 month and after 1 year of treatment, a significant decrease in the mean firing rate of substantia nigra pars reticulata neurons was found.
 Subtle changes in the response of pars reticulata neurons to striatal stimulation were seen after extended haloperidol intake.
 No consistent effects of haloperidol administration for 4 weeks or 13 to 14 months were found for either the number of spontaneously active dopamine neurons or their firing rates.
 Histopathologic assessment of tissue from dorsomedial, dorsolateral and ventrolateral sectors of the striatum revealed no significant effect of long-term haloperidol treatment on neuronal cell counts.
 The results are discussed with reference to neuroleptic-induced tardive dyskinesias.
",20
3305,"Progress in characterizing anatomic injury.
 A three-valued description of anatomic injury is presented.
 Anatomic profile (AP) components A, B, and C summarize serious injuries (greater than AIS 2) to the head/brain or spinal cord; to the thorax or front of the neck; and all remaining serious injuries.
 Relationships between AP components and survival rate reaffirm the seriousness of head injury.
 Logistic function models relating AP components and the Injury Severity Score (ISS) to survival probability were based on 20,946 Major Trauma Outcome Study (MTOS) patients (9.2% mortality rate) submitted through 1986.
 Model performance comparisons were based on 5,939 MTOS patients (7.8% mortality rate) submitted during 1987.
 The AP better discriminated survivors from nonsurvivors and provided a 31% increase in sensitivity when compared with the ISS.
 Neither the ISS nor the AP alone reliably predict patient outcome.
 The predictive power of methods for estimating patient survival probability which include physiologic indices or profiles, patient age, and an anatomic profile should be compared with current methods.
 The AP, which is based on the severity and location of all serious injuries, provides a more rational basis for comparing patient samples than the ISS.
",20
3306,"Injured drivers and alcohol use: culpability, convictions, and pre- and post-crash driving history.
 The culpability, crash-related traffic convictions, and pre- and post-crash driving records of a group of injured impaired (blood alcohol level greater than 80 mg/dl) drivers (N = 58) who were admitted to a Level I trauma center were compared with a group of admitted unimpaired drivers (N = 92).
 Both groups of drivers were 21 years of age or older, sustained moderate injuries (defined as having no injury of the brain, spinal column or cord, extremity, or pelvis with an Abbreviated Injury Score of greater than 2), and were discharged home.
 In the 140 crashes in which culpability was clearly defined, the impaired drivers caused a significantly greater percentage of their crashes (92.7%) compared to unimpaired (64.7%) drivers (p less than 0.001).
 Of the 55 unimpaired drivers who were considered culpable of causing their crashes, 12.7% received a traffic conviction compared with 39.2% of the 51 culpable impaired drivers.
 The mean number of total pre-crash traffic violations was higher for impaired drivers than for unimpaired drivers (p less than 0.01).
 While the mean number of total post-crash convictions for unimpaired and impaired was not significantly different, the mean number of pre- and post-crash alcohol convictions was significantly higher for impaired drivers compared to unimpaired drivers (p less than 0.02).
 The data suggest that injury protects from legal prosecution and does not alter impaired driving practices.
",20
3307,"The effect of prehospital fluids on survival in trauma patients.
 The effect of prehospital intravenous fluids upon survival was studied in 6,855 trauma patients.
 Mean prehospital time was 36 minutes in both the group of patients who received fluids and the group that did not.
 The volume of fluid administered was not significantly different in the group who survived compared to those who died.
 Eighty-five per cent of the patients had an Injury Severity Score (ISS) less than 25 and the mortality rate in the 56% of patients in this group who received fluids was similar to that of the patients who did not receive fluids (0.7% vs.
 0.5%).
 Twelve per cent of the patients had an ISS between 25 and 50.
 Sixty per cent of these patients received fluids and the mortality rates were similar to the patients who received fluids compared to those who did not (23% vs.
 22%).
 Three per cent of patients had an ISS of greater than 50 and the mortality rate was highest in this group but was not influenced by the administration of fluids (90% vs.
 86%).
 Comparison of groups with similar probability of survival according to the TRISS methodology also failed to show an influence of fluid administration on survival.
 The mortality rate in patients with an initial systolic blood pressure (BP) of 90 torr or greater was compared to the rate in patients with an admission BP less than 90 torr.
 Although hypotension was associated with a significantly higher mortality rate, the administration of fluids had no influence on this rate.
",20
3308,"Blunt trauma in adults and children: a comparative analysis.
 Trauma remains the major cause of death in children and young adults.
 Adult and pediatric patients differ significantly in both mechanism of and physiologic response to injury.
 We reviewed the records of all consecutive adult and pediatric blunt trauma patients admitted to a major metropolitan trauma center for a 10-year period.
 An extensive computerized database has been maintained for all patients since 1977.
 A comparative statistical analysis of mechanism of injury, specific organ injury, and clinical outcome was performed.
 Altogether, 1,722 adults and 289 children were treated during the study period.
 Blunt trauma accounted for 82.8% of adult and 94.3% of pediatric injury (p = 0.00005), and only these patients were considered for analysis.
 Diagnostic peritoneal lavage was performed in 249 children and 1,464 adults, with a respective accuracy of 99.6% and 97.2%.
 Mechanism of injury was comparable for both groups, although children were far more likely to be injured by falls, bicycle accidents, or struck by an automobile.
 Comparative analysis of specific injuries demonstrated significantly fewer pediatric chest (p = 0.001), spine (p = 0.03), and pelvic (p = 0.003) injuries.
 Central nervous system (CNS) injury in children was a strong determinant of outcome: serious pediatric CNS trauma was associated with a tenfold increase in mortality.
 Mortality for children in the absence of CNS injury was less than 3%.
 Spinal injury also appeared to be a predictor of poor outcome in the pediatric population, with an associated mortality of greater than 50%.
 Overall, survival was age independent (82.5% of adults and 85.8% of children were survivors.
",20
3309,"Alcohol intoxication, injuries, and dangerous behaviors--and the revolving emergency department door.
 Suicides, homicides, motor vehicle crashes, and other violent deaths and injuries are linked inextricably to alcoholism.
 The association of injury and alcoholism should be particularly obvious to Emergency Department (ED) physicians.
 We sought to determine the extent to which intoxicated patients in an ED were properly diagnosed, counselled, and referred for substance abuse care.
 We reviewed the charts of 153 consecutive patients seen in a teaching hospital ED who had blood alcohol levels above 100 mg%.
 Most were male (70%), white (62%), young (mean age, 34 years) and severely intoxicated (mean BAL, 245; range, 109-558 mg%).
 Forty-six per cent of visits were for trauma; half of the patients were victims of violent assaults.
 The intoxicated patients received extensive medical and surgical management: an average of five tests or X-rays were performed per patient; 75% received at least one medication; at discharge 48% were referred for followup to medical or surgical clinics.
 In contrast, few patients were evaluated for dangerous behaviors or referred for treatment of alcoholism: only 19 patients (12.5%) were asked about depression, suicide, or homicide; 15% were advised to stop drinking; 13% received a referral to a psychiatrist, mental health worker, or alcohol rehabilitation facility.
 Forty-seven per cent of patients received ""stat"" intravenous thiamine (although the Wernicke-Korsakoff syndrome is rare).
 In contrast, only 16% received a stat on-site psychiatric consultation (although dangerous behaviors are common in alcoholics).
 There was a strong, statistically significant negative association between the occurrence of an injury and the decision to initiate treatment and referrals for alcoholism.
",20
3310,"Oxygen delivery and consumption in head-injured and multiple trauma patients.
 Critically ill patients often demonstrate that whole body oxygen consumption (VO2) is dependent on oxygen delivery (DO2).
 In this retrospective study, the relationship of VO2 to DO2 in patients with isolated head injury (HI, n = 18) was compared to that in patients with multiple trauma (MT, n = 60) without serious head injury.
 Mean pulmonary capillary wedge pressure, central venous pressure, arterial PCO2, cardiac index, and oxygen delivery were significantly lower in HI, but oxygen consumption was not different in the groups.
 In both groups, changes in DO2 (delta DO2) within each patient were significantly correlated with changes in VO2 (delta VO2) in that same patient.
 This relationship was not different between the HI patients, (delta VO2 = (0.20 +/- 0.02) delta DO2), and the MT patients (delta VO2 = (0.17 +/- 0.01) delta DO2).
 When these groups were further divided into those with high hematocrit (greater than 32%) and low hematocrit (less than 32%), HI patients with a low hematocrit demonstrated a steeper regression slope, with 26 +/- 3% of the DO2 change being reflected in the VO2 change.
 This was significantly greater than the slope in HI patients with high hematocrit (13 +/- 3%) and the MT patients at high (19 +/- 2%) or low (16 +/- 2%) hematocrits.
 These data show a correlation between changes in oxygen delivery and consumption that is similar in both head-injury patients and multiple trauma patients without serious head injury.
 This relationship was greatest in head-injured patients at low hematocrit.
 This relationship of VO2 and DO2 in both groups suggests an influence of neurohumoral factors rather than local tissue phenomena.
",20
3311,"Skeletal transfixation in treatment of comminuted fractures of the distal end of the radius in the elderly.
 Ninety-five patients (71 females and 24 males), average age, 69 years (35-92 years), with comminuted distal radial fractures were treated with transfixation wires (Kirschner wires) through the bases of metacarpals II-V and an above-elbow plaster cast.
 Two cases of early infections and four of Sudeck's dystrophy (4.2%) were encountered.
 Followup studies which lasted an average of 24 months (9-50 months) could be conducted on 77 patients.
 Using Sarmiento's ratings 27 patients fell into the very good category, 44, good, eight, fair, and two, poor.
 Although most of the cases were of the comminuted intra-articular fracture types, good results were achieved with this simple and quite straightforward method.
",20
3312,"Serum phospholipase A2 in patients with multiple injuries.
 Catalytic phospholipase A2 activity (CA-PLA2) and the concentration of immunoreactive pancreatic PLA2 (IR-PLA2) were measured in serum samples from 12 patients with multiple injuries (median Injury Severity Score: 41).
 CA-PLA2 was increased in all patients and positive correlations were found between the extent of the increase of CA-PLA2, mortality, and impairment of pulmonary function.
 IR-PLA2 values were slightly increased in the serum of nine patients with multiple injuries.
 Of these nine patients, eight had an additional blunt abdominal trauma.
 On the other hand, no relationship was found between IR-PLA2 and CA-PLA2 values.
 This finding was confirmed by immunoadsorption experiments with an antiserum to human pancreatic PLA2, which demonstrated that the increased serum levels of IR-PLA2 were not responsible for the increased CA-PLA2 values.
 The results suggest the existence of at least two immunologically different phospholipase A2 enzymes in sera of patients with multiple injuries.
",20
3313,"A reassessment of the peritoneal lavage leukocyte count in blunt abdominal trauma.
 Nine hundred and three patients undergoing diagnostic peritoneal lavage (DPL) over a 6-year period were retrospectively reviewed to evaluate the utility of the white blood cell (WBC) count in the lavage fluid.
 Eleven patients (1.2%) had dialysate WBC counts greater than 500/mm3, with erythrocyte counts less than 10(5)/mm3.
 Nine of these patients who were lavaged within 4 hours of injury had no intra-abdominal pathology.
 Two patients, lavaged after 4 hours, demonstrated intra-abdominal injury.
 Two hundred twenty-three patients (24.7%) had grossly clear dialysate which was not sent for laboratory analysis.
 None of these patients required laparotomy.
 We conclude that the WBC count in DPL fluid is of no diagnostic value in victims of blunt abdominal trauma who are lavaged within 4 hours of injury.
 In addition, laboratory analysis of clear dialysate is not required in these patients.
",20
3314,"Analysis of 46 intra-abdominal aortic injuries from blunt trauma: case reports and literature review.
 Blunt trauma causing aortic injury is infrequent and primarily involves the thoracic aorta.
 Abdominal aortic injury after blunt trauma is much less frequent and has a varied presentation.
 Within a 3-month period, our trauma unit diagnosed and treated two cases of abdominal aortic injury secondary to blunt trauma.
 One was a belted passenger in a motor vehicle accident, and one was secondary to a crush injury.
 The addition of these two cases brings the number found in the literature to 46.
 Reviewing these cases has emphasized the need for prompt recognition and treatment of this vascular catastrophe.
",20
3315,"Reduced dependency on arteriography for penetrating extremity trauma: influence of wound location and noninvasive vascular studies.
 Indications for arteriography in penetrating extremity trauma remain controversial.
 We reviewed our clinical experience in 454 patients (514 extremities) with penetrating trauma admitted during a prior 3 1/2-year period.
 Injuries were caused by stab wounds in 60 (11.7%) extremities and by gunshot wounds in 454 (88.3%) extremities.
 Thirty-three of the 60 stab wounds (55%) required urgent exploration, and 27 underwent arteriography.
 No arteriograms were positive for unsuspected arterial injury in this group.
 Forty-two of 454 gunshot wounds (9.3%) underwent mandatory exploration; arteriograms were performed on 412 extremities.
 Forty-four arteriograms (10.7%) demonstrated evidence of unsuspected arterial injuries.
 During the last year, randomly selected extremities (n = 23) have been studied with B-mode ultrasonography and segmental Doppler pressure measurements.
 Using the subsequent arteriography as the ""gold"" standard, sensitivity was 83% and specificity was 100%.
 Gunshot wounds were categorized according to location and positive arteriograms.
 Injuries to the lateral thigh and arm resulted in no positive arteriograms, while positive studies were observed in 11% of medial and posterior arm, 14% of antecubital fossa, 25% of forearm, 7.5% of medial and posterior thigh, 8% of popliteal fossa, and 26% of calf injuries.
 We recommend arteriography for gunshot injuries to identified high-risk areas, while clinical evaluation alone is accurate in all stab wounds to the extremities and gunshot wounds to the lateral thigh and outer arm.
 Preliminary data suggest expanded use of B-mode ultrasonography may further reduce our dependency on arteriography in these cases.
",20
3316,"The impact of volume on outcome in seriously injured trauma patients: two years' experience of the Chicago Trauma System.
 The American College of Surgeons has stated that in considering the development of trauma systems it is important to ensure an appropriate volume of seriously injured patients be seen by each trauma center in order to achieve acceptable mortality rates.
 Clinical data supporting this recommendation are lacking.
 An analysis was performed on 1,643 seriously injured trauma patients to determine the relationship between volume and mortality rates.
 Three separate statistical methods were used: Pearson correlation coefficients, mortality odds ratios, and direct pairwise mortality comparisons.
 In addition, Tobit analysis was introduced as a method to analyze the relationship between volume and mortality.
 Mortality rates were adjusted for the confounding variable of serious head injury.
 Pearson correlation coefficients for volume vs.
 adjusted mortality was -0.65.
 Mortality odds ratios comparing the low-volume (less than 140 pts) trauma centers vs.
 the high-volume (greater than 200 pts) trauma centers was 1.3 for adjusted mortality rates (95% CI = 1.01-1.66; p = 0.04).
 Categorical analysis showed significantly different mortality rates in the centers before and after adjusting for patient mix.
 Tobit analysis showed the relationship between volume and mortality to be significant, accounting for 30-40% of the observed variation in mortality rates.
 In addition, Tobit analysis allowed construction of a model to predict mortality rates, given specific volumes of patients.
 Our data suggest that an inverse relationship exists between volume and mortality, and support the necessity of configuring trauma systems in a manner that will ensure designated trauma centers will see a high volume of seriously injured patients.
",20
3317,"Acute hospital costs of trauma in the United States: implications for regionalized systems of care.
 As part of a larger effort to determine total direct and indirect costs of injury in the United States, national estimates of the numbers and expenditures associated with acute hospitalization due to traumatic injury were derived using data from the 1984, 1985, and 1986 National Hospital Discharge Surveys (NHDS).
 Estimates of the numbers of hospital episodes and total expenditures are reported in this paper for subgroups of patients defined by age, sex, and body region and AIS severity of the injuries sustained.
 In 1985 2.1 million individuals sustained a traumatic injury which resulted in hospitalization.
 Hospital expenditures totaled $11.4 billion inclusive of professional fees.
 Adolescents and young adults aged 15-44 years accounted for nearly one half of all discharges and total hospital costs.
 The elderly, who represent only 12% of the population, accounted for an additional one quarter of total discharges and hospital costs.
 Nearly three quarters of the hospitalizations and one half of total expenditures were for minor (ICD/AIS = 1, 2) injuries.
 Moderate (ICD/AIS = 3) and severe (ICD/AIS = 4, 5), injuries respectively accounted for 23% and 3% of total episodes and 37% and 11% of total expenditures.
 Only 12% of patients and 25% of trauma care dollars involved injuries sufficiently severe to require treatment at a trauma center.
",20
3318,"Geographic patterns of urban trauma according to mechanism and severity of injury.
 The purpose of this study was to investigate the distribution of various mechanisms of injury and the relative severity of such injury cases throughout the different geographic zones of a large urban area using a computerized emergency medical services (EMS) dispatch/patient record database.
 The study city (population, 2 million residents) was divided into 156 geographic grids (each 4.5 by 3 miles) and the incidence and relative severity of various injury mechanisms were determined for each zone.
 Results: In one year (1988), there were more than 115,000 separate EMS incidents involving more than 150,000 patients, 26,000 of whom were transported for injuries incurred in 10,064 motor vehicle accidents, 4,587 falls, 4,015 lacerations/stabwounds, 1,796 beatings, 1,270 gunshots, and 952 auto-pedestrian accidents.
 Analysis of the 156 zones showed a disproportionate number of EMS responses in the city center with two centralmost grids accounting for about 25% of all responses.
 Call volume then progressively diminished toward the periphery of the city.
 However, with some very minor exceptions, the relative incidence and severity of the various injury mechanisms remained proportionally uniform within each zone, regardless of geographic location.
 Therefore, contrary to popular notoriety, the incidence and associated severity of any given injury type generally was not necessarily predicted by any particular neighborhood predilection for it, but rather by the overall demand for EMS in that zone of the city.
",20
3319,"Management of complex perineal soft-tissue injuries.
 Debridement, fecal diversion, and rectal washout have been proposed as the primary therapy for complex perineal lacerations, but, in most series, survivors have a pelvic sepsis rate of 40-80%.
 In a retrospective study, six of 18 patients sustaining severe perineal lacerations died within the first few hours of injury due to exsanguination from pelvic injuries.
 The remaining 12 patients underwent sigmoidoscopy, diversion of the fecal stream with irrigation of the distal rectal stump, and radical initial debridement of necrotic soft tissue.
 Enteral access was obtained in two patients.
 In the patients with mandatory daily debridement and pulsatile irrigation, no pelvic sepsis occurred.
 In three patients without daily debridement, pelvic sepsis complicated recovery.
 The ability of patients to resume oral nutrition was significantly delayed, necessitating total parenteral nutrition in three patients.
 We conclude that sigmoidoscopy, total diversion of the fecal stream with irrigation of the distal rectal stump, enteral access for feeding, radical initial debridement of necrotic soft tissue, and mandatory daily debridement with pulsatile irrigation optimize recovery from this devastating injury.
",20
3320,"Intra-abdominal and retroperitoneal organ injuries diagnosed on dynamic computed tomograms obtained for assessment of renal trauma.
 The efficacy of dynamic computed tomography in assessment of renal, intra-abdominal, and retroperitoneal organ injuries is analyzed in some 444 patients.
 This technique contributed most valuable information toward the diagnosis of such coexistent injuries in patients who sustained blunt trauma.
 CT identified associated abdominal or retroperitoneal organ injuries in 85% of the patients (277 of 324), clinical examination in only 26%.
 CT proved invaluable for assessment of injury to bowel and mesentery, pancreas, and retroperitoneal vascular structures, giving rise to hematomas.
 CT diagnosed all such injuries, clinical examination from 0% (pancreas) to 11% (retroperitoneal hematomas).
 In patients with penetrating injury, dynamic CTs added valuable information on the status of viability of the injured organs.
 A relatively high number of false positive diagnoses resulted in only four unnecessary explorations.
 In all other patients, the erroneous diagnosis was revealed on repeat CTs undertaken because of inconsistency of the clinical course and clinical findings with the initially suggested CT diagnosis or at time of exploration undertaken for correction of other confirmed injuries.
 Discovery of associated intra- or retroperitoneal organ injuries, particularly in patients who sustained blunt trauma, has resulted in modification of treatment which prevented late sequelae and complications and thereby substantially reduced hospitalization time.
",20
3321,"Rehabilitative techniques for athletes after reconstruction of the anterior cruciate ligament [published erratum appears in Mayo Clin Proc 1991 Jan;66(1):114]
 A wide spectrum of protocols is available for rehabilitation after anterior cruciate ligament reconstruction, and little agreement exists on the specifics of strengthening exercises or the sequence of activities.
 In this article, we discuss the current rehabilitative techniques used at the Mayo Clinic for athletes who have undergone anterior cruciate ligament reconstruction.
 These techniques are based on established principles of rehabilitation, clinical experience, and new information about the related biomechanics of the knee.
 An illustrative case reflects the benefits of this rehabilitation program, which lasts up to 1 year and is divided into five stages.
 The early stages focus on protected mobilization and a strengthening program that emphasizes closed rather than open kinetic chain exercises.
 Later, neuromuscular-proprioceptive training and sport-specific agility training redevelop the reaction time and the ""coordination engrams"" necessary for athletic competition.
 High-quality surgical care and a closely supervised rehabilitation program, based on kinesiologic and biomechanical factors as they pertain to the anterior cruciate ligament, are necessary for a successful outcome.
",20
3322,"Specialist versus general practitioner treatment of problem drinkers 
 The efficacy of specialist versus general practitioner (GP) treatment of problem drinkers was assessed in a randomised controlled trial.
 40 problem drinkers referred consecutively to a specialist alcohol clinic by their GP were, after assessment, randomly allocated to either GP or specialist clinic treatment groups.
 All subjects received initial advice and counselling in the clinic about their drinking.
 The specialist clinic group received continued care from the clinic including, if necessary, admission to hospital.
 Patients in the GP group were returned to the care of the GP who was contacted and supported by the specialist.
 After 6 months of follow-up, there were significant reductions in alcohol consumption and alcohol-related problems in both groups.
 No significant difference was found between the two groups with respect to the main outcome measures.
 No differential treatment effect was found with the more severely dependent drinkers.
 The findings show that after an initial detailed assessment and advice session, the treatment provided by GPs is at least as effective as that from a specialist clinic with respect to improvements in drinking behaviour and alcohol-related problems.
 After initial assessment and advice, specialist clinics should encourage GPs to become more involved in the subsequent care of problem drinkers.
 Such a practice should be based on the individual patient's needs and the adequacy of support offered to GPs.
",20
3323,"Managing segmental facial nerve injuries by surgical repair.
 This report describes our experiences and evolving philosophy with regard to managing segmental facial nerve injuries.
 We present the results of 13 facial nerve repairs of traumatic injury to a segment of the facial nerve.
 All peripheral facial nerve branches contribute essential elements to normal mimetic facial movement; therefore, we recommend early, appropriate repair of the nerve segment.
 This recommendation is based on principles established for managing disruptions of the main trunk of the facial nerve.
 It offers the patient the chance for complete recovery of facial function.
",20
3324,"Vaginal birth after cesarean delivery: results of a 5-year multicenter collaborative study.
 Cesarean delivery has become the most frequently performed major operation in the United States.
 Widespread use of vaginal birth after previous cesarean delivery could potentially eliminate up to one-third of cesareans.
 However, many physicians have been reluctant to adopt this policy without large studies conclusively demonstrating its safety.
 This study evaluated the maternal and perinatal outcomes of over 5000 cases of labor after previous cesarean delivery.
 This multicenter study began in 1984 and initially included nine California hospitals.
 During the first 2 years, there were 1776 trials of labor resulting in 1314 vaginal births.
 In January 1986 two additional hospitals joined the collaborative project.
 Over the next 3 years, there were 3957 trials of labor resulting in 2977 vaginal births at the 11 participating hospitals.
 During the entire study period, 5733 patients opted for a trial of labor and 4291 (75%) delivered vaginally.
 There were no maternal deaths in the trial-of-labor group, and perinatal mortality was not significantly different from that of the general obstetric population.
 These results support the findings of numerous smaller studies that have concluded that the policy of routine repeat cesarean delivery should be abandoned.
",20
3325,"Tibial defects. Reconstruction using the method of Ilizarov as an alternative.
 Although used in the USSR since the 1950s, the method of Ilizarov has only recently been employed in North America to manage bone defects.
 Seven cases of patients with tibial bone defects are presented (five with deep infection) that were treated by gradual compression at the defect with one or two transported tibial segments that not only filled the tibial defect but preserved or regained the original bone length.
 Six of the seven patients had their defect obliterated while leg length was maintained.
 The method is minimally invasive, allows immediate weight-bearing and permits modifications in strategy while treating the bone defects but requires close attention to detail and has a steep learning curve.
",20
3326,"Preoperative planning for the treatment of nonunions and the correction of malunions of the long bones.
 A detailed analysis of the steps of preoperative planning as employed in our clinic has been presented.
 We have found these techniques to be of great value in anticipating the requirements that must be fulfilled to correct malalignments and obtain healing when the malalignments occur alone or are associated with nonunion.
 Besides helping one to decide where a malalignment is best corrected to anatomically match the normal extremity, tracings aid in allowing the surgeon to appreciate the kinetics of the operative procedure, as well as to define the best methods of stabilizing the resulting correction.
",20
3327,"Treatment of tibial malunions and nonunions with reamed intramedullary nails.
 Reamed intramedullary nailing is an effective, relatively low-risk technique for the management of delayed union, nonunion, and malunion of the tibia.
 Closed technique should be used where possible and open realignment, when necessary, should be executed with minimal dissection.
 Bone grafting is rarely indicated.
 The use of interlocking nails provides an added degree of security in the control of rotation.
",20
3328,"The treatment of nonunions and pseudarthroses of the humeral shaft.
 In summary, if one follows the AO/ASIF principles of open reduction and stable internal fixation of nonunions and pseudarthroses of the humerus, mostly with plate fixation supplemented by shingling or petaling, cement for loose screws when necessary, and bone grafting of defects or atrophic nonunions, then successful healing with one operative procedure can be achieved in over 95%, with almost full correction of preoperative deformity.
 Return of useful function and range of motion can also be achieved in 75% to 90% by early active exercises, physiotherapy, and occasional continuous passive motion, supported by hinged braces or cast braces in the postoperative period until union occurs.
 Union was achieved in an average of 6.6 months after the operative procedure.
",20
3329,"Intraarticular malunions and nonunions.
 The principles of intraarticular fracture care and stable internal fixation, when applied to intra-articular nonunions and malunions, can result in the restoration of an amazing function to joints that seem almost totally doomed to either an arthrodesis or an arthroplasty.
 The high degree of success achieved in almost all cases illustrates the amazing recuperative powers of human joints once articular cartilage congruence and stability is re-established together with correction of axial deformities and the mobilization of joints.
",20
3330,"Diagnosis and treatment of nonunions and malunions of acetabular fractures.
 The surgical treatment of nonunions and malunions of acetabular fractures is often a challenge.
 The diagnosis of a nonunion or malunion rests on clinical and radiologic examination.
 Apart from the union troubles involving only one column, all other cases justify the use of the extensile approach.
",20
3331,"Heat illness. Fluid and electrolyte issues for pediatric and adolescent athletes.
 The primary mechanism for maintaining normal body temperature during physical exercise in the heat is the evaporation of sweat.
 With profuse sweating, water loss far exceeds electrolyte loss.
 Rigorous exercise in the heat places the athlete at risk for thermoregulatory dysfunction from dehydration.
 Because children are inherently less efficient thermoregulators than adults, they are at even greater risk for heat illness.
 The three primary syndromes of heat illness are heat cramps, heat exhaustion, and heat stroke.
 Treatment of heat illness is based on reduction of body temperature and rehydration.
 Heat stroke is a true medical emergency with a high mortality rate; immediate reduction of body temperature is critical to the survival of these patients.
 Prevention of heat illness is based on reducing known risk factors.
 Physical activity should be modified in the face of high ambient temperature and humidity.
 The athlete should begin exercise well hydrated; frequent consumption of cold water during exercise decreases likelihood of significant dehydration.
 After exercise, the athlete should continue drinking to replace fluid losses.
 Clothing should be lightweight; the more skin exposed, the greater the available evaporative surface.
 A preseason conditioning program, when combined with an 8- to 14-day period of acclimatization, further reduces the risk of heat injury.
 Although athletes engaged in endurance sports may benefit from drinking carbohydrate/electrolyte-containing solutions, for the majority of young athletes, cold water remains the preferred choice for fluid replacement during exercise.
 The relatively greater body surface area of young athletes also places them at risk for hypothermia.
 Special attention should be given when these athletes are competing under cold environmental conditions.
",20
3332,"A review of the use of prophylactic knee braces in football.
 A review of nine studies of prophylactic knee braces worn by players in American tackle football lends some support for the use of double-hinged braces at the high-school level.
 Evidence for their use at the college level seems less persuasive.
 Caution should be exercised in interpreting these studies owing to the probable presence of bias and confounding variables and to difficulty in generalizing results beyond the study populations.
 The two studies that assigned braces randomly found lower injury rates for knees and knee ligaments among high-school and high-school size players.
 Conversely, a large, multiteam collegiate study found a significantly higher rate of knee injuries among brace users, a difference that remained when controlled for position, skill, and previous injury.
",20
3333,"Strength training in children and adolescents.
 Strength is the ability to exert muscular force against resistance.
 It is a fundamental requirement of most daily physical activities of children and of adults.
 Strength training is the use of progressive resistance exercise methods specifically to increase strength.
 Strength training for children and adolescents is not without risk.
 Proven medical concerns relate to back, shoulder, and other joint injuries and to hypertension and related diseases.
 However, the rate of injury is probably rather low, comparable to many youthful activities that are considered safe.
 Also, the incidence and severity of injury can probably be minimized by adherence to the guidelines presented.
 Children may be expected to become stronger with appropriate training.
 Increased strength can enhance their performance in those athletic activities in which strength, power, or speed are required.
 It may reduce the incidence and severity of overuse injury in sport.
 However, it cannot reasonably be expected to protect against serious, acute injury in sport.
",20
3334,"Substance abuse education in pediatrics.
 Historically, physicians have received little formal education related to alcohol or other drug abuse and dependence.
 A survey of all pediatric programs in the United States was conducted to assess the current status of alcohol/drug education in pediatrics.
 At the medical student and residency training levels, only 44% and 40% of programs, respectively, required any formal instruction, and only 27% and 34%, respectively, offered an elective for medical students or residents.
 Although most respondents endorsed the inclusion of both required and elective alcohol and drug education in the curriculum, few programs that did not include it already had a future plan for it.
 Major impediments identified were curriculum time constraints (86% medical student level, 68% resident level) and the lack of a qualified instructor (55% medical student level, 50% resident level).
 The survey results suggest a strong need for development of faculty and structured alcohol and drug abuse educational plans specific to pediatrics.
",20
3335,"Predictive value of visible lesions (cheeks, lips, oropharynx) in suspected caustic ingestion: may endoscopy reasonably be omitted in completely negative pediatric patients? 
 The relationship between absence or presence of grossly visible lesions in the cheeks, lips, and oropharynx (C.L.O.
 burns) and the incidence, site, and degree of visceral burns was evaluated in all children referred to our hospital for a suspected caustic ingestion during a 10-year period.
 All children underwent eso-gastro-duodenoscopy within 24 hours.
 Of the 156 children, 96 (61.6%) showed no visible signs of contact with the caustic substance; however, in 36/96 (37.5%), endoscopy revealed burns in one or more visceral sites.
 Eight of 36 children (22.2%) sustained potentially dangerous lesions (second to third degree).
 Sixty of 156 children (38.4%) showed visible lesions; in 30/60 (50%), endoscopy revealed other burns in one or more visceral sites.
 Fourteen of 30 patients (46.6%) sustained potentially dangerous lesions (second to third degree).
 A total of 50 esophageal burns have been recorded: first degree (E1), 32; second degree (E2), 12; third degree (E3), 6.
 Two of 12 patients with E2 lesions and 6/6 with E3 lesions developed esophageal stenosis.
 One patient in this latter group died because of complications related to a tracheostomy.
 A total of 31 gastric burns have been recorded: G1 (22), G2 (6), G3 (3).
 One gastric perforation was observed in the G3 group, whereas the remaining two lesions healed with residual asymptomatic scarring.
 Minimal scarring was observed in two of six patients with G2 burns.
 A total of eight lesions have been recorded in the larynx [L1 (3), L3 (1)] and in the duodenum [D1 (2), D2 (2)].
",20
3336,"Initial management of trauma. The next 60 minutes.
 If and when hemodynamic stability has been achieved in a trauma patient, a detailed physical examination and appropriate diagnostic studies are performed.
 The successful management of trauma demands that immediately life-threatening problems receive top priority and that patients be continuously reexamined and problems reprioritized as conditions change.
 Finally, it is imperative that appropriate surgical evaluation and treatment be undertaken as soon as possible.
 Trauma patients should not be allowed to languish or undergo extensive examination in a hospital lacking surgical or other specialists trained to treat the problems identified.
 Transfer to another facility, whether for specialized diagnostic tests or for evaluation and treatment by surgical specialists, should be accomplished as quickly as possible.
",20
3337,"A trilaminar skin coverage technique for treatment of severe degloving injuries of the extremities and torso.
 A 60 percent degloving injury involving the torso and lower extremities of an 8-year-old boy is described.
 Successful management employed the use of a new trilaminar skin coverage technique.
 With the avulsed flap still attached to its bed, a 0.14-inch split-thickness graft of epithelium and superficial dermis is raised with a power-driven dermatome.
 From the same harvest site, one level deeper, a second layer consisting of split-thickness dermis (0.14 inch) is taken.
 Both the first and second layers are meshed and expanded.
 The remaining degloved flap is excised and, on a sterile bench, defatted to produce a third layer of deep dermis.
 In our case, this third layer was ultimately lost, but it functioned well as a temporary biologic dressing.
 Depending on donor-site morbidity, other potential applications of this method (i.e., major burn injuries) may be feasible.
",20
3338,"Brachial plexus injury associated with chest restraint seatbelt: case report.
 Rapid deceleration while wearing a lap-shoulder strap seatbelt may result in a traction injury to the brachial plexus on the side of the shoulder strap.
 Occult vascular injury should be considered in patients with this injury pattern.
 The deficit will recover after a neuropraxic type injury.
",20
3339,"Biochemical analysis of electroejaculates in spinal cord injured men: comparison to normal ejaculates.
 To address the consistent finding of asthenospermia in spinal cord injured men we compared the biochemical constituents of antegrade fractions of electroejaculates of 6 such patients with the manual ejaculates of 6 volunteers.
 Semen samples in each group were analyzed for 19 biochemical parameters, pH and osmolality.
 Organic components included triglycerides, glucose, fructose, uric acid, creatinine, urea, total protein, albumin and cholesterol.
 Metabolic enzymes, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase, lactate dehydrogenase and alkaline phosphatase, were measured.
 Inorganic constituents included chloride, sodium, potassium, zinc and phosphorous.
 Although not significant, higher levels of blood urea nitrogen and creatinine were demonstrated in most electroejaculates suggesting urinary contamination of the antegrade specimens.
 In electroejaculates significantly lower levels (p less than 0.05) of fructose, albumin, GOT and alkaline phosphatase as well as significantly higher levels (p less than 0.05) of chloride were noted.
 No significant difference in osmolality or pH was found.
 Moreover, in the electroejaculates the levels of glucose, uric acid and all inorganic constituents approached their corresponding levels in serum.
 We conclude that biochemical abnormalities of the seminal plasma may contribute to seminal dysfunction of spinal cord injured men and may result from neurological injury to the accessory sex glands or from the electroejaculation procedure itself.
",20
3340,"Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism.
 Using the dopamine D2 receptor clone lambda hD2G1, Blum et al recently found that the D2/Taq I allele (A1) was present in 69% of 35 deceased alcoholics but in only 20% of an equal number of controls.
 To assess this association further, we evaluated the D2/Taq I polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3' noncoding region of the D2 receptor gene.
 We studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees.
 The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians.
 The SADS-L interviews and other data were then used to ascertain diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria.
 Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history.
 No significant differences in either D2/Taq I or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls.
 The PCR-SSCP polymorphism provided independent information against linkage at the D2 receptor locus.
 Several recombinants between the D2/Taq I locus and alcoholism were observed in two white families with an alcoholic parent who possessed the A1 allele.
 This study does not support a widespread or consistent association between the D2 receptor gene and alcoholism.
",20
3341,"Nicotine-replacement therapy with use of a transdermal nicotine patch--a randomized double-blind placebo-controlled trial 
 The rate of smoking was significantly reduced in volunteer subjects by providing effective nicotine replacement, self-help material, and weekly visits with a nurse for 6 weeks.
 Nicotine-replacement therapy with a transdermal nicotine patch (Nicolan) almost doubled the 6-week smoking-cessation rate in comparison with that in a placebo group (77% versus 39%; P = 0.002) among subjects who were smoking at least 20 cigarettes per day at baseline.
 Although most subjects who used the active nicotine patches had skin reactions, the reactions were primarily mild.
 For use of both active and placebo patches, the level of patient compliance was high.
 Among subjects who continued to smoke, the use of cigarettes was decreased to less than 50% of the baseline smoking level in 7 of 7 with active nicotine patches and in 15 of 19 with placebo patches.
 Outcomes beyond 6 weeks showed a substantial relapse rate in both groups.
 Thus, when nicotine-replacement therapy is provided, a need exists for concurrent behavioral intervention and training for prevention of a relapse, neither of which was part of this protocol.
",20
3342,"Prefabrication of composite free flaps through staged microvascular transfer: an experimental and clinical study.
 The feasibility of prefabricating free flaps by inducing, through the process of staged reconstruction, an arteriovenous bundle and its surrounding fascia to perfuse a selected block of tissue was investigated experimentally and clinically.
 Sixteen rat knee joints were wrapped with their ipsilateral superficial inferior epigastric (SIE) fascia.
 In 8 joints, the composite flaps were resected en bloc and were immediately replaced orthotopically pedicled upon the superficial inferior epigastric vessels.
 In the remaining joints, the resection and orthotopic transfer were performed 2 weeks later.
 Only the joints in the latter group, which benefited from the staging period, were found to be perfused.
 The long finger proximal interphalangeal joint of a child was reconstructed by the staged microvascular transfer of his second toe proximal interphalangeal joint.
 At the first stage, a temporalis fascia flap was wrapped around the toe proximal interphalangeal joint and revascularized to the dorsalis pedis vessels.
 Six weeks later, the joint and its temporalis fascia envelope were dissected, and the ""prefabricated"" joint flap was transferred to the hand and revascularized to the wrist vessels.
 Bony union progressed uneventfully with excellent recovery of the range of motion.
 We conclude that regardless of the indigenous vascular anatomy, an unlimited array of composite free flaps can be constructed and transferred based on induced large vascular pedicles.
",20
3343,"Blunt trauma in children: significance of peritoneal fluid.
 Seven hundred ninety consecutively seen children who had not undergone peritoneal lavage underwent imaging with computed tomography (CT) after blunt trauma.
 Collections of peritoneal fluid were prospectively characterized as small (51 children), moderate (32 children), or large (40 children).
 Associated injuries included hepatic or splenic injury in 74%, isolated renal or pancreatic injury in 5%, isolated pelvic fracture in 5%, isolated hollow viscus injury in 5%, and a combination of the above in 7%.
 Peritoneal fluid was the only CT abnormality in three children.
 A significant correlation was found between presence and increasing size of peritoneal fluid collections and clinical signs of hemodynamic instability such as lower trauma score (P = .0008 by analysis of variance), the presence of arterial hypotension (P = .0001 by chi 2 test), and hematocrit less than 30% (0.30) (P = .0001 by chi 2 test).
 Additionally, the presence and amount of peritoneal fluid correlated with need for laparotomy and with mortality (P = .0001 by chi 2 test for both).
",20
3344,"The clinical efficacy of triple-injection wrist arthrography.
 Triple-injection wrist arthrography has been demonstrated to increase the likelihood that all the ligamentous perforations in an injured wrist will be diagnosed.
 However, compared with imaging after single injection of contrast material into the radiocarpal joint, triple-injection arthrography not only increases patient expense but also significantly increases the time required of both patients and arthrographers to obtain the diagnosis.
 With the goal of decreasing the number of triple injections, the author reviewed 50 consecutive triple-injection wrist arthrograms.
 Using a technique based on high-volume injection of contrast material to achieve complete distention of the joint, the author achieved a false-negative rate for demonstration of complete perforations with radiocarpal injection alone of only 2% (10% if partial perforations were included).
 In none of these cases was patient treatment altered by the additional information provided by the second and third injections.
 This false-negative rate is significantly lower than that reported previously and raises the question of whether there are circumstances in which the easier and less time-consuming single radiocarpal injection might be appropriate.
",20
3345,"Accumulation of erythrocyte nucleotides and their pattern in lead workers.
 Nucleotides in erythrocytes of lead-exposed subjects were analyzed by high-performance liquid chromatography (HPLC).
 Most of the pyrimidine levels correlated well with blood lead concentrations (Pb-B) and pyrimidine 5'-nucleotidase (P5N) activity.
 Highly significant correlations were found between Pb-B and uridine 5'-diphosphate-glucose (UDPG), cytidine 5'-triphosphate (CTP), or CDP-choline (CDPC).
 The levels of these compounds were sharply elevated when P5N activity was reduced to levels less than 7 mumole/h.g hemoglobin (Hb), which corresponded to a Pb-B of 60 micrograms/100 g.
 Therefore, concentration of these nucleotides may provide a useful index of lead poisoning.
 Adenosine 5'-triphospate (ATP) concentrations were correlated negatively with Pb-B, whereas adenosine 5'-monophosphate (AMP) concentrations were correlated positively with Pb-B.
 These results suggest that lead affects not only pyrimidine nucleotide metabolism but also purine nucleotide metabolism (energy production system).
",20
3346,"Occult exposure to asbestos in steel workers revealed by bronchoalveolar lavage.
 To investigate the asbestos burden in a steelplant environment, we counted asbestos bodies (ABs) in the bronchoalveolar lavage fluid (BALF) of 65 steel workers who had retired during the previous 5 y.
 They had worked for at least 15 y in the same area of the plant (coke oven or blast furnace) as maintenance or production workers.
 On the basis of occupational anamnesis, 28 had occasional past professional exposure to asbestos; the remaining 37 workers denied any contact with asbestos.
 A total of 54 white-collar workers who had no occupational exposure to asbestos were included in the study as controls.
 An increased prevalence and concentration of ABs was found in the BALF of steel workers.
 Electron microscopy and EDAX analysis of AB from steel workers revealed that the core fibers were mainly amphiboles.
 More ABs were found in the BALF of maintenance workers than in production workers.
 However, the BALF from steel workers who denied any contact with asbestos revealed an increased AB burden v.
 controls.
 This demonstrates that steel workers may be subject to an occult exposure to amphiboles in the steelplant environment.
",20
3347,"High mortality and shortened life-span in patients with itai-itai disease and subjects with suspected disease.
 A follow-up study was conducted from 1967 to 1987 for patients diagnosed as having itai-itai disease, subjects who were suspected of having the disease, and controls.
 Ninety-five subjects per category were selected after matching for age, sex, and residential area.
 The cumulative survival rate of the patients who had a definite diagnosis of itai-itai disease was significantly lower than that of the control group in every period after the first 3 y.
 The cumulative survival rate of the subjects who were suspected of having itai-itai disease and who had severe renal dysfunction due to cadmium pollution was significantly lower than that of the control group.
 These results demonstrate (1) the enduring negative influence of itai-itai disease on prognosis and (2) that the cadmium pollution-induced renal disorder adversely affects the health of the inhabitants of a cadmium-polluted area.
",20
3348,"Blunt traumatic cardiac rupture. A 5-year experience.
 Blunt traumatic cardiac rupture is associated with a high rate of mortality.
 A review of the computerized trauma registry (1983 to 1988) identified 32 patients with this injury (ages 19 to 65 years; mean age, 39.5 years; 21 men and 11 women).
 Twenty-one patients (65.6%) were injured in vehicular crashes, 3 (9.4%) in pedestrian accidents, 3 (9.4%) in motorcycle accidents; 3 (9.4%) sustained crush injury; 1 (3.1%) was injured by a fall; and 1 (3.1%) was kicked in the chest by a horse.
 Anatomic injuries included right atrial rupture (13[40.6%]), left atrial rupture (8 [25%]), right ventricular rupture (10[31.3%]), left ventricular rupture (4[12.5%]), and rupture of two cardiac chambers (3 [9.4%]).
 Diagnosis was made by thoracotomy in all 20 patients presenting in cardiac arrest.
 In the remaining 12 patients, the diagnosis was established in seven by emergency left anterolateral thoracotomy and in five by subxyphoid pericardial window.
 Seven of these 12 patients (58.3%) had clinical cardiac tamponade and significant upper torso cyanosis.
 The mean Injury Severity Score (ISS), Trauma Score (TS), and Glasgow Coma Scale (GCS) score were 33.8, 13.2, and 14.3, respectively, among survivors and 51.5, 8.3, and 7.0 for nonsurvivors.
 The overall mortality rate was 81.3% (26 of 32 patients), the only survivors being those presenting with vital signs (6 of 12 patients [50%]).
 All patients with rupture of two cardiac chambers or with ventricular rupture died.
 The mortality rate from myocardial rupture is very high.
 Rapid prehospital transportation, a high index of suspicion, and prompt surgical intervention contribute to survival in these patients.
",20
3349,"The role of inhalation injury in burn trauma. A Canadian experience.
 From 1977 to 1987, 1705 thermally injured patients were admitted to the Firefighters' Burn Center at the University of Alberta Hospitals.
 Thirteen hundred forty-four were male (78.8%) and 361 were female (21.2%), with a mean total burn surface area (TBSA) of 15.1 (SEM +/- 0.4%) and a range of 1% to 99% TBSA.
 Sixteen hundred thirty-five patients survived to be discharged from hospital, with an overall survival rate of 95.9%.
 One hundred twenty-four burn patients (7.3%) suffered concomitant inhalation injury diagnosed by bronchoscopy.
 Patients with inhalation injury suffered from larger TBSA (39.7% +/- 2.8% versus 12.2% +/- 0.3%; p less than 0.01) than those without inhalation injury.
 Inhalation injury increased the number of deaths from burn injury (34.7% versus 1.7%; p less than 0.01) independent of age and TBSA.
 Inhalation injury was associated with a threefold prolongation of hospital stay (23.7 +/- 0.7 versus 74.4 +/- 6.2 days; p less than 0.01) and was independent of age and TBSA.
 Multifactorial probit analysis was performed for both inhalation- and noninhalation-injured burned patients to allow TBSA and age adjusted rates of mortality for the burn population presented.
 The maximum detrimental effects of inhalation injury in burn patient outcome occurred when it coexisted with moderate (15% to 29% TBSA) to large (30% to 69% TBSA) thermal injuries.
 These data demonstrate that inhalation injury is an important comorbid factor in burn injury that increases the number of deaths substantially.
 Most importantly such injuries also independently prolong the duration of hospitalization in a highly unpredictable fashion as compared to patients with cutaneous burns only.
 As such our data illustrate the extreme importance of inhalation injury as a comorbid factor following thermal injury and reveal the present limitations for accurate quantification of the magnitude of respiratory tract injury accompanying thermal trauma.
",20
3350,"Antibody to human retroviruses among drug users in three east coast American cities, 1972-1976.
 Between 1972 and 1976, 585 persons attending methadone maintenance clinics at East Coast veterans hospitals were enrolled in a survey of hepatitis antibody prevalence.
 Sera were tested for human immunodeficiency virus (HIV) and human T lymphotropic virus (HTLV) using both HTLV-I and HTLV-II immunoblots.
 Clinical and death records were also reviewed.
 None of the sera had HIV antibodies (upper 95% confidence limit, 0.5%); however, 103 (18%) had reactivity to HTLV.
 The profile of reactivity suggested that these subjects had been exposed to HTLV-II rather than to HTLV-I.
 Prevalence was as high in the early 1970s as today and correlated with duration of drug use rather than age.
 Neither cancers, specific neurologic diseases, nor excess deaths from any cause (overall 14%) could be ascribed to seropositivity.
 Therefore, HTLV (probably HTLV-II) has been a common infection of drug users for many years but adverse outcomes following infection were not demonstrated.
",20
3351,"Movement of hemostatic clips from the ventricles through the aqueduct to the lumbar spinal canal. Case report.
 The authors report a patient in whom rebleeding after operation for a left temporal arteriovenous malformation resulted in the dislocation of multiple hemostatic clips.
 Several clips, including a Yasargil aneurysm clip, were detected incidentally in the lumbar spinal canal.
 No clinical signs or symptoms were noted.
 Retrospectively, passage of the aneurysm clip through the aqueduct could be detected on computerized tomography scans performed to evaluate a series of epileptic seizures.
",20
3352,"Conservative management of duodenal trauma: a multicenter perspective.
 The experience of eight trauma centers with duodenal injuries was analyzed to identify trends in operative management, sources of duodenal-related morbidity, and causes of mortality.
 During the 5-year period ending December 1988, 164 duodenal injuries were identified.
 Patient ages ranged from 5 to 78 years.
 There were 38 Class I, 70 Class II, 48 Class III, four Class IV, and four Class V injuries.
 Injury mechanism was penetrating in 102 (62%) patients and blunt in 62.
 Primary repair of the duodenal injury was performed in 117 (71%) patients, including 27 patients also managed with pyloric exclusion and 12 with tube duodenostomy.
 Duodenal resection with primary anastomosis was used in six (4%) patients and pancreatoduodenectomy was necessary in five (3%).
 There were 30 (18%) deaths.
 The cause of death was uncontrolled hemorrhage from severe hepatic or vascular injuries in 22 (73%) patients.
 In only two (1%) patients could death be attributed to the duodenal injury; each as the result of duodenal repair dehiscence and subsequent sepsis.
 Duodenal-related morbidity was documented in 29 (18%) patients, including 22 patients with intra-abdominal abscess, six with duodenal fistula, and five with frank duodenal dehiscence.
 In summary, this analysis demonstrated: 1) the great majority of duodenal injuries can be managed by simple repair; 2) tube duodenostomy is not a mandatory component of operative treatment; 3) pyloric exclusion is a useful adjunct for more complex injuries; 4) pancreatoduodenectomy is rarely necessary for civilian duodenal trauma; 5) morbidity following duodenal trauma is more dependent on associated intra-abdominal injuries than the extent of duodenal trauma; and 6) mortality following duodenal injuries is primarily related to associated vascular and hepatic trauma.
",20
3353,"Mortality in trauma patients: the interaction between host factors and severity.
 Data on host factors influencing mortality in trauma patients is sparse and contradictory.
 To develop a model for health policy decisions, we examined all trauma admissions to acute care hospitals in the state of California in the year 1986.
 We looked at the influence of the following host factors: age, gender, and preinjury medical conditions, on mortality stratified by injury severity.
 The study group (N = 199,737) had an overall mortality rate of 1.9%.
 Mortality increased starting at age 40 years and was independently influenced by gender, the presence of pre-existing disease, and the body region injured.
 In patients with minor injury, mortality rates became higher in the elderly at age 65+.
 However, in patients with injuries of moderate severity, mortality increased in both middle age (40-64) and elderly groups (65+).
 Male gender was also a risk factor, present in both the elderly and middle age groups.
 While the presence of both pre-existing medical disease or injury to head or abdomen was related to increased mortality in middle-aged patients at all severity levels, neither accounted for the effect of gender.
 Conclusion.
 Age and gender influence mortality in trauma patients.
 These effects are not explained by documented pre-existing disease or region of injury.
 Age and gender serve only as observable markers for subgroups of patients with impaired response to injury.
 Middle-aged males comprise a previously unrecognized high-risk subgroup for this impaired response.
",20
3354,"The management of large soft-tissue defects following close-range shotgun injury.
 Large soft-tissue defects following close-range shotgun blasts remain a major technical challenge to trauma surgeons.
 During the period 1980 through 1988, 43 patients who survived greater than 48 hours following this injury were managed in our center.
 The locations of their soft-tissue defects were: extremity, 22; abdomen/chest, 18; and head/neck, three.
 All patients underwent immediate surgical exploration and wide debridement of all devitalized tissue along with repair of associated injuries.
 Management included mandatory frequent dressing changes, debridement, irrigation in the operating room, and the perioperative administration of broad-spectrum antibiotics.
 Four patients whose abdominal wall defects could not be initially closed had temporary placement of rayon cloth to prevent evisceration.
 Overall, four patients underwent delayed primary closure, eight were covered with split-thickness skin grafts, nine had closure with myocutaneous flaps, and 19 closed by secondary intent.
 Two patients, who were transferred to us following initial management, developed wound sepsis due to inadequate debridement and both eventually required amputation as did one patient who developed early myonecrosis following lengthy arterial repair.
 Frequent operative dressing changes, adequate debridement, and irrigation minimize sepsis following close-range shotgun blasts and should be the treatment of choice for this devastating injury.
 Techniques of wound closure need to be individualized to the particular situation.
",20
3355,"Nonoperative management of blunt liver injuries in adults: the need for continued surveillance.
 Computed tomography (CT) scanning after blunt abdominal trauma has allowed nonoperative management of selected patients with liver injuries.
 This report describes 52 adult patients with liver injuries who were treated without immediate surgery.
 Thirty-four of these hepatic injuries were relatively minor (Grade I-II), and 18 were considered major (Grade III-V).
 Free intraperitoneal blood in small to large amounts was evident on CT in 37 patients.
 There were no deaths in this series, no major complications, no known missed intra-abdominal injuries, and no delayed hemorrhage.
 While most liver injuries appear to heal rapidly by serial CT scans, a small percentage of these patients have residual liver defects persisting for several months and may be at risk for future complications.
",20
3356,"Dynamic computerized tomography of the occiput-atlas-axis complex in trauma patients with odontoid lateral mass asymmetry.
 Over a 23-month period, 25 patients aged 11 to 74 years presented to our Level I trauma center with odontoid lateral mass asymmetry of 2 to 5 mm on properly centered AP open-mouth X-rays: 32% of patients were asymptomatic, 68% had cervical pain, and 32% had limited range of motion.
 Patients with cervical spine fractures or dislocations and those with fixed deformity were excluded.
 The clinical significance of asymmetry was determined utilizing dynamic axial CT scanning of the occiput (C0), atlas (C1) and axis (C2) with the head neutral and with 15 degrees to 30 degrees active rotation.
 Nineteen patients demonstrated greater than 5 degrees of relative motion of C1 on C2 bilaterally.
 Three patients had less than 5 degrees of relative motion bilaterally and three patients had less than 5 degrees relative motion with left rotation only.
 No patient had formal treatment and all had nearly normal cervical range of motion on clinical examination at the time of hospital discharge.
 The finding of an asymmetric odontoid-lateral mass interspace on properly centered open-mouth AP X-rays in the presence of otherwise normal cervical spine X-rays, in conscious patients without fixed deformity, appears to be incidental and requires no further evaluation or treatment.
",20
3357,"Complications in evaluating abdominal trauma: diagnostic peritoneal lavage versus computerized axial tomography.
 We reviewed our experience with 2,809 DPL's and 1,331 CT's obtained in the resuscitative phase over a 3-year period in our trauma system to determine the significant complications associated with each modality.
 There were 25 DPL complications: eight false negatives, three false positives, and 14 technical errors.
 There were 46 CT complications including 25 false negative scans, three false positive scans, and 18 delays to the operating room from obtaining abdominal CT evaluation, with two of these delays resulting in preventable deaths.
 Although both modalities had low complication rates (0.9% DPL vs.
 3.4% CT), DPL was associated with less preventable mortality and morbidity than CT in the evaluation of abdominal trauma.
",20
3358,"Blunt carotid artery dissection: incidence, associated injuries, screening, and treatment.
 Blunt carotid dissection (BCD) is a rare injury occurring in less than one in 1,000 victims of blunt injuries.
 Using a 4-year experience in a trauma system with 14 cases of BCD, we performed a matched blunt trauma patient case-control analysis to determine if there were patterns of injuries that were associated with increased risk of BCD.
 Patients with combinations of head, facial, and cervical spine injuries with or without extremity fractures proved to be at significantly increased risk for BCD.
 Duplex scanning appears to be a useful screening tool for these patients.
 Anticoagulation was the preferred treatment once neurologic deficits were present.
",20
3359,"Unintentional injury death rates in rural Appalachia.
 Rural unintentional injury (UI) death rates are higher than rates for urban regions.
 Our trauma center serves 49 rural Appalachian (AP) counties in a 120-county rural state.
 We investigated the impact of prehospital and hospital resources on UI death rates in our referral area.
 Age-adjusted and average age- and sex-specific UI death rates from 1979-1985 were compared among 49 rural AP counties, the 71 non-Appalachian (NAP) counties, and the United States.
 Counties were grouped for comparisons by level of prehospital care (Advanced Life Support [ALS] vs.
 Basic Life Support [BLS]) and by presence (H) or absence (NH) of a hospital.
 Death rates were calculated using data from the 1980 population census, the National Center for Health Statistics (NCHS), and state vital statistics.
 Within AP, all 49 counties have ambulance service.
 Only 9/49 (18%) have ALS service and 13/49 (26%) have no hospital.
 Age-specific AP rates were higher than NAP and US rates in the 25-44 and 45-64 year age groups.
 AP death rates were highest for BLS and NH counties across all age groups.
 Rural UI death rates in the region remain unacceptably high.
 The reason(s) that AP death rates exceed the NAP rates is uncertain.
 ALS service and an available hospital were associated with lower death rates.
 We propose both educational and epidemiologic programs to better identify and define additional problems.
",20
3360,"Do trauma centers improve outcome over non-trauma centers: the evaluation of regional trauma care using discharge abstract data and patient management categories.
 Development of regional medical care systems to treat patients who sustain major accidental injuries (trauma victims) has been based on autopsy studies which demonstrate that hospitals that meet certain accepted criteria of readiness (trauma centers) can prevent needless deaths of trauma victims.
 However, since only autopsy data have been available from non-trauma centers, it has not previously been possible to compare morbidity data between trauma centers and non-trauma hospitals.
 This study examines discharge abstract data and a new patient classification system called patient management categories (PMC) which are generated from this abstract data to evaluate length of stay (LOS), complications, and death to compare morbidity and mortality data from trauma centers and non-trauma centers.
 Discharge abstracts for 1,332 patients with the PMC of femoral shaft fracture with operation were obtained from all hospitals in Western Pennsylvania and Maryland for 1 year.
 Data from trauma centers were identified and compared to non-trauma centers using the following criteria: time to OR (less than or equal to 2 days vs.
 greater than 2 days), age (0-12, 13-55, greater than 55 years), associated injuries, and development of complications and death.
 Patients treated in trauma centers had significantly fewer complications (21% vs.
 33%; p less than 0.001) and lower mortality rates (p less than 0.05) than those treated in non-trauma centers.
 Associated injuries, age, complications, and/or delay in time to OR significantly increased intensity and length of stay in both trauma and non-trauma centers.
 This significantly increased the cost of care provided to these patients in both types of centers.
",20
3361,"Management issues for trauma patients with alcohol.
 An estimated 20-25% of patients treated in emergency departments or as inpatients for trauma have been drinking and most of them have BACs of 0.10 gm/dL (22 mmol/L) or higher.
 Many are problem drinkers or alcoholics, smokers, and also abuse other drugs.
 Both acute ingestion and chronic abuse of alcohol increase the frequency and severity of injury, and may complicate patient management by mimicking head trauma, masking intra-abdominal injury, causing circulatory collapse, reducing immune response, altering hepatic metabolism, or causing delirium tremens.
 Proper management of a trauma patient with alcohol includes BAC determination, careful history taking for alcoholism with referral for further evaluation or treatment when indicated, and determination whether other drugs are also being misused.
 Failure to do these may put a physician at legal risk both for improper care of the patient and for exposing others to injury if the patient crashes after being discharged from the emergency department while still impaired by alcohol.
",20
3362,"Metabolism of platelet activating factor (PAF) and lyso-PAF in polymorphonuclear granulocytes from severely burned patients.
 We studied the metabolism of 3H-platelet activating factor (PAF) and lyso-PAF in human polymorphonuclear granulocytes (PMN) from severely burned patients (n = 6) on days 1, 5, 9, 15, and 25 post-trauma.
 All patients suffered from a severe burn trauma of more than 30% total body surface area.
 Stimulation of PMN in healthy donors (n = 10) with the Ca-ionophore resulted in the conversion of 3H-lyso-PAF into PAF (18 +/- 2% of total radioactivity) and alkyl-acyl-glycero-phosphorylcholine (alkyl-acyl-GPC, 50 +/- 6%).
 In burned patients a significantly reduced formation of 3H-PAF was observed between days 1 and 15 post-trauma (day 9: 1 +/- 1%, p less than 0.0001).
 This pattern was normalized again in patients (n = 5) who survived the trauma after septic periods and was observed during the second week post-trauma.
 In one patient who succumbed to his injuries a sustained inhibition of PAF formation was observed up to his death.
 The decreased formation of PAF correlated weakly with the appearance of immature granulocytes within the analyzed cell fraction (ratio of immature cells versus PAF-formation, r = -0.55, p = 0.02).
",20
3363,"Management of close-range shotgun injuries to the chest by diaphragmatic transposition: case reports.
 A method of reconstructing the chest wall following close-range shotgun injuries is described.
 This technique requires detaching the diaphragm peripherally and suturing it above the chest wall defect, resulting in an intact chest cavity and an abdominal wall defect.
 This latter problem can then be addressed by a variety of standard methods.
 Two patients are presented with excellent long-term results of diaphragmatic transposition, which should be in the armamentarium of all surgeons who deal with trunk trauma.
",20
3364,"Fractures of the coracoid process: presentation of seven cases and review of the literature.
 Coracoid process fracture is a rare and uncommon clinical entity.
 Seven cases of the base of the coracoid process are presented.
 This fracture was isolated in one case, being in the other six cases combined with injuries, either to acromioclavicular dislocation or to fracture of the superior glenoid cavity disorder.
 One of these patients had associated fractures of the clavicle and the coracoid process.
 The treatment was conservative in all cases.
 Results were satisfactory and therefore nonoperative management is advocated.
",20
3365,"Civilian gunshot wounds to the head: a prospective study.
 Previous retrospective studies of cranial gunshot wounds have failed to determine whether aggressive field resuscitation, triage to a neurosurgical center, and early surgical intervention can improve the assumed poor outcome of these severely injured patients.
 Therefore, we studied 100 consecutive patients prospectively to establish a systematic approach to treatment.
 If the patient retained two or more neurological signs after aggressive field resuscitation/intubation, a computed tomographic scan was performed.
 Rapid surgical debridement was done unless the patient deteriorated to clinical brain death.
 The Glasgow Coma Scale (GCS) score after resuscitation was 3 to 5 in 58 patients, 6 to 8 in 8 patients, 9 to 12 in 12 patients, and 13 to 15 in 22 patients.
 Seventy-six computed tomographic scans and 43 craniotomies were performed.
 The Glasgow Outcome Scale scores showed that 60 patients died, 2 were vegetative, 6 were severely disabled, 20 were moderately disabled, and 13 had good outcomes.
 There were 10 postoperative deaths.
 No patient with a GCS score of 3 to 5 had a satisfactory outcome; however, outcome progressively improved as the GCS score increased.
 We conclude that all cranial gunshot patients should initially receive aggressive resuscitation.
 Patients with stable vital signs should be examined by computed tomographic scan.
 If the patient's GCS score after resuscitation is 3 to 5 and no operable hematomas are present, then no further therapy should be offered.
 All patients with a GCS score greater than 5 should receive aggressive surgical therapy.
",20
3366,"Concepts of soft-tissue trauma repair.
 The proper evaluation and treatment of soft-tissue trauma to the face is extremely important because of the psychologic, cosmetic, and functional sequelae that can occur from these injuries.
 The facial trauma surgeon should have a wide armamentarium of techniques to manage soft-tissue facial trauma and should approach the repair in a meticulous and scientific fashion.
 Although the best possible repair of the acute trauma is the goal, it is usually necessary to perform later some camouflage or revision procedures on the scar because of the high likelihood of hypertrophic scarring or inappropriate healing in the trauma scar.
",20
3367,"Sagittal index in management of thoracolumbar burst fractures.
 In an effort to quantify the risk for late progression in burst fractures, the sagittal index (SI) was defined to help to assess the segmental deformity at the level of the fracture.
 The SI is a measurement of the kyphotic segmental deformity corrected for the normal sagittal contour at the level of the deformed segment.
 A prospective study was devised in 1986 for burst fracture treatment.
 Complete data were available on 35 patients (22 males, 13 females), with an average follow-up of 27 months.
 SI was greater than 15 degrees in the first group, the members of which were treated surgically.
 The technique is described.
 SI was less than 15 degrees in the third group, the members of which were treated conservatively.
 The second control group included patients with SI greater than 15 degrees but who were not treated according to the authors protocol for independent reasons.
 The results suggest that SI is a useful criteria to assess deformity and predict progression of segmental kyphosis.
",20
3368,"Nonoperative observation of clinically occult arterial injuries: a prospective evaluation 
 Forty-seven patients with 50 clinically occult injuries of major arteries were studied prospectively to determine the natural history of these lesions and the safety of nonoperative management.
 Penetrating trauma was the predominant mechanism and lower extremity arteries were most commonly involved.
 The morphology of these arterial injuries included 22 cases of intimal flaps, 21 cases of segmental arterial narrowing, 6 pseudoaneurysms, and 1 acute arteriovenous fistula.
 There was one death as a result of unrelated causes and another three injuries operated on immediately after arteriographic diagnosis.
 The remaining 46 injuries were followed up nonoperatively by serial arteriography (39) or clinical examination (7) during a mean interval of 3.1 months (range, 3 days to 27 months).
 Complete resolution was documented for 29 injuries (63%), whereas 3 improved, 9 remained unchanged, and 5 worsened during the period of follow-up.
 All worsened cases involved small or occult pseudoaneurysms that subsequently enlarged and then underwent immediate surgical repair without subsequent morbidity.
 Because 89% of the followed injuries never required surgery, nonoperative observation appears to be a safe and effective management option for clinically occult arterial injuries.
",20
3369,"Axis II comorbidity in substance abusers 
 OBJECTIVE: To assess the complex relationship between substance abuse and personality disorders, the authors determined the prevalence of personality disorders in a group of middle-class substance abusers and compared the subjects who had personality disorders with those who did not.
 METHOD: The subjects were drawn from patients consecutively admitted to an inpatient substance abuse program in a private psychiatric hospital; they were the first 100 who agreed to participate.
 Substance dependence was diagnosed according to DSM-III-R, and the patients were assessed with the Structured Clinical Interview for DSM-III-R Personality Disorders, Alcohol Use Inventory, MMPI, Health and Daily Living Form, Shipley Institute of Living Scale, and measures of chemical use and life satisfaction.
 RESULTS: Of the 100 substance abusers, 57 had personality disorders.
 These patients differed significantly from the 43 patients without personality disorders in several ways: they had greater involvement with illegal drugs, had different patterns of alcohol use, had greater psychopathology, were less satisfied with their lives, and were more impulsive, isolated, and depressed.
 CONCLUSIONS: Because of the marked differences between the substance abusers with and without personality disorders, a uniform approach to substance abuse treatment may be inadequate.
",20
3370,"Psychiatric morbidity in adult inpatients with childhood histories of sexual and physical abuse.
 OBJECTIVE: To extend the knowledge on long-term effects of childhood abuse in psychiatric patients to a large sample, the authors explored childhood sexual and physical abuse in adult inpatients over 1,040 consecutive admissions.
 METHOD: The 947 patients were admitted to a tertiary-care military medical center.
 Each patient was interviewed, and abuse history, DSM-III-R diagnosis, and other characteristics were recorded.
 RESULTS: The prevalence of reported childhood abuse was 18% overall: 9% for sexual abuse (with or without physical abuse), 10% for physical abuse (with or without sexual abuse), and 3% for combined abuse.
 More female than male patients reported abuse.
 Alcohol use disorders were more common in victims of physical or combined abuse than in sexually abused or nonabused patients.
 Axis II diagnoses, particularly borderline personality disorder, were more frequent in abuse victims than in nonabused patients.
 Histories of drug and alcohol abuse were more common in patients reporting physical or combined abuse than in nonabused patients.
 Suicidality was also more frequent in abused than nonabused inpatients and was noted in 79% of the patients with histories of combined abuse.
 Combined abuse in women and physical abuse in men were associated with a family history of psychiatric illness, most commonly alcoholism in male relatives.
 CONCLUSIONS: These findings emphasize the need for greater attention to family dynamics, aggressive diagnosis and treatment of alcoholism within the family, and, especially, determination of patients' abuse histories, even if repeated questioning is necessary.
",20
3371,"Accidental firearm fatalities among New Mexico children.
 STUDY HYPOTHESIS: Risk factors associated with unintentional gunshot fatalities among children include gender and race of the decedent, type of firearm used, and whether loaded guns are stored within the home.
 STUDY POPULATION: All New Mexico children 0 to 14 years old unintentionally killed by a firearm between 1984 and 1988.
 METHODS: The New Mexico Office of the Medical Investigator master mortality file was reviewed retrospectively to identify all unintentional firearm fatalities occurring in New Mexico children during a five-year period.
 Medical investigator, autopsy, and police reports were analyzed to identify epidemiologic factors associated with these deaths.
 Chi-square and Fisher's exact tests were used to analyze the data.
 RESULTS: Twenty-five unintentional firearm fatalities were identified.
 These deaths occurred most frequently among children playing with loaded firearms found within the home.
 A disproportionate number involved handguns.
 CONCLUSIONS: The study results provide a basis for preventive strategies that limit accessibility or decrease lethality of loaded firearms within the home.
",20
3372,"Under-reporting of contaminated needlestick injuries in emergency health care workers.
 STUDY HYPOTHESIS: There is considerable under-reporting of contaminated occupational needlestick and other sharp object injuries among emergency health care workers.
 POPULATION: A convenience sample of emergency physicians, emergency nurses, and emergency medical technicians (EMTs).
 METHODS: A survey instrument eliciting demographic and work-related factors was developed and administered; survey items included age, sex, occupation, years in occupation, number of procedures performed per week, number of contaminated needlestick (and other ""sharps"") injuries recalled, and number of these injuries formally reported during the previous five years.
 Nonsegmented visual analog scales were used to assess eight attitudes possibly associated with nonreporting.
 Analysis was by analysis of variance and multiple linear regression with stepwise variable election.
 RESULTS: Two hundred fifty-nine subjects recalled 643 contaminated exposures during the five-year study period, but only 228 (35%) were formally reported.
 One or more injuries occurred in 55% of EMTs compared with 72% of nurses and 80% of physicians (P less than .05).
 Physicians recalled a mean of 3.8 contaminated exposures, whereas nurses recalled 2.8 and EMTs recalled only 1.8 (P less than .05).
 Physicians formally reported a mean of 0.26 exposures, whereas EMTs reported 0.85 and nurses reported 1.25 (P less than .05).
 Physicians formally reported only one eighth of their injuries compared with EMTs and nurses, who each reported two thirds of these events (P less than .05).
 Perception of risk, occupation, years in occupation, and concern about excessive paperwork were the most powerful predictors of low reporting rate (P less than .05).
 CONCLUSIONS: Work-related contaminated sharp object injuries are under-reported by emergency health care workers, especially emergency physicians.
",20
3373,"Hangman's fracture in a 7-week-old infant.
 The ""hangman's fracture"" in infancy and childhood is a bilateral avulsion of the pedicles or their synchondroses from the C-2 vertebral body, frequently with anterior dislocation of C-2 or C-3.
 We present the case of the youngest infant in the medical literature with a hangman's fracture and discuss anatomy, kinematics of injury, radiographic diagnosis, and treatment.
",20
3374,"Psychiatric disorders in relatives of probands with opiate addiction.
 Previous research has documented high rates of major depression and antisocial personality in opiate addicts.
 This study was designed to investigate the relationship of dual diagnosis in opiate-addicted probands to family history of psychiatric disorders and substance use disorders in biological relatives.
 Psychiatric disorders and substance use disorders were evaluated using direct interview and family history in a sample of 877 first-degree relatives of 201 opiate addicts and 360 relatives of 82 normal controls.
 Results indicate that (1) compared with relatives of normal subjects, opiate addicts' relatives had substantially higher rates of alcoholism, drug abuse, depression, and antisocial personality; (2) relatives of depressed opiate-addicted probands had elevated rates of major depression and anxiety disorders but not of other disorders, suggesting the validity of subtyping opiate addicts by the presence or absence of major depression; and (3) in contrast, relatives of antisocial opiate addicts had rates of disorders that were not significantly different from those of relatives of opiate addicts without antisocial personality.
 Implications of these findings for the classification and treatment of substance abuse are discussed.
",20
3375,"Psychiatric diagnoses of treatment-seeking cocaine abusers.
 In a sample of 298 cocaine abusers seeking inpatient (n = 149) or outpatient (n = 149) treatment, rates of psychiatric disorders were determined by means of the Schedule for Affective Disorders and Research Diagnostic Criteria.
 Overall, 55.7% met current and 73.5% met lifetime criteria for a psychiatric disorder other than a substance use disorder.
 In common with previous reports from clinical samples of cocaine abusers, these overall rates were largely accounted for by major depression, minor bipolar conditions (eg, hypomania, cyclothymic personality), anxiety disorders, antisocial personality, and history of childhood attention deficit disorder.
 Affective disorders and alcoholism usually followed the onset of drug abuse, while anxiety disorders, antisocial personality, and attention deficit disorder typically preceded drug abuse.
",20
3376,"Symptoms of tobacco withdrawal. A replication and extension.
 Smokers (n = 315) who wished to quit were randomly assigned in a double-blind manner to groups using either nicotine or placebo gum.
 Self-reported and observed symptoms of tobacco withdrawal were collected before cessation and at follow-ups of 1 to 2 weeks, 1 month, and 6 months.
 Self-reported and/or observed anger, anxiety, craving, difficulty concentrating, hunger, impatience, and restlessness were the most prominent symptoms of tobacco withdrawal.
 These symptoms had returned to precessation levels by 1 month except increased weight, hunger, and craving continued for 6 months in many smokers.
 Nicotine gum decreased most symptoms, including craving and hunger but not weight.
 Abstinent smokers with more intense withdrawal were not more likely to relapse.
 Abstinent smokers who gained more weight were less likely to relapse.
",20
3377,"Hyperactive boys almost grown up. V. Replication of psychiatric status.
 We previously reported a prospective follow-up study of 101 young adult males whose conditions had been diagnosed as hyperactivity in childhood.
 Compared with controls, probands had significantly higher rates of attention-deficit, antisocial, and drug use disorders at follow-up (mean age, 18 years).
 The present study was an attempt to replicate these findings on an independent sample of 94 hyperactive boys who were seen at the same clinic, compared with 78 normal controls.
 Assessments were made by clinicians who were blind to group membership.
 Information was obtained for 90% of the original cohort.
 As in the previous study, significantly more probands than controls were given ongoing diagnoses of attention-deficit disorder (43% vs 4%), antisocial disorders (32% vs 8%), and drug use disorders (10% vs 1%).
 Furthermore, the absolute rates of these disorders were comparable for corresponding groups across studies, and the adjusted odds ratios did not differ significantly.
 As previously, there was no increased risk for affective disorders in the grown hyperactive children.
 The present study provides a powerful replication of the nature of the young adult outcome of childhood hyperactivity.
",20
3378,"An outbreak of pneumococcal pneumonia in two men's shelters 
 We report a retrospective study of 39 homeless men hospitalized for acute pneumonia from April 1988 to March 1989.
 All of them had recently stayed in one of two shelters.
 A Streptococcus pneumoniae serotype 1, resistant to cotrimoxazole, was isolated in 29 patients (74 percent).
 Blood cultures were positive in 24 (61 percent).
 The patients were relatively young; none was over 70 years old.
 Thirty-five (90 percent) were heavy smokers; 32 (82 percent) were alcoholics.
 The radiologic pattern was atypical in 14 cases (36 percent).
 The only fatal case was linked to the adult respiratory distress syndrome.
 It is likely that the rate of outbreaks of pneumococcal pneumonia is underestimated.
 The homeless are at high risk for pneumococcal pneumonia.
 In addition, the closeness existing in shelters favors the occurrence of outbreaks.
 Consequently, we suggest that shelter residents would benefit from pneumococcal vaccination.
",20
3379,"Trajectory reconstructions. I: Trace evidence in flight.
 This paper reviews the use of trace evidence recovered from spent bullets in helping to establish trajectories.
 The use of information derived from such trace evidence combined with that from geometrical techniques of trajectory reconstruction and other data is discussed.
 Five cases are reviewed in which the analysis of trace evidential materials adhering to bullets was used to help reconstruct the event.
",20
3380,"An application of probability theory to a group of breath-alcohol and blood-alcohol data.
 Many jurisdictions have ""per se"" driving-while-intoxicated (DWI) status expressed in terms of a blood-alcohol concentration (BAC) standard (in grams per 100 mL or the equivalent).
 Since breath-alcohol (BrAC) analysis is typically employed to determine BAC, there is often challenge to the use of an assumed 2100:1 conversion ratio.
 This concern may be relevant in light of considerable data that show a low percentage of cases in which BrAC greater than BAC, and this concern increases when the BrAC is used to predict BAC in the context of ""per se"" legislation.
 Probability theory provides a basis for estimating the likelihood of an individual having a BrAC greater than or equal to g/210 L with a corresponding BAC less than 0.10 g/100 mL.
 Actual field data from the state of Wisconsin (n = 404) were evaluated to determine the probability of this occurrence.
 The probability for this occurrence involves the multiplication law for independent events.
 The computed probability from the data was 0.018.
 The actual number of occurrences where BrAC greater than or equal to 0.10 g/210 L and BAC less than 0.10 g/100 mL was 5, resulting in a probability of 0.012.
 The concern of having BrAC greater than BAC at the critical ""per se"" level has a very low probability of occurrence, which thus supports the reasonableness of ""per se"" DWI legislation based upon a blood-alcohol standard determined by breath-alcohol analysis.
",20
3381,"The usefulness of lung surfactant phospholipids (LSPs) in the diagnosis of drowning.
 The authors have studied the usefulness of some lung surfactant phospholipids (LSPs) isolated from lung tissues as markers of drowning.
 Two different groups of rabbits were sacrificed by drowning in fresh and salt water, and their phospholipid compositions were compared with those of a non-drowned control series.
 For the phospholipids studied in lung lavages (phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl glycerol) the proportions differed between the control group and the drowned group, and between the fresh-water and salt-water drowned animals.
 According to these results, the lipids we have analyzed can be employed as markers in forensic autopsies, where it is necessary to differentiate between death by drowning and postmortem immersion and between fresh-water and salt-water drowning.
 In lung tissue, only phosphatidyl choline and phosphatidyl inositol showed significative differences.
 These results also confirm that LSPs are strongly affected in drowning.
",20
3382,"A death resulting from trichlorotrifluoroethane poisoning.
 Fatalities due to accidental exposure to chlorinated hydrocarbon in an industrial setting have been infrequently reported.
 The deaths in these cases have occurred within poorly ventilated, enclosed compartments or areas.
 A case is presented of a 16-year-old male who died as a result of exposure to trichlorotrifluoroethane while working in an open pit.
 Chromatographic results and tissue concentrations are presented.
",20
3383,"The tubular ""cookie cutter"" bullet: a unique projectile.
 Recently marketed PMC (Pan Metal Corporation) Ultramag tubular hollow point ammunition is uniquely constructed with a two-part projectile composed of a tubular copper bullet and a Teflon wad.
 A fatal gunshot wound with this ammunition is described.
 A unique radiographic pattern and the results of test firing are also presented.
",20
3384,"The use of human skin in the fabrication of a bite mark template: two case reports.
 Comparison of a suspected biter's dental arches with the patterned injury of a bite mark is especially difficult when the bite occurs in an anatomic location with a small radius of curvature or with complex or compound curves.
 The authors present two case reports in which human skin was used as a template for the reproduction of a bite.
 In one case the victim's skin was used; in the other, the skin of a anatomically similar person was used.
 The use of inked dental casts, photography, and transparent overlays significantly reduced the errors common to analysis of bite marks in these highly curved areas.
",20
3385,"Combat-related PTSD and psychosocial adjustment problems among substance abusing veterans.
 The purpose of this study were the following: a) to determine the prevalence of combat-related posttraumatic stress disorder (PTSD) symptoms among veterans seeking assistance at a Veterans Administration medical center substance abuse treatment facility, b) to examine the relative contribution of Vietnam war zone variables to PTSD symptom development, and c) to study psychosocial adjustment problems associated with Vietnam combat exposure and with PTSD symptoms among help-seeking substance abusing men.
 Of 489 male veterans presenting for treatment, 10.7% had significant Vietnam combat-related PTSD symptoms as measured by the Mississippi Scale for Combat-Related PTSD.
 Clinically significant PTSD symptoms occurred among 46% of the subsample of combat-exposed Vietnam veterans with substance abuse problems.
 Degree of combat exposure was the most important military stressor that distinguished Vietnam veterans with PTSD from those without PTSD, but the groups also differed on age of war zone duty, duration of war zone duty, and whether they were wounded.
 Veterans who served in Vietnam did not differ from veterans who had no war zone duty on various parameters of psychosocial adjustment.
 However, the subgroup of Vietnam veterans with PTSD symptoms reported significantly greater psychosocial adjustment problems than their counterparts who did not have PTSD.
 The deleterious effects associated with combat-related PTSD appeared to be confined to adjunctive psychiatric difficulties and unemployment and did not increase risk of arrests for antisocial conduct beyond that found for veterans without PTSD.
 Methodological and clinical implications of these findings are discussed.
",20
3386,"Psychological absorption. Affect investment in marijuana intoxication.
 Absorption (a trait capacity for total attentional involvement) was reported to increase during episodes of marijuana intoxication.
 Several subsets of the absorption scale items specifically characterized marijuana intoxication, and groups of users and nonusers showed differential affective involvement with these experiences.
 Additionally, within the drug-using group, a positive correlation between frequency of marijuana use and affective ratings of these experiences was found.
 The findings support the hypothesis that a specific type of alteration in consciousness that enhances capacity for total attentional involvement (absorption) characterizes marijuana intoxication, and that this enhancement may act as a reinforcer, possibly influencing future use.
",20
3387,"Lag screw fixation of anterior mandibular fractures.
 A technique of applying lag screws for treating fractures of the anterior mandible is presented.
 A review of 41 patients who had lag screws placed to treat such fractures showed that it is a successful method of providing rigid internal fixation.
 The advantages of this technique over bone-plate fixation are discussed.
",20
3388,"The Gillies method for fractured zygomas: an analysis of 105 cases.
 This prospective study analyzed 105 cases treated using the Gillies temporal approach for fractures of the zygoma.
 In 97 cases (92%) this was sufficient.
 Only eight cases required open reduction.
 It is suggested that the Gillies method be used more frequently, because it is associated with minimal morbidity and a short duration of general anesthesia.
",20
3389,"Low-dose caffeine physical dependence in humans.
 This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans.
 Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior.
 In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week.
 Data from the remaining three subjects provided no evidence of withdrawal.
 In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days.
 Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect.
 Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.
",20
3390,"Hyperbaric oxygen therapy for acute smoke inhalation injuries.
 Hyperbaric oxygen therapy is an important adjunct in the management of respiratory injuries secondary to smoke inhalation, especially when injury is complicated by inhalation of a toxic chemical such as carbon monoxide or cyanide.
 For carbon monoxide poisoning, such therapy has become a standard of practice.
 As more information becomes available concerning the ability of hyperbaric oxygen to reduce reperfusion injuries, we anticipate that this therapy will become a standard of practice for managing smoke inhalation injuries and cyanide poisoning as well.
",20
3391,"Biomechanics of fracture risk prediction of the hip and spine by quantitative computed tomography.
 In this review, we have made use of some simple engineering concepts to summarize current efforts relating QCT measures to bone density and strength.
 From a variety of in vitro experiments on cadaveric vertebrae and femora, it is evident that both apparent and ash densities are strong linear functions of QCT measures, with coefficients of determination ranging from 0.49 to 0.90 and relative errors from 44.9% to 7.1%.
 QCT data also can be used (with somewhat less confidence) to determine the compressive modulus (R2s from 0.36 to 0.68, relative errors from 45.0% to 35.5%) and compressive strength (R2s from 0.58 to 0.70, relative errors from 56.5% to 39.9%) of trabecular bone from the proximal femur and vertebral body.
 In cortical bone, material properties are only correlated weakly with QCT measures.
 Experiments designed to relate QCT data to failure loads for the proximal femur and vertebral body have been remarkably successful.
 Coefficients of determination have ranged from 0.32 to 0.93, with relative errors from 31.1% to 13.9%.
 However, when the in vitro failure loads determined in these experiments are compared against available estimates of in vivo loads on the spine and hip, it is apparent, at least in the elderly, that in vivo loads are relatively close to those that cause fracture in vitro.
 To assess the possibility of developing QCT-based clinical predictors of fracture risk for individual patients, we have introduced the concept factor of risk often used in engineering design to account for uncertainties in estimates of service loads and component strength.
 The factor of risk for a particular loading condition is defined as the ratio of expected service loads to the known failure loads.
 To extend this concept to densitometric fracture risk prediction in vivo, it is important to recognize that densitometric data must not only be used to predict the ultimate load carrying capacity of the region of interest, but that this ultimate load must then be compared to the forces expected in vivo under comparable loading conditions.
 One difficulty with this approach is that little is known about the in vivo forces that are associated with atraumatic age-related fractures of the hip and vertebrae and even less about the forces applied to the hip and spine during traumatic events such as falls.
 However, from available estimates of in vivo loads during bending and lifting, it is apparent that in the elderly, factors of risk for the spine can easily approach 1.(ABSTRACT TRUNCATED AT 400 WORDS).
",20
3392,"Immediate closed reduction of cervical spine dislocations using traction.
 Cervical facet dislocations may be reduced rapidly and effectively using axial traction with weights applied at over the traditional 45-pound limit.
 Fifty-three sequential patients with cervical facet dislocations were reviewed.
 Thirty-nine patients required more than 50 pounds of traction to achieve rapid reduction.
 Sixty-eight percent of the entire series showed significant improvement in neurologic function.
 There were no cases of significant loss of function.
 A cadaver study confirmed that the cranial tongs could support over 100 pounds of traction.
 Careful application of up to 100 pounds seems to be associated with a low risk of neurologic compromise or tong failure, but results in effective reduction of dislocations.
",20
3393,"Strategies for trauma resuscitation.
 Victims of penetrating trauma often arrive at a trauma center within minutes of sustaining their injury but nevertheless are in a state of deep circulatory shock.
 Such patients require extensive resuscitative efforts; in particular, some benefit from rapid, massive normothermic fluid resuscitation.
 During an initial one year period, 153 of 730 patients required immediate operation and, of these, 33 required rapid infusion defined as greater than 5 liters per hour during the first hour.
 The over-all survival rate of those operated upon was 79 per cent.
 Encouraged by these data, the rapid infusor (Level 1 H-500) (Level 1, Technologies, Inc.) was modified to further increase normothermic fluid delivery to 500 milliliters per minute.
 Eleven of the subsequent 205 patients required rapid infusion.
 There was a statistically significant improvement in clinical flow rates, decrement in resuscitation times and unexpected survival.
 In particular, the latter group (nine survivors) included four who were clinically dead in the field or on arrival at the trauma center, or both.
 Rapid infusion of normothermic fluids may be of benefit not only in penetrating trauma but also more generally in the management of massive hemorrhage.
",20
3394,"Increased intraocular pressure in severely burned patients 
 Six eyes of three patients with severe body burns had intraocular pressure ranging from 37.2 to 81.7 mm Hg.
 Because of extreme orbital congestion, lateral canthotomies were performed, which caused abrupt decrease in intraocular pressure (range, 17.6 to 49.0 mm Hg).
 None of the patients had a history of glaucoma, narrow angles, or any precondition for a pupillary block mechanism.
 Two patients survived and neither had optic nerve damage or increased intraocular pressure after hospital discharge.
 Tonometry should be performed in patients with severe burns and orbital congestion, especially in those patients receiving large amounts of intravenous fluids.
 Lateral canthotomies may be of benefit to relieve potentially damaging high intraocular pressure.
",20
3395,"Utility of the Self-Administered Alcoholism Screening Test (SAAST) in schizophrenic patients.
 The utility of the Self-Administered Alcoholism Screening Test (SAAST) in determining alcohol abuse and alcoholism was assessed in a preliminary study of 21 schizophrenic patients during their hospitalization in an acute care psychiatric unit; on admission all met DSM-III-R criteria for schizophrenia and none were detected to have any alcohol-related diagnosis.
 SAAST scores ranged from 2 to 26 with a mean score of 10.8.
 Forty-eight percent (10/21) had SAAST scores greater than or equal to 10, indicating ""probable alcoholism""; 62% (13/21) scored 8 or higher.
 Every patient with a SAAST score of 8 or higher also met DSM-III-R criteria for alcohol abuse or dependence on the basis of patient interview, independent chart reviews, and interviews of significant others.
 In contrast, only half (5/10) of the high SAAST scorers would actually admit to a problem with drinking during the extensive study interviews.
 Six SAAST items were found to be highly predictive of abuse or alcoholism; the SAAST had greater sensitivity than the interviews.
 Sixty-two percent (8 of 13) of the schizophrenic patients who met the DSM-III-R criteria for alcohol abuse reported a first degree relative with an alcohol-related problem, in contrast to only 25% of the ""nonalcoholic"" patients.
 The patterns of the alcoholic schizophrenic patients' responses on the different SAAST items revealed even greater denial and lack of insight than those of nonschizophrenic alcoholic subjects.
",20
3396,"Alcohol and secobarbital effects as a function of familial alcoholism: acute psychophysiological effects.
 Previous research has demonstrated response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism.
 These response differences are thought to reflect differences in vulnerability to dependence on alcohol.
 Thus, the role of positive family alcoholism history in increasing risk of addiction to a variety of drug classes might be studied by determining whether FHP subjects show different responses to drug classes other than alcohol.
 This was done in the present study by determining dose-effect functions for a variety of physiological (heart rate, skin conductance, skin temperature), subjective (analog mood and drug effect, Subjective High Assessment Scale), and psychomotor measures (hand tremor, body sway, Digit Symbol Substitution Test, eye-hand coordination, and numeric recall) in FHP and FHN college-aged males for secobarbital (0, 100, 200 mg by mouth) and ethanol (1 g/kg).
 FHP and FHN subjects were matched on light-to-moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use.
 At equivalent blood alcohol levels family-history positive subjects reported greater effects of ethanol than did family-history negative subjects on almost all subjective measures.
 Following the high dose of secobarbital, FHP but not FHN subjects showed elevated subjective effects; these effects were substantially less and were evident in fewer measures than following ethanol.
 In contrast to effects on the subjective measures, ethanol and secobarbital produced comparable impairment in both groups of subjects for most psychomotor responses.
 Group differences were not obtained on any physiological measures.
",20
3397,"Sons of alcoholics report greater hangover symptoms than sons of nonalcoholics: a pilot study.
 We investigated alcohol-induced hangovers among college men at high and low risk for alcoholism.
 Thirteen sons of alcoholics reported significantly (p less than 0.001) greater hangover symptoms in the past year than 25 sons of nonalcoholics.
 The two groups reported comparable quantity-frequency of recent drinking.
 To the extent that hangover represents an acute withdrawal syndrome to alcohol, this raises the question of whether sons of alcoholics are ""dependence-prone."".
",20
3398,"Taste reactivity in alcohol preferring and nonpreferring rats.
 Taste reactivity tests were used to examine the orofacial responses of alcohol preferring (P) rats and alcohol nonpreferring (NP) rats to the taste of alcohol.
 In the initial exposure, naive rats were tested for reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40% v/v), water, and one solution each of sucrose and quinine.
 A two-bottle consumption test was then given for a 3-week period to allow the rats access to 10% alcohol.
 After the preference test, a second taste reactivity test was done using the same solutions as in the initial reactivity test.
 The results indicated no significant differences in taste reactivity between P rats and NP rats on the initial exposure, except that NP rats made significantly more mouth movements.
 During the two-bottle tests, consumption of alcohol by P rats was consistently higher than that of NP rats across all test days.
 On the second taste reactivity test, P rats showed an increase in the number of ingestive responses and a decrease in the number of aversive responses to alcohol.
 NP rats' taste reactivity to alcohol remained unchanged from Exposure 1 to Exposure 2.
 P rats' and NP rats' responses to sucrose and quinine did not change from Exposure 1 to Exposure 2.
 It was concluded that there were no innate taste response differences between P and NP rats to alcohol but that following alcohol experience, P rats showed a significant increase in ingestive responses and a concomitant decrease in aversive responses to the taste of alcohol.
",20
3399,"Subject selection bias in alcoholics volunteering for a treatment study.
 Baseline differences in alcoholism problem severity were compared between alcoholics who did and did not volunteer to participate in a treatment effectiveness study.
 A positive relationship was found between self-reports of alcohol-related problems and the degree of research participation.
 Group differences were also revealed in the rate of treatment completion.
 Possible explanations and solutions for this volunteer bias are discussed.
",20
3400,"Alcohol abuse among grandsons of alcoholics: some preliminary findings.
 Drawing upon self-reports of family history for alcoholism, the present study compared the level of alcohol abuse among grandsons of alcoholic maternal and paternal grandfathers.
 Although based on a small sample of grandsons (N = 29), the results indicated a significantly higher level of alcohol abuse among maternal compared with paternal grandsons.
",20
3401,"Relationships between neuropsychological test performance and event-related potentials in alcoholic and nonalcoholic samples.
 Are event-related potentials and nonconcurrently measured neuropsychological test performance correlated? Sober male and female middle-aged alcoholics and peer controls were administered an ""oddball"" event-related potential (ERP) task and several hours later, a battery of neuropsychological (NP) tests.
 Alcoholics performed significantly poorer than controls on NP tests.
 Male alcoholics had significantly altered ERP responses (N1, NdA, and P3 amplitudes) but female alcoholics did not differ on any ERP variables from controls.
 A number of significant correlations between ERP and NP measures were present.
 The most consistent findings were positive correlations between perceptual-motor (PM) tests and the P3 amplitude at Pz in both male and female alcoholics and in male alcoholics, a negative correlation between PM tests and P3 latency at Pz, findings similar to those seen in Parkinson patients.
 Significant correlations were most numerous in family history positive alcoholics.
 The results lead to two conclusions: first, Grant's postulation that sober alcoholics may manifest an intermediate duration organic mental disorder is supported; second, given the lack of ERP differences in the females, ERP measures should not be considered as being causally related to NP performance.
",20
3402,"Comparison of the Self-Administered Alcoholism Screening Test (SAAST) and the Khavari Alcohol Test (KAT): results from an alcoholic population and their collaterals.
 This study examined the reports of patients and their collaterals on drinking practices, as measured by the summary scale of the Khavari Alcohol Test (the annual absolute alcohol intake, AAAI) and alcohol related behavioral patterns, as assessed by the Self-Administered Alcoholism Screening Test (SAAST).
 In- and outpatients from two Milwaukee area substance abuse treatment hospitals, and a number of their collaterals, participated in this study.
 Patients' and collaterals' responses on the AAAI and the SAAST were compared through the use of a paired t test.
 Results indicated no significant differences between patients' self-reports compared with collateral reports, and demonstrated a direct relationship on the AAAI (two tailed p less than 0.001) and SAAST (two-tailed p less than 0.001).
 Self-reports of patients who volunteered collaterals compared with self-reports of patients who did not volunteer collaterals also showed no significant differences on the AAAI or the SAAST, demonstrating consistency of reporting whether the patients believed their reports would be compared with information provided by a collateral or not.
 The AAAI and the SAAST corroborated in their diagnoses of patients as suffering from alcoholism (r = 0.515, p less than 0.001).
 Multivariate analysis revealed no significant effect of demographic variables on either the AAAI or the SAAST.
 This study shows: (a) impressive concordance between patient and collateral reports; (2) apparent intactness of memory, and little evidence of denial, as measured by the instruments; and (3) the efficacy of measures such as the AAAI and the SAAST, two vastly different scales measuring dimensions of alcoholism.
",20
3403,"Formation of the 37KD protein-acetaldehyde adduct in liver during alcohol treatment is dependent on alcohol dehydrogenase activity.
 Protein-acetaldehyde adducts (protein-AAs) are formed in vivo during chronic alcohol ingestion.
 These protein-AAs reported thus far include a 37KD protein-AA in liver cytosol, cytP450IIE 1-AA in hepatic microsomes, hemoglobin-AA, and serum protein-AAs.
 It has been postulated that acetaldehyde or perhaps a reactive acetaldehyde radical generated by the microsomal ethanol oxidizing system (MEOS or cytP450IIE1) explains the formation of the cytP450IIE1-AA.
 The source of acetaldehyde responsible for the formation of the cytosolic 37KD protein-AA has not been determined.
 In this report, we have examined the effects of pyrazole (an ADH inhibitor) and cyanamide (an aldehyde dehydrogenase inhibitor) on the formation of the 37KD liver protein-AA in vivo and in vitro.
 It was found that feeding rats with an alcohol-containing liquid diet supplemented with cyanamide enhanced while a diet supplemented with pyrazole completely abolished the formation of the 37KD liver protein-AA.
 The liver of rats fed the pyrazole supplemented alcohol-containing diet showed significantly higher content of cytP450IIE1 than that of rats fed the diet containing alcohol alone.
 On the other hand, feeding the cyanamide supplemented alcohol-containing liquid diet did not further enhance the content of cytP450IIE1.
 Similarly, adding cyanamide to the culture medium enhanced while adding 4-methylpyrazole inhibited the production of the 37KD protein-AA by cultured hepatocytes even though the combination of alcohol and 4-methylpyrazole increased the content of cytP450IIE1 2-fold over that in control cells.
 These results demonstrate that the formation of the 37KD liver Protein-AA is dependent on ADH and not on MEOS.
",20
3404,"Acute alcohol ingestion reduces fatty acid extraction of the heart, liver, and small intestine.
 Ethanol may have profound effects on both the distribution of perfusion and substrate utilization by the liver and heart due to its vasodilating properties and the generation of high levels of circulating acetate and lactate.
 Since fatty acids are highly extracted by the heart and liver under normal circumstances, changes in the relationship of perfusion/fatty acid uptake may be a sensitive indicator of both altered perfusion and changes in metabolic substrate availability.
 To test this hypothesis, studies were performed in rats fed 3.1, 6.2, and 9.3 g/kg doses of ethanol.
 Fatty acid uptake was estimated with a 3-methyl substituted reagent with a chain length equivalent to 17 carbons.
 The methyl group in the three position prevented beta oxidation and prolonged the residence of fatty acids in the tissue.
 Eighteen hours after acute alcohol administration, fatty acid uptake was reduced in the heart and the small intestine; in the liver uptake was increased or unchanged.
 Acute ethanol administration also resulted in increased perfusion, as indicated by enhanced uptake of 201thallium by the heart, liver, and small intestine.
 The fatty acid extraction of the heart, liver, and small intestine, defined as the concentration of fatty acid divided by the concentration of 201thallium, was markedly decreased by alcohol ingestion.
 These alcohol effects were dose-dependent and temporally related.
 The data suggest that ethanol ingestion could potentially alter heart function during exercise or following a prolonged fast, when the heart relies primarily upon fatty acids extracted from the circulation to generated adenosine triphosphate (ATP).
",20
3405,"Indications for surgical debridement in 125 human bites to the hand.
 Indications for operative intervention following human bites to the hand were determined based on physical examination and time elapsed since injury.
 One hundred twenty-four patients admitted to Charity Hospital of New Orleans, La, were stratified according to time elapsed from injury to treatment (early, less than 24 hours; delayed, 1 to 7 days; and late, greater than 7 days).
 Patients in the early group were mainly treated with conservative wound care, consisting of local wound exploration and irrigation in the emergency department, while those in the late group underwent surgical debridement.
 Patients in the delayed group either received conservative wound care or underwent debridement in the operating room.
 The early and late groups recovered excellent hand function while results within the delayed group were variable with improved results depending on rapid surgical debridement or drainage.
",20
3406,"Effects of granulocyte-macrophage colony-stimulating factor in burn patients.
 We studied the effects of granulocyte-macrophage colony-stimulating factor in burn patients.
 Serial measurements of granulocyte oxidative function were obtained in treated patients and in a group of controls matched for age and total burn size.
 The administration of granulocyte-macrophage colony-stimulating factor resulted in a 50% increase in mean leukocyte counts.
 Both groups showed significant baseline increases in granulocytic cytosolic oxidative function.
 Treated patients showed normal stimulated cytosolic oxidative function, which was significantly depressed compared with that of untreated patients.
 Myeloperoxidase activity was increased in treated patients during the first postburn week but then declined to normal levels.
 Untreated patients had a significant increase in myeloperoxidase activity for the first 3 weeks following injury.
 Untreated patients exhibited a significant decrease in superoxide activity during the second 3 weeks following injury.
 Treated patients demonstrated normal superoxide activity.
",20
3407,"Universal precautions are not universally followed.
 Adherence to universal blood and body fluid precautions was studied in surgical patient care areas of a university hospital in an effort to identify potentially hazardous health care personnel practices.
 Surgical teams of an 18-unit operating room, three surgical ward patient care teams, and patient care personnel in a 16-bed surgical intensive care unit were observed during routine patient care activities before (study 1) and after (study 2) specific educational programs were held to improve universal precaution compliance.
 Overall, infractions occurred in 57% of 549 observed procedures in study 1 and in 58% of 616 observed procedures in study 2.
 In study 1, infractions occurred in 75% of operating room procedures, 30% of surgical ward procedures, and 75% of surgical intensive care unit procedures.
 Study 2 procedure infraction rates were 81%, 32%, and 40%, respectively.
 Only surgical intensive care unit compliance significantly improved.
 Noncompliance with universal precautions occurs frequently during the care of patients who have undergone surgery, with the type of infraction and specific offender varying according to patient locale.
 These violations appear unamenable to one-time educational efforts.
 Substantial overall improvement may arise from ongoing educational programs directed at specific personnel who care for patients who have undergone surgery.
",20
3408,"Seatbelt effectiveness and cost of noncompliance among drivers admitted to a trauma center.
 Enactment of seatbelt legislation in Maryland presented the opportunity to compare seatbelt compliance among seriously injured drivers admitted to a Level I trauma center and to establish levels of severity, length of stay, and hospital cost differences among the study population.
 Fifty-five randomly selected drivers were examined from a total surgical population of 689.
 Seatbelt compliance rate was 41.8%, reflecting the rate in the community.
 Seatbelts reduced the total number of injuries by 34%, major injuries by 57%, and minor injuries by 20%.
 No deaths occurred among the belted group.
 The unbelted group had a mean Injury Severity Score two times as great as the belted group and were hospitalized 1.6 times longer at double the cost.
 Major injuries to the face, chest, and pelvic regions were prevented by the seatbelt.
 Among the belted group, severe injuries did occur to the head, neck, and abdominal regions.
 It is recommended that both air bags and automatic restraining devices be required for all drivers if the trauma occurring daily on highways is to be eliminated and acute hospital cost minimized.
",20
3409,"Carbidopa-levodopa overdose.
 A 57-year-old woman ingested 15 to 17 tablets of carbidopa-levodopa 10/100 tablets (carbidopa 150 mg and levodopa 1,500 mg) along with ibuprofen, carisoprodol, hydrocodone, and acetaminophen.
 The patient developed choreiform movements that persisted despite obtundation and attempts to extinguish them with naloxone, morphine, and diazepam.
 When the patient developed a rising level of creatine phosphokinase and myoglobinuria, she was treated with ventilatory support and pancuronium.
 She required paralysis for 60 hours, when her chorea resolved.
",20
3410,"The Three Rivers Regatta accident: an EMS perspective.
 The Three Rivers Regatta accident occurred on August 7, 1988 when a Formula I racing craft collided with shore, injuring 24 spectators.
 The authors retrospectively examined the prehospital-based response for this multiple-casualty incident that used emergency medical service (EMS) physicians and 32 paramedics stationed at water and land-based posts to triage and evacuate 24 patients in 32 minutes.
 Patients were transported to 5 hospitals including 4 Level I trauma centers; this was accomplished in 53 minutes.
 The EMS response was unique in a number of respects.
 This was a prehospital-based rescue with the entire triage and stabilization phase accomplished by River Rescue units that transported paramedic divers, EMS physicians, and trauma supplies for 30 patients.
 Also of significance was the inordinate proportion of pediatric patients that accounted for 50% (12/24) of the cases.
 Successful medical care was the result of planning based on ""Daily Routine Doctrine"" or escalation of existing treatment protocol; adequate supplies, personnel and transport adapted to local geography and patient population; communications, including all services--EMS, police, and fire; and prehospital physician input to ensure correct triage order and patient disposition.
",20
3411,"Measurement of end-expiratory pressure during transtracheal high frequency jet ventilation for laryngoscopy 
 An anaesthetic technique using high frequency jet ventilation has been proposed for direct laryngoscopy, but this may expose the patients to the risk of barotrauma.
 In order to assess this risk, we have measured end-expiratory airway pressure (EEP) through the injector using two three-way solenoid valves mounted in series.
 At the end of insufflation the first valve was switched off and the apparatus deadspace connected to atmosphere through a large exit port during an adjustable time (decompression time).
 Then the second valve was switched off and the injection line connected to a transducer, allowing measurement of EEP through the injector.
 The accuracy of this measurement was tested against airway pressure measured directly in the trachea (Pt) in a lung model.
 Provided that the decompression time was long enough (70 ms) and the apparatus deadspace was small (6 ml), the difference between EEP and Pt was less than 1 cm H2O for frequencies up to 5 Hz.
 A clinical evaluation was performed in 64 patients under general anaesthesia before laryngoscopy.
 EEP correlated with end-expiratory pulmonary volume above apnoeic FRC inferred from abdominal and thoracic displacements.
 At jet frequencies up to 5 Hz, the correlations between these two variables were satisfactory (r greater than 0.88), suggesting that EEP is a good indicator of pulmonary overdistension.
",20
3412,"The history and classification of knee braces.
 There has been a great deal of concern within the orthopedic community regarding the lack of objective data available on the multitude of knee braces flooding the marketplace.
 This article hopes to fill that void by presenting an overview of the history and classification of knee braces.
",20
3413,"Choosing functional knee braces.
 Choosing a functional brace for knee injury is a complex issue complicated by a lack of quantitative research on the subject and an increasing number of braces currently on the market.
 The correct brace decision will be facilitated by a better understanding of knee injury biomechanics and by a thorough understanding of the choices available.
 The ultimate selection of a brace should be based on sound mechanical criteria and individualized for each patient.
 The brace must be mechanically effectual and one the patient likes, has confidence in, and will tolerate.
 In combination with aggressive rehabilitation, the functional brace can make a significant contribution to returning individuals to functional activity.
",20
3414,"Functional analysis of anterior cruciate ligament braces.
 Whether or not anterior cruciate ligament (ACL) braces work has been the subject of some debate.
 Research efforts undertaken to understand these braces have been divided into two fronts: static and functional analysis.
 This article explores those issues surrounding the functional analysis of ACL braces.
",20
3415,"The use of knee braces during rehabilitation.
 This article has profiled the use of knee braces as an augmentation to the overall rehabilitation program following knee injury.
 It has also outlined other aspects of rehabilitation, the use of continuous passive motion devices, and other forms of exercises and training that, together with bracing, may enhance patient recovery.
 Continuous passive motion devices have been used for many different orthopedic problems with good success.
 Understanding the mechanics of how these devices move the knee and the forces that can be applied to the knee is helpful in deciding on their use after ligamentous reconstructions.
 Rehabilitation of the knee following surgery requires a good understanding of the effects that each exercise has on the knee and the reconstruction.
 Gradual progression of exercises to the knee following knee ligament reconstruction will not overstress healing tissues.
 Many different types of knee braces exist, and careful evaluation of them may enhance patient recovery.
",20
3416,"The effect of bracing on the collateral ligaments of the knee.
 Disruption of the ligamentous structures of the knee is commonly seen in competitive sports.
 The role of prophylactic and functional bracing is controversial.
 Currently, prophylactic bracing has not been shown, conclusively, to be protective.
 Functional braces appear to have a capacity to provide some protective effect.
",20
3417,"Clinical significance and evaluation of prophylactic knee brace studies in football.
 A review of nine studies of prophylactic knee braces in American tackle football found some support for the use of double-hinge braces in high school but little support for their use at the collegiate level.
 Problems with bias and confounding make it necessary that caution be exercised in the interpretation of the results of these studies, however,.
 To which groups these results might apply must also be considered.
 The two studies that assigned braces randomly found lower injury rates among high school and high-school-sized players for knee injuries and knee ligament injuries.
 Conversely a large, multiteam collegiate study found a significantly higher rate of knee injuries among brace users, a difference that remained when controlled for position, skill, and previous injury.
",20
3418,"Management of smooth-blunt gastric foreign bodies in asymptomatic patients.
 Guidelines for management in the asymptomatic patient with a smooth-blunt gastric foreign body are not well established in the pediatric literature.
 Questionnaires were sent to pediatricians, family practitioners, pediatric gastroenterologists and pediatric surgeons with an over-all response rate of 62.2%.
 There was no agreement in regard to how long one should observe such patients before recommending intervention.
 There was no correlation of years of clinical experience and length of observation recommended either.
 Review of the pre-endoscopic literature revealed spontaneous evacuation in 93-99% of all types of foreign bodies in 1477 pediatric patients.
 An observation period of at least eight weeks should be strongly considered in an asymptomatic patient with a smooth-blunt gastric foreign body.
 Exceptions would include an anatomic abnormality of the gastric outlet, previous gastric outlet surgery as well as a possibly toxic object.
",20
3419,"The clinical value of magnetic resonance imaging in the evaluation of meniscal disorders.
 This prospective double-blind study was designed to evaluate the capability of magnetic resonance imaging to serve as a diagnostic tool in patients who have a clinically suspected disorder of the meniscus.
 The imaging studies provided a diagnostic accuracy of 72 per cent, a sensitivity of 88 per cent, and a specificity of 57 per cent.
 The positive and negative predictive values were 66 and 83 per cent.
 The diagnostic sensitivity was 94 per cent for lesions of the medial meniscus; this value differed significantly from that of 78 per cent for lesions of the lateral meniscus (p less than 0.05).
 The 37 per cent specificity for lesions of the medial meniscus was extremely low compared with the rate of 69 per cent for lesions of the lateral meniscus (p less than 0.01).
 In the intermediate part of the meniscus, the diagnostic sensitivity was 37 per cent on the medial side and 23 per cent on the lateral side; these values were significantly less than the average of 74 per cent for the other meniscal segments (p less than 0.001).
 The imaging studies provided an over-all accuracy of 67 per cent in the detection of degeneration of the meniscus, 78 per cent in the identification of meniscal tears, and 82 per cent in the delineation of postoperative lesions.
",20
3420,"Accuracy of diagnoses from magnetic resonance imaging of the knee. A multi-center analysis of one thousand and fourteen patients.
 Magnetic resonance images of the knee were made for 1014 patients, and the diagnosis was subsequently confirmed arthroscopically.
 The accuracy of the diagnoses from the imaging was 89 per cent for the medial meniscus, 88 per cent for the lateral meniscus, 93 per cent for the anterior cruciate ligament, and 99 per cent for the posterior cruciate ligament.
 The magnetic resonance examinations were done at several centers, and the results varied substantially among centers.
 The accuracy ranged from 64 to 95 per cent for the medial meniscus, from 83 to 94 per cent for the lateral meniscus, and from 78 to 97 per cent for the anterior cruciate ligament.
 The results from different magnetic-resonance units were also compared, and the findings suggested increased accuracy for the units that had a stronger magnetic field.
 Of the menisci for which the magnetic resonance signal was reported to be Grade II (a linear intrameniscal signal not extending to the superior or inferior meniscal surface), 17 per cent were found to be torn at arthroscopy.
",20
3421,"Carpometacarpal dislocations. Long-term follow-up.
 Twenty patients who had a dislocation of one or all of the medial four carpometacarpal joints were followed for an average of 6.5 years (range, 1.5 to 20.5 years).
 Fifteen patients were treated with open reduction and internal fixation during the first three weeks after injury and the long-term result was excellent in thirteen of them.
 Three of the four unsatisfactory results were in patients who had injuries to the normally rigid second and third carpometacarpal joints or had a concomitant ulnar-nerve injury.
",20
3422,"Healing of digital flexor tendons: importance of the interval from injury to repair. A biomechanical, biochemical, and morphological study in dogs.
 The effect of an elapsed interval of time between injury and operative repair of the flexor tendons was investigated in a canine model.
 Transected intrasynovial flexor tendons were repaired either immediately or after a delay of seven or twenty-one days.
 The biomechanical, biochemical, and morphological characteristics were compared at three and six weeks.
 The values for angular rotation, linear excursion, ultimate load, and linear slope were determined; concentrations of collagen and reducible collagen cross-links, an index of newly synthesized collagen, were measured; and the ultrastructural morphology of the tendons was examined by high-voltage electron microscopy.
 For the tendons that were repaired immediately, the values for angular rotation were 9.4 +/- 3.2 and 13.0 +/- 3.7 degrees at three and six weeks; for those that were repaired at seven days, 4.1 +/- 1.3 and 2.5 +/- 1.4 degrees; and for those that were repaired at twenty-one days, 2.7 +/- 0.8 and 4.7 +/- 0.7 degrees.
 There was a significant effect of the delay until repair on the angular rotation and linear excursion in all three groups (p less than 0.005 for both).
 Tensile testing of the bone-tendon complex revealed no significant effect of the delay on the values for ultimate load (p greater than 0.05).
 There were no significant differences in total concentration of collagen at the sites of repair or in the levels of reducible Schiff-base cross-links (indicators of newly synthesized cross-links) in tendons from the three groups.
",20
3423,"Fat distribution and steroid hormones in women with alcohol abuse.
 Anthropometric, hormonal and liver function parameters were examined in 18 premenopausal women with a history of early alcohol abuse, and compared with the data for randomly selected controls of the same age.
 The alcoholic women showed slightly elevated levels of transaminases, but no clinical or laboratory signs of advanced liver damage.
 These women were characterized by an increased waist-to-hip ratio, due to enlarged waist circumference.
 Several endocrine abnormalities were found, including irregular or absent menses as well as low oestrogen, progesterone and delta-4-androstendione levels.
 The concentration of free testosterone was high and that of sex-hormone-binding globulin was low.
 These data suggest abdominal distribution of body fat, as well as hyperandrogenicity in alcoholic, premenopausal women.
 It is postulated that the endocrine abnormalities might be responsible for the abdominal fat distribution.
",20
3424,"Association of self-reported injury and alcohol consumption in medical outpatients.
 OBJECTIVE: This study was designed to examine the association between minor injury and level of alcohol consumption among adult outpatients.
 DESIGN: Self-administered survey of alcohol use and level of injury in prior month.
 SETTING: Adult outpatients attending a university-based general internal medicine private practice.
 PATIENTS/PARTICIPANTS: During a four-month period, 1,011 patients aged 18-65 years were asked to complete questionnaires while waiting to see a physician.
 The 791 who completed all forms appropriately are included in this study.
 INTERVENTION: None.
 MEASUREMENTS AND MAIN RESULTS: The total number of drinks and the total number of injuries reported during the preceding month were calculated.
 Nondrinkers reported an average of 0.51 (SD = 1.18) injuries in the prior month; and drinkers, 0.92 (SD = 1.70) injuries.
 Minor injuries were reported more frequently by heavier alcohol consumers only among younger patients (RR = 1.88).
 There was no association between reported injury and alcohol consumption among patients over 50 years of age (RR = 0.90).
 CONCLUSIONS: Minor injury is associated with heavier alcohol consumption in younger patients attending a general medical practice, but not among older patients.
 Further research is needed to establish a causal relationship between alcohol drinking and minor injury.
",20
3425,"Massive transfusion: outcome in blunt trauma patients.
 Over a 54-month period 6,142 patients were consecutively admitted to our Level I trauma center.
 Ninety-two blunt trauma patients required massive transfusion (MT) of 20 or more units of packed red blood cells (range, 20-126).
 Eighty-two per cent of all transfused blood was given within 24 hours of admission.
 Forty-eight patients (52%) were long-term survivors.
 Twenty-six patients died (28%) within 24 hours and 21 of these exsanguinated.
 Eighteen patients died greater than 24 hours: nine (50%) died from multiple organ failure, and nine (50%) died from severe closed head injury (CHI).
 Clinical predictors of increased mortality were: shock on admission, closed head injury, and age.
 Forty-three survivors were followed for a mean of 2.5 years (range, 1-5 years).
 No patient died during followup.
 All patients were home at 1 year; only four patients required continued medical assistance.
 Thirty-two patients (74%) returned to work.
 We conclude that: 1) blunt and penetrating trauma patients receiving MT have similar survival rates of 50%; 2) shock, closed head injury, and age predict increased mortality but do not preclude survival; 3) long-term outcome in blunt patients requiring MT is excellent.
 Post-discharge death is rare and 3/4 of the survivors return to work, justifying the high cost of acute care.
",20
3426,"How to save fuel and reduce injuries in automobiles.
 Increased fuel economy and reduced injuries have been portrayed as incompatible goals, based on the false assumption that vehicle weight is the determining factor in both.
 Physics predicts that size and velocity, not weight, are the primary factors affecting crash forces, while increased weight or increased velocity consumes more fuel.
 Analysis of fatal injury rates, injury costs, and fuel use relation to vehicle weight, vehicle size, and engine horsepower confirms that weight is of minimal importance in injury severity compared to the other two factors.
 Fuel use is a function of weight and horsepower.
 Injuries and fuel use can be reduced by reducing vehicle horsepower without changing vehicle size.
",20
3427,"High-pressure injection injuries of the hand.
 The majority of high-pressure injection injuries can produce serious damage to the hand.
 Nevertheless, the injury may follow a relatively benign course if the injected substance possesses a less harmful nature.
 Treatment for these injuries requires immediate and aggressive surgery in most circumstances, but conservative treatment may be justified in certain instances.
 During a 4-year period, eight cases of high-pressure injection injury were encountered.
 The types of injected material were: four from paint, and one each from grease, water, benzene, and hydraulic oil.
 Time is an important factor regarding the results, while the types of injected material modify the clinical courses.
 It is advisable that the etiology of high-pressure injection injury should be established initially, and this factor be taken into consideration in choosing treatment options.
",20
3428,"Traumatic rupture of the interventricular septum and tricuspid valve: case report.
 Cardiac injury following blunt trauma is an important cause of morbidity and mortality and is often unsuspected.
 Isolated chamber rupture and valvular injury are infrequent but recognized consequences of nonpenetrating trauma.
 This report describes a patient who developed a perimembranous ventricular septal defect and disruption of the septal leaflet of the tricuspid valve as a consequence of blunt trauma.
 Diagnosis and management of traumatic ventricular septal rupture are discussed.
",20
3429,"Bullet fragment venous embolus to the heart: case report.
 This report describes a case of bullet fragment embolus to the heart following a small-caliber gunshot wound to the mouth.
 Skull and C-spine films appeared to account for the projectile; however, chest X-ray followed by fluoroscopy and two-dimensional echocardiography demonstrated a venous missile embolus in the right heart.
 The bullet was palpated, trapped in the right ventricle, and easily extruded.
",20
3430,"Penetrating injury of a duplicated ureter: case report.
 Duplications of the genitourinary tract are uncommon and may be a source of confusion in the early diagnosis of ureteral trauma when their presence is not suspected.
 We present a case of delayed diagnosis of a penetrating injury to a duplicated ureter and its management.
",20
3431,"Traumatic scapulothoracic dissociation: case report.
 A 23-year-old man suffered traumatic scapulothoracic dissociation (TSD) in a car-vs.-bicyclist accident.
 TSD is a devastating forequarter injury characterized by brachial plexus damage, major upper extremity musculoskeletal disruption, and exsanguinating hemorrhage: our patient survived a hematocrit of 7.
 Prompt recognition and aggressive management of TSD's multiple injuries are crucial.
",20
3432,"Improved outcome with early fixation of skeletally unstable pelvic fractures.
 Thirty-seven consecutive patients with unstable pelvic fractures were divided into two groups: Group 1 (July 1981 to December 1984; n = 18), when early fixation was not routinely used, and Group 2 (January 1985 to March 1988; n = 19), when early fixation was performed unless contraindicated.
 Hospital stay decreased by 37.8% in Group 2 (p = 0.04).
 Of Group 1 patients, 60% were disabled for at least 6 months versus 15.7% in Group 2 (p = 0.001), and 45% were discharged to a rehabilitation facility versus 26.4% in Group 2.
 Group 1 had more complications, 1.3 per patient, versus 1.0.
 Patients in Group 2 (undergoing early fixation) required 27.2% fewer units of blood than those in Group 1 in whom fracture surgery was delayed.
 Survival was better in Group 2, 100% versus 83.3% (p = 0.06).
 Early pelvic fracture fixation reduces hospital stay, long-term disability, and may result in fewer complications, decreased blood loss, and better survival.
",20
3433,"Early measurement of systemic lipid peroxidation products in the plasma of major blunt trauma patients.
 We sought evidence of oxidant-induced biological membrane damage in 43 resuscitated blunt trauma patients (average ISS, 36.9) within 2-6 hours of injury and before anaesthesia and surgery.
 The plasma levels of the lipid peroxidation products (conjugated dienes, CDs A 233 nm) and malondialdehyde (MDA, nMol/ml) and the oxidant-inducing effect of the trauma plasma on normal FMLP-stimulated neutrophils were compared to those of control subjects.
 No differences were observed in the plasma levels of MDA (1.73 +/- 2.15 vs.
 1.45 +/- 0.70 nMol/ml) and CDs (2.07 +/- 2.16 vs.
 1.28 +/- 0.60 A 233nm), or on stimulated neutrophil superoxide production (26.4 +/- 6.9 vs.
 29.0 +/- 6.2 nMol O2-/2 x 10(6) PMNs).
 These observations persisted when the patients were analyzed based on injury severity, the presence of long bone fractures, and the class of shock at presentation.
 We conclude that there is no evidence of oxidant-induced membrane damage manifested by increased plasma levels of CDs or MDA within 2 to 6 hours of blunt injury.
",20
3434,"Spine trauma and associated injuries.
 A longitudinal, prospectively gathered data base of spine trauma has been developed.
 A review of 508 consecutive hospital admissions identified the presence of associated injuries in 240 (47%) individuals, most frequently involving head (26%), chest (24%), or long bones (23%).
 Twenty-two per cent had one associated injury, 15% had two, and 10% had three or more.
 Most spine fractures involved the lower cervical (29%) or thoracolumbar junction (21%).
 Comparisons of presence or absence of associated injuries and spine fracture level showed significant differences (p less than 0.001).
 Eighty-two per cent of thoracic fractures and 72% of lumbar fractures had associated injuries compared to 28% of lower cervical spine fractures.
 While there was no significant relationship between type of associated injury and spine fracture level, those with associated injuries were less likely to have a neural deficit (p less than 0.05).
 After hospital admission, there were seven deaths.
 Early assessment and transport of spine trauma victims must be carried out with appropriate management of associated injuries.
 Conversely, multiple trauma victims must be handled with due regard for a possible spine fracture.
 The value of spinal units with specially trained personnel is emphasized.
",20
3435,"The epidemiology of seatbelt-associated injuries.
 This study examined the frequency of spine and abdominal injuries to motor vehicle occupant crash victims, the relationship between the two types of injuries, and the association with restraint use.
 There were 303 motor vehicle occupants treated at a regional trauma center for spine and/or abdominal injuries over a 5-year period.
 Patients with Chance-type fractures of the lumbar spine were much more likely to be rear seat passengers and to be using a lap belt than were patients with other types of spinal injuries.
 Similarly, patients with hollow viscus injuries were more likely to be rear seat passengers and to be lap belted than were patients with injuries to the spleen, liver, pancreas, or kidneys.
 Nearly two thirds of the lumbar Chance-type fractures were associated with hollow viscus injuries, including six of seven children.
 This increased risk of Chance-type fractures and hollow viscus injuries was associated with increased use of lap-belt seat restraints in the population.
",20
3436,"Fibrinogen degradation product-D, fibrinogen, and serum change polymorphonuclear granulocyte activity--possibly important post-trauma?
 Severe trauma favors the susceptibility of patients to infection.
 It has been shown that proteins or protein fragments are responsible for an endogenous immunodepression.
 After trauma a coagulopathy accompanied by increased serum levels of fibrinogen degradation products (FDP) is often found.
 Therefore, we examined whether FDP-D can influence the activity of polymorphonuclear neutrophils (PMN).
 PMN-activation was measured by two different superoxide-specific methods (Cytochrome-C-test, INT-test).
 With both methods we found a decrease of PMN activity by FDP-D compared to fibrinogen.
 Albumin, which was used as a control protein, only influenced PMN activity in unphysiologically high concentrations.
 The third method used to quantify PMN activity was chemiluminescence, which is a more unspecific method since it is developed not only by oxygen radical species but also by activating the lipoxygenase pathway.
 In contrast to the superoxide specific tests we found an inhibitory effect of fibrinogen and also serum compared to FDP-D using chemiluminescence.
",20
3437,"Delayed union of fibular fractures accompanying fractures of the tibial shaft.
 Among 440 adult patients with tibial shaft fracture and accompanying fibular fracture there were eight cases with radiographically ununited fibulae 4 months after the injury, each with uneventful tibial union.
 Fractures with severe soft-tissue injuries were excluded from this study.
 In 293 patients the treatment method of the tibial fracture was conservative, comprising closed reduction and immobilization by long plaster cast.
 In 147 patients it was intramedullary Kuntscher nailing, and all the eight cases with delayed fibular union occurred among these, the frequency being 5.4%.
 The typical accompanying fibular fracture to develop delayed union was a comminuted one in the middle or distal third of the bone.
 At a followup examination 5 to 8 years after the original injury four of the eight fractures were found to have ultimately spontaneously united, while three showed a radiographically indisputable nonunion.
 One patient had undergone segmental fibular ostectomy because of persistent local pain but in the remaining patients the subjective symptoms were negligible.
 The occurrence of delayed fibular union in association with rigid intramedullary nailing of concomitant tibial shaft fracture is a phenomenon of which trauma surgeons should be aware even if the natural course of the condition often seems to be benign.
",20
3438,"Alcohol and cocaine use among first-year college students.
 We surveyed 1528 first-year students at the University of Virginia, 1 month after their arrival on campus, who had used alcohol at some time in their lives.
 Our survey was designed to identify alcohol and cocaine use, and related psychosocial patterns.
 Men drank more and more often than women.
 Our data suggest that body weight should be considered in defining those who drink heavily and often.
 We define 'frequent heavy drinking' as five or more drinks in a row each week for men and three to four drinks or more in a row each week for women.
 Frequent heavy drinkers, cocaine users, and students with psychosocial problems appeared disproportionately among students planning to join fraternities and sororities.
 Although first-year students used cocaine infrequently, its users followed the patterns of frequent heavy drinkers.
 We believe efforts to correct alcohol and cocaine misuse by college students should be directed, in part, at social organizations such as Greek-letter societies.
 Also, we must attend to psychosocial features that predispose to alcohol and cocaine misuse.
",20
3439,"Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal syndrome 
 We used a pharmacokinetically derived phenobarbital dosing protocol to treat alcohol withdrawal syndrome in patients admitted to a family medicine inpatient service.
 We describe the protocol and include two case reports documenting its efficacy.
 Although benzodiazepine agents are considered by many to be the primary agents of choice, based upon our experience and its ease of administration, relative safety, therapeutic efficacy, and lower cost, phenobarbital should be reconsidered as a promising alternative.
 Comparative trials between these two therapeutic classes will clarify their roles in the treatment of alcohol withdrawal syndrome.
",20
3440,"A survey of drinking patterns during medical school.
 Several studies have documented the common use of alcohol among medical students and the significant fraction of students (7% to 17%) who show a pattern of alcohol abuse.
 Many authors have pointed out the implications of physician impairment due to alcoholism, presently estimated at about 10%.
 We surveyed 263 junior and senior medical students, and our data support earlier surveys of the prevalence of alcohol abuse and indicate that students tend to drink less heavily and less frequently after entering medical school.
 The clinically proven CAGE questions used in the survey showed statistically significant associations between heavy or frequent drinking before and during medical school, but only 4.2% of respondents indicated that school officials had asked whether they had a drinking or drug abuse problem.
 Given these findings, we suggest the routine administration of screening instruments to medical students, using education and minimal intervention strategies with individuals at risk.
",20
3441,"Comparison of lung alveolar and tissue cells in silica-induced inflammation.
 The silicon dioxide mineral, cristobalite (CRS) induces inflammation involving both alveolar cells and connective tissue compartments.
 In this study, we compared lung cells recovered by whole lung lavage and by digestion of lung tissue from rats at varying times after 8 days of exposure to aerosolized CRS.
 Control and exposed rats were examined between 2 and 36 wk after exposure.
 Lavaged cells were obtained by bronchoalveolar lavage with phosphate-buffered saline.
 Lung wall cells were prepared via collagenase digestion of lung tissue slices.
 Cells from lavage and lung wall were separated by Percoll density centrifugation.
 The three upper fractions, containing mostly macrophages, were cultured, and the conditioned medium was assayed for effect on lung fibroblast growth and for activity of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase.
 Results demonstrated that the cells separated from the lung walls exhibited different reaction patterns compared with those cells recovered by lavage.
 The lung wall cells exhibited a progressive increase in the number of macrophages and lymphocytes compared with a steady state in cells of the lung lavage.
 This increase in macrophages apparently was due to low density cells, which showed features of silica exposure.
 Secretion of a fibroblast-stimulating factor was consistently high by lung wall macrophages, whereas lung lavage macrophages showed inconsistent variations.
 The secretion of NAG was increased in lung lavage macrophages, but decreased at most observation times in lung wall macrophages.
 No differences were found among cells in the different density fractions regarding fibroblast stimulation and enzyme secretion.
",20
3442,"Emergency center laboratory evaluation of pediatric trauma victims.
 Emergency center (ER) trauma evaluations often include leukocyte count (LC), serum amylase (SA), electrolytes (EL), and urine analysis.
 We reviewed records of 100 pediatric ER patients to determine utility of these tests in management of blunt injury.
 SA was evaluated in 65 patients and ranged from 30-146 U/L (mean 50.6 U/L); 14 patients with normal CT scans had SA from 30-68 U/L (mean 49.1 U/L).
 Six patients with intraabdominal or retroperitoneal injuries had SA from 30-130 U/L (mean 64.0 U/L), P = NS.
 LC was determined in 76 patients and ranged 2.3-28.3 k/ml (mean 13.8 k/ml).
 Patients with normal abdominal CT (12) had mean LC 14.8 k/ml (range 7.2-19.6 k/ml).
 Eight patients with injuries on CT had mean LC 14.4 k/ml (range 3.5-27.1 k/ml).
 ER, SA, and LC did not alter patient management.
 Thirty-four patients had serum sodium, 36 potassium, and 33 chloride and bicarbonate determinations.
 Sodium, potassium, and chloride levels were uniformly normal; bicarbonate and leukocyte counts were uniformly abnormal in initial evaluations.
 These changes are expected in response to severe injury and their determinations did not alter patient care.
 Combined laboratory urinarlysis (LA) and urine dipstick (DA) analysis for hematuria had sensitivity 75.0 per cent (specificity 81.6%).
 LA predicted injury with sensitivity 75.0 per cent (specificity 81.6%).
 DA predicted injury with sensitivity 60.0 per cent (specificity 79.2%).
 DA accurately represented LA results (sensitivity 100%, specificity of 94.5%).
 DA is a rapid and effective replacement of LA in evaluation of trauma patients in the emergency center.
",20
3443,"Real-time digital contrast enhancement and magnification in the assessment of scaphoid and other wrist injuries.
 A study on the value of a commercially available desk-top digital magnifier-contrast enhancer (DETECT System) was made in a series of 550 patients presenting with an acute wrist injury.
 Four radiologists, of varying experience, independently reviewed the radiographs on a conventional lightbox and later with the digitizer.
 In the scaphoid series (350 cases), the performance of the two more experienced radiologists was marginally better with the digitizer, whereas the less experienced radiologists performed slightly worse.
 Overall the digitizer improved the confidence of the radiologists in diagnosing correctly the presence of a scaphoid fracture but, for the less experienced radiologists, this was at the expense of identifying normality.
 In the wrist series (200 cases), the use of the digitizer resulted in a minor increase in the true positive and decrease in the false negative observations, but this was offset by a concomitant minor increase in the false positive and decrease in the true negative categories.
 Evaluation of the soft-tissue planes around the wrist joint showed a limited value in the identification of a scaphoid fracture with an overall positive predictive value of 0.26.
 Correlation of soft-tissue changes and the presence or absence of a scaphoid fracture was slightly worse with the digitizer.
 Possible causes for the apparently poorer performance of the digitizer are discussed, as well as the relative merits and potential value of the unit.
",20
3444,"The prognostic significance of radiologically detected knee joint effusions in the absence of associated fracture.
 The significance of radiologically detected knee joint effusion as a marker of soft tissue injury following trauma is uncertain.
 In this study 100 patients presenting to the casualty department following acute injury, with effusions but no fracture, were assessed.
 Of those available for follow-up, 20% required further investigation and 11% proceeded to surgery for significant soft tissue injury.
 It is concluded that radiologically detected knee joint effusions are a useful marker for underlying soft tissue injury.
",20
3445,"Assessment of efficacy of activated charcoal for treatment of acute T-2 toxin poisoning.
 ""Superactive"" charcoal was assessed for efficacy in decreasing the lethality of both oral and parenteral exposure to T-2 toxin, a fungal metabolite which can cause death or illness upon ingestion.
 In vitro binding studies, analyzed using the Langmuir adsorption isotherm, showed that activated charcoal had a maximal binding capacity of 0.48 mg toxin/mg charcoal and a dissociation constant of 0.078 mg charcoal/l.
 In vivo, orally administered, activated charcoal was assessed for treatment of acute oral or parenteral exposure to T-2 toxin in mice.
 Following oral toxin administration (5 mg/kg), untreated mice showed only 6% survival after 72 hr.
 Charcoal treatment (7 g/kg,po) either immediately or 1 hr after toxin exposure resulted in significant improvement in survival with values of 100% and 75%, respectively.
 Following parenteral toxin exposure (2.8 mg/kg, sc), untreated and charcoal-treated (7 g/kg, po) mice showed 50% and 90% survival, respectively, after 72 hr.
 LD50 value for T-2 toxin, determined at 96 hr after intoxication, increased significantly from 2 mg/kg for untreated controls to 4.5 mg/kg for activated charcoal treatment.
",20
3446,"The occupational risk of cytomegalovirus infection among day-care providers.
 We prospectively studied day-care providers at six day-care centers in south-eastern Iowa to determine their occupational risk for primary cytomegalovirus infection and to define epidemiologic risk factors.
 Ninety-six (38%) of 252 day-care providers were seropositive for cytomegalovirus by latex agglutination at entry into the study.
 Among 82 seronegative providers available for follow-up, seven seroconversions occurred at only two of the six participating centers, yielding an annualized seroconversion rate of 7.9%.
 Median time to seroconversion among these providers was 13 months.
 Using Kaplan-Meier estimates of risk, we determined that the overall risk of seroconversion among providers at various centers ranged from 0% to 22% by 12 months and from 0% to 40% by 16 months.
 Risk of cytomegalovirus acquisition by providers was independent of race, age, education, the presence of a child at home, or caring for children younger than 2 or 3 years in the day-care center.
 However, the risk of seroconversion among day-care providers appeared to parallel rates of cytomegalovirus excretion and acquisition among children at each center.
",20
3447,"Multiple alcohol-related problems in the United States: on the rise?
 Are drinking problems on the rise in the U.S.
 general population? Surveys of drinking practices and problems conducted in the United States in 1967, 1969, 1979 and 1984 included numerous questions on alcohol-related problems that were identical or nearly identical in wording.
 Using data from these surveys, we tested for ordered increases over time in the prevalence of an indicator of multiple problems, considered on both a current (1-year) and lifetime basis.
 We studied prevalence in men and women between the ages of 22 and 59 in all four surveys.
 Prevalence of the multiple problem indicator was rare, especially when considered on a current basis.
 However, relative increases in prevalence ranging from 53% to over 200% were found from 1967 to 1984 in the multiple problem indicator for men and women, for lifetime as well as current problems.
 With the exception of current problems in women (a very rare condition even in the 1984 survey), these changes were all statistically significant or showed a trend toward significance.
 When respondents were subgrouped by age, all subgroups still showed increases since 1967, although sample sizes decreased and significance tests of ordered increases over time were not so consistent.
",20
3448,"Alcohol-predictive cues enhance tolerance to and precipitate ""craving"" for alcohol in social drinkers.
 This study attempts to show that tolerance to alcohol is in large part a ""learned"" response, precipitated by contextual cues predictive of the unconditional drug effect.
 It also aims to show that the contextual cues integral to such ""environment-dependent"" tolerance function to increase motivational desire to drink alcohol.
 Male students (N = 40), drinking on average 10-20 units of alcohol per week, were randomly assigned to one of four groups.
 Two groups ingested 1.2ml/kg alcohol: one (AL-EXPT) with exteroceptive contextual cues typically associated with alcohol use, and the other (AL-UNEXPT) in a context not normally associated with alcohol.
 A third group (placebo) believed that they were drinking alcohol but, in fact, consumed a nonalcoholic beverage in the alcohol-expected context.
 The fourth group drank juice in the alcohol-unexpected context.
 As predicted, tolerance to the deleterious effects of alcohol on cognition and motor-performance, and subjective desire to consume alcohol, were influenced by the alcohol-predictive contextual cues.
 A physiological index (pulse rate) also tended to confirm that these cues elicited a conditioned compensatory response to alcohol.
 The implications of these findings for tolerance to and motivation to drink alcohol in a nonpathological population are discussed.
",20
3449,"Some boundary conditions for effective use of alcohol placebos.
 The present research assessed the conditions under which subjects who consume alcohol and those who consume a placebo beverage, and who report consuming alcohol on a manipulation check question, are equivalent with respect to subjective responses to alcohol.
 Male subjects were told that they were drinking alcohol and consumed one of four beverages: alcoholic beer, nonalcoholic beer, vodka and tonic with lime, or tonic with lime.
 Measures of subjective intoxication, body sensations and breath alcohol were taken at different times during and after beverage consumption.
 Subjective intoxication ratings were higher for subjects who received alcohol, compared to subjects who received a placebo and reported consuming alcohol, when alcohol subjects achieved blood alcohol concentrations at and above .04%.
 These two groups did not differ in subjective intoxication ratings when alcohol subjects achieved blood alcohol concentrations below .04%.
 These data suggest that the orthogonal manipulation of alcohol consumption and expectancy effects is problematic at and above blood alcohol concentrations of .04%.
",20
3450,"Diagnostic validity of the MAST and the alcohol dependence scale in the assessment of DSM-III alcohol disorders.
 The comparative validity of the Michigan Alcoholism Screening Test (MAST) and the Alcohol Dependence Scale (ADS) in screening for current DSM-III alcohol abuse/dependence disorders is evaluated.
 These scales were administered to 501 patients presenting for treatment of alcohol or drug problems.
 DSM-III alcohol disorders are diagnosed using the Diagnostic Interview Schedule.
 Receiver Operating Characteristic (ROC) analysis is used to determine optimum threshold scores for the MAST and ADS and to compare the screening ability of the two instruments.
 Optimum cut points for the MAST and the ADS are 12/13 and 8/9, respectively.
 The overall accuracy of classification for both instruments using these threshold scores is 88%.
 The areas under the ROC curves are .91 and .90 (SD = .02) and there are no significant differences between the MAST and the ADS in their ability to screen for alcohol abuse or dependence in this population.
 The MAST and the ADS correlate highly with each other (.79).
 The results reported in our study should be applicable to the revised DSM-III since a field trial found a high level of agreement on alcohol disorders between the diagnostic systems.
 Categorical versus dimensional approaches to the assessment of alcoholism are discussed.
",20
3451,"Recent trends in the development of alcohol and drug treatment services in Ontario.
 This article summarizes the major trends in the development of alcohol and drug treatment services in Ontario since 1979.
 These trends are contrasted to the objectives of a province-wide Addiction Research Foundation (ARF) community development program designed to establish or expand addiction services within this same time period.
 Data were obtained from all treatment services in the province by surveys undertaken in 1980, 1983 and 1986.
 Across the period of analysis, there have been rapid increases in the number of addiction programs, their total cost and the total treatment caseload.
 Some specific changes have been quite consistent with ARF objectives: a stabilization in the use of hospital beds for addictions treatment, an increase in community-based versus hospital-based treatment resources, an increase in the province-wide capacity for comprehensive client assessment and a larger representation of women in addictions programs.
 Other ARF objectives have yet to be achieved.
 In particular, a major increase in nonresidential treatment alternatives and an increase in the proportion of treated cases from special populations such as youth or the elderly are still required.
 Suggestions are made concerning future program development.
",20
3452,"Prediction of adults' drinking patterns from the drinking of their parents.
 While studies have shown relationships between adolescent and parental drinking patterns, it is not known if these parental influences are maintained when the children are adults and further removed from early influences.
 A representative general population sample of 6,364 adults living in New York State were interviewed regarding their current drinking as well as about their family structure and the drinking patterns of their parents while they were growing up.
 A logit modeling analysis revealed that natural father's drinking while growing up, natural mother's drinking while growing up, family structure (father present or not) and sex of the respondent were all significant predictors of current heavy drinking of adults even while controlling for all of the other variables in the model.
 It is concluded that early family influences may have long-term consequences on drinking behaviors.
",20
3453,"Drinking in college: consumption patterns, problems, sex differences and legal drinking age.
 Data from 606 (75.8%) undergraduate respondents drawn from a random sample (N = 800) at Rutgers University demonstrate that, although fewer college students may be drinking when compared to some previous estimates, there is still a large number of heavy drinkers.
 In addition, traditional demographic variables continue to predict alcohol consumption levels.
 Students also report a similar variety of drinking related problems as in previous college drinking studies.
 Women constitute half as many heavy drinkers as men, but report an equal amount of alcohol-related problems in this sample.
 When controlling for race, it appears that white students continue to drink the most, and show heavy drinking rates comparable to a previous large college sample in the northeast.
 Students who live on campus drink more than their commuting counterparts, and the drinking age has little effect on consumption levels or total reported alcohol-related problems, although it alters the context of drinking somewhat.
 Findings are generally compared to previous as well as more recent college drinking data.
 Sex differences and similarities are discussed, as well as the findings concerning legal drinking status.
 Implications for prevention efforts are suggested.
",20
3454,"Family background of alcohol abuse and its relationship to alcohol consumption among college students: an unexpected finding.
 The purpose of this study was to determine the possible association between positive family background of alcohol abuse (having a parent or grandparent who sometimes or often drank too much) and the amount of alcohol consumed per week among college students.
 It was additionally to determine the possible differences between students with positive, compared to students with negative, family backgrounds of alcohol abuse in regards to drinking patterns, using a survey instrument that indirectly measures family background for alcohol abuse.
 For this cross-sectional study, a quota sample of 971 college students from all four regions of the United States was selected.
 Results revealed no association between family history and mean amount of alcohol consumed per week for the total sample (r = .007), or for men (r = .04) or women (r = .02).
 Curve analysis indicated a slightly positively skewed curve for the total group and also for male and female students.
 A t test and chi-square analysis found no significant difference between positive and negative family backgrounds and mean amount of alcohol consumed or drinking patterns.
 Among those with positive family backgrounds there was no clustering on a scatter plot for either heavy or light amounts of alcohol consumed.
 The results showed remarkable similarity in alcohol consumption and drinking patterns between students who were classified as having a positive, as opposed to negative, family background.
 It was concluded that having a positive family background for heavy drinking was not associated with either light or heavy alcohol consumption among this national sample of college students.
",20
3455,"Drinking styles of adolescents and young adults.
 Drinking among adolescents and young adults has received more attention during the recent past, but little research has focused on the drinking styles that might characterize younger people.
 A typology of drinking behavior has special relevance for this group, since the adolescent years and young adult years are formative in the development of drinking habits.
 This study used a model that had been applied to ""normal"" drinking behaviors of adults.
 However, the set of drinking variables was expanded to cover a wider range of activities, and a second set of behaviors, intended to reflect potential ""problem"" drinking, were derived from the National Council on Alcoholism criteria for the diagnosis of alcoholism.
 The set of 55 ""normal"" drinking behaviors was factor analyzed, yielding a six-factor structure.
 The first four factors were quite similar to previous work on adult drinking styles, and the remaining two factors clearly related to the drinking of younger people.
 The ""problem"" drinking variables yielded a two-factor structure, one set consisting of serious but uncommon experiences and the second set consisting of less serious and more common experiences.
 Several of the ""normal"" drinking factors were significant predictors of the ""problem"" drinking scores, suggesting that certain styles of drinking are more likely than others to lead to later problems.
",20
3456,"Low-level lead exposure and children's cognitive function in the preschool years.
 In a cohort of 170 middle and upper-middle class children participating in a prospective study of child development and low-level lead exposure, higher blood lead levels at age 24 months were associated with lower scores at age 57 months on the McCarthy Scales of Children's Abilities.
 The mean blood lead level at age 24 months was 6.8 micrograms/dL (SD = 6.3; 75th, 90th, and 99th percentiles: 8.8, 13.7, 23.6, respectively) and for all but 1 child was less than 25 micrograms/dL, the current definition of an ""elevated"" level.
 After adjustment for confounding, scores on the General Cognitive Index decreased approximately 3 points (SE = 1.4) for each natural log unit increase in 24-month blood lead level.
 The inverse association between lead level and performance was especially prominent for visual-spatial and visual-motor integration skills.
 Higher prenatal exposures were not associated with lower scores at 57 months except in the subgroup of children with ""high"" concurrent blood lead levels (ie, greater than or equal to 10 micrograms/dL).
 The concentration of lead in the dentine of shed deciduous teeth was not significantly associated with children's performance after adjustment for confounding.
",20
3457,"Early asbestosis: evaluation with high-resolution CT.
 To determine the earliest stage at which lesions in asbestosis can be diagnosed and to assess their progression, 23 asbestos-exposed patients with minimal or no abnormalities at plain radiography were examined with high-resolution computed tomography (HRCT) twice, with an interval of 12-37 months between examinations.
 In 21 of the patients, parenchymal abnormalities were found.
 Major parenchymal features seen at CT included thickened intralobular and interlobular lines, subpleural curvilinear lines, pleural-based nodular irregularities, hazy patches of increased attenuation, small cystic spaces, and small areas of low attenuation.
 At paired serial CT, subpleural isolated dots or branching structures connected with the most peripheral branch of the pulmonary artery started to appear in lower subpleural zones and then became confluent to create pleural-based nodular irregularities.
 CT-pathologic correlation led to the conclusion that the confluence of subpleural peribronchiolar fibrosis creates subpleural fibrosis.
",20
3458,"Splenic trauma: can CT grading systems enable prediction of successful nonsurgical treatment?
 The capability of computed tomographic (CT) grading systems to enable prediction of successful nonsurgical treatment of splenic trauma in children and adults was evaluated.
 Fifty-six patients with documented splenic injury were examined with CT by use of standard trauma protocols.
 Each CT scan was graded according to two recently proposed grading systems.
 The charts of these patients were then reviewed, and correlations between the CT grade and clinical outcome were determined with each grading system.
 Forty patients underwent successful nonsurgical treatment; three of these patients (8%) underwent delayed celiotomy for splenic rupture after failure of nonsurgical treatment.
 Two of these three had grades that indicated nonsurgical treatment was viable.
 In each of these three patients, splenectomy was necessary.
 In the 16 patients who underwent surgery, eight cases (50%) of CT grading errors were documented with surgery.
 In four cases, the extent of the injury was underscored with CT, and in another four cases the injury was overscored.
 It is still not clear whether the severity of splenic injury as defined with CT correlates with clinical outcome.
",20
3459,"Bullet identification with radiography.
 The authors provide a simple radiographic method for estimating bullet weight and caliber of both deformed and undeformed bullets that enables accurate determination of caliber for the gamut of bullet shapes, with known degrees of confidence.
 The weight-determination procedure is based on the correlation between bullet cross-sectional area, as derived from three orthogonal radiographs, and bullet weight, as determined from a data base of the properties of 48 bullets removed from humans.
 Different equations were developed for bullets weighing 5.8 g or less, or more than 5.8 g.
 For relatively undeformed bullets an additional method calculated caliber directly from the diameter of the bullet body on radiographs.
 Both methods enabled correct prediction of the weight and caliber of the bullets; if one method could not be used, results of the other were reliable.
 Testimony based on these results has been accepted in a local police case and may meet requirements for testimony in U.S.
 court cases involving gunshots.
",20
3460,"Assessing the nutritional needs of the critically ill patient.
 Because critical illness often creates a vigorous metabolic response to permit the repair of injured tissues, nutritional considerations are essential in the medical management of the critically ill patient.
 Individuals with seemingly adequate endogenous nutritional reserves may rapidly develop complications of starvation.
 Nutritional supplementation is essential; however, critically ill patients may not readily tolerate nutritional support.
 Calories may need to be withheld until the patient is able to tolerate and utilize nutritional support.
 Once the decision to initiate nutritional support is made, nutritional status, level of stress, metabolic condition, and vital organ function influence the patient's nutritional requirements.
 An assessment of the patient's metabolic condition provides data useful in determining the need for supplemental electrolytes or macronutrients.
 These data also provide information regarding vital organ function, which is necessary for utilization of the fuel and substrate.
 Aggressive monitoring and judicious nutritional supplementation will afford the critically ill patient the best chance of recovery.
",20
3461,"Familial alcoholism in primary unipolar major depressive disorder.
 OBJECTIVE: Some studies have suggested relationships between depression in probands and alcoholism in relatives.
 Other studies have not, but some of these have used inappropriate control groups or failed to divide probands by sex.
 METHOD: The present study controlled for sex of probands and used several comparison groups to further explore the familial relationship between depression and alcoholism.
 Diagnoses for 723 directly interviewed relatives of 326 probands with primary unipolar depression were compared to diagnoses in 469 control subjects chosen by an acquaintanceship method to demographically resemble the relatives of affective disorder probands.
 Diagnoses in the uninterviewed relatives of both control and depressed subjects were used for comparisons as well.
 RESULTS: Results indicated higher rates of alcoholism in the families of depressed women but not in the families of depressed men.
 CONCLUSIONS: This familial association between alcoholism and depression may be the result of either genetic or environmental factors or an interaction between the two.
",20
3462,"The effect of financial management on alcohol-related hospitalization.
 OBJECTIVE: Treatment-unresponsive alcoholics in New Zealand who are unable to care for themselves tend to be hospitalized for lengthy periods of time.
 The author examined the effect of adding financial management to the therapeutic management of such patients.
 The null hypothesis was that this would have no effect on the duration of alcohol-related hospitalization.
 METHOD: All 61 alcoholic patients registered with an alcohol outpatient clinic who received financial management over a period of 6 years were included in the study.
 Their alcohol-related disabilities were so severe that they had resulted or were likely to result in lengthy or frequent periods of hospitalization.
 The financial management involved putting each patient's income into a checking account for which a budget advisory officer was cosignatory for withdrawals.
 The advisor saw to it that patients' basic living requirements were being met and that expenditure on alcohol was not having a detrimental effect.
 Participation was voluntary for voluntary patients and involuntary for committed patients.
 The durations of each patient's alcohol-related hospitalizations were compared for two equal periods of time before and after financial management was instituted.
 RESULTS: The null hypothesis was not supported.
 The duration of alcohol-related hospitalizations after financial management was instituted was 86% less than it was before such management.
 CONCLUSIONS: For the patient who is struggling in the face of excessive drinking to cope with the tasks of daily living, including the provision of adequate shelter and nutrition, the benefits of adding financial management to other therapeutic strategies should be considered.
",20
3463,"Drug abuse in schizophrenic patients: clinical correlates and reasons for use.
 OBJECTIVE: This study aimed to 1) determine substance abuse prevalence and preference in a diverse sample of schizophrenic, schizoaffective, and schizophreniform inpatients, 2) compare drug-abusing and non-drug-abusing patients on demographic and clinical variables during the acute and stabilization phases of their hospital course, and 3) obtain data from patients on reasons for drug abuse and on acute state-related changes during periods of intoxication.
 METHOD: Eighty-three psychotic inpatients consecutively admitted to a New York City teaching hospital were evaluated.
 Sixty-eight had schizophrenia, 12 had schizoaffective disorder, and three had schizophreniform disorder diagnosed according to the Structured Clinical Interview for DSM-III-R.
 Each patient received ratings on the Brief Psychiatric Rating Scale, the Global Assessment Scale, and the Scale for the Assessment of Negative Symptoms at admission and at discharge, an evaluation of premorbid adjustment, and an extensive interview on drug and alcohol use.
 RESULTS: Forty (48%) of the patients received diagnoses of drug or alcohol abuse or dependence.
 The drug-abusing patients primarily used cannabis (N = 26), alcohol (N = 21), and cocaine (N = 14) and reported that they abused drugs to get ""high,"" to relieve depression, and to relax.
 They had significantly fewer positive and negative symptoms at discharge, better sexual adjustment and worse school performance during adolescence, and more family histories of drug abuse than the non-drug-abusing patients.
 CONCLUSIONS: Schizophrenic patients who abuse drugs may represent a subgroup of patients with better prognoses and less severe clinical characteristics of schizophrenia, but their drug abuse may adversely affect global outcome.
",20
3464,"X-ray fluorescence measurements of lead burden in subjects with low-level community lead exposure.
 A k-x-ray fluorescence (K-XRF) instrument that can measure in vivo bone lead at low levels was used on a population of 34 adults with no known history of excessive lead exposure.
 A questionnaire that gathered information relevant to occupational and environmental lead exposure was administered prior to the measurement.
 A 30-min measurement that produced an average estimated uncertainty of 6 mcg lead/g bone mineral was taken at the mid-tibial diaphysis for each subject.
 Eighteen subjects had bone lead levels below the measurement uncertainty.
 The remainder had bone lead levels ranging up to 21 mcg lead/g bone mineral.
 Bone lead levels were greater among older subjects.
 Among young adult subjects, bone lead levels greater than the measurement uncertainty were confined entirely to subjects who had grown up in housing that was estimated to have been build prior to 1955.
 Such a childhood environment is at high risk of fostering exposure to biologically absorbable lead through ingestion of lead paint-contaminated dust and lead pipe-contaminated water.
 We conclude that the K-XRF technique has the potential to distinguish between low levels of lead burden in epidemiologic studies.
",20
3465,"A clinical pathologic study of four adult cases of acute mercury inhalation toxicity.
 We report four cases of fatal mercury vapor inhalation, a rare occurrence.
 The mercury vapor was released at a private home, where one of the occupants was smelting silver from dental amalgam containing an unknown amount of mercury.
 Within 24 hours of the incident, all occupants began having shortness of breath necessitating hospital admission.
 The clinical courses are briefly detailed; however, all included rapid deterioration with respiratory failure.
 Chest roentgenograms in all four cases were consistent with adult respiratory distress syndrome.
 All patients were treated with dimercaprol, a mercury chelator, but all died, with survival varying from 9 to 23 days postexposure.
 Autopsies were performed on all four patients.
 The lungs in all cases were heavy, firm, and airless.
 Histologic examination revealed severe diffuse alveolar damage, with variable amounts of fibrosis, conforming with acute lung injury in various stages of organization.
 Additional postmortem findings included acute proximal renal tubular necrosis, vacuolar hepatoxicity, and a spectrum of central nervous system alterations including multifocal ischemic necrosis, gliosis, and vasculitis.
",20
3466,"Circadian variation of heart rate is affected by environment: a study of continuous electrocardiographic monitoring in members of a symphony orchestra 
 Twenty four hour ambulatory ST segment monitoring was performed on 48 members (43 players and five members of the management/technical team) of the British Broadcasting Corporation (BBC) symphony orchestra without a history of cardiac disease.
 This period included final rehearsals and live performances (for audience and radio) of music by Richard Strauss and Mozart at the Royal Festival Hall (n = 36) and Rachmaninov and Tchaikovsky at the Barbican Arts Centre (n = 21).
 During the period of monitoring one person (2%) had transient ST segment changes.
 Mean heart rates were significantly higher during the live performances than during the rehearsals.
 Mean heart rates during the live performance of Rachmaninov and Tchaikovsky were significantly higher than during Strauss and Mozart in those (n = 6) who were monitored on both occasions.
 Mean heart rates in the management and technical team were higher than those of the players.
 The recognised circadian pattern of heart rate, with a peak in the morning waking hours, was altered similarly during both concert days, with a primary peak occurring in the evening hours and a lesser peak in the morning for both musicians and management/technical staff.
 This study showed that environmental factors are of primary importance in defining the circadian pattern of heart rate.
 This has important implications when identifying peak periods of cardiovascular stress and tailoring drug treatment for patients with angina pectoris.
",20
3467,"Abuse of elderly people by their carers 
 OBJECTIVE--To assess the prevalence of abuse of elderly people by their carers and the characteristics of abusers and the abused.
 DESIGN--Information on abuse and risk factors was collected over six months from carers and patients.
 Risk factors were identified in the abused group and compared with those in a non-abused control group.
 SETTING--Carers were interviewed at home; patients were examined in the wards of Putney and Barnes geriatric hospitals, London.
 SUBJECTS--All patients referred from any source for respite care to the geriatric services over a six month period and their carers.
 MAIN OUTCOME MEASURES--Amount of physical and verbal abuse or neglect.
 Quantification of risk factors and correlation with the presence or absence of abuse.
 RESULTS--45% Of carers openly admitted to some form of abuse.
 Few patients admitted abuse.
 The most significant risk factor for physical abuse was alcohol consumption by the carer (p less than 0.001).
 Other significant risk factors were a poor pre-morbid relationship and previous abuse over many years.
 Abuse was often reciprocated and was associated with social dysfunction in many patients.
 Service delivery, respite care, and level of mental and physical disability were not significantly associated with abuse.
 CONCLUSION--The high level of abuse found in elderly patients in respite care was particularly associated with alcohol abuse and long term relationships of poor quality, which are difficult to change.
 Even with increased provision of services, care in the community may not be the best solution for these people.
",20
3468,"Intrapulmonary distribution of bronchial blood flow after moderate smoke inhalation.
 The systemic blood flow to the airways of the left lung was determined by the radioactive microsphere technique before and 17 h after smoke inhalation in six conscious sheep (smoke group) and six sheep insufflated with air alone (sham group).
 Smoke inhalation caused a sixfold increase in systemic blood flow to the lower trachea (baseline 10.6 +/- 1.7 vs.
 injury 60.9 +/- 16.1 ml.min-1.100 g-1) and an 11- to 14-fold increase to the intrapulmonary central airways (baseline range 9.5 +/- 1.9 to 13.5 +/- 3.7 ml.min-1.100 g-1 vs.
 injury 104.6 +/- 32.2 to 187.3 +/- 83.6 ml.min-1.100 g-1).
 There was a trend for this hyperemic response to be greater as airway diameter decreased from the trachea to 2-mm-diam central airways.
 In airways smaller than 2 mm, the hyperemic response appeared to diminish.
 The total systemic blood flow to whole lung is predominantly to small peripheral airways and showed no significant increase from its baseline level of 17.5 +/- 3.7 ml.min-1.100 g-1 in the lung homogenate.
 Occlusion of the bronchoesophageal artery decreased central airway blood flow 60-80% and peripheral airway blood flow 40-60% in both the sham and the smoke groups.
",20
3469,"Toxic epidermal necrolysis (Lyell syndrome).
 Toxic epidermal necrolysis is perhaps the most formidable disease encountered by dermatologists.
 Uncommon but not rare, toxic epidermal necrolysis occurs in 60 to 70 persons per year in France.
 It remains as puzzling a disorder as it was 34 years ago, when described by Lyell.
 Whether or not toxic epidermal necrolysis is the most severe form of erythema multiforme is still the subject of discussion.
 The physiopathologic events that lead to this rapidly extensive necrosis of the epidermis are not understood.
 Indirect evidence suggests a hypersensitivity reaction, but the search for potential immunologic mechanisms has resulted in little data to support this hypothesis.
 Accumulated clinical evidence points to drugs as the most important, if not the only, cause of toxic epidermal necrolysis.
 Sulfonamides, especially long-acting forms, anticonvulsants, nonsteroidal anti-inflammatory agents, and certain antibiotics are associated with most cases of toxic epidermal necrolysis.
 Many other drugs have been implicated in isolated case reports.
 All organs may be involved either by the same process of destruction of the epithelium as observed in the epidermis or by the same systemic consequences of ""acute skin failure"" as seen in patients with widespread burns.
 Sepsis is the most important complication and cause of death.
 Approximately 20% to 30% of all patients with toxic epidermal necrolysis die.
 Elderly patients and patients with extensive lesions have a higher mortality rate.
 Surviving patients completely heal in 3 to 4 weeks, but up to 50% will have residual, potentially disabling ocular lesions.
 The prognosis is improved by adequate therapy, as provided in burn units, that is, aggressive fluid replacement, nutritional support, and a coherent antibacterial policy.
 Corticosteroids, advocated by some in high doses to halt the ""hypersensitivity"" process, have been shown in several studies to be detrimental and should be avoided.
",20
3470,"Protective behavior of captopril on Hg(++)-induced toxicity on kidney mitochondria. In vivo and in vitro experiments.
 Mercurials are known to induce morphological and functional modifications in kidney mitochondria.
 In this work we studied in vitro and in vivo the protective effect of captopril on the deleterious effect of Hg(++)-induced nonspecific membrane permeability changes to Ca++ and membrane de-energization.
 In vivo the administration of captopril prevented the toxic effects of mercury poisoning on membrane permeability, oxidative phosphorylation and Ca++ homeostasis.
 Moreover, captopril preserves kidney tissue morphology from Hg(++)-induced damage.
 The protective effect of captopril is most likely related to the existence of a sulfhydryl group in the drug.
",20
3471,"Energy balance in elderly patients after surgery for a femoral neck fracture.
 To study energy and protein balances in elderly patients after surgery, spontaneous energy and protein intake and resting energy expenditure (REE) were measured in 20 elderly female patients with a femoral neck fracture (mean age 81 +/- 4, SD, range 74-87 years; weight 53 +/- 8, range 42-68 kg) during a 5-6 day period following surgery.
 REE, measured over 20-40 min by indirect calorimetry using a ventilated canopy, averaged 0.98 +/- 0.15 kcal/min on day 3 and decreased to 0.93 +/- 0.15 kcal/min on day 8-9 postsurgery (p less than 0.02).
 REE was positively correlated with body weight (r = 0.69, p less than 0.005).
 Mean REE extrapolated to 24 hr (24-REE) was 1283 +/- 194 kcal/day.
 Mean daily food energy intake measured over the 5-day follow-up period was 1097 +/- 333 kcal/day and was positively correlated with 24-REE (r = 0.50, p less than 0.05).
 Daily energy balance was -235 +/- 351 kcal/day on day 3 (p less than 0.01 vs zero) and -13 +/- 392 kcal/day on day 8-9 postsurgery (NS vs zero) with a mean over the study period of -185 +/- 289 kcal/day (p less than 0.01 vs zero).
 When an extra 100 kcal/day was allowed for the energy cost of physical activity, mean daily energy balance over the 5-day study period was calculated to be -285 +/- 289 kcal/day (p less than 0.01 vs zero).
 Measurements of total 24-hr urinary nitrogen (N) excretion were obtained in a subgroup of 14 patients.
",20
3472,"Use of human growth hormone combined with nutritional support in a critical care unit.
 The administration of growth factors may potentially accelerate recovery during critical illness by reducing body protein catabolism, enhancing wound healing, and improving skeletal muscle function.
 The purpose of this phase 1 study was to evaluate the safety and initial efficacy of a recombinant growth factor, human growth hormone (GH), combined with nutritional support in a critical care unit.
 Following an initial control week, 11 individuals received GH (10 mg/day) daily for 1-6 consecutive weeks.
 Near constant nutrient intake was provided via parenteral and/or enteral feedings throughout the study period.
 Vital signs and other clinical parameters, blood values, and nutrient excretion were monitored daily.
 GH administration was not associated with clinically significant adverse effects.
 During the first 2 weeks of study, nitrogen excretion decreased from 1356 +/- 157 mmol/day (19.0 +/- 2.2 g/day) during control to 899 +/- 107 mmol/day (12.6 +/- 1.4 g/day) with growth hormone (p less than 0.002) in association with markedly reduced urea generation.
 Significant reductions in potassium excretion (control 100 +/- 11 mmol/day vs 69 +/- 6 with GH; p less than 0.01) and phosphorus excretion (31 +/- 5 mmol/day vs 18 +/- 3; p less than 0.025) also occurred during GH.
 The protein-conserving effects of GH were sustained during several weeks of treatment.
 Growth hormone enhanced the efficiency of administered protein and facilitated nitrogen retention without clinically significant adverse effects in this small patient group.
 Controlled trials are indicated to determine whether use of this anabolic hormone reduces hospitalization time and improves other clinical outcomes in severely injured patients when combined with appropriate nutritional support.
",20
3473,"Factors contributing to increased energy expenditure in thermal injury: a review of studies employing indirect calorimetry.
 In summary, a remarkably close agreement exists for the mean MEE measured in 28 studies of severe burn trauma.
 This is especially surprising given the variability in sample sizes, measurement techniques, study designs, and DPBs studied.
 The mean MEE calculated from the data published in these reports is listed in the final column of Table I.
 For more than 450 cases, an unweighted MEE is 2750 +/- 85 kcal/day.
 For those studies prior to 1980, the mean MEE exceeds 3000 kcal/day in eight of 14 reports vs only two of 14 published after 1980.
 Even so, the mean MEE for the pre-1980 reports differs by only 200 kcal/day (2960 +/- 120, n = 14).
 The accepted notion that the degree of elevation in MEE is in proportion to the % BSAB up to about 60% BSAB is useful in a general sense but must be applied with caution.
 The recent studies, which include proportionately more burns exceeding 80% BSAB, suggest an elevation in MEE in these cases.
 Nevertheless, a physiologic plateau apparently exists at or slightly below 2 x normal RMR at the peak of MEE.
 The magnitude of the MEE response results from an undefined interaction among several factors of which some have been examined while others such as inflammatory mediators are only beginning to receive study.
 The contributions to reduction in MEE from interventions to control cardiac output and peripheral cooling, core temperature, evaporative water (heat) loss, and substrate cycling have been reviewed.
 The importance of indirect calorimetry in patient care is highlighted by the large variability in similarly injured individuals and in the unexplained component of regression analyses.
",20
3474,"Biomechanics of lumbar pedicle screw/plate fixation in trauma.
 This investigation was conducted to determine alterations in the biomechanical strength and stiffness characteristics of the lumbar spine fixated with Steffee instrumentation.
 Comparative studies of these parameters were conducted using seven lumbar columns from fresh human cadavers.
 Three runs were conducted on each T12-L5 column: control, injured, and fixated.
 The specimens were loaded under the compression-flexion mode until failure (control run) and then reloaded (injury run) to the failure deformation determined in the control run.
 Screw/plates were then inserted one level proximal and distal to injury, and the specimens were reloaded (fixation run).
 Radiographs were taken before and after each trial.
 Data on deformation and force histories were gathered.
 The load-deflection response of the injured and fixated specimens were bimodal with two representative stiffnesses.
 Control failure loads and stiffnesses were higher than those for the injured (P less than 0.001) or fixated (P less than 0.01) spine.
 Initial stiffness was significantly higher for the fixated than for injured columns (P less than 0.001), but the final stiffnesses were similar.
 The increase in the initial stiffness in the fixated specimen compared to the injured specimen indicates the strength added to the posterior region of the spine.
 The relatively smaller alteration in the final stiffness between the fixated and the injured columns, corresponding to the load shared by the anterior column, may suggest that, above a critical strain level, the anterior column absorbs a higher portion of the external load and posterior fixation may be inadequate as sole treatment in trauma.
",20
3475,"Free vascularized thin corticoperiosteal graft.
 This paper describes a new thin corticoperiosteal graft harvested from the medial condylar and supracondylar areas of the femur.
 It is based on the articular branch of the descending genicular artery and vein and consists of periosteum with a thin (0.5 to 1.0 mm) layer of outer cortical bone.
 By retaining the cortex, the cambium layer is preserved, and this is thought to have a better osteogenic capacity than vascularized periosteal grafts.
 This graft was used to treat six patients with fracture nonunion of the upper extremity in which conventional treatment had failed.
 Uneventful bony union was achieved in all patients within 10 weeks.
",20
3476,"Simultaneous bilateral forearm revascularization.
 A successful simultaneous bilateral forearm revascularization was performed on a 17-year-old boy.
 Functional recovery of both forearms was evaluated 42 months after injury.
 The patient can use both hands for the activities of daily living.
 So far, he has been employed and has no significant psychological problems.
 Temporary intraluminal silicone shunts are extremely helpful for reducing ischemic damage to the injured limb.
 The sufficient skeletal shortening of the upper limb replantation is crucially important.
 The wounds must be managed by aggressive and repeated debridement.
 Accurate primary nerve repair is essential, and the early postoperative rehabilitation is also important to achieve a satisfactory functional return.
 The functional replanted or revascularized upper extremity is superior to an amputation or prosthesis, especially in the cases of bilateral upper extremity amputation or devascularization.
",20
3477,"Theodor Kocher and the Scientific Foundation of Wound Ballistics.
 The systemic and rational approach used by Kocher, coupled with his interest in research of wound ballistics for more than 40 years, resulted in a clear elucidation of the principles that form the basic scientific foundation of modern wound ballistics.
 The validity of his work has been proved repeatedly on the battlefields of the world for more than a century.
 Presently, more than ever before, the sound scientific precepts revealed by Kocher are essential to keep technologic investigation within the framework of good judgment.
",20
3478,"Nail-gun suicide.
 Two cases are reported of young men who committed suicide using a nail gun.
 One shot himself through the heart and left lung.
 The other shot himself in the head.
 No cases of completed suicide by nail gun have previously been reported in the English literature.
 These cases are reported because of their uncommon nature and because they represent a potentially fatal use of a relatively common industrial implement.
",20
3479,"Suicides by starter's pistols and air guns.
 We report the case of a 25-year-old depressed woman who committed suicide with a starter's pistol loaded with CS tear-gas ammunition.
 The propellant gases of the contact shot entered her chest through the left sixth intercostal space.
 Exsanguination was caused by perforations of the pericardium and apex of the heart.
 Autopsy did not reveal any metallic or other foreign bodies that might have originated from the propellant, the cartridge, or any bulletlike material.
 Her injuries were thus caused by the propellant alone.
 0.5 mg L-1 of the CS degradation product cyanide was detected in the cardiac blood.
 We also report the case of a 54-year-old man, suffering from depressive psychosis, who committed suicide with an air rifle.
 The lead-pointed Diabolo bullet entered his brain through the right large wing of the sphenoid bone, traversed the right temporal brain pole, damaged the right middle cerebral artery and the right optic tract, and finally lodged in the left central ganglia.
 There was extensive basal subdural hemorrhage and tamponade of all cerebral ventricles.
 Death was attributed to cerebral failure.
 We furthermore list another 26 cases of suicide by rarely used weapons from 1947 to 1989.
",20
3480,"Forensic photography. Ultraviolet imaging of wounds on skin.
 The use of ultraviolet light (UVL) to study and document patterned injuries on human skin has opened a new frontier for law enforcement.
 This article discusses the photographic techniques involved in reflective and fluorescent UVL.
 Documentation of skin wounds via still photography and dynamic video photographic techniques, which utilize various methods of UV illumination, are covered.
 Techniques important for courtroom presentation of evidence gathered from lacerations, contusions, abrasions, and bite marks are presented through case studies and controlled experiments.
 Such injuries are common sequelae in the crimes of child abuse, rape, and assault.
",20
3481,"A suicide by thiopentone infusion.
 A suicide by intravenous thiopentone infusion is described.
 A search of the literature revealed only four cases, but this paucity is possibly due to under-reporting, as these suicides occur amongst medical personnel.
",20
3482,"Homicide-suicide by stabbing.
 It is rare that an assailant kills someone and afterward commits suicide by stabbing himself on the scene.
 This report describes how a young soldier killed his young girlfriend and then killed himself.
",20
3483,"Wrist slashing in a detention center. Case report and review of the literature.
 Suicides that occur in custody are rare and thus require extensive forensic analysis.
 Asphyxia by hanging is the most common means of suicide: at least 87.5% of successful suicides are committed in this way.
 A unique case of suicide in custody is presented in which a prisoner slashed his wrist with an eyeglass lens.
 The evidence and proceedings that led to this suicide are reviewed and the data are compared with known behavioral patterns.
 The world literature concerning suicide while incarcerated is reviewed.
",20
3484,"Suicide by chloroform ingestion following self-mutilation.
 A case of suicide is described that combined elements of psychotic self-mutilation, both chronic and terminal, and poisoning with ingested chloroform.
 This illustrates the need to consider unusual methods when investigating the deaths of people with patterns of bizarre behavior and access to unusual, fatal materials.
",20
3485,"Ineffectiveness of dantrolene sodium in the treatment of heatstroke.
 STUDY OBJECTIVE: To determine the efficacy of dantrolene sodium in the treatment of heatstroke.
 DESIGN: Randomized, double-blind, placebo-controlled trial.
 SETTING: Heatstroke center in Makkah, Saudi Arabia.
 PATIENTS: Fifty-two adult patients with heatstroke.
 INTERVENTIONS: Patients were assigned to receive either dantrolene sodium (2 mg/kg body weight iv) or placebo.
 Conventional cooling therapy was initiated in all.
 MEASUREMENTS AND MAIN RESULTS: There was no significant difference in the mean cooling times for the treatment and control groups (67.9 vs.
 69 min).
 There was only one death in the control group.
 Complications were seen in six (23%) patients receiving dantrolene sodium and seven (27%) patients receiving placebo; the difference was not statistically significant.
 There was no significant difference in the mean number of hospital days (4.7 +/- 2.0 vs.
 2.9 +/- 0.9 days).
 CONCLUSION: Treatment with dantrolene sodium at the dose used, did not prove beneficial to patients with heatstroke.
",20
3486,"Mandibular ramus anatomy as it relates to the medial osteotomy of the sagittal split ramus osteotomy.
 The sagittal split ramus osteotomy is probably the most frequently used procedure for correction of mandibular skeletal dentofacial deformities.
 Despite numerous improvements in the technique in the 30 years since the procedure was introduced, a number of troublesome complications still occur.
 These include unfavorable fracture during surgery, paresthesia, and relapse.
 The purpose of this study was to determine where fusion of the buccal and lingual cortical plates occurs in the upper mandibular ramus, as it is thought that placement of the horizontal medial osteotomy above the point of fusion (without any intervening medullary bone) may lead to unfavorable fracture during splitting.
 Forty-nine human mandibles were sectioned vertically at three locations perpendicular to the surface of the ramus and the occlusal plane.
 Measurements were made to locate vertically the point of fusion of the buccal and lingual cortical plates relative to the lingula and to the depth of the sigmoid notch.
 The point of fusion occurred between 7.5 and 13.3 mm above the lingula.
 Only 2% of mandibles had fusion at or below the level of the lingula in the anterior ramus, whereas in the posterior ramus, 6.1% of mandibles were fused at that level.
 At a level halfway from the lingula to the sigmoid notch, 20% of mandibles were fused in the anterior ramus, whereas in the mid- to posterior ramus, the incidence was as high as 39%.
 The location of the medial horizontal osteotomy should be at or just above the tip of the lingula.
 A higher level of cut may be associated with an increased difficulty in splitting or incidence of unfavorable fracture.
",20
3487,"Cocaine metabolite detection in homicide victims.
 We analyzed the blood of homicide victims for the presence of cocaine's major metabolite, benzoylecgonine.
 During 1989 in Fulton County, Georgia, 81% of 275 homicide victims were tested for benzoylecgonine; 40% tested positive.
 The proportions of blacks and victims of firearm injuries who tested positive for benzoylecgonine were significantly larger than the respective proportions for whites and victims of injuries not involving firearms.
 The data show overall proportions of benzoylecgonine positivity much larger than those previously reported in the literature.
 The relationships between homicide, race, firearms, and cocaine use deserve further study.
",20
3488,"Predictive value of historical and physical characteristics for the diagnosis of child abuse.
 Child abuse by burning may be difficult to recognize, especially since the injuries are often small.
 Historical and physical findings that can be elicited in the initial examination can be helpful in initiating a more in-depth investigation.
 An injury inconsistent with the history given or a delay in seeking medical treatment were the two most frequent reports that elicited suspicion.
 As isolated findings, however, they had a low predictive value.
 The presence of two or more of 13 factors increased the yield in child abuse identification to more than 60%.
",20
3489,"Childhood firearms fatalities: the Metropolitan Dade County experience.
 I reviewed the cases of childhood firearms fatalities in the files of the Medical Examiner Department of Metropolitan Dade County, in Miami, Florida.
 Comparison of cases during the 5-year period from 1966 through 1970 to those during the 5-year period from 1984 through 1988, noting basic epidemiologic parameters, showed that death due to firearms is increasing among children aged 14 years and younger.
",20
3490,"Anterolateral ankle dislocation without fracture.
 Dislocation of the tibiotalar joint without associated fracture is rare.
 We have presented a case of open anterolateral ankle dislocation with complete ligamentous disruption.
 In contrast to reports that internal fixation is not required to maintain reduction of tibiotalar joint dislocation, we found this dislocation to be grossly unstable, requiring both a syndesmotic screw and a calcaneotalotibial transfixing pin for stabilization.
",20
3491,"Alcohol abuse in adolescents.
 Alcohol abuse among teenagers is an increasing problem with serious physical and social consequences.
 Early diagnosis of adolescent alcoholism may be delayed for two reasons: the physical indicators of alcohol abuse seen in adults are often not identifiable in teenagers, and alcoholism is generally believed to be an adult problem.
 If the history is taken carefully, with respect and confidentiality, it can help the family physician determine the extent of a young person's alcohol abuse and begin the process of treatment for both the adolescent patient and the family.
",20
3492,"Left ventricular size, mass and function in relation to the duration and quantity of heavy drinking in alcoholics.
 Left ventricular (LV) hypertrophy and mild dysfunction are frequently observed in alcoholics but little is known about how they relate to the duration and severity of alcohol abuse.
 LV size, mass and function were studied using echocardiography and systolic time intervals in 78 middle-aged male alcoholics who also gave detailed accounts of the duration of heavy drinking, the quantity of recent ethanol consumption and the duration of abstinence.
 Compared with 34 healthy nonalcoholics, alcoholics had a higher LV mass index (85 +/- 2 [mean +/- standard error] vs 77 +/- 2 g/m2, p = 0.001), a thicker posterior wall (11 +/- 0.2 vs 10 +/- 0.2 mm, p = 0.02), a longer end-systolic diameter index (18 +/- 0.3 vs 17 +/- 0.3 mm/m2, p = 0.02), and a higher preejection period/ejection time ratio (0.36 +/- 0.01 vs 0.33 +/- 0.01, p = 0.002).
 In multivariate linear regression models, these abnormalities proved independent of the drinking history, except that posterior wall thickness was weakly related to the duration of heavy drinking (standardized correlation coefficient 0.36, p = 0.01).
 Univariate analyses suggested that the LV mass index and systolic time interval ratio had, if anything, a curvilinear relation to the total duration of heavy alcohol consumption.
 It is concluded that the LV hypertrophy and dysfunction found in alcoholics are poorly related to the duration and severity of self-reported alcohol abuse.
 Together with other data, this suggests that there is no simple linear dose-injury relation in the long-term cardiotoxicity of ethanol.
 Factors modifying the myocardial effects of ethanol need to be studies more in the future.
",20
3493,"Motorcycle licensure, ownership, and injury crash involvement.
 The interrelationships among motorcycle licensure, ownership, and injury crash involvement were investigated in a sample of 2,723 motorcycle drivers severely or fatally injured in California in 1985-86.
 Owners of motorcycles in such crashes (""driver-owners"") were less likely to have valid licenses than a random sample of motorcycle owners who had not been in crashes (42 vs.
 57 percent).
 Thirty-three percent of the crash-involved drivers had valid motorcycle driver's licenses; 39 percent were operating motorcycles they did not own (""driver-nonowners"").
 Driver-nonowners were less likely to be validly licensed than driver-owners (20 percent vs.
 44 percent).
 The licensing rate of crash-involved driver-nonowners was 15 percent if the owner was also unlicensed.
 Rates of valid licensure were lowest among the youngest drivers.
 Virtually no crash-involved driver-nonowners under age 21 were licensed in cases in which the owner was also young and unlicensed.
",20
3494,"Alcohol use and abuse in random samples of physicians and medical students.
 BACKGROUND.
 This study sought to resolve conflicting views about whether physicians are especially prone to alcohol abuse.
 METHODS.
 Using an anonymous, mailed questionnaire on substance use, we surveyed 500 physicians, 510 pharmacists, and 974 of their students.
 The physicians and pharmacists were selected randomly from the state society's membership lists, and students selected were from local school lists.
 Follow-up surveys were sent to nonresponders at two-week intervals.
 RESULTS.
 The physicians and medical students did not drink especially heavily and were no more vulnerable to alcoholism than were their counterparts in pharmacy and other professions.
 Physicians differed from pharmacists in their style of drinking (greater frequency, smaller quantity), but not in total amount of alcohol consumed.
 Drinking habits among physicians were not associated with medical specialty or type of practice, but were positively related to gender (males drank more than females) and to age (older doctors were more apt to qualify as heavy drinkers than were younger doctors).
 CONCLUSIONS.
 Physicians were no more likely to abuse substances nonmedically than were other professionals.
 Any group in which alcohol use is nearly universal incurs a risk of abuse and impairment that cannot be ignored.
",20
3495,"Responsible alcohol service: a study of server, manager, and environmental impact.
 A responsible alcohol-service training program was evaluated for its impact on changing beliefs, knowledge, and behavior in 97 servers and 43 managers and on changing establishment policies that encourage safer drinking environments.
 The training program had a significant impact on changing the beliefs and knowledge of both servers and managers.
 Observation 4 to 6 weeks after training showed no effects on server behavior, but there was a tendency toward more establishment policies compared with controls.
",20
3496,"Spinal cord injury: prognosis for ambulation based on sensory examination in patients who are initially motor complete.
 The purpose of this retrospective study was to document that patients with motor complete injury, but preserved pin appreciation, in addition to light touch, below the zone of injury have better prognoses with regard to ambulation than patients with only light touch preserved.
 Medical records were examined of all spinal cord injury (SCI) patients admitted between 1982 and 1988.
 Twenty-seven Frankel B patients with upper motor neuron lesions admitted within 72 hours of injury were identified.
 These patients were divided into two groups (B-1 and B-2).
 Group B-1 (n = 18) were patients who had touch sensation but no pin appreciation below the zone of injury.
 Group B-2 (n = 9) were patients who had partial or complete pin appreciation and light touch below the zone of injury.
 The charts were examined for the patient's ability to walk independently using a reciprocal gait for at least 200 feet.
 The data were analyzed by the Fisher Exact test.
 Eight of the nine Group B-2 patients ambulated as compared to two of the 18 Group B-1 patients (p less than .0002).
 Frankel B SCI patients with only touch preserved below the zone of injury had poor prognoses for ambulation; those with preserved pin appreciation below the zone of injury had excellent prognoses to regain functional ambulation.
",20
3497,"Chronologic age, time since injury, and time of measurement: effect on adjustment after spinal cord injury.
 People are now living longer after spinal cord injury (SCI), yet only limited research has addressed the issue of aging and adjustment after SCI.
 The purpose of this study was to use a time-sequential design to identify the relationship between adjustment after SCI and three facets of aging; chronologic age, time since injury, and time of measurement.
 Life Situation Questionnaires were obtained from one sample of participants with SCI in 1974 (n = 256) and from a second sample in 1985 (n = 193).
 Participants were grouped into five cohorts based on chronologic age, five cohorts based on time since injury, and two groups based on time of measurement (1974, 1985).
 Two two-way MANOVA's were performed, one between chronologic age and time of measurement, and the other between time since injury and time of measurement.
 Results indicated that chronologic age and time since injury often worked in opposing directions; as some aspects of adjustment declined with greater chronologic age, but other aspects improved with increasing time since injury.
 Activity was strongly related to chronologic age, but medical stability was more strongly related to time since injury.
 Both chronologic age and time since injury were correlated with some aspects of life satisfaction.
 Comparisons between the two times of measurement (1974, 1985) indicated some limited positive changes in adjustment with time.
 The results point to the complexity of the relationship between aging and adjustment and the need for rehabilitation professionals to consider multiple aging factors.
",20
3498,"Post-traumatic hyperlipofuscinosis in the human retinal pigment epithelium.
 Light microscopy (including fluorescence microscopy) and electron microscopy were applied to a study of the photoreceptor-retinal pigment epithelium (RPE) complex in a human eye which had been severely traumatised nine months prior to enucleation.
 The main feature of interest was a massive accumulation of lipofuscin in the retinal pigment epithelium at the posterior pole, and quantitative fluorescence microscopy provided values three times those obtained in appropriate control tissue.
 The photoreceptor layer was normal at the posterior pole but became progressively atrophic towards the periphery.
 The concentration of lipopofuscin was proportional to the degree of preservation of the retinal photoreceptors.
 By electron microscopy the cells in the RPE were seen to be packed with a mixture of lipofuscin granules and melanolysosomal complexes, but occasional photoreceptor phagosomes were found.
 Bruch's membrane and the choriocapillaris were normal.
 We attribute this hitherto unreported abnormality of the RPE after trauma to a dysfunction consequent on an overload of the monolayer by photoreceptor debris at the time of trauma.
",20
3499,"Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression.
 Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy.
 Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value.
 In vivo studies in our laboratory have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice.
 Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated.
 C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure.
 On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined.
 Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects.
 For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice.
 At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice.
 These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.
",20
3500,"Bell ringers' bruises and broken bones: capers and crises in campanology 
 OBJECTIVE--To determine the incidence, aeriology, and outcome of injuries due to bell ringing.
 DESIGN--Retrospective review of the last six years' issues of Ringing World, advertisement in Ringing World, and a postal questionnaire sent to 20 active ringing towers.
 SUBJECTS--Regular bell ringers.
 RESULTS--Seventy nine injuries were identified both from review and by advertisement in Ringing World.
 The incidence of injury among 221 ringers identified by postal questionnaire was 1.8% a year.
 CONCLUSION--Although sonerous, bell ringing can be dangerous and occasionally even fatal.
 Doctors should be aware of the dangers to which campanologists expose themselves.
",20
3501,"Occurrence and repetition of hospital admissions for accidents in preschool children 
 OBJECTIVES--To examine trends over time in the rates of admission to hospital for accidents of preschool children and to study patterns of repeated admissions for accidents in these children.
 DESIGN--Analysis of linked, routine abstracts of hospital inpatient records for accidents.
 SETTING--Six districts in the Oxford Regional Health Authority covered by the Oxford record linkage study.
 SUBJECTS--Records for 19,427 children aged 5 years and under at the time of first recorded admission to hospital.
 MAIN OUTCOME MEASURE--Number of admissions to hospital.
 RESULTS--Records were analysed in three groups: person based annual admission rates were calculated for each calendar year; each child's first recorded admission in 1976-85 was identified, and the child's record was followed up by linkage for one year from that admission; each child's first recorded admission in 1976-81 was identified and followed up for five years.
 Overall, 19,427 children from an average annual resident population of 163,000 children in 1976-86 had 20,657 admissions for accidents before they were 6 years of age.
 Of these admissions 13,983 were for injuries, 5717 for poisonings, and 957 for burns.
 Admission rates declined after 1976 for poisoning, but no substantial changes over time were found in admission rates for injuries or burns.
 A total of 17,724 children were followed up for one year and 10,889 for five years; 470 (2.6%) of the children who were followed up for one year and 926 (8.5%) of those followed up for five years had at least one further admission for an accident.
 Of those followed up for one year the 4 and 5 year old children were least likely and those under 1 and 1 year old were most likely to have a further admission for an accident.
 The number of children who had more than one accident was greater than would be expected if accidents were random occurrences.
 Those who had a poisoning at first admission were more likely to have another poisoning than an injury or burn; and those who had a burn at first admission were more likely to have another burn.
 CONCLUSIONS--Hospital admissions for accidents in children are common: on average 1 child in 88 in this population was admitted each year.
 Multiple admissions are uncommon but none the less occur more often than would be expected by chance.
",20
3502,"Dose-response relationships for the effects of insulin on glucose and fat metabolism in injured patients and control subjects.
 1.
 Twenty-four patients were studied at around 7 days after musculoskeletal injuries in order to define the nature of the impairment of sensitivity to insulin.
 Insulin was infused at 6, 35, 200 or 1200 m-units min-1 m-2 for 2 h and the plasma glucose concentration was 'clamped' at 5 mmol/l.
 Forearm (uninjured) glucose extraction and blood flow were measured, and whole-body substrate oxidation and energy production rates were assessed by indirect calorimetry.
 The patients were compared with normal control subjects.
 2.
 Plasma insulin concentrations during infusion were similar in patients and control subjects, showing a similar metabolic clearance of insulin.
 At each infusion rate, the rate of glucose infusion needed to maintain euglycaemia was less in the patients than in the control subjects.
 The dose-response curve for whole-body glucose infusion rate against plasma insulin concentration showed diminished sensitivity and diminished maximal response in the patients.
 A similar pattern was seen for forearm glucose uptake, with a marked impairment of both sensitivity to insulin and maximal responsiveness.
 3.
 The resting metabolic rate was increased in the patients compared with the control subjects, but failed to respond to insulin infusion, so that final metabolic rates were similar in patients and control subjects.
 At the higher insulin infusion rates, the final rate of whole-body oxidation of carbohydrate was significantly less in the patients than in the control subjects, and that of fat was significantly greater.
",20
3503,"Percutaneous screw fixation for fractures of the scaphoid.
 We describe a percutaneous technique for screw fixation of all types of fractures of the scaphoid.
 During a 15-year period ending in 1984, 280 cases were treated by this method; 198 of them returned for evaluation in 1986 and comprise the material for this report.
 After a mean postoperative time of 82 months, 89% of the recent fractures had united as well as 81.8% of those with delayed or nonunion and 42.8% of those with sclerotic nonunion.
",20
3504,"Fracture-separation of the distal humeral epiphysis.
 We have reviewed 12 cases of fracture-separation of the distal humeral epiphysis, three of which were initially misdiagnosed as fractures of the lateral condyle and one as an elbow dislocation.
 Cubitus varus deformity is as common after this fracture-separation as it is following supracondylar fracture, and is most common in children under two years of age.
 Closed reduction and simple immobilisation is adequate for the older child, but we recommend for those under two years of age that closed reduction should be followed by percutaneous pinning, so that the carrying angle can be assessed immediately after reduction.
 If the elbow is then in varus the wires should be removed, reduction repeated and treatment by straight lateral traction used to maintain a valgus carrying angle.
",20
3505,"Bone structure after removal of internal fixation plates.
 We used single-photon absorptiometry to assess the forearm bones after the removal of internal fixation plates in 14 patients.
 We found convincing evidence of cortical atrophy in only one patient, in whom the plates had been removed prematurely after only 16 months.
 It is suggested that such plates should be retained for at least 21 months, to allow bone density to return to its prefracture level.
 The recommendations of the AO/ASIF group are supported.
",20
3506,"Femoral head blood flow in femoral neck fractures. An analysis using intra-osseous pressure measurement.
 We studied 50 patients with fractures of the femoral neck, 33 intracapsular and 17 extracapsular.
 Intraosseous pressure was measured by a transducer within the bone to quantify blood flow, and intracapsular pressure by a needle introduced into the joint space.
 The mean intracapsular pressure was lower in the extracapsular fractures.
 In these, the mean intraosseous pressure in the femoral head was unchanged by aspiration of the joint.
 However in the intracapsular fractures aspiration produced a significant decrease in intra-osseous pressure and an increase in pulse pressure within the femoral head.
 The results suggest that aspiration of intracapsular haematoma produced an increase in femoral head blood flow by relieving tamponade.
",20
3507,"Alcohol consumption and synthesis of ethyl esters of fatty acids in adipose tissue.
 Ethyl esters of fatty acids (EEFA) have been found to be formed during ethanol metabolism.
 Human adipose tissue contains high concentrations of free fatty acids, the substrate for EEFA synthesis, and might therefore be a tissue with great potential for EEFA formation.
 In order to explore their potential usefulness as markers of alcohol abuse, the EEFA concentration and the activity of EEFA-synthesizing enzyme were therefore determined in adipose tissue from men belonging to the following categories: teetotalers, social drinkers, alcoholics under treatment, or established alcoholics found to have died as a result of alcohol intoxication.
 In order to estimate the half-life of EEFA and the synthase activity induction, the alcoholics were examined after different time periods of abstinence from alcohol.
 Comparisons were also made with several established markers of alcohol abuse.
 EEFA were not found in teetotalers, and were found in low concentrations in some of the social drinkers.
 EEFA were found in several alcoholics, and the forensic cases had high concentrations.
 EEFA-synthesizing enzyme activity was found in all subjects, increasing from teetotalers to social drinkers, and being 2-fold higher in alcoholics and 5-fold higher in dead alcoholics.
 The induction of the enzyme after abstinence appeared to have a half-life of the order of several weeks.
 Correlations were found between EEFA synthase activity and previously established markers of alcohol abuse known to remain for a long time period after abstinence, such as mean erythrocyte corpuscular volume.
 This preliminary study suggests the possibility that EEFA synthase induction in adipose tissue might have a longer half-life than previously used markers of alcohol abuse.
 It is therefore suggested that the induction of EEFA synthase might be a potentially useful new marker for alcohol abuse because of its apparent proportionality to alcohol intake over a prolonged time period, its presumed specificity, and long-term elevation after alcohol abstinence.
 This potential marker should be analysed further.
",20
3508,"A landmark case in asbestosis.
 The first published account of disease attributed to occupational asbestos exposure was that of Nellie Kershaw, who died in 1924.
 The circumstances relating to that case are described and explanations are given for its not having a greater impact on policy at that time.
 This case, starting in 1898, is set in the context of missed opportunities for preventing a major public health hazard.
 The effects of this hazard are still being witnessed today.
",20
3509,"Diving-related inner ear injuries.
 Diving-related inner ear barotrauma (IEB) and inner ear decompression sickness (IEDS) most often result in permanent severe cochleovestibular deficits, unless immediate diagnosis is reached and the correct treatment is commenced early.
 Nine cases of sport-diving-induced inner ear injuries that were referred to the Israeli Naval Hyperbaric Institute between October 1987 and September 1989 are presented with regard to evaluation, treatment, and follow-up.
 The diagnosis was IEB in five divers and IEDS in four.
 Explorative tympanotomy was carried out with remarkable results in two patients with IEB, while the remaining three were relieved by bed rest alone.
 Three of the four IEDS patients were recompressed according to the extended US Navy Table 6 with good short-term results.
 The role of complete otoneurological evaluation in the decision-making process leading to the correct diagnosis and treatment is emphasized.
",20
3510,"Three-dimensional computerized tomography in the evaluation of laryngeal injury.
 A comparison of diagnostic information obtained from the physical examination, conventional two-dimensional axial computerized tomography scanning (2-D CT), and three-dimensional display computerized tomography (3-D CT) was performed in five patients sustaining laryngeal trauma.
 Four patients had laryngeal fractures and one patient had an incompletely ossified thyroid cartilage (normal variant) simulating a fracture by 2-D CT.
 Three-dimensional display computerized tomography was found superior to conventional 2-D CT in assessing the presence and nature of the laryngeal injuries while correctly identifying the anatomic variant.
",20
3511,"Secondary prevention of low-back pain. A clinical trial.
 A clinical trial, aimed at secondary prevention of low-back pain, was performed in 142 hospital employees reporting at least three annual episodes of this condition.
 Participants were randomly assigned to one of three groups: a calisthenics program (CAL) for 3 months with biweekly sessions of flexion exercises, a back school program (5 sessions), and a control group.
 The effectiveness of the two intervention programs was evaluated over a 1-year period.
 Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected.
 A monthly surveillance for the whole year showed a mean of 4.5 ""painful months"" in the CAL group versus 7.3 and 7.4 months in the back school and control groups, respectively (P less than 0.0001).
 The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength.
 The increased trunk flexion was associated with the rate of participation in the CAL sessions.
 Further research is needed to answer the question of ""intensity versus type of exercise"" by comparing different intervention programs, with similar intensity.
",20
3512,"Effect of 3-hydroxybutyrate on posttraumatic metabolism in man.
 Of 20 patients suffering trauma, with Injury Severity Scores greater than 20, 11 patients received DL-3-hydroxybutyrate (3-OHB) at a rate of 25 mumol/kg/min for 3 hours.
 The remaining nine patients received sodium DL-lactate at the same rate as the control subjects.
 With increased arterial concentrations of ketone bodies, the femoral arteriovenous difference (arterial concentration minus venous concentration) of ketone bodies increased proportionally in the 3-OHB group (R = 0.853, p less than 0.001).
 Venous concentrations of nonesterified free fatty acids, alanine, glycine, and valine were decreased significantly in the 3-OHB group as compared to the control group.
 The concentration difference between femoral vein and artery (venous concentration minus arterial concentration) for these substrates also decreased, indicating decreased release from the extremity.
 A decrease in venous concentration of alanine and difference between femoral vein and artery reached 102.3 +/- 69.3 mumol/L and 32.6 +/- 22.8 mumol/L (mean +/- SD), respectively, after 3-OHB infusion.
 Decreased alanine release from muscle during 3-OHB infusion in traumatized patients suggests a suppressive effect of ketone body on posttraumatic protein catabolism.
",20
3513,"Use of a composite skin graft composed of cultured human keratinocytes and fibroblasts and a collagen-GAG matrix to cover full-thickness wounds on athymic mice.
 In patients with extensive full-thickness burns, wound coverage may be accelerated if skin can be expanded to produce a skin replacement that reproducibly supplies blood to the wound and has good structural qualities.
 In addition, development of skin replacements may benefit patients who require reconstruction or replacement of large areas of abnormal skin.
 We have developed a composite skin replacement composed of cultured human keratinocytes (HK) and fibroblasts.
 Cultured human fibroblasts are seeded into the interstices, and cultured HKs are applied to the surface of a matrix composed of type I collagen crosslinked with a glycosaminoglycan, which has a defined physical structure.
 After HKs reach confluence on the matrix surface, the composite grafts are placed on full-thickness wounds on the dorsum of athymic mice.
 Graft acceptance, confirmed by positive staining with antibodies specific for human HLA-ABC antigens on HKs, is approximately 90%.
 A defined skin structure is present histologically by day 10 after grafting, with a differentiated epithelium and a subepidermal layer densely populated by fibroblasts and capillaries without evidence of inflammation.
 Fluorescent light microscopy to identify laminin and type IV collagen and electron microscopy confirm the presence of basement membrane components by 10 days after grafting.
 Attachment of the graft to the wound is similar with and without the addition of human basic fibroblast growth factor, a potent angiogenic agent, to the skin replacement before graft placement on wounds.
",20
3514,"Relation between respiratory symptoms, type of farming, and lung function disorders in farmers.
 Respiratory symptoms and function were examined in a random sample of 181 farmers (124 pig farmers and 57 dairy farmers) with a mean age of 43 years.
 Wheezing and shortness of breath during work in the animal house were significantly associated with pig farming (odds ratio 11.4), current smoking (odds ratio 2.2), bronchial hyperreactivity (odds ratio 3.8), and low FEV1 (odds ratio 3.4).
 Pig farmers had a slightly lower FEV1 than dairy farmers (101% versus 104% predicted, NS).
 Symptomatic farmers had significantly lower FEV1 than symptomless farmers (93% versus 106% predicted).
 A multiple linear regression analysis of the cross sectional values of FEV1 showed that there was a decline in FEV1 associated with pig farming (-12 ml/year of pig farming) and smoking (-23 ml/pack year) in addition to the age related decline of 32 ml/year.
 A multiple linear regression analysis of PC20 histamine showed that bronchial reactivity increased with age, number of pack years, and number of years in pig farming.
 Work in closed pig rearing units is a pulmonary health hazard and causes decline in lung function.
",20
3515,"Characteristics of 60 adult chronic hair pullers.
 OBJECTIVE: This study was constructed to detail the demographic and phenomenological features of chronic hair pullers as well as to assess psychiatric comorbidity in a sizable study group.
 METHOD: Subjects were drawn from an outpatient population of chronic hair pullers who had been referred to a trichotillomania clinic or had responded to a newspaper advertisement announcing a treatment study of adults who pull out their hair.
 Sixty adult chronic hair pullers completed a semistructured interview that focused on their hair-pulling behavior and demographic characteristics and that incorporated screening questions for DSM-III-R axis I disorders.
 The data were tabulated to derive a comprehensive picture of this group.
 RESULTS: The typical subject was a 34-year-old woman who had pulled hair from two or more sites for 21 years.
 All subjects described either tension before or relief/gratification after pulling hair from the primary site, but 17% (N = 10) failed to describe both of these characteristics and thus failed to fulfill the DMS-III-R criteria for trichotillomania.
 Forty-nine subjects (82%) qualified for past or current axis I diagnoses other than trichotillomania.
 Several characteristics of the study group suggested phenomenological differences between obsessive-compulsive disorder and trichotillomania.
 CONCLUSIONS: Adult trichotillomania is a chronic disorder, frequently involving multiple hair sites, and is associated with high rates of psychiatric comorbidity.
 Its relation to obsessive-compulsive disorder requires further clarification.
 The tension-reduction requirement in DSM-III-R for the diagnosis of trichotillomania may be overly restrictive.
",20
3516,"Transdermal nicotine and smoking behavior in psychiatric patients.
 The authors used a double-blind crossover design to observe the effect of transdermally administered nicotine on the smoking behavior of 13 psychiatric patients who were not trying to stop smoking.
 The patients smoked significantly fewer cigarettes while receiving nicotine than while receiving placebo.
 These data suggest that transdermally administered nicotine can be a useful adjunct in treating nicotine-addicted psychiatric patients in a non-smoking environment.
",20
3517,"Diagnostic peritoneal lavage. Limited indications due to evolving concepts in trauma care.
 This study was undertaken to determine the appropriateness of celiotomy in 100 consecutive patients who underwent celiotomy solely because of positive diagnostic peritoneal lavage (DPL) following blunt (B) or stab (S) abdominal trauma.
 A total of 32 (32%) patients had positive DPL by laboratory criteria: blunt trauma: greater than 100K RBC/mm3, greater than 500 WBC/mm3; stab trauma: greater than 50K RBC/mm3, greater than 250 WBC/mm3.
 DPL in 68 patients was positive by gross inspection; 18 of these 68 patients' DPL laboratory results returned after surgery and did not satisfy the laboratory definition of positive DPL.
 In all 61 per cent underwent therapeutic celiotomy (TC) and 39 per cent underwent nontherapeutic celiotomy (NTC).
 Grade I and II spleen and/or liver injuries led to 79 per cent of NTCs.
 Positive DPL, determined by gross inspection or by laboratory testing, has a very poor accuracy rate when evaluated in light of evolving beliefs that promote nonoperative therapy for grade I and II liver and spleen injuries.
 When positive DPL is the sole indication for celiotomy in patients with blunt or stab abdominal trauma, an unacceptably large number of NTCs will be performed.
 DPL should have a limited role in the evaluation of patients with abdominal trauma.
",20
3518,"Splenic trauma. Choice of management.
 The modern era for splenic surgery for injury began in 1892 when Riegner reported a splenectomy in a 14-year-old construction worker who fell from a height and presented with abdominal pain, distension, tachycardia, and oliguria.
 This report set the stage for routine splenectomy, which was performed for all splenic injury in the next two generations.
 Despite early reports by Pearce and by Morris and Bullock that splenectomy in animals caused impaired defenses against infection, little challenge to routine splenectomy was made until King and Schumacker in 1952 reported a syndrome of ""overwhelming postsplenectomy infection"" (OPSI).
 Many studies have since demonstrated the importance of the spleen in preventing infections, particularly from the encapsulated organisms.
 Overwhelming postsplenectomy infection occurs in about 0.6% of children and 0.3% of adults.
 Intraoperative splenic salvage has become more popular and can be achieved safely in most patients by delivering the spleen with the pancreas to the incision, carefully repairing the spleen under direct vision, and using the many adjuncts to suture repair, including hemostatic agents and splenic wrapping.
 Intraoperative splenic salvage is not indicated in patients actively bleeding from other organs or in the presence of alcoholic cirrhosis.
 The role of splenic replantation in those patients requiring operative splenectomy needs further study but may provide significant long-term splenic function.
 Although nonoperative splenic salvage was first suggested more than 100 years ago by Billroth, this modality did not become popular in children until the 1960s or in adults until the latter 1980s.
 Patients with intrasplenic hematomas or with splenic fractures that do not extend to the hilum as judged by computed tomography usually can be observed successfully without operative intervention and without blood transfusion.
 Nonoperative splenic salvage is less likely with fractures that involve the splenic hilum and with the severely shattered spleen; these patients usually are treated best by early operative intervention.
 Following splenectomy for injury, polyvalent pneumococcal vaccine decreases the likelihood of OPSI and should be used routinely.
 The role of prophylactic penicillin is uncertain but the use of antibiotics for minor infectious problems is indicated after splenectomy.
",20
3519,"Increased gut permeability following burn trauma.
 Twenty female Hartley guinea pigs, weighing 350 to 400 g, were given a 30% full-thickness burn injury.
 Gastrointestinal permeability was assessed before burn and on postburn days 1 through 3, 7, and 14 by administering 5 mL of an isotonic mixture of 8% lactulose and 1.15% L-rhamnose by gavage and measuring the urinary excretion for the next 7 hours.
 In normal guinea pigs, lactulose (molecular weight, 342d) is mostly absorbed by the paracellular route, whereas L-rhamnose (molecular weight, 164 d) is mostly absorbed by the transcellular route.
 Gut permeability to L-rhamnose did not increase after burn injury (211 micrograms before burn vs 230, 260, 180, 238, and 221 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn).
 By contrast, gut permeability to lactulose increased significantly and was greatest in the first 48 hours after burn injury (60 micrograms before burn vs 380, 354, 203, 364, and 279 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn).
 Gut permeability to low-molecular-weight compounds increases immediately after burn trauma, and this may be by a paracellular rather than transcellular mechanism.
",20
3520,"Injecting drug use and female street-working prostitution in Glasgow.
 There are considerable difficulties associated with calculating the prevalence of covert, illegal and stigmatized activities.
 This paper outlines new methods we have developed for calculating the prevalence of both drug-injecting street prostitution and non-injecting street prostitution in Glasgow.
 Our data indicate that Glasgow has a much higher level of injecting drug use than has been reported among prostitutes in other British cities.
",20
3521,"Downregulation of the platelet surface glycoprotein Ib-IX complex in whole blood stimulated by thrombin, adenosine diphosphate, or an in vivo wound.
 In washed platelet systems, thrombin has been demonstrated to downregulate the platelet surface expression of glycoprotein (GP) Ib and GPIX.
 In the present study, we addressed the question as to whether, in the more physiologic milieu of whole blood, downregulation of platelet surface GPIb and GPIX can be induced by thrombin, adenosine diphosphate (ADP), and/or by an in vivo wound.
 Thrombin-induced downregulation of GPIb and GPIX on the surface of individual platelets in whole blood was demonstrated by the use of flow cytometry, a panel of monoclonal antibodies (MoAbs) and, to inhibit fibrin polymerization, the peptide glycyl-L-prolyl-L-arginyl-L-proline.
 Platelets were identified in whole blood by a GPIV-specific MoAb and exclusion of monocytes by light scattering properties.
 Flow cytometric analysis of whole blood emerging from a standardized bleeding-time wound established that downregulation of platelet surface GPIb and GPIX can occur in vivo.
 A GPIb-IX complex-specific antibody indicated that the GPIb and GPIX remaining on the surface of platelets activated in vivo or in vitro were fully complexed.
 Simultaneous analysis of individual platelets by two fluorophores demonstrated that thrombin-induced platelet surface exposure of GMP-140 (degranulation) was nearly complete at the time that downregulation of platelet surface GPIb-IX was initiated.
 However, degranulation was not a prerequisite because ADP downregulated platelet surface GPIb-IX without exposing GMP-140 on the platelet surface.
 Inhibitory effects of cytochalasins demonstrated that the activation-induced downregulation of both GPIX and GPIb are dependent on actin polymerization.
 In summary, downregulation of the platelet surface GPIb-IX complex occurs in whole blood stimulated by thrombin, ADP, or an in vivo wound, and is independent of alpha granule secretion.
",20
3522,"Superior humeral dislocation. A complication following decompression and debridement for rotator cuff tears.
 Very large rotator cuff tears may be surgically irreparable and under such circumstances debridement of the edges of the cuff and bursal decompression may relieve pain.
 In this paper, four cases are described of the development of superior migration of the humeral head following a debridement and bural decompression.
 In all four patients attempts were made to repair the rotator cuff.
 In each case the repair failed and the humeral head migrated.
 Two of the patients had the humeral head replaced because of a fracture; in these patients the prosthesis displaced upwards.
 This serious complication may follow debridement and release of the subacromial bursa when rotator cuff repair cannot be achieved.
 In the correction of superior humeral migration, reestablishment of the roof of the bursa was carried out in two cases.
 This procedure appears effective and may be considered in the future for such cases.
",20
3523,"The surgical treatment of severe comminuted intraarticular fractures of the distal radius with the small AO external fixation device. A prospective three-and-one-half-year follow-up study.
 Although fractures of the distal radius are very common, an optimal treatment has not been clearly delineated.
 This is a prospective study of 40 patients, mainly young and active adults, with comminuted and unstable intraarticular fractures of the distal radius.
 The end results of closed reduction and rigid fixation with the small AO external fixator includes 36 patients (90%) with excellent and good results.
 Roentgenograms of 33 of these patients showed accurate alignment of the healed fractures.
 Four patients (10%) had a fair functional result, with a partial restriction of the range of movement, although roentgenograms demonstrated good alignment of the healed fractures.
 The small AO external fixator is both a useful and convenient method for the reconstruction and treatment of comminuted intraarticular fractures of the distal radius.
",20
3524,"A semiinvasive method for articular Colles' fractures.
 An external fixation device that allows limited motion of the wrist joint without disruption of the anatomic alignment was used for the articular Colles' fractures in this study.
 From July 1985 to April 1989 during a 45-month period, 87 patients with 90 articular Colles' fractures (three cases with bilateral involvement) were treated with a modified dynamic external skeletal device after a closed reduction in full supination of the forearm.
 Excellent anatomic reduction near 91% of the sound wrist as well as satisfactory functional results around 90.5% of the sound wrist were gained during the 24-month follow-up period.
 Forearm muscles exert compression forces on distal radial metaphyseal fractures throughout the healing period.
 Any procedure or device that cannot provide constant counterforce to the action of forearm muscles during fracture healing will result in the loss of anatomic reduction.
 Adequate distraction counter-force was provided by an external fixation device that was superior to other conventional methods because of its simple application, low rate of complications, and excellent anatomic and functional results.
",20
3525,"Diagnostic and operative arthroscopy of the wrist.
 The evaluation and diagnosis of wrist disorders has traditionally been difficult and problematic.
 Ligamentous wrist sprains and their associated carpal instabilities, triangular fibrocartilage complex disruptions, and cartilage injuries have been virtually impossible to fully assess because of the inadequacy of current diagnostic techniques.
 Arthroscopy of the wrist allows a thorough evaluation of the soft-tissue structures and cartilaginous surfaces within the radiocarpal and midcarpal joints.
 In selected cases, wrist arthroscopy can be employed to surgically modify the intraarticular lesions and to assist in the planning of reconstructive operations.
",20
3526,"Intercondylar notch measurements with special reference to anterior cruciate ligament surgery.
 The femoral intercondylar notch width was measured in 93 patients with chronic anterior cruciate ligament (ACL) insufficiency (Group 1), in 62 patients with an acute tear of the ACL (Group 2), and in 38 fresh anatomic specimen knees (Group 3).
 In six of the specimen knees, further anatomic studies of the intercondylar notch were performed after tissue removal.
 The average intercondylar distance was 16.1 mm in Group 1, 18.1 mm in Group 2, and 20.4 mm in Group 3.
 All differences were highly significant.
 The intercondylar notch was wider in the posterior part and had no crossing bony ridges but had generally concave walls, which provided a functional shelf for the ACL to insert on the lateral side.
 Significant osteophyte formation and stenosis of the anterior outlet of the intercondylar notch occur early in the ACL-deficient knee.
 A narrow anterior outlet of the intercondylar notch without osteophytes was also found in knees with an acute ACL rupture.
 At reconstruction of the ACL, notchplasty should be performed concomitantly.
",20
3527,"Anterior-cruciate-insufficient knees treated with physiotherapy. A three-year follow-up study of patients with late diagnosis.
 To evaluate a functional neuromuscular training program focusing on strength, endurance, postural control, and agility, 26 patients with a rupture of the anterior cruciate ligament (ACL) diagnosed late were examined before starting a training period and then followed for three years.
 During the study period, four of the patients had an ACL reconstruction.
 Twenty-two patients treated without surgery were satisfied with the improvement in their knee function and activity level after three to six months of physiotherapy.
 Compliance with the rehabilitation program was good and the improvement achieved on completion of the training period was maintained for three years in this group of recreational sportsmen and women.
 Quadriceps strength, functional knee score, activity level, and functional performance were all improved after training and were maintained during the follow-up period.
",20
3528,"Dislocation of the knee.
 The results of treatment for vascular and ligamentous injuries in 17 patients who suffered complete dislocation of the knee were reviewed.
 Eight patients had 23 associated injuries.
 All nine patients who had injuries of the popliteal artery had arterial reconstruction with saphenous vein bypass grafts, which were successful in eight (89%).
 Intraoperative arteriography after vascular repair showed a narrowed anastomosis requiring revision in two (22%) of the nine patients and distal thrombi requiring removal in five (55%) patients.
 Delay in arterial repair was responsible for the one failure.
 Eleven patients had satisfactory results after early open ligament repair.
 The results were less favorable in the patients not treated with early ligament repair.
",20
3529,"Varus of the talus in the ankle mortise secondary to calcaneus fracture. A case report.
 Varus displacement of the talus in the ankle mortise secondary to a calcaneus fracture was observed in a 33-year-old man.
 Similar to the calcaneus fracture-dislocation, the mechanism involved inferior and medial displacement of the talus into the body of the calcaneus.
 The patient's ankle deformity was not corrected by a lateral ankle ligament reconstruction.
 Correction required a distraction subtalar bone block fusion.
 Successful reconstruction of the hindfoot after calcaneus fractures requires a careful analysis of the pathologic lesion.
 In this unusual case, correction required restoration of lost hindfoot bone structure.
",20
3530,"Blunt traumatic rupture of the heart and pericardium: a ten-year experience (1979-1989).
 Blunt traumatic rupture of the heart and pericardium, rarely diagnosed preoperatively, carries a high mortality rate.
 From 1979 to 1989, more than 20,000 patients were admitted to a Level I trauma center.
 A retrospective review identified 59 patients requiring emergency surgery for this condition.
 Injuries resulted from vehicular accidents (68%), motorcycle crashes (10%), pedestrians being struck by vehicles (7%), falls (5%), crushing (7%), and being struck by a horse (2%) or crane (2%).
 Seventeen patients (29%) had isolated rupture of the pericardium; 37 (63%) had ruptures of one or more cardiac chambers.
 All patients had signs of life at the scene or during transportation, but only 29 (49%) had vital signs on admission: 15 with chamber injury, 12 with pericardial rupture, and two with combined injuries.
 Diagnosis was established by emergency thoracotomy in the 30 patients who arrived in cardiac arrest.
 In the remaining 29 patients, diagnosis was made by urgent thoracotomy (41%), by subxiphoid pericardial window (34%), during laparotomy (21%), or by chest radiography (3%).
 The overall mortality rate was 76% (45 patients), but only 52% for those with vital signs on admission.
 Rapid transportation and expeditious surgical treatment can save many patients with these injuries.
",20
3531,"Functional outcome of pediatric trauma patients identified as 'non-salvageable survivors'.
 A retrospective study of 305 pediatric trauma patients seen over 17 months was undertaken to evaluate the functional outcome of patients categorized as ""non-salvageable survivors"" (NSS).
 Functional outcome was determined by Denver Developmental Screen Tests (DDST) for children less than 5 years of age and Rappaport Severity Rating Scale (RDRS) for those 5 years old and older.
 Each patient was assigned Abbreviated Injury Scores (AIS).
 Injury Severity Score (ISS), Glasgow Coma Scale (GCS), and Trauma Score (TS).
 The total number of patients classified as severe was 65 (21%), and 13 were classified as non-salvageable, with seven non-salvageable survivors and six non-preventable deaths.
 Our study suggests that current trauma scoring systems tend to overestimate the non-salvageable population.
 Those identified as non-salvageable and who survived have a high probability of meaningful functional recovery.
 Current trauma scoring systems are in need of revision to better identify non-salvageable survivors and those children who will not make a meaningful neurologic recovery.
",20
3532,"Humeral mobility after treatment with hanging cast.
 A retrospective review of 23 patients after treatment of humeral fractures with hanging cast was performed.
 The average followup time was 8.59 years (range, 1.0 to 15.5 years).
 Functional results were good in eight (34.8%) and excellent in 15 patients (65.2%).
 To assess the flexibility of shoulder and elbow joints 24 parameters were measured on each body side using the neutral-zero method of Debrunner.
 A cumulative comparison of each parameter revealed decreased flexibilities of the upper limb after treatment with hanging cast: reduced abduction without moving shoulder blade (84.08 +/- 7.53 vs.
 77.34 +/- 11.38; p less than 0.05), reduced free abduction (166.09 +/- 14.4 vs.
 158.22 +/- 19.28; p less than 0.01), reduced anteelevation (155.26 +/- 10.12 vs.
 149.35 +/- 3.22; p less than 0.01), reduced external rotation with hanging arm (48.96 +/- 19.05 vs.
 41.18 +/- 16.75; p less than 0.01), increased flexion of the shoulder (25.65 +/- 10.37 vs 27.3 +/- 10.0; p less than 0.05) and reduced extension of the elbow (0.86 +/- 6.92 vs.
 -2.68 +/- 9.63; p less than 0.05).
 These findings show that longterm deficiencies of humeral mobility after treatment with hanging casts exist.
",20
3533,"Results of operative treatment for intra-articular fractures of the calcaneus.
 Since 1980 our treatment of displaced intra-articular calcaneal fractures consists of open reduction with distractor, bone grafting, and internal fixation.
 Thereby no splints are applied and early postoperative movement is possible.
 For precise preoperative planning a CT scan is required.
 Proper timing and careful preoperative planning are essential to prevent soft-tissue complications.
 In a total of 16 fractures good clinical and radiologic results were achieved in 50% of the cases; results were satisfactory in 25% and poor in 25%.
 The patients returned to work after an average of 5 months.
 Only three patients (19%) received disability compensations, which compares favorably with nonoperative treatment.
 We believe that a majority of comminuted intra-articular fractures of the calcaneus profit from open reduction and internal fixation and that more reliable functional results are achieved than with conservative therapy.
",20
3534,"Differential regulation of T- and B-lymphocyte activation in severely burned patients.
 We studied the in vitro expression and regulation of the CD23 and CD25 (Tac) surface antigens by peripheral blood lymphocytes (PBL) from severely burned patients (burn injuries ranging from 25% to 72% TBSA) in order to evaluate T- and B-lymphocyte activation processes after thermal trauma.
 The spontaneous and cytokine (IL-4, IL-2)-induced expression of CD23 which represents a B-cell activation marker was significantly reduced during the second to fifth week postburn when compared to healthy donors.
 In contrast, CD25, which is expressed on activated T cells, showed a marked increase both spontaneously, indicating an in vivo activation, and after stimulation with IL-2 or PHA.
 Concomitantly, T-cell proliferation induced by PHA or Con A was suppressed.
 However, the number of T and B cells remained unchanged.
 The data demonstrate the impairment of early events in the lymphocyte program in severely burned patients.
 The activation of B cells is downregulated, since they become refractory to external helper signals.
 In addition, T cells are highly activated but fail to proceed to proliferation in response to mitogenic stimuli.
",20
3535,"Sonographic screening of mass casualties for abdominal and renal injuries following the 1988 Armenian earthquake.
 The value of sonography in acute trauma evaluation is generally underestimated, and the opinions are controversial.
 Sonography was performed as a primary screening procedure in 400 of 750 mass casualty patients with trauma admitted to a large hospital within the first 72 hours after the 1988 Armenian earthquake.
 Two real-time sector scanners were used in the reception area of the hospital, and the average time spent on one patient was 4 minutes.
 More than 130 followup sonographic examinations were required.
 Trauma-associated pathology of the abdomen and retroperitoneal space was detected in 12.8% of the patients, with 1% false negatives and no false positives.
 The authors believe that sonographic screening of mass casualties is a quick and effective means for detection of abdominal and retroperitoneal injuries.
 Sonography should be used for this purpose more routinely to gain experience and maintain preparedness of the sonographers for screening of trauma cases in mass casualty situations.
",20
3536,"Delayed diagnosis of extremity injuries in patients with multiple injuries.
 A total of 340 patients treated in the Intensive Care Unit of the Department of Orthopedics and Traumatology at Helsinki University Central Hospital were analyzed in this study.
 They had in all 1,071 fractures and luxations of the pelvis and extremities, of which the trauma surgeons and radiologists on duty initially missed 45 injuries, i.e., 4.2%.
 Taking into account the eventual late symptoms, the most severe delayed diagnoses were of injuries located around the hip and knee joints.
 The patients with delayed diagnoses were, on the average, the most severely ill: their needs for primary blood transfusions and assisted respiration resembled the needs of patients who later died of their trauma or its complications.
 The most common causes of the delay in diagnosis were: radiographs not done in 60% of patients, and no notation of visible injury in radiographs in 31%.
 Inferior quality of radiographs, unnoticed radiologists' reports, a fracture visible at the outermost corner of a radiograph, a fracture hidden by other fractures, or excessive obesity of the patient may also contribute to a delay.
 The study presents measures for improving diagnostic strategies, but it would appear that delayed diagnoses cannot be totally eradicated.
",20
3537,"Successful replantation of both legs in a child--5-year followup: case report.
 Replantation of lower extremities is an infrequent procedure, and is rarely indicated, due to the usual severity of the primary injury plus the possibility of good prosthetic substitution.
 We report a case of successful replantation of both legs in an 8-year-old boy (despite Aspergillus flavus septicemia) with followup of 5 years.
 This case suggests that leg replantation should be considered in young patients.
 This appears to be the second reported case of successful replantation of both legs.
",20
3538,"Spontaneous healing of a traumatic thoracic aortic tear: case report.
 A patient with deceleration trauma of the thoracic aorta causing significant intimal disruption is described in whom complete angiographic resolution was documented during a period of medical management.
 Review of the literature, along with our experience, suggests that traumatic aortic disruption constitutes a spectrum of injury rather than an all-or-none phenomenon.
 Immediate surgery, especially in multiply injured patients, may be delayed or even postponed indefinitely if the injury is relatively limited.
",20
3539,"The role of computerized tomography in the diagnosis of an occult femoral neck fracture associated with an ipsilateral femoral shaft fracture: case report.
 We report a nondisplaced femoral neck and head fracture diagnosed acutely by CT scanning.
 This case illustrates the potential benefits of an acute femoral neck/head CT scan in obtunded polytrauma patients with high-energy femoral shaft fractures.
",20
3540,"Bilateral fracture-dislocation of the sacroiliac joint: a case report.
 Bilateral fracture-dislocation of the sacroiliac joint with intrapelvic displacement of the sacrum is a rare and extremely severe injury.
 We treated a patient with bilateral fracture-dislocation of the sacroiliac joint using a nonoperative method and obtained an excellent functional result.
",20
3541,"Traumatic renal avulsion into the chest: case report.
 This is a case report of a patient who survived blunt renal avulsion and herniation of the kidney through a ruptured diaphragm.
 Symptoms were mild considering the severity of injury.
 Prompt diagnosis of this unusual combination of injuries was aided by contrast-enhanced computed tomography (CT).
",20
3542,"Educational status and drinking patterns: how representative are college students?
 Using data from a large, nationally representative sample, multiple regressions using sex, ethnicity, age and educational status showed that drinking patterns of college students differed significantly from those of dropouts, high school graduates and former college students.
 College students were more likely to use alcohol but tended to drink less quantity per drinking day than nonstudents of the same age.
 Sex differences were smaller among college students than among other groups, especially in proportions of abstainers.
 While whites were most likely to drink if they were in college, among blacks the college students were the least likely to drink.
 Age had little association with drinking.
 Conclusions based on in-school samples may not generalize well to nonschool populations and should be tested, if possible, using more representative databases.
",20
3543,"Associations between alcohol and cocaine use in a sample of problem-drinking employees.
 Increases in cocaine use have created a new and challenging cohort of problem drinkers with dual or multiple addictions.
 As part of a randomized trial comparing alternative alcoholism treatments at a 10,000-employee industrial plant, we interviewed 224 new alcoholic clients of an employee assistance program (EAP); 40% used cocaine during the 6 months just prior to EAP intake.
 Compared to employees reporting no recent cocaine use, the cocaine users were younger, less often married and reported heavier drinking and more alcohol-related problems, on the job and off.
 Even after controlling for demographic and occupational factors, and drinking indicators, cocaine users reported more binges (being drunk 24 hours or more), more blackouts (marginally significant, p = .06), more absenteeism and more warnings about unacceptable job performance.
 Alcoholic EAP clients who use cocaine appear to engage in riskier drinking and to have more trouble on the job than do those who report no cocaine use, and this seems to be a difference specifically attributable to their use of cocaine.
",20
3544,"Sex differences in personality traits and coping styles of hospitalized alcoholics.
 Forty inpatients on an alcohol detoxication unit of a large municipal hospital were administered a battery of tests consisting of a Coping Styles scale, a Personality Profile scale, a Depression scale and the Brief MAST.
 A demographically comparable comparison group of 40 outpatients attending the medical screening clinic at the same hospital also completed the battery.
 The two groups did not differ in terms of age, education or the ratio of men to women.
 There were significant differences in coping styles and personality characteristics between alcoholics and nonalcoholics and, to a large extent, between men and women within the alcoholic group.
 Practically no significant differences were found between the men in the two groups, but female alcoholics differed greatly from nonalcoholic women in terms of coping styles, personality variables and also in terms of conflict.
 These findings indicate that the differences between alcoholic and nonalcoholics in the sample were due largely to patterns uniquely characterizing the female alcoholic group.
 Results are discussed in terms of cultural expectations.
",20
3545,"The effectiveness of alcoholism screening in an ambulatory care setting.
 Two hundred and eighty subjects in three ambulatory care clinics participated in this study designed to assess the psychometric properties of the SMAST using DSM-III criteria for alcoholism as the diagnostic standard.
 Eighty-two subjects (30%) who completed the NIMH Diagnostic Interview Schedule met DSM-III criteria for alcohol abuse and/or dependence.
 The sensitivity of the SMAST, using the generally accepted weighted cut-off score of five or greater, was .56 and the specificity was .83.
 An unweighted cut-off score of two or greater produced a sensitivity of .72 and a specificity of .64.
 The results of this study suggest that, when the SMAST is used for screening in an ambulatory care clinic population, the optimum balance of sensitivity and specificity is achieved using an unweighted cut-off score of two or greater.
 In addition, the alcohol subscale of the Diagnostic Interview Schedule was easy to administer and should be considered for use as the diagnostic standard in clinical settings.
",20
3546,"Factors associated with alcohol use in later adolescence.
 The relative influence of a number of family and individual characteristics on the frequency and intensity of alcohol use in a group of older adolescents was assessed.
 The sample consisted of 8,661 persons ranging in age from 20 to 21 years obtained from the ""High School and Beyond"" study.
 Logistic regression analyses performed on both frequency and intensity of alcohol use indicated that white males from higher socioeconomic backgrounds, living in urban or suburban areas and having an external locus of control and a weak family orientation, tended to drink more frequently and consume a larger quantity of alcohol per drinking episode.
 Results are explained from a sociocultural perspective.
",20
3547,"Development of a measure examining children's roles in alcoholic families.
 A measure assessing the roles played by children in their alcoholic families is presented.
 In Study 1, an item pool was generated targeting four distinct roles discussed in the alcohol literature, and the items were reviewed by a panel of experts.
 The Children's Roles Inventory (CRI) was then administered to 140 adult children of alcoholics and their responses were used to refine the measure.
 Observed levels of internal consistency seemed adequate (Cronbach's alpha ranged from .89 to .95).
 In a replication effort (Study 2), the CRI was administered to 142 adult children of alcoholics.
 Internal consistency remained at acceptable levels, ranging from .90 to .95.
 Study 3 examined the CRI's convergent and discriminant validity.
 A sample of 138 adult children of alcoholics as well as a sample of 105 adults from nonalcoholic families completed the CRI, a measure of self-esteem and an index of one's use of social support.
 Reliability results from Studies 1 and 2 were replicated (in both samples).
 Likewise, in both samples the CRI subscales were differentially predictive of self-esteem as well as size of and satisfaction with one's social support network.
",20
3548,"Children of alcoholic parents in the community.
 The relationship between parental alcoholism and risk for maladjustment in the offspring was investigated in a community sample.
 Children of parents who met criteria for DIS/DSM-III alcohol abuse or dependence and children of parents who met criteria for ten other diagnoses were compared to children of ""normal"" parents.
 The data were obtained from the merging of the data banks of two major psychiatric epidemiology studies of the adult (17-64) and child (4-16) population of Puerto Rico.
 Results indicated that parental alcoholism in addition to creating an adverse family environment had an effect on the relative risk for maladjustment in the offspring (as measured by scores on the Child Behavior Checklist).
 Although previous studies have reported higher levels of externalizing behaviors in children of alcoholics, an increased risk for internalizing symptoms was observed in the children studied.
 Similar findings were obtained for the children of parents with other psychiatric disorders suggesting that the effects of parental alcoholism in children ages 4 to 16 may not be different from the consequences of parental mental illness per se.
",20
3549,"Nitinol gooseneck snare for removal of foreign bodies: experimental study and clinical evaluation.
 The authors describe their use of a new right-angle snare made of nickel-titanium (nitinol) cable for retrieval of foreign bodies and iatrogenically placed devices.
 The snare loop is at right angles to the cable and comes in five sizes (5, 10, 15, 25, and 35 mm); its radiographic visualization is enhanced by gold-plated tungsten coils.
 This snare was used to retrieve wire and catheter fragments introduced into the thoracic vasculature of four dogs.
 Eleven of 13 attempts were successful.
 Three attempts to retrieve intravascular foreign bodies were successful in two patients; in one of these patients, a 10-mm snare was used to remove a fractured end of a ventriculoatrial shunt tube from the left pulmonary artery.
 In three other patients, four ureteral stents were successfully removed under fluoroscopic guidance.
 All retrievals were performed through a vascular sheath and with standard techniques and angiographic equipment.
 No complications were seen in any of the patients or dogs.
",20
3550,"Tears of cruciate ligaments and menisci: evaluation with cine MR imaging.
 A cine magnetic resonance (MR) imaging technique, involving the acquisition of kinematic sagittal images during knee movement, was used to evaluate 52 symptomatic knee joints.
 Results were compared with those obtained by means of static three-dimensional (3D) MR imaging.
 Twenty-seven of the 28 anterior cruciate ligament (ACL) tears and 22 of 24 normal ligaments were correctly identified at cine MR imaging for a sensitivity of 96% and a specificity of 92%.
 Static 3D MR imaging yielded a sensitivity of 71% and a specificity of 88%.
 All four posterior cruciate ligament tears were identified at cine and 3D MR imaging.
 For meniscal tears, cine MR imaging yielded a sensitivity of 48% and a specificity of 96%; the sensitivity and specificity for 3D MR imaging were 71% and 96%, respectively.
 Cine MR imaging proved to be more useful than static MR imaging in assessing the tightness of cruciate ligaments, especially of those that were partially torn, and in assessing the movement of meniscal-free fragments.
 The increased information obtained with cine MR imaging may warrant continued investigation and clinical application.
",20
3551,"Skateboarding injuries in children. A second wave.
 Motivated by a number of skateboard-related injuries seen in an emergency department, we undertook an investigation of skateboarding injuries in the mid-1980s.
 We studied US Consumer Product Safety Commission injury frequency estimates, which indicated a resurgence of these injuries: 19,182 in 1984 and 37,180 in 1985.
 Children 10 to 14 years old were injured with greatest frequency.
 Nontrivial injuries were more common among children younger than 5 years old, reflecting a larger proportion of head and neck injuries.
 Boys sustained more frequent and more severe skateboard-related injuries.
 Observed injury patterns (head and neck injuries in younger children, extremity injuries in older children, and more severe head and neck injuries in older children) probably reflect the role of psychomotor development on both risk exposure and biomechanics.
 Likely prevention strategies include warnings against skateboard use by children younger than 5 years, prohibition of skateboards on streets and highways, and the promotion of use of helmets and other protective gear.
",20
3552,"Predicting onset and chronicity of women's problem drinking: a five-year longitudinal analysis.
 BACKGROUND.
 Longitudinal studies of adult drinking have typically excluded or sampled only small numbers of problem drinking women, and have measured a limited range of influences on women's drinking behavior.
 METHODS.
 To study the development of women's problem drinking over time, five-year follow-up interviews were conducted with two groups of respondents from a 1981 national survey of women's drinking: 143 problem drinkers and 157 nonproblem drinkers.
 Regression analyses examined effects of 1981 predictors on six measures of 1986 problem drinking, for problem drinkers and nonproblem drinkers separately.
 RESULTS.
 Among 1981 nonproblem drinkers, predictors of onset of problem drinking indicators by 1986 included younger age, cohabiting, and lifetime use of drugs other than alcohol.
 The most consistent predictor of persistent (chronic) problem drinking was sexual dysfunction; other predictor included being employed part-time or never married, and experiencing recent depression.
 Divorce or separation predicted lower levels of subsequent alcohol dependance among problem drinkers.
 CONCLUSIONS.
 Findings suggest that different personal and social factors predict the onset of problem drinking as compared with its continuation, and point to nontraditional life-style, sexual dysfunction, and role deprivation as potentially important variables.
",20
3553,"On the importance of planned health education. Prevention of ski injury as an example.
 The planning of health education aimed at preventing sports injuries is often incomplete and not stated explicitly.
 In most instances, the evaluation is incomplete or nonexistent.
 We present a theoretical framework for planning and evaluating health education, illustrating the main points by using as an example the health education for downhill skiers.
 Systematic planning consists of analyzing the magnitude of the problem and the behavioral risk factors, studying behavior determinants, designing an optimal intervention, and implementing the intervention.
 The evaluation phase deals with the effects on these five levels (implementation, intervention, determinants, behavior, and incidence of injury).
 Some common pitfalls are mentioned and special attention is given to the study of determinants of behavior and to the design of the intervention.
 The importance of pretesting health education material and the community approach in educating sports participants is underlined.
 Health education, together with regulations and facilities, constitutes the health promotion strategy in the prevention of sports injuries.
 For most sports, there seems to be a strong need for further research on the etiology and determinants of behavior before effective prevention can be realized.
",20
3554,"Meniscus repair in the anterior cruciate deficient knee.
 From 1979 to 1986, isolated repair of a peripheral vascular zone meniscal tear was performed in 22 patients (23 menisci) who had ACL insufficiency.
 For various reasons none of these patients underwent repair or reconstruction of their ACL.
 The meniscus repair was done by open arthrotomy in 12 cases and by arthroscopic techniques in 11 cases.
 The purpose of this study was to evaluate the success rate of a meniscal repair in an anterior cruciate deficient knee.
 The average age of the patients at the time of surgery was 25 years and the average followup was 56 months.
 Six patients (26%) had mild occasional pain not requiring medication and one patient had moderate pain requiring nonnarcotic pain medication.
 Eight patients (26%) had occasional giving way episodes and one of them underwent ACL reconstruction 5 years later because of frequent giving way.
 One patient required a postoperative manipulation for inadequate range of motion, but there were no neurovascular injuries or infections.
 There were three patients (13%) who had failed repairs or a retear and required subsequent subtotal meniscectomies.
 None of the other patients had any clinical symptoms or signs of a meniscal tear.
 There were no significant differences between the results of open or arthroscopic repair.
 Even though the failure rate of meniscus repair may be greater in an unstable knee, we conclude that meniscus repair is not contraindicated in an anterior cruciate deficient knee.
",20
3555,"The conservative treatment of the anterior cruciate deficient knee.
 Seventy-nine recreational athletes (average age, 26 years) with complete ACL tears were treated with nonligamentous arthroscopic surgery, monitored rehabilitation, functional bracing, and activity modification.
 The average followup was 52 months (range, 36 to 102 months).
 Six (8%) patients ultimately underwent ligament reconstruction and were considered failures of nonreconstructive treatment.
 The remaining 73 patients were the subject of detailed analysis.
 There were 9 (11%) excellent, 25 (32%) good, 17 (22%) fair, and 28 (35%) poor results.
 Although 71 patients (97%) were satisfied with their knee for activities of daily living, only 36 (49%) were satisfied with their knee for sports.
 Twenty-nine (40%) had significantly modified their athletic activities.
 Age, sex, interval from injury to treatment, associated meniscal tears (49 or 67%), and articular cartilage damage (21 or 29%) had no apparent effect on the outcome.
 Poor results were noted in 29 (40%) patients with significant pivot shifts.
 Multiple repeat injuries, repeat arthroscopy, isokinetic deficits, and increased length of followup were also associated with poor results.
",20
3556,"Prevention of common overuse injuries by the use of shock absorbing insoles. A prospective study.
 Sedentary individuals, particularly new military recruits, who start a physical training program have a substantial risk of developing an overuse injury of the lower limb.
 In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training.
 The experimental group consisted of 237 randomly selected new recruits, while 1151 recruits were the control group.
 Insoles were given to the experimental group and compliance was monitored.
 A panel of doctors documented and classified all injuries occurring during the 9 week period.
 A total of 54 (22.8%) and 237 (31.9%) injuries were reported in the experimental and control groups, respectively.
 In both groups, the majority of injuries were overuse (experimental group, 90.7%; control group, 86.4%).
 The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower (P less than 0.05) in the experimental group.
 The mean incidence of stress fractures was lower in the experimental group but not significantly so (0.05 less than P less than 0.1).
 This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles.
",20
3557,"Diagnostic capabilities of magnetic resonance imaging and computed tomography in acute cervical spinal column injury.
 The present study was conducted to evaluate the imaging capabilities of magnetic resonance imaging (MRI) in evaluating acute cervical spinal column injury and compare these results to that of computed tomographic (CT) imaging.
 Forty-nine patients undergoing MRI at a Level I and regional spinal cord trauma center to evaluate cervical spinal column injury were studied.
 Seventy-one injuries were identified by MRI.
 These injuries were classified as osseous (fracture/dislocation) (n = 21), disc herniation (n = 29), and spinal cord injury (edema/contusion/transection) (n = 21).
 Diagnostic imaging results in 33 of the 49 patients undergoing both MRI and CT were compared.
 CT demonstrated 22 fracture/dislocations compared to 10 on MRI.
 MRI demonstrated 19 disc protrusions compared to 7 on CT.
 Additionally, MR imaged 13 cord injuries as compared to 0 by CT.
 MR imaging proved superior in demonstrating spinal cord pathology and intervertebral disc herniation.
 CT was superior to MRI in demonstrating osseous injury.
 CT and MRI may be useful together in determining presence and extent of spinal column injury.
",20
3558,"Barium sulfate bronchography. Report of a complication.
 Alveolarization of the barium sulfate and subsequent retention of barium sulfate for years was demonstrated in three patients in whom dilute suspension of barium sulfate in water was used for bronchography.
 Pathologic examination in one patient showed barium sulfate within macrophages in the alveolar spaces and walls and in the perivascular and peribronchial interstitium.
 Since the residual barium sulfate interferes with imaging procedures of the lungs, it represents an unwanted event in patients with pulmonary disease.
 High-resolution computed tomography is the preferred method of evaluating for bronchiectasis.
 If bronchogram is performed, it should be performed after bronchoscopy using oily propyliodone (Dionosil).
",20
3559,"The 1990 Everett Idris Evans memorial lecture: the inhalation injury.
 The most important question that had to be answered from our animal data was whether a significant difference existed between the two groups.
 It could be observed that the resuscitation with Ringer's lactate did not lead to any increased lymph flow or total transcapillary protein flow in spite of the drop in protein and oncotic pressure in plasma.
 With Ringer's lactate there was a lower lymph to plasma protein ratio, which might be significant.
 No negative difference could be observed either in the pulmonary capillary wedge pressure or pulmonary vessel resistance.
 All animals survived throughout the experiment, and in all experiments no advantages regarding the vital parameters could be ascertained with the administration of albumin; however, several factors must be borne in mind.
 The inhalation injury was from a heat source alone and no toxic substances were involved.
 Only inhalation trauma was induced in the absence of a surface burn wound.
 The duration of the observation was for only 36 hours.
 Thus some caution must be observed in applying these findings to a clinical situation.
 In our evaluation of the clinical results, we have seen that no differences could be established in regard to pulmonary capillary wedge pressure and extravascular lung water between the Ringer's lactate and the albumin group.
 In spite of a 50% drop in oncotic pressure, however, this is only valid for the first 24 to 36 hours, after which one could assume that a further protein drop coupled with a still raised hydrostatic filtration coefficient would lead to interstitial edema.
",20
3560,"Persistence of fetal bovine serum proteins in human keratinocytes.
 Cultured human keratinocytes are used for skin grafts, but their success is limited by late graft loss.
 Development of antibody to fetal bovine serum (FBS) protein used in culture media for in vitro keratinocyte growth has been identified.
 The persistence of FBS antigen in skin grafts is important in the induction of the immune response and the susceptibility of the keratinocytes to immune-mediated injury.
 The magnitude and longevity of FBS protein persistence on human keratinocytes was studied.
 Secondary passage human keratinocytes were grown in media supplemented with 5% FBS.
 The media was changed to one supplemented with pooled human AB serum, and the amount of FBS protein incorporated in the tissue was measured over the following 8 days by an ELISA reaction directed against FBS antigen.
 Incorporated FBS antigen decreased for the first 3 days to 31% of maximum.
 There was no further significant decrease for 5 days.
 Keratinocytes grown in alternative serum supplements (NuSerum [Collaborative Research Inc., Bedford, Mass.] and Serum Plus [Hazelton Research Products Inc., Lenexa, Kan.]), which contain reduced amounts of FBS, offered no significant reduction in FBS protein incorporation.
 This duration of antigen persistence would make human keratinocytes susceptible to cell destruction by immune response to FBS and may contribute to delayed loss of human keratinocyte grafts.
",20
3561,"Time course of alterations in lung lymph and bronchial blood flows after inhalation injury.
 The effects of inhalation injury on the pulmonary microvascular fluid flux and bronchial blood flow were examined in a long-term study of sheep (N = 13).
 They were insufflated with either 48 breaths of cotton smoke (n = 8) or air (n = 5) while they were deeply anesthetized with halothane.
 After injury, anesthesia was discontinued and the animals were mechanically ventilated throughout the experimental period (24 hours).
 Bronchial blood flow increased significantly at all time points recorded and reached its peak 20 minutes after the inhalation trauma (11 +/- 1 ml/hr to 106 +/- 18 ml/hr; p less than 0.05).
 Thereafter, bronchial blood flow decreased to a value that was six to eight times above the baseline measurement for the remainder of the study period.
 With these changes in blood flow, there was a concomitant increase in lung lymph flow.
 This variable gradually increased and was 633% of the baseline value (6 +/- 1 ml/hr to 44 +/- 8 ml/hr) 24 hours after the challenge with smoke.
 The control animals showed little or no change in cardiopulmonary function during the experimental period.
 There is no correlation between the increase in bronchial blood flow and lung lymph flow patterns after cotton smoke inhalation injury.
",20
3562,"Elevated serum aluminum levels in severely burned patients who are receiving large quantities of albumin.
 Aluminum contaminates various fluids that are used in intravenous therapy, and it is associated with bone disease and encephalopathy.
 Albumin is highly contaminated with aluminum, which is eliminated primarily by renal excretion.
 Patients with burns receive large quantities of albumin and have impaired renal function, which puts them at hypothetical risk for aluminum loading.
 To assess the risk of aluminum loading we analyzed sera from 12 patients with burns for aluminum concentrations.
 Serum aluminum concentration was elevated in 8 of the 12 patients, and levels were at or near toxicity in 3 of the 8.
 Serum aluminum and serum creatinine levels directly correlated, r = 0.71 and p less than 0.005.
 No relation was found between serum aluminum and amount of albumin received.
 However, patients with the highest serum aluminum levels were the most severely burned and none survived.
 Thus patients with burns who are receiving albumin are at risk for aluminum loading.
 Impaired renal function contributes to aluminum retention.
",20
3563,"Observations on stability and contraction of composite skin grafts: xenodermis or allodermis with an isograft overlay.
 Composite skin grafts of xenodermis or allodermis with a thin split-thickness isograft overlay were evaluated for stability and contraction.
 Male inbred Lewis rats were used as recipients, with Buffalo rats serving as allogeneic dermis donors.
 Cryopreserved human skin was used for xenodermis grafts.
 The two components of the composite graft, the xenodermis or allodermis and the isograft overlay, were grafted in one operation to a surgically created wound.
 Wounds were observed for 1 year.
 The composite skin grafts took fairly well, although spotty loss of the overlaid isograft was noted.
 The xenodermis and allodermis remained grossly intact even at 1 year after grafting.
 However, composite skin grafts in this animal model contracted more than did sheet isografts alone.
",20
3564,"Burns from hot oil and grease: a public health hazard.
 We examined the incidence, etiology, and morbidity of burns due to hot oil and grease.
 Over a 10-year period from 1976 to 1985, of 1818 patients hospitalized for burns, 85 (4.7%) injuries were due to hot grease or oil.
 The mean age was 20 years; 34% of patients were less than 8 years old.
 The mean total body surface areas of second- and third-degree burns was 11.5% (range 0.5% to 40%), and the average length of hospital stay was 19.6 days.
 Fifty-eight percent of patients required split-thickness skin grafting (n = 49), three required intubation, and one required tracheostomy.
 Seventy-eight percent of oil burns occurred in the home.
 The most common circumstances consisted of children who grabbed the handle or electric cord of a frying pan and pulled the hot oil down onto themselves.
 (Nineteen of the 29 children were less than 8 years old (66%).) Burns due to cooking oil and grease are associated with considerable morbidity.
 The high boiling point, high viscosity, and potential combustibility of oil increase the potential soft-tissue damage when compared with typical scald injuries from hot water.
 The dangers of children pulling on the appliance, the dangers of transporting hot oil, the importance of supervision while children are cooking, and the importance of knowledge of the management of grease fires is stressed.
 Public education is needed to underline the potential seriousness of these burns.
",20
3565,"A descriptive summary of New Jersey's 1985 burn population.
 Data obtained from the New Jersey State Department of Health on the 1985 hospitalized patients with burns and data collected from the National Burn Victim Foundation's standard burn reporting form were analyzed to gather information about the epidemiology of burns.
 Children (0 to 4 years of age) continue to be the largest percentage of the 0- to 18-year-old age group who sustain burn injuries, and 67% of those injuries are sustained by children under the age of 5.
 Males accounted for 69% of the total burn population; 58% of admissions were white; 69% of patients were admitted for partial-thickness burns, and 31% were admitted for full-thickness burns; the largest primary payer was third-party payers; and 92% of patients with burns were discharged to home or self-care.
 Data were also analyzed by examination of selected age groups to determine individual needs of specific groups.
 An analysis of burn injuries reported to the National Burn Victim Foundation confirmed previous reports that the home is the most likely place for a burn injury to occur and that flame and scald injuries predominate; scald injuries comprise 50% of all sustained burns.
 Gasoline vapors accounted for 54% of burn injuries caused by flames.
 The data supported efforts to develop programs that address the needs of the urban child, the 17- to 19-year-old age groups, and the elderly.
 The information that was collected served to redefine objectives for burn prevention programs.
",20
3566,"Drugs and femoral neck fracture: a case-control study.
 Two hundred consecutive patients with femoral neck fractures (FNF) and 200 controls matched by age, sex, nursing home residency and number of admissions within the last 2 years, were interviewed about recent drug use.
 The matching criteria were chosen to achieve case and control groups that were comparable with regard to overall physical disability.
 Thus a preliminary study had shown FNF to be strongly associated with nursing home residency and to be correlated with the number of recent hospital admissions.
 FNF was found to be negatively associated with use of coronary drugs (OR = 0.27; 95% CI = 0.11-0.70) and positively associated with drug use in general (OR = 2.00; 95% CI = 1.04-3.05).
 The OR for the various classes of psychotropic drugs was consistently greater than 1., although this was not statistically significant.
 An inherent problem in interpreting such findings is that underlying disease may predispose the subject to both FNF and drug use, thus creating a non-causal relationship.
",20
3567,"Controlled drinking, treatment effectiveness, and the disease model of addiction: a commentary on the ideological wishes of Stanton Peele.
 Despite a long history of extravagant claims followed by sobering discomfirmations, advocates of controlled drinking continue to promote nonabstinent treatment goals and procedures for alcoholics.
 Recent claims by Stanton Peele in favor of controlled drinking are examined critically in the context of a continuing debate concerning empirical studies of nonabstinent treatment goals, treatment effectiveness, and inpatient versus out-patient treatment of alcoholism.
 Peele's views concerning ""conventional disease-based alcoholism treatment,"" controlled drinking, and ""the disease model"" are shown to be based largely on inadequate scholarship, misrepresentations of the literature, inappropriate comparisons, unwarranted generalizations, and straw-man arguments.
",20
3568,"Are universal precautions effective in reducing the number of occupational exposures among health care workers? A prospective study of physicians on a medical service 
 Using a daily questionnaire, we prospectively studied 277 physicians from two hospital medical services for incidents of exposure to blood and body fluids and barrier use before and after the implementation of universal precautions.
 We found that implementation significantly increased the frequency of barrier use during exposure incidents from 54% before implementation to 73% after implementation of universal precautions.
 Implementation led to a decrease in the number of exposure incidents that resulted in direct contact with blood and body fluids (actual exposures), from 5.07 to 2.66 exposures per physician per patient care month, and to an increase in averted exposures in which direct contact was prevented by the use of barrier devices, from 3.41 exposures per patient care month before implementation to 5.90 exposures per patient care month after implementation.
 Implementation affected neither the types of body fluid or procedures involved nor the overall rate of exposure incidents (8.5 per patient care month) but, through an increase in barrier use, it did prevent direct contact with blood and body fluids and thus converted what would have been an actual exposure into an averted one.
 We conclude that universal precautions were effective in reducing the risk of occupational exposures among physicians on a medical service.
",20
3569,"Catastrophic injuries and fatalities in high school and college sports, fall 1982-spring 1988.
 Direct and indirect deaths and catastrophic injuries, defined as any injury incurred during participation in a high school/college sponsored sport in which there is permanent severe functional neurological disability (nonfatal) or transient but not permanent functional neurologic disability (serious), are presented for all sports during the period of fall 1982 to spring 1988.
 Football contributed the greatest numbers of catastrophic injuries but also had the largest number of participants.
 Ice hockey, gymnastics, and wrestling are the other sports where participants are at greatest risk of catastrophic injury or death.
 Mechanisms of injury in each sport and corrective actions are identified and discussed.
 While high school and college catastrophic injuries may never be totally eliminated, they can be dramatically reduced by reliable injury data collection and analysis.
",20
3570,"Use of clinical toxicology resources by emergency physicians and its impact on poison control centers.
 STUDY OBJECTIVE: The need for clinical toxicology resources by emergency physicians is unclear and may have implications for future training and resource availability.
 This study was designed to assess current emergency physician use of available resources.
 DESIGN: Prospective evaluation by mail using a 49-item questionnaire.
 TYPE OF PARTICIPANTS: All 170 emergency physicians in Utah.
 INTERVENTIONS: None.
 RESULTS: The response rate was 75.3% (128 of 170).
 Resources ""outside their own fund of knowledge"" were consulted ""occasionally"" to ""frequently"" by 98.3%.
 They used the following resources ""occasionally"" to ""frequently"": poison control center (PCC) (93.7%), toxicology textbook (77.6%), ""expert colleague"" (34.0%), and ""in-house POISINDEX"" (23.9%).
 They often contacted the PCC for toxicity information (93.7%) and management recommendations (87.3%) and for acute, symptomatic overdose cases (88.3%).
 They ""almost never"" contacted the PCC for adverse drug reactions (76.6%), pill identification (70.2%), consultation with physician toxicologist (68.1%), asymptomatic exposures (62.9%), chronic toxicity (50.4%), or solely to report the case to the American Association of Poison Control Centers data base (90.2%).
 Those who had access to in-house POISINDEX often did not consult the PCC (82.6%).
 Of those who did not have in-house POISINDEX, 42.8% contacted the PCC to access it.
 Providing access to physician toxicologist consultations was thought to be an important role for the PCC by 86.7%, but only 32% of physicians were using this option.
 CONCLUSION: The vast majority of emergency physicians in Utah consult the PCC only for acute, symptomatic overdoses.
 They view access to physician toxicologist consultation as an important role for the PCC but seldom use it.
 The availability of in-house POISINDEX decreases the likelihood of PCC consultations from emergency departments.
 The frequency of emergency physician consultation with the PCC may decrease as POISINDEX becomes available at more hospitals.
",20
3571,"Flumazenil: a new benzodiazepine antagonist.
 Flumazenil is a recently discovered pharmacologic antagonist of the CNS effects of benzodiazepines.
 It acts by binding CNS benzodiazepine receptors and competitively blocking benzodiazepine activation of inhibitory GABAergic synapses.
 Animal studies and some human studies appear to demonstrate that flumazenil has weak intrinsic agonist activity; on the other hand, studies are inconclusive in demonstrating any inverse agonist effects of this agent.
 Evidence available suggests that flumazenil is well tolerated in human beings over a broad range of doses when given either orally or parenterally and does not produce serious adverse effects.
 In the setting of isolated benzodiazepine overdose, flumazenil is capable of completely reversing coma within one to two minutes, with this effect lasting between one and five hours.
 Repeat doses can be given safely to reverse recurrent effects of longer-acting benzodiazepines.
 Flumazenil is undergoing further evaluation by the Food and Drug Administration; should this drug receive approval, it is likely to be used in emergency departments as well as in a variety of other clinical settings.
 First, it could be used to effect rapid reversal of benzodiazepine-induced sedation that has been administered to facilitate medical, orthopedic, and surgical procedures, particularly in the event of inadvertent respiratory depression.
 Second, flumazenil might have a therapeutic role in the management of patients who have taken benzodiazepine overdoses.
 Although most of these patients can be managed successfully with supportive therapy alone, it is possible that the use of flumazenil may obviate the need for intubation and respiratory support in such patients and eliminate the possible adverse effects of even short-term endotracheal intubation.
 Finally, flumazenil could have both diagnostic and therapeutic value in patients with acute alterations of mental status of unknown etiology, particularly when possible drug overdose is a consideration.
 Because flumazenil appears to be specific in its antagonism of benzodiazepine-induced respiratory and CNS depression, it could be used empirically to confirm or exclude a role of benzodiazepines in the generation of mental status changes in the setting of overdose or coma of unknown origin.
 This in turn might obviate the need for further expensive (eg, computed tomography) and sometimes invasive (eg, lumbar puncture) diagnostic modalities.
 This might be particularly useful because there is nothing about benzodiazepine-induced coma that clearly distinguishes it from other causes of coma; thus, there are no signs or symptoms that may reasonably allow benzodiazepine overdose to be confirmed or eliminated on clinical grounds.
 Further studies will continue to define the ultimate use of this new agent.
",20
3572,"Risk factors and manifestations of digoxin toxicity in the elderly.
 The incidence of digoxin toxicity increases with age, largely because the two most common conditions that benefit from use of digoxin, congestive heart failure and atrial fibrillation, are markedly more prevalent in old age.
 Whether the elderly are more sensitive to the effects of digoxin because of age per se is unclear.
 However, several other factors render the elderly more susceptible to digoxin toxicity.
 These include an age-related decline in renal function and a decrease in volume of digoxin distribution.
 There is also an increase in the number of comorbid conditions, including cardiovascular and chronic obstructive pulmonary disease, which heighten susceptibility to digoxin toxicity.
 Moreover, treatment of these diseases with such interactive medications as quinidine and calcium channel blockers may increase the serum level of digoxin.
 Similarly, such electrolyte imbalances as hypokalemia and hypomagnesemia occur more frequently in the elderly as a result of diuretic therapy.
 However, recent data suggest that manifestations of digoxin toxicity among younger and older patients do not differ.
 Similar incidences of cardiac toxicity, gastrointestinal toxicity, and altered mental status are found in both patient populations.
 Treatment of digitalis toxicity in the elderly is the same as for younger patients.
 Response rates to Digibind are not diminished in the elderly.
",20
3573,"Results of multicenter studies of digoxin-specific antibody fragments in managing digitalis intoxication in the pediatric population.
 Digitalis toxicity continues to be a problem for pediatric patients undergoing therapy with cardiac glycosides for heart failure or arrhythmias, as well as in accidental ingestions.
 In this article the previous use of digoxin-specific antibody Fab fragments to treat digitalis overdose or intoxication in children is reviewed.
 The case reports cited in the medical literature and the 57 pediatric cases gathered as a result of the multicenter clinical trial and postmarketing surveillance study reported here indicate that digoxin-specific antibody Fab fragments are effective in ameliorating signs of digitalis poisoning in children.
 Not only can Fab fragments rapidly eradicate potentially life-threatening arrhythmias and conduction defects, but they are also effective in treating hyperkalemia and other noncardiac manifestations of digitalis toxicity.
 In the small samples of patients studied to date, complications have been minimal and no allergic reactions to digoxin-specific Fab fragments have been observed.
 Recommendations for the management of digitalis intoxication in children are outlined.
",20
3574,"Recognition and management of digitalis intoxication: implications for emergency medicine.
 Digitalis intoxication is among the most common serious adverse drug reactions in clinical medicine.
 While the recent development of a radioimmunoassay to accurately measure serum concentrations of digoxin has been of assistance, digitalis intoxication remains a difficult diagnosis to make with certainty.
 The difficulty in diagnosing digitalis intoxication arises from the nonspecificity of its associated signs and symptoms.
 The most common symptoms include fatigue, weakness, nausea, and anorexia.
 These symptoms can occur with many illnesses other than digitalis intoxication.
 Similarly, the electrocardiographic disturbances caused by cardiac glycosides may be nondiagnostic.
 The arrhythmias commonly associated with digitalis toxicity are often nonspecific and can be a reflection of the patient's underlying heart disease.
 The measurement of serum digoxin levels is useful, but studies have demonstrated overlap of the levels between groups with and without toxicity.
 Due to the modulation of the cardiac effects of digitalis glycosides by such clinical variables as underlying myocardial or renal disease, electrolyte and acid-base imbalances, and other factors, the correlation of toxicity with particular serum digoxin concentrations may vary.
 Because of the inherent difficulties in confirming the diagnosis of digitalis intoxication in some cases, digoxin-specific Fab antibodies may play a role as a diagnostic tool.
 Certainly, digoxin-specific Fab antibodies play a significant part in the treatment of digitalis intoxication.
 Fab antibodies have been successfully used to reverse the effects of digoxin, digitoxin, and oleander poisoning.
 These antibodies are useful in the treatment of acute and chronic digitalis intoxication in all age groups, including geriatric and pediatric populations.
",20
3575,"Changing patterns in the management of fractures in children.
 Advances in radiographic imagery have greatly facilitated the diagnosis and treatment of pediatric musculoskeletal injuries.
 In recent years, the indications for operative intervention in the treatment of children's fractures have become more clearly defined.
",20
3576,"Influences of the protected passive mobilization interval on flexor tendon healing. A prospective randomized clinical study.
 A prospective multicenter clinical study was carried out to determine whether improved tendon gliding could be achieved with greater durations of daily passive-motion rehabilitation after flexor tendon repair.
 Fifty-one patients were placed randomly into two controlled passive-motion protocols.
 Group 1 patients received greater intervals of passive-motion rehabilitation using a continuous passive-motion device.
 Group 2 patients were treated with a traditional early passive-motion protocol for tendon rehabilitation.
 For Group 1 patients, the mean interval of controlled motion rehabilitation was 75 hours a week, and the mean number of cycles was 12,000.
 For Group 2 patients the mean interval of controlled passive motion was four hours a week, and the mean number of cycles was 1000.
 The minimum follow-up time was six months (mean, 10.8 months).
 Using Strickland and Glogovac's formula, the mean active motion for digits in Group 1 was 138 degrees +/- 6 degrees.
 Mean motion for tendons in Group 2 was 119 degrees +/- 8 degrees.
 The difference between Groups 1 and 2 was statistically significant.
 The effect of the number of tendons injured per digit within each group was not significant.
 The data from this experiment indicate that the duration of the daily controlled motion interval is a significant variable insofar as postrepair flexor tendon function is concerned.
",20
3577,"Fracture of the index metacarpal base with subluxation of the trapeziometacarpal joint. A case report.
 A 40-year-old man fell on his outstretched arm and suffered a fracture of the index metacarpal base with subluxation of the thumb basal joint.
 The small fracture fragment at the base of the index metacarpal was attached to the base of the thumb metacarpal by a strong ligament, as noted at the time of surgery.
 This pattern of injury, a ligament-reversed Bennett's fracture, seems not to have been previously reported.
",20
3578,"Pes anserinus interposition in a proximal tibial physeal fracture. A case report.
 A ten-year-old girl suffered a Salter-Harris Type II fracture of the proximal tibia.
 Inspection revealed interposition of the pes anserinus (PA) within the open physis, which prevented reduction.
 This may be the first case report of PA interposition.
",20
3579,"The occurrence of accessory immunologic cells in bone induction.
 The differentiating tissues in fracture healing and in demineralized bone-powder-induced (DBP) bone formation were investigated with monoclonal antibodies with respect to the occurrence of Ia-positive cells, macrophages, and lymphocytes with interleukin-2 receptors (IL-2).
 Ia refers to molecules on the cell surface belonging to Class II of the major histocompatibility complex and is specific for the species and the individual.
 In both types of granulation tissues (fracture healing and following DBP implantation), the mesenchymal cells from the surrounding musculature were accompanied by large numbers of Ia-positive cells and common macrophages.
 The occurrence of IL-2 receptors was sparse in fracture healing but rich in DBP induction, probably because of its immunogenic properties, though weak.
 On Day 7, almost all existing cells in DBP induction were Ia-positive, signifying an immunologic effector phase apparently directed to the remaining still-passive bone powder in the periphery, while the central part of the inserted bone powder was producing cartilaginous cells and matrix.
 The presence of accessory immunologic cells in fracture healing is perhaps due to a surveillance function (a standard response on injury), but the cell differentiation might also be dependent on the active mediators emitted from Ia-positive cells and macrophages.
 This investigation strengthens the concept that induced bone development occurs in experimental fracture healing.
",20
3580,"The stimulating effect of growth hormone on fracture healing is dependent on onset and duration of administration.
 The effect of onset and duration of growth hormone administration on the biomechanical properties of healing rat tibial fractures was investigated after 40 days of healing.
 Biosynthetic human growth hormone, 2.7 mg/kg body weight/day, was given in two daily injections to three groups of rats: (1) for the entire healing period; (2) for the first 20 days; and (3) for the last 20 days of healing.
 Three corresponding groups of control rats were injected with saline.
 In Group 1, maximum load and stiffness of the healing fractures increased to 165% and 175%, respectively, compared to the control group.
 In Group 2, maximum load, stiffness, maximum stress, and energy absorption at maximum load increased to 222%, 175%, 171%, and 247%, respectively, compared to the control group.
 In Group 3, no statistically detectable effects were found.
 The results show that growth hormone stimulates fracture healing both when given during the first part of the healing period and when given during the entire healing period.
",20
3581,"Surgical treatment of brachial plexus birth palsy.
 Brachial plexus birth palsy remains a challenging condition.
 In the 1000 infants followed from 1977 to 1988, functional results were much improved over those obtained by observation only, if surgical exploration and repair were performed when no clinical recuperation of biceps function occurred by three months of age.
 Recovery is slow, and comprehensive follow-up study of reconstructed and conservatively managed children is required to prevent joint contractures.
 Children who will benefit from palliative procedures such as tendon transfers must also be identified.
",20
3582,"Individualized care for the treatment of alcoholism.
 Through a discussion of several case vignettes, the author emphasizes the utilization of an individually tailored treatment approach when working with people experiencing problems related to alcohol consumption.
 Patients may achieve abstinence without believing in the disease concept of alcoholism, and attending Alcoholics Anonymous meetings need not always be a part of the treatment.
 Furthermore, for some patients, controlled drinking may be as desirable an outcome as abstinence.
 The importance of entertaining a multiplicity of perspectives when conducting clinical work with such patients is discussed.
",20
3583,"Staffing patterns of American methadone maintenance programs.
 Methadone maintenance is the most frequently utilized treatment for heroin addiction and also represents one of the best AIDS-prevention tools for the IV drug using population.
 Despite these important roles, very little has been reported about how methadone maintenance clinics are staffed.
 Surveys covering various aspects of program operations, including staffing, were sent to all clinics (N = 557) listed in the 1984 National Directory of Drug Abuse and Alcohol Treatment Programs.
 Using ANOVA, staffing patterns were compared across programs as a function of clinic size, city size, region of the country, and funding resources.
 While few differences were found based on city or clinic size, staffing patterns varied as a function of regional location as well as the sources of a clinic's funding.
",20
3584,"Depression among alcoholics in a Turkish sample.
 The aim of the present study was to identify the predictor variables of depression among alcoholics in a Turkish mental hospital.
 A questionnaire and the Beck Depression Inventory (BDI) were utilized to collect data from 71 male alcoholics.
 A stepwise multiple regression analysis between the BDI scores and demographic and health-related variables resulted in the identification of marital problems and physical problems due to alcohol as the risk factors.
 The findings are discussed within the context of the findings from Western countries and the similarities are pointed out.
",20
3585,"Management of auto-emasculation in the psychotic state.
 We report 2 cases of self-inflicted penile amputations, which offered differing surgical options and contrasting surgical results due to varying time delays.
 In 1 case repair was done immediately, while repair in the other case was delayed by 3 days due to the psychotic state of the patient.
 The psychiatric backgrounds of such episodes are discussed, as well as the techniques of repair and reconstruction.
",20
3586,"Evidence that histamine is the causative toxin of scombroid-fish poisoning 
 BACKGROUND.
 The highest morbidity worldwide from fish poisoning results from the ingestion of spoiled scombroid fish, such as tuna and mackerel, and its cause is not clear.
 Histamine could be responsible, because spoiled scombroid fish contain large quantities of histamine.
 Whether histamine is the causative toxin, however, has remained in question.
 To address this issue, we investigated whether histamine homeostasis is altered in poisoned people.
 METHODS.
 The urinary excretion of histamine and its metabolite, N-methylhistamine, was measured in three persons who had scombroid-fish poisoning (scombrotoxism) after the ingestion of marlin.
 We measured 9 alpha, 11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid (PGD-M), the principal metabolite of prostaglandin D2, a mast-cell secretory product, to assess whether mast cells had been activated to release histamine.
 RESULTS.
 The fish contained high levels of histamine (842 to 2503 mumol per 100 g of tissue).
 Symptoms of scombrotoxism--flushing and headache--began 10 to 30 minutes after the ingestion of fish.
 In urine samples collected one to four hours after fish ingestion, the levels of histamine and N-methylhistamine were 9 to 20 times and 15 to 20 times the normal mean, respectively.
 During the subsequent 24 hours, the levels fell to 4 to 15 times and 4 to 11 times the normal values.
 Levels of both were normal 14 days later.
 PGD-M excretion was not increased at any time.
 Two persons treated with diphenhydramine had prompt amelioration of symptoms.
 CONCLUSIONS.
 Scombroid-fish poisoning is associated with urinary excretion of histamine in quantities far exceeding those required to produce toxicity.
 The histamine is most likely derived from the spoiled fish.
 These results identify histamine as the toxin responsible for scombroid-fish poisoning.
",20
3587,"It may be more significant than you think: BB air rifle injury to a child's head.
 BB guns of 20 years ago were constructed of coils and springs which generated relatively little force, so that a projectile posed little threat of serious injury.
 Today, the coil and spring construction has been replaced by pump action pneumatic chambers which allow generation of muzzle velocities near 350 ft/sec.
 Speeds of 150 ft/sec and 200 ft/sec are required for skin penetration and bone penetration, respectively.
 We present a seven-year-old boy who suffered intracranial parenchymal injury from an air-powered BB gun projectile while playing with friends.
 We discuss literature which suggests these once-innocent toys are now harbingers of severe, if not fatal, injury.
",20
3588,"Early definitive bone and soft-tissue reconstruction of major gunshot wounds of the face.
 The use of craniofacial surgical techniques, extended open reduction, rigid fixation with plates and screws, and the replacement of severely damaged or missing bone with immediate bone grafting in the treatment of complex facial fractures has been applied to the management of severe gunshot wounds of the face.
 Early definitive bone and soft-tissue reconstruction has been performed in 37 patients.
 One-hundred and seventy-seven primary bone grafts were utilized in 33 patients for orbital, nasal, zygomatic, and maxillary reconstruction.
 Twenty-six patients required mandibular repair with compression or reconstruction plates.
 Soft-tissue reconstruction was provided by a combination of flaps.
 Four patients had extensive soft-tissue loss replaced by free vascularized omental flaps.
 The omentum provided circumferential coverage of the mandibular reconstruction and reconstruction of the floor of the mouth and was then tunneled in a circle through both cheeks into the middle and upper face.
 The omentum reconstructed deficits in the hard palate and upper buccal sulcus and was then wrapped around all zygomatic, orbital, and midfacial bone grafts and used to fill in dead space in the maxillary, ethmoid, and frontal sinuses.
 The omentum is not used to provide contour and bulk, but to cover bone grafts and plates and fill in dead space.
 Carefully shaped bone grafts provide the correct craniofacial scaffold.
 Early restoration of a midfacial bony scaffold and the prevention of soft-tissue contraction facilitate secondary reconstruction.
 Four late total nasal reconstructions with tissue-expanded forehead skin wrapped around bone grafts were performed.
",20
3589,"The healing of facial bone fractures by the process of secondary union.
 The mechanism of healing of facial bone fractures was investigated in a rabbit model.
 Twelve New Zealand white rabbits underwent surgically induced fractures of the right infraorbital rim and fracture ostectomies (4 to 5 mm) of the left infraorbital rim.
 Animals were sacrificed 2, 4, and 8 weeks postfracture.
 Bone, including periosteum, obtained from each fracture or fracture osteoctomy site was divided longitudinally for hematoxylin and eosin staining, fluorescent microscopy, microangiography, and microradiography.
 Sequential fluorochrome labels of oxytetracycline (30 mg/kg), alizarin complexone (30 mg/kg), DCAF (20 mg/kg), and xylenol orange (90 mg/kg) were administered 24 hours preoperatively and at 1, 2, 4, and 8 weeks postfracture.
 All fracture and fracture ostectomy sites demonstrated vascular ingrowth, mineralization, and woven bone formation by 2 to 4 weeks postoperatively, beginning with a cartilage precursor.
 Subsequently, the woven bone was replaced with remodeled lamellar bone, resulting in complete bony healing by 8 weeks postoperatively.
 These steps were substantiated by microscopic, microradiographic, and radiologic examination of the specimens.
 This study demonstrates that fractures of the facial bones in a rabbit model heal by a process of new bone formation that resembles secondary union in endochondral bones.
",20
3590,"Analysis of the soft-tissue response to components used in the manufacture of breast implants: rat animal model.
 The implant-tissue response to the silicone gel mammary prosthesis requires a more thorough evaluation in light of recent concerns related to human connective-tissue diseases, contracture, infection, and neoplasia.
 The silicone prosthesis is not a homogeneous implant but is a milieu of various silicone chemistries.
 Silicone polymer precursors and prosthesis components (silicone shells, shells extracted of their low-molecular-weight components, silica-free silicone, silicone oil, fumed silica, and silicone extract) were implanted subcutaneously using a nonhemorrhagic technique into the backs of Lew/SsN rats (n = 90), two implants per rat, for periods of 7, 14, 28, 56, and 90 days for a total of 6 implants per material per time period.
 Histologic analysis was performed on specimens from the harvested soft tissue.
 The intensity of the cellular and capsular response was lowest for the silicone oil and increased as the material's molecular weight increased and material compliance decreased.
 Fumed silica elicited the most highly reactive cellular response.
 From this study it is apparent that the polymer's molecular weight influences its migration, encapsulation, and intensity of cellular response.
 Further, the silicone extract distillate elicited a highly intense cellular response with pronounced lymphocyte invasion.
 The human relevance of this work awaits further correlation with implant retrieval and in vivo performance.
",20
3591,"Further experience in rehabilitation of zone II flexor tendon repair with dynamic traction splinting.
 A review of all flexor tendon repairs in the ""no man's land"" performed from January of 1985 to June of 1987 was done to evaluate the efficacy of our method of rehabilitation.
 There were 60 fingers (57 patients) with complete laceration of the flexor digitorum profundus and flexor digitorum superficialis tendons in zone II.
 Fingers with phalangeal fractures, joint injuries, or significant skin loss were excluded.
 Follow-up ranged from 12 to 48 months.
 Rehabilitation consisted of a 12-week protocol using the U.S.
 military combined regimen of controlled motion.
 Features from the technique of controlled active extension against rubber band passive flexion as well as those of controlled passive extension and passive flexion were incorporated.
 The palmar pulley modification of Kleinert's dynamic traction splint was utilized.
 Strickland's total active motion formula was employed to determine results.
 The results were classified into the four categories of excellent, good, fair, and poor.
 Fifty-two fingers (86 percent) were rated excellent, 4 fingers (7 percent) were rated good, 1 finger (2 percent) was rated fair, and 3 fingers (5 percent) were rated poor.
",20
3592,"Island flap supplied by the dorsal branch of the ulnar artery.
 Two cases are reported in which a fasciocutaneous island flap was employed supplied by the ulnaris dorsalis artery after the method proposed by Becker and Gilbert.
 The original technique has been modified by the authors, and this produces a better venous outflow.
 The vascular pedicle includes, besides the ascending branch of the artery and the venae comitantes, one of the superficial veins together with its respective subdermal band.
 A technique is also described that provides an optimal length for the vascular pedicle.
",20
3593,"Strut fixation of an extensive flail chest.
 The indications for and preferred approaches to operative stabilization of posttraumatic chest wall instability are uncertain.
 We suggest this simple, rapid, and effective approach to surgical stabilization by Luque rod strutting of the flail segment when operation is required.
",20
3594,"Electrophysiologic investigation of mandibular nerve injury.
 Isolated lesions of the mandibular branch of the trigeminal nerve have only rarely been reported.
 We report the occurrence of an isolated lesion of the mandibular nerve associated with a unilateral mandibular fracture, and its substantiation electrophysiologically.
 A 65-year-old man was involved in a motor vehicle accident resulting in multiple fractures, including a unilateral mandibular fracture and temporomandibular joint dislocation.
 No evidence of intracranial pathology by CT scan was noted and the neurologic examination was nonfocal except for dysfunction of the mandibular nerve ipsilateral to the fracture site.
 Bilateral facial nerve latency and blink reflexes were normal.
 EMG evaluation of the muscles of facial expression and mastication demonstrated denervation confined to the muscles innervated by the mandibular branch of the trigeminal nerve.
 In patients complaining of facial sensory dysfunction, malocclusion, or weakness of muscles of mastication after mandibular fracture, an electrophysiologic examination can assist in evaluating cranial nerve integrity.
",20
3595,"Operative exposure of the abdominal arteries for trauma.
 Traumatic injuries to the abdominal arteries require operative exposures that allow for flexible repair.
 Dividing the abdominal arterial tree into four zones, based on exposure, provides expedient and precise repair of all major abdominal arteries.
",20
3596,"Why surgeons prefer not to care for trauma patients.
 A survey of the Washington State Chapter of the American College of Surgeons was undertaken to document the opinions of surgeons on trauma care issues.
 Thirty-nine percent of the total sample of surgeons who responded would prefer not to treat any trauma patients.
 These surgeons were more likely to be older, to practice in an urban setting, to feel that trauma call has a negative impact on elective practice, and to believe more strongly that reimbursement from trauma patients is not equal to that of nontrauma patients.
 They also agreed more strongly with the statements that these patients require a greater time commitment and pose an increased medicolegal risk.
 The most significant influence on preference not to treat trauma patients was exerted by the perception of a negative impact on practice, older age, and perception of increased medicolegal risk.
 Reimbursement issues and location of practice were less influential factors.
 This information can be used to target concerns and barriers to active, willing participation in a trauma care system and to tailor strategies to deal with them effectively.
",20
3597,"Serious childhood injuries caused by air guns.
 OBJECTIVE: To determine the severity of nonfatal injuries to children caused by air guns and pellet guns.
 DESIGN: Case series (hospital chart review).
 SETTING: Inpatient wards of the Children's Hospital of Eastern Ontario.
 PATIENTS: All children under 18 years of age admitted to the hospital from Jan.
 1, 1979, to Dec.
 31, 1989, under ICD code E917, E922, E955, E965, E970 or E985 who had suffered air gun injuries.
 MAIN OUTCOME MEASURES: Personal data, circumstances of event and clinical data.
 RESULTS: The 43 children (37 boys) had a median age of 12 years.
 The circumstances of the accident were known in 20 cases: 17 children were playing and 3 were cleaning the gun when it went off.
 Four children thought the gun was unloaded.
 In five cases the bullet ricocheted into the eye.
 Nine injuries were self-inflicted.
 Injury was to the extremities in 21 (49%), the eyes in 15 (35%) and the head and neck in 7 (16%).
 The median length of hospital stay was 4 days.
 Six children had long-term disabilities, all the result of eye injuries; two had cataract surgery, and four required enucleation of the eye.
 CONCLUSIONS: Air guns can cause serious injury to children.
 Their sale needs to be banned or at least carefully regulated.
",20
3598,"Adequate resuscitation of burn patients may not be measured by urine output and vital signs.
 OBJECTIVE: To compare vital sign and urine output monitoring of seriously burned patients with invasive monitoring during early resuscitation.
 DESIGN: Retrospective review.
 SETTING: A university hospital burn unit.
 PATIENTS: Fourteen seriously burned patients who had pulmonary arterial monitoring.
 Monitoring data were compared at baseline and after fluid challenges.
 RESULTS: There was no correlation between invasively derived physiologic variables and vital signs and urine output.
 Vital signs and urine output changed little after fluid challenge, while variables from invasive monitoring demonstrated significant change.
 In half of the patients, oxygen consumption increased after fluid challenge; vital signs and urine output did not distinguish these patients.
 CONCLUSIONS: The use of urinary output and vital signs to guide initial burn resuscitation may lead to suboptimal resuscitation.
 Invasive cardiorespiratory monitoring may be necessary to optimize resuscitation of seriously burned patients.
",20
3599,"Outcome following prolonged intensive care unit stay in multiple trauma patients.
 OBJECTIVE: To describe the hospital course and outcomes of trauma patients requiring ICU stays greater than 30 days and the charges they incur.
 DESIGN: A retrospective case series analysis of data collected from patient charts and trauma registry.
 SETTING: A Level I regional trauma center that is part of a statewide trauma system.
 PATIENTS: Over a 3-yr period, 87 patients (3% of all trauma ICU admissions) had prolonged stays (greater than 30 days) in the ICU; they constitute the study group.
 Blunt trauma was responsible for 90% of injuries, and the mean Injury Severity Score was 34 +/- 16 SD.
 RESULTS: Mechanical ventilation was required for 78.5% of the time spent in the ICU.
 The mean time spent on mechanical ventilators was 47 +/- 23 days; in the ICU, 60 +/- 27 days; and in the hospital, 72 +/- 29 days.
 Infectious complications occurred in 90% and organ dysfunction was seen in 76% of patients.
 The overall mortality rate was 17.2% (31% for patients greater than 65 yr).
 Patients less than 40 yr had lower mortality rates despite a significantly higher Injury Severity Score and lower Glasgow Coma Scale score compared with those greater than 65 yr.
 More patients greater than 65 yr were discharged to chronic care facilities than those younger (23% vs.
 5%).
 The number of patients followed at 3 and 12 months after discharge was 74% and 54%, respectively, with only two deaths.
 The mean hospital and professional charges to the patients were $101,000 +/- 61,000 and $35,000 +/- 13,000, respectively.
 CONCLUSION: Length of ICU stay was most closely associated with the need for mechanical ventilation.
 The presence of premorbid illness, age greater than 65 yr, and organ dysfunction was associated with increased mortality.
 Although trauma patients requiring prolonged ICU stays utilize many resources, the ultimate outcome may be fairly good.
",20
3600,"An unusual treatment for a rare dilemma (oesophageal foreign body).
 Identification of an intramural oesophageal fishbone at operation is difficult.
 Such a case is discussed with an attempted accurate radiological localization of site pre-operatively.
 No such case has so far been reported.
",20
3601,"Motor vehicle crash injury patterns and the Virginia seat belt law.
 Injuries to front seat occupants in tow-away crashes in the Charlottesville, Va, area were compared for 1 year before and 1 year after Virginia's seat belt use law took effect.
 Vehicle and occupant data were combined to examine crash and injury patterns.
 Reported seat belt use in crashes increased after the law, and there were substantial decreases in injuries.
 Front seat occupants were less likely to receive medical treatment following a crash in the postlaw period.
 The reduction in the number of injuries was greater for passengers in the right front seat than for drivers and for frontal crashes than for other types of crashes.
 The injury reduction effects occurred primarily through reductions in the number of head and face injuries, particularly those that occur from contact with windshields and instrument panels.
",20
3602,"Efficacy of eyepad in corneal healing after corneal foreign body removal 
 30 patients with corneal epithelial defect due to removal of corneal foreign bodies were randomly allocated to receive either chloramphenicol with continuous application of an eyepad or chloramphenicol without the eyepad.
 Almost all corneal defects were healed at 24 h, and all were healed by 48 h, with no statistically significant difference between the two groups.
 Discomfort at 24 h was greater in the eyepad group than in the control group.
 An eyepad seems to confer no benefit in healing and is uncomfortable.
",20
3603,"Anterior cruciate ligament injuries. Evaluation, arthroscopic reconstruction, and rehabilitation.
 The advantages of arthroscopic reconstruction of the anterior cruciate ligament tear over arthrotomy are quite obvious: reduced pain and morbidity.
 Some arthroscopists are performing these procedures on an outpatient basis.
 The physician can choose from several graft substitutes for anterior cruciate ligament replacement.
 Autografts consisting of the iliotibial band, semitendinosus, gracilis, and meniscus have been used as grafts.
 The most common autograft is the bone-patellar tendon-bone, which has been used since 1930 and has been shown to have a tensile strength near that of the anterior cruciate ligament.
 The state of the art in surgical alternatives for anterior cruciate ligament tears is arthroscopic reconstruction using the midthird of the patellar tendon.
 Treatment of anterior cruciate ligament injuries requires prompt and adequate evaluation of the laxity of the ligament as well as other structures in the knee, appropriate treatment options offered to the patient with complete descriptions of knee function after each treatment option, and comprehensive rehabilitation program.
 Patient compliance is an integral part of the success of this procedure.
 The nurse must include a description of the injury, preoperative testing, surgical intervention, and rehabilitation program when educating the patient.
 The successful postoperative anterior cruciate ligament rehabilitation program is multifaceted.
 In general, there must be specific guidelines applied by a physical therapist who has knowledge of the surgical procedure, understands principles of ligament healing, and has the ability to individualize the program as needed.
 For any level of athlete or active person, there must be achievement of all goals per phase to a high performance level.
 In addition, there must always be objective measurements to document progress to the physical therapist and physician but, perhaps most importantly, to reassure the patient that normalcy is being restored.
",20
3604,"Stress fractures in athletes.
 Most stress fractures are preventable.
 Proper conditioning and preseason training is essential.
 Selection of the appropriate age-related sport must be taken into consideration.
 Adequate warm-up and cool-down is important to prevent muscle injuries that may contribute to stress fractures later on.
 The athlete should be aware of not ""over-doing it"" because fatigue is a contributing factor to the stress injury rate.
 Proper dress and equipment are necessary.
 Using the basic methods of prevention, along with good sportsmanship, safe participation in any sport may be anticipated.
 Because the demands and expectations of our high-performance athletes are more prevalent, education and rehabilitation of the sports-injured patient have become ever important.
 With the emergence of sports medicine as a discipline, injured athletes are returned to the playing arenas much more rapidly with newer protocols and techniques.
 We must be ready rapidly to assess, diagnose, and treat all sports injuries; however, we must be aware and alert to the possibility that it is an injury of ""wear and tear"" when making any diagnosis and prescribing any treatment regime.
",20
3605,"Common spinal injuries in athletes.
 Special needs of athletes with spine injuries must be considered when planning for treatment of these patients.
 The patients wish to return to competition safely but rapidly.
 Nurses must understand the patients'/athletes' need but put them into perspective with respect to the diagnosis, treatment, and degree of disability.
 Support, encouragement, and understanding from a knowledgeable health professional are invaluable.
",20
3606,"Pelvic fracture patient care. Reflections on the past, implications for the future.
 Nursing care of patients with pelvic fractures has changed dramatically in the past two decades.
 Fracture care that necessitated long periods of immobility and consequent complications has been influenced by new classification systems, the use of external fixation, and the more recent use of internal fixation.
 The evolution of pelvic fracture patient care has greatly influenced nursing care of these patients.
",20
3607,"Bone stimulators for fusions and fractures.
 Even though a complete understanding of electrical responses of bone has not been fully obtained, useful data toward this end have been gathered.
 The development of devices that use what is known about the bone's electrophysiologic properties has impacted patient care.
 Many health care professionals remain skeptical about the effects of electrical stimulation in bone healing.
 Therefore, further research is needed to help the practitioner formulate a more educated opinion on this form of therapy.
",20
3608,"Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial.
 In a prospective, double-blind comparison, we assessed the efficacy of transdermal clonidine with that of chlordiazepoxide in the treatment of moderately severe acute alcohol withdrawal syndrome.
 While having significant withdrawal symptoms, 50 hospitalized men were randomly assigned to receive either transdermal clonidine or chlordiazepoxide over a 4-day study period.
 Outcome was evaluated daily, medically and psychiatrically, using both objective and subjective measurements for dependent variables.
 No patient in either study group had seizures or progression to delirium tremens.
 The group receiving transdermal clonidine had a more significant response globally for the signs and symptoms of alcohol withdrawal, as measured by the Alcohol Withdrawal Assessment Scale.
 Also, clonidine more effectively lowered elevated systolic and diastolic blood pressure and heart rate.
 The core target symptom, anxiety, decreased significantly more in the patients receiving transdermal clonidine when measured by the Hamilton Anxiety Rating Scale and its subscale for somatic anxiety.
 Cognitive function responded equally in both study populations.
 Clonidine-treated patients reported less diarrhea, dizziness, headache and fatigue, and the chlordiazepoxide-treated patients reported less nausea and vomiting.
 We conclude that transdermal clonidine is effective treatment for the acute alcohol withdrawal syndrome.
",20
3609,"Pediatric injury surveillance: use of a hospital discharge data base.
 Mortality data traditionally have been used to describe the epidemiology of childhood injury.
 Fatal outcomes, however, represent less than 1% of injury events and thus provide a limited characterization of the problem.
 Future epidemiologic study resulting in injury prevention depends upon the development of morbidity-based injury surveillance systems.
 ""E-coded"" hospital discharge data bases (used to indicate external cause of injury) are a valuable source of information for monitoring and controlling serious, nonfatal injuries.
 An E-coded injury discharge data base was developed and evaluated at The Children's Hospital of Alabama in Birmingham.
 In addition to patient demographics, length of stay, total charge, and method of payment, E-code and ""N-code"" (to indicate the anatomic site of injury) data were collected.
 During the 2-year study period, 1077 discharges from the hospital were documented in children with serious injuries under 15 years of age for an adjusted discharge rate of 78.0 per 10,000 child-years.
 Injuries accounted for $5.3 million in total charges and 4899 total days of stay.
 Falls, unintentional poisonings, burns, and bicycle, motor vehicle-passenger, and motor vehicle-pedestrian injuries were the six most common causes of injury.
 Closed-head trauma accounted for 55.4% of motor vehicle-passenger injuries, 67.6% of bicycle injuries, and 51.8% of falls.
 Hot water scalds caused 36.4% of burns, and clonidine ingestion accounted for 22.1% of unintentional poisonings.
",20
3610,"Fatal incidents involving pickup trucks in Alabama.
 Death or injury resulting from crashes involving light trucks (ie, pickup trucks) is a significant problem.
 Data show that fatal crashes and occupant fatalities involving light trucks have steadily increased since 1983.
 This project describes vehicle crashes involving passengers riding in the beds of pickup trucks.
 Actual crashes were identified through the Fatal Accident Reporting System (FARS) of the National Highway Traffic Safety Administration.
 The 40 incidents studied involved 204 pickup truck passengers.
 Of these, 45 were killed, 107 sustained visible injuries or were carried from the scene, 6 had bruises and abrasions, and 2 had no visible injury but were briefly unconscious or had a documented complaint of pain.
 The risk of death among pickup truck passengers who were fully ejected from the vehicle was nearly six times that of passengers not fully ejected.
 Correspondingly, the risk of ejection from the truck was 26.7 times greater among occupants riding in the bed than occupants riding in the cab.
",20
3611,"Isolated subclavian artery dissection after blunt trauma.
 We present a case report of a patient with an isolated dissection of the subclavian artery after blunt trauma.
 The patient who was admitted to our center after a motor vehicle accident, complained of chest and neck pain and physical findings of diminished left extremity pulses.
 Arteriography showed an occluded subclavian artery with the possibility of a dissection.
 The dissection was confirmed at surgery with the proximal extent originating just distal to the origin of the vertebral artery.
 The distal extent of the dissection was not determined.
 Operative repair was performed by a carotid-to-subclavian artery bypass obliterating the false lumen of the dissection with a running vascular anastomosis.
 The patient, who was discharged 5 days after repair, had normal extremity neurovascular function at 4 months follow-up.
",20
3612,"Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds.
 Recombinant platelet-derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-beta 1) influence the rate of extracellular matrix formed in treated incisional wounds.
 Because incisional healing processes are difficult to quantify, a full-thickness excisional wound model in the rabbit ear was developed to permit detailed analyses of growth-factor-mediated tissue repair.
 In the present studies, quantitative and qualitative differences in acute inflammatory cell influx, glycosaminoglycan (GAG) deposition, collagen formation, and myofibroblast generation in PDGF-BB (BB homodimer)- and TGF-beta 1-treated wounds were detected when analyzed histochemically and ultrastructurally.
 Although both growth factors significantly augmented extracellular matrix formation and healing in 10-day wounds compared with controls (P less than 0.002).
 PDGF-BB markedly increased macrophage influx and GAG deposition, whereas TGF-beta 1 selectively induced significantly more mature collagen bundles at the leading edge of new granulation tissue (P = 0.007).
 Transforming growth factor-beta 1-treated wound fibroblasts demonstrated active collagen fibrillogenesis and accretion of subfibrils at the ultrastructural level.
 Myofibroblasts, phenotypically modified fibroblasts considered responsible for wound contraction, were observed in control, but were absent in early growth-factor-treated granulating wounds.
 These results provide important insights into the mechanisms of soft tissue repair and indicate that 1) PDGF-BB induces an inflammatory response and provisional matrix synthesis within wounds that is qualitatively similar but quantitatively increased compared with normal wounds; 2) TGF-beta 1 preferentially triggers synthesis and more rapid maturation of collagen within early wounds; and 3) both growth factors inhibit the differentiation of fibroblasts into myofibroblasts, perhaps because wound contraction is not required, due to increased extracellular matrix synthesis.
",20
3613,"Clinical utility of a position-monitoring catheter in the pulmonary artery.
 Unsuspected distal migration of the tip of the pulmonary artery catheter may cause life-threatening complications.
 We prospectively evaluated the clinical utility of the PA Watch Catheter in 25 patients after cardiac surgery by hourly measurements of pulmonary artery (distal lumen), right ventricular (middle lumen), and central venous (proximal lumen) pressures.
 The catheter was considered to be in the proper position when the middle lumen port, located 10 cm from the tip, transmitted a right ventricular pressure waveform.
 Satisfactory initial catheter placement was obtained in 24 of 25 patients.
 During the 28.4 +/- 1.8 h of postoperative monitoring, clinically unsuspected distal catheter migration, indicated by the presence of a pulmonary artery pressure waveform in the middle lumen port, occurred in 12 of the 25 patients (48%).
 In these patients, 20 episodes occurred and required catheter withdrawal distances of 1.8 +/- 0.3 cm (range 1-6 cm).
 The PA Watch Catheter proved to be a useful indicator of unsuspected distal catheter migration in the postoperative period.
 The PA Watch Catheter allows assessment of catheter tip placement in the proximal pulmonary artery and may decrease catheter-induced complications.
",20
3614,"An animal model for human masseter muscle: histochemical characterization of mouse, rat, rabbit, cat, dog, pig, and cow masseter muscle.
 The masseter muscle of several animal species was investigated by use of a histochemical method for the demonstration of acid-stable and alkali-stable myosin adenosine triphosphatase (ATPase).
 The following subdivisions of fiber types were used: Type I fibers show weak ATPase activity at pH 9.4, type IM fibers react moderately, and type II fibers react strongly.
 Rat and mouse masseter muscles contained type II fibers only, as did some rabbit masseter muscles, whereas other rabbit masseter muscles possessed equal amounts of type I and II fibers.
 Cat and dog masseter muscles possessed both type II and I fibers, with type II predominating.
 Cow masseter muscle consisted mainly of type I fibers, although some cow masseter muscles contained a very small number of type II fibers.
 Pig masseter muscle had both type I, II, and IM fibers.
 One of the characteristics of human masseter muscle is type IM fibers, which are rarely seen in muscles other than the masticatory muscles.
 Therefore, pig masseter muscle might be a suitable animal model for experimental studies, such as an investigation of the distribution and diameter of fiber types in the masticatory muscles before and after orthognathic surgery.
",21
3615,"Collagen of the dystrophic hamster diaphragm.
 The collagen content of the diaphragm was measured in normal and dystrophic hamsters aged 130 and 270 days.
 The diaphragm collagen content was greater in dystrophic hamsters than in control hamsters of the same age.
 The effect was greater in the older hamsters whether the collagen content was expressed in terms of the percentage of dry weight, in relation to surface area, or as total collagen.
 This increase was apparently at the expense of muscle tissue and may be a major factor contributing to respiratory muscle weakness as dystrophy advances.
",21
3616,"Cellular and metabolic requirements for induction of macrophage procoagulant activity by murine hepatitis virus strain 3 in vitro.
 The cellular basis for the variation in induction of monocyte procoagulant activity (PCA) by murine hepatitis virus strain 3 (MHV-3) was examined using a set of recombinant inbred strains of mice derived from the resistant (A/J) and susceptible C57B1/6J (B) progenitors.
 Induction of PCA by MHV-3 required live virus and host protein and RNA synthesis.
 Absolute restriction for induction of PCA was observed at the level of the macrophage.
 Peritoneal macrophages from resistant parental A/J and RI strains (AXB5) could not be induced to express PCA when stimulated by MHV-3 alone or in the presence of lymphocytes from susceptible and H-2 compatible RI mice (AXB3) although they did respond to endotoxin (LPS).
 In contrast, macrophages from both susceptible (AXB3) and semisusceptible (AXB1) RI strains of mice expressed a similar increase in PCA after stimulation with MHV-3 in the absence of lymphocytes.
 The levels of PCA expressed by macrophages in the presence of Thy-1.2+ lymphocytes correlated with susceptibility to disease.
 Thy-1.2+ lymphocytes from susceptible RI AXB3 mice could induce levels of PCA in macrophages from semisusceptible RI AXB1 mice equivalent to that seen in cultures of macrophages and lymphocytes from susceptible mice.
 Further subfractionation of Thy-1.2+ cells demonstrated that L3T4+ cells instructed macrophages to produce PCA.
 Thy-1.2+ cells from MHV-3 immunized resistant AXB5 mice, but not from non-immunized mice, were able to suppress induction of PCA.
 This suppressor cell activity could be detected 4 days after immunization, reaching maximal activity at day 7 with significant suppression even at 28 days.
 The PCA was shown to have direct prothrombin cleaving activity (prothrombinase) by ELISA and immunofluorescence staining using the mAb 3D4.3.
 These results demonstrate that induction of a unique PCA (prothrombinase) is restricted at the level of the macrophage and define a regulatory role for T lymphocytes in its induction.
",21
3617,"Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons.
 Moderate non-progressive cognitive impairment is a consistent feature of Duchenne muscular dystrophy (DMD), although no central nervous system (CNS) abnormality has been identified.
 Recent studies have elucidated the molecular defect in DMD, including the absence of the protein dystrophin in affected individuals.
 Normal brain tissue contains dystrophin messenger RNA and dystrophin is present in low abundance in the brain and seems to be regulated in this tissue, at least in part, by a promoter that differs from that in muscle.
 Until now, antibodies and immunocytochemical methods used to demonstrate dystrophin at the plasma membrane of mouse and human muscle have proven inadequate to localize precisely dystrophin in the mammalian CNS.
 We have now made an antibody (anti 6-10) which is much more sensitive than those previously available to immunolabel dystrophin in the CNS.
 Using this antibody, we found that in the mouse, dystrophin is particularly abundant in the neurons of the cerebral and cerebellar cortices, and that it is localized at postsynaptic membrane specializations.
 Dystrophin may have a different role in neurons than in muscle, and an alteration at the synaptic level may be the basis of the cognitive impairment in DMD.
",21
3618,"Parental MHC molecule haplotype expression in (SJL/J x SWR)F1 mice with acute experimental allergic encephalomyelitis induced with two different synthetic peptides of myelin proteolipid protein.
 To determine if the Ag that induces an autoimmune disease influences parental MHC haplotype molecule expression in situ in MHC heterozygotes, acute experimental allergic encephalomyelitis (EAE) was induced with different encephalitogenic peptides in (SJL/J x SWR)F1 mice.
 The mice were sensitized with either a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 103-116 YKTTICGKGLSATV which induces EAE in SWR (H-2q), but not SJL/J (H-2s) mice or a synthetic peptide corresponding to PLP residues 139-151 HCLGKWLGHPDKF which is encephalitogenic in SJL/J but not SWR mice.
 Mice were killed when they were moribund or at 30 days after sensitization.
 Twelve of 18 F1 mice given PLP peptide 103-116 and 12 of 17 mice given PLP peptide 139-151 developed EAE within 2 to 3 wk after sensitization.
 Cryostat sections of brain samples from F1 and parental mice were immunostained with a panel of mAb identifying H-2s and H-2q class I and II MHC molecules.
 In brains of controls, class I MHC molecules were expressed on choroid plexus, endothelial cells, and microglia whereas class II MHC molecules were absent.
 In EAE lesions, class I and II MHC molecules were present on inflammatory and parenchymal cells, but the degree of parental haplotype molecule expression did not vary with the different peptide Ag tested.
 Thus, in (SJL/J x SWR)F1 mice, myelin PLP peptides 103-116 and 139-151 are co-dominant Ag with respect to clinical and histologic disease and parental haplotype MHC molecule expression.
 We propose a unifying hypothesis consistent with these results and previous observations of differential Ia expression in (responder x non-responder)F1 guinea pigs.
 We suggest that MHC molecules may bind locally derived peptide Ag in inflammatory sites and that these interactions influence levels of MHC haplotype molecules on APC.
",21
3619,"Dystrophin is required for normal thin filament-membrane associations at myotendinous junctions.
 Dystrophin, the deficient gene product in Duchenne muscular dystrophy, is located subjacent to the muscle cell membrane at myotendinous junctions, as well as along the entire muscle cell.
 Myotendinous junctions are sites at which thin filaments normally are linked to one another and to the cell membrane, by both lateral and end-on associations between the thin filaments and membrane.
 The cell membrane at these sites in normal muscle is folded extensively.
 Dystrophic junctions display normal contacts between the ends of thin filaments and subsarcolemmal densities.
 However dystrophic junctions are deficient in lateral associations between thin filaments and the membrane and display less membrane folding than controls.
 These structural defects would result in stress concentrations at sites of thin filament attachment to the membrane, which can cause membrane tearing during muscle activation, especially in large-diameter and mature muscle cells.
 This deficiency in dystrophic myotendinous junction structure may contribute to our understanding of previously unaccountable aspects of the etiology of Duchenne muscular dystrophy.
",21
3620,"Role of influenza B virus in hepatic steatosis and mitochondrial abnormalities in a mouse model of Reye syndrome.
 The hepatic steatosis observed in the influenza B virus mouse model of Reye syndrome has been attributed to infectious virus or, alternately, to decreased food intake in the virus-treated mice or impurities in the virus preparation.
 To resolve this issue, 4- to 6-wk-old male Balb C mice were given, by intravenous injection, 12,800 hemagglutination units of influenza B Lee/40 virus in phosphate buffered saline/1% bovine serum albumin using virus prepared by ultra-centrifugation from infected allantoic fluid, by sucrose density-gradient purification of virus prepared by ultracentrifugation from infected allantoic fluid or by irradiation of virus prepared by ultracentrifugation from infected allantoic fluid to inactivate virus.
 The infectivity titer of virus prepared by ultracentrifugation from infected allantoic fluid was much higher than that of sucrose density-gradient purified virus prepared from infected allantoic fluid: 50% egg infectious dose for virus prepared by ultracentrifugation from infected allantoic fluid was 3.9 x 10(4)/hemagglutination unit vs.
 8.7 50% egg infectious dose/hemagglutination unit for sucrose density-gradient purified virus prepared from infected allantoic fluid.
 Control mice received phosphate-buffered saline/1% bovine serum albumin or uninfected allantoic fluid diluted in phosphate-buffered saline/1% bovine serum albumin.
 Mice were fasted to eliminate dietary variation, and livers were obtained 36 hr after virus administration.
 Of the above treatments, only virus prepared by ultracentrifugation from infected allantoic fluid caused clinical illness and increased hepatic triglycerides (p less than 0.02) compared with controls.
 Hepatic triglycerides in virus prepared by ultracentrifugation from infected allantoic fluid correlated with histopathological vacuolization scores (r = 0.5773; p less than 0.03).
",21
3621,"X-irradiation improves mdx mouse muscle as a model of myofiber loss in DMD.
 The mdx mouse, although a genetic and biochemical homologue of human Duchenne muscular dystrophy (DMD), presents a comparatively mild histopathological and clinical phenotype.
 These differences are partially attributable to the greater efficacy of regeneration in the mdx mouse than in DMD muscle.
 To lessen this disparity, we have used a single dose of X-irradiation (16 Gy) to inhibit regeneration in one leg of mdx mice.
 The result is an almost complete block of muscle fiber regeneration leading to progressive loss of muscle fibers and their replacement by loose connective tissue.
 Surviving fibers are mainly peripherally nucleated and, surprisingly, of large diameter.
 Thus, X-irradiation converts mdx muscle to a model system in which the degenerative process can be studied in isolation from the complicating effect of myofiber regeneration.
 This system should be of use for testing methods of alleviating the myofiber degeneration which is common to mdx and DMD.
",21
3622,"Low zinc intake affects maintenance of pregnancy in guinea pigs.
 Zinc deficiency during pregnancy has severe effects in animals.
 To what extent the effects in animals apply to human pregnancy is not known.
 Because the pregnant guinea pig shares characteristics with pregnant women that make it a useful model, three experiments were done with guinea pigs in which Zn intake was reduced beginning on the 30th d of gestation.
 Reduced Zn intake in two of the three experiments resulted in abortion or premature delivery.
 Zinc-supplemented animals with feed intake restricted to that of Zn-deficient animals also aborted or delivered prematurely.
 Zinc-supplemented animals fed for ad libitum access delivered living young at term.
 Fetal/neonatal liver Zn concentration was low in the guinea pigs compared to that reported for other animals and was affected to a lesser extent by low Zn intake by the dam.
 Zinc concentration of neonatal plasma was also less than that in several other species.
 Change in activity of angiotensin-converting enzyme with addition of Zn in vitro was greater in the plasma of Zn-deficient guinea pigs than in that of Zn-adequate guinea pigs and may be useful as an indicator of Zn status.
",21
3623,"Dystrophin expression in myotubes formed by the fusion of normal and dystrophic myoblasts.
 Mdx mouse dystrophy is characterized by the absence in the muscle cytoplasmic membrane of a high molecular weight protein called dystrophin.
 A possible avenue for treatment of muscular dystrophies is to inject normal myoblasts in a dystrophic muscle to form hybrid muscle fibers.
 Hybrid myotubes were formed in vitro by the fusion of normal rat and dystrophic mouse (mdx) myoblasts.
 Staining with Hoechst dye 33258 permitted the clear distinction of mouse and rat nuclei.
 Immunostaining demonstrated that dystrophin was present over the entire membrane of all hybrid myotubes even when nuclei ratio normal/dystrophic was low.
",21
3624,"Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes.
 OBJECTIVE--To study the effects of amenorrhoea and intensive back exercise on the bone mineral density of the lumbar spine in female athletes.
 DESIGN--Cross sectional study comparing amenorrhoeic with eumenorrhoeic athletes and rowers with non-rowers.
 SETTING--The British Olympic Medical Centre, Northwick Park Hospital.
 PATIENTS--46 Elite female athletes comprising 19 rowers, 18 runners, and nine dancers, of whom 25 were amenorrhoeic and 21 eumenorrhoeic.
 MAIN OUTCOME MEASURE--Trabecular bone mineral density of the lumbar spine measured by computed tomography.
 RESULTS--Mean trabecular bone mineral density was 42 mg/cm3 (95% confidence interval 22 to 62 mg/cm3) lower in the amenorrhoeic than the eumenorrhoeic athletes; this difference was highly significant (p = 0.0002).
 Mean trabecular bone mineral density was 21 mg/cm3 (1 to 41 mg/cm3) lower in the non-rowers than the rowers; this was also significant (p = 0.05).
 There was no interaction between these two effects (p = 0.28).
 CONCLUSION--The effect of intensive exercise on the lumbar spine partially compensates for the adverse effect of amenorrhoea on spinal trabecular bone density.
",22
3625,"Nuclear techniques for the analysis of urinary calculi.
 Sections of urinary calculi were prepared and point-by-point analyses along a line-scan were carried out using the techniques of proton-induced X-ray emission (PIXE) and nuclear reaction analysis (NRA).
 Correlations between several pairs of elements (including trace elements) were noted and it was also clear that the composition of a stone varied markedly at different stages of development.
",22
3626,"Single lumen ileum with myectomy: a possible alternative to the pelvic reservoir in restorative proctocolectomy.
 An alternative procedure to construction of a pelvic ileal reservoir was assessed which avoids the need for a pouch, while providing an adequate rectal substitute and good continence.
 Thirty-six female adult beagles were allotted randomly to undergo total colectomy with (a) ileo-anal anastomosis alone, (b) ileo-anal anastomosis with two 15 cm myectomies, (c) ileo-anal anastomosis and myectomy with an ileo-ileal valve, or (d) ileo-anal anastomosis with a duplicated J pouch.
 The animals were studied before operation and at 4-weekly intervals for 20 weeks after operation.
 Mortality rates were similar.
 Ileal compliance was increased significantly by myectomy from 0.64 ml/mmHg (median, interquartile range 0.49-0.78) after ileo-anal anastomosis alone to 1.65 mmHg (1.16-1.93), P less than 0.01, an increase which was maintained.
 Ileal capacity was also increased both by myectomy and by the J pouch: ileo-anal anastomosis = 85 ml (75-100 ml), ileo-anal anastomosis and myectomy = 139 ml (116-156 ml), ileo-anal anastomosis and myectomy and ileo-ileal valve = 125 ml (range 85-145 ml), ileo-anal anastomosis and J pouch = 130 ml (range 75-165 ml) (P less than 0.01).
 Bowel function in the other three groups was markedly superior to ileo-anal anastomosis alone.
 Mean transit time was significantly less after ileo-anal anastomosis, 5.2 h (2.6-8.2 h) than after both ileo-anal anastomosis and myectomy, 10.5 h (9.6-13.9 h), P less than 0.05 and ileo-anal anastomosis and J pouch, 11.0 h (8.4-13.0 h), P less than 0.05, but addition of an ileo-ileal valve did not produce a further increase in transit time, 12.9 h (range 10.5-14.5 h), P = n.s.
 Myectomy of single lumen ileum may be a useful alternative to a pelvic ileal reservoir in restorative proctocolectomy.
",22
3627,"Evidence that a receptor-operated event on the neutrophil mediates neutrophil accumulation in vivo. Pretreatment of 111In-neutrophils with pertussis toxin in vitro inhibits their accumulation in vivo.
 The role of neutrophil chemoattractant receptors in neutrophil stimulation in vitro is well established, however, the precise mechanisms underlying local neutrophil accumulation at inflammatory sites in vivo have not been defined.
 A fundamental question that remains open is whether chemoattractants act on the endothelial cell or the neutrophil to initiate the process of neutrophil migration in vivo.
 To address this question we have investigated whether neutrophil accumulation in vivo can occur if chemoattractant receptor occupancy is uncoupled from neutrophil stimulation.
 For this purpose we have used pertussis toxin (PT) as the pharmacologic tool.
 We have investigated the effect of in vitro pretreatment of rabbit neutrophils with PT on their responses in vitro and on their accumulation in vivo.
 Pretreatment of rabbit neutrophils with PT inhibited FMLP- and C5a-, but not PMA- induced increases in CD18 expression, neutrophil adherence, and degranulation in vitro.
 This pretreatment procedure with PT inhibited the accumulation of radiolabeled neutrophils in vivo in response to intradermally injected FMLP, C5a, C5a des Arg, leukotriene B4, IL-8, and zymosan in rabbit skin.
 Further, in contrast to the in vitro results, PT inhibited the PMA-induced 111In-neutrophil accumulation in vivo.
 Interestingly, pretreatment of neutrophils with PT also inhibited accumulation in response to intradermally injected IL-1, despite the reports that IL-1 lacks neutrophil chemoattractant activity in vitro.
 Although the experimental techniques used cannot distinguish the different stages of neutrophil migration involved, these results suggest that the accumulation of neutrophils induced by local extravascular chemoattractants in vivo depends on a pertussis toxin-sensitive receptor operated event on the neutrophil itself.
 Further, PMA and IL-1 may release secondary chemoattractants in vivo.
",22
3628,"Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect.
 Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration of neutrophils under agarose and enhanced their migration in the multiwell chemotaxis chamber.
 To assess the physiological significance of these differing in vitro TNF effects, ex vivo and in vivo investigations were performed using animal models.
 Neutrophils from the peripheral blood of rabbits preadministered systemic TNF showed impaired ability to migrate toward chemoattractants in vitro.
 In addition, systemic TNF administration suppressed zymosan-activated plasma-induced local accumulation of leukocytes in mouse skin.
 The results indicate that circulating TNF may act as a suppressor for local inflammatory reaction.
",22
3629,"Expression and characterization of TCA3: a murine inflammatory protein.
 TCA3 is a cDNA originally isolated from activated T cells.
 Transcription of this gene has been shown to correlate with Ag-induced cellular activation of both T cells and mast cells.
 Based on the predicted amino acid sequence encoded by the cDNA, we previously proposed that TCA3 represents a cytokine.
 In this report we have used rDNA technology to express TCA3 in two mammalian cell lines.
 In both cases, TCA3 was expressed as a secreted molecule with an apparent molecular mass of 16 kDa.
 Digestion of the (rTCA3) with the enzyme N-glycanase revealed that approximately 8 kDa is caused by N-linked glycosylation.
 Intradermal injection of rTCA3 into mouse footpads resulted in a rapid swelling response.
 The sites of injection were characterized histologically by a local accumulation of neutrophils.
 These findings are discussed with particular attention to a family of related proteins, some of whose members also have inflammatory properties.
",22
3630,"Cytokine regulation of IL-1 beta gene expression in the human polymorphonuclear leukocyte.
 Although recently polymorphonuclear leukocytes (PMN) have been identified as producers of IL-1 beta in response to LPS and granulocyte/monocyte colony stimulating factor, little is known regarding the ability of other cytokines to induce the production of IL-1 beta in the PMN.
 Inasmuch as IL-1 and TNF have been shown to be important priming agents, as well as agents that induce migration of PMN, we investigated their effect on IL-1 beta gene expression in human peripheral blood PMN.
 In the present study, we demonstrate that human peripheral blood PMN produce IL-1 beta in response to IL-1 alpha, IL-1 beta, and TNF-alpha.
 Control (unstimulated) human PMN had virtually undetectable levels of IL-1 beta mRNA.
 Either IL-1 beta or TNF, induced PMN to transiently express IL-1 beta mRNA with peak expression at 1 h, returning to untreated levels by 2 h.
 A dose response indicated that as little as 0.05 ng/ml of IL-1 beta or TNF resulted in IL-1 beta induction, with maximal effects at 1 ng/ml of IL-1 beta and 5 ng/ml of TNF.
 IL-1 alpha or IL-1 beta exhibited similar dose responses in IL-1 beta mRNA induction.
 Inasmuch as cytokines have been shown to have synergistic effects in cell function studies, we induced PMN with a combination of maximally effective doses of TNF plus IL-1 beta.
 They demonstrated a cooperative effect on IL-1 beta gene expression, in that mRNA levels were sustained for three hours.
 IL-1 beta Ag expression, as measured by ELISA, paralleled IL-1 beta mRNA expression with cell associated peak levels at 2 to 4 h.
 IL-1 beta Ag levels in PMN lysates and supernatants correlated with IL-1 beta mRNA levels, i.e., TNF + IL-1 greater than TNF greater than IL-1.
 Thus, these studies represent the first demonstration of IL-1 and TNF induction of IL-1 beta gene expression in the PMN.
 Furthermore, the time course of induction is unique to the PMN, with peak induction of mRNA at 1 h, which is consistent with the short lived nature of these cells in inflammatory lesions.
",22
3631,"Retroviral expression of transforming growth factor-alpha does not transform fibroblasts or keratinocytes.
 Transforming growth factor alpha (TGF alpha) is a peptide so named because it helps to impart anchorage-independent growth to normal rat kidney (NRK) cells in vitro and is secreted by many rodent and human tumor cells.
 To directly investigate the transforming properties of this factor, we constructed a replication-defective murine retrovirus that expresses the human sequence coding for TGF alpha.
 Infection of NIH/3T3 cells with the TGF alpha retrovirus led to the integration of a transcriptionally active provirus and overexpression of biologically active TGF alpha, but failed to induce morphologic transformation.
 Similarly, the TGF alpha retrovirus failed to induce morphologic transformation of five other types of rodent fibroblasts.
 We also investigated the effect of TGF alpha expression on the growth of BALB/MK mouse keratinocytes, which require epidermal growth factor (EGF) for proliferation.
 We show that exogenously added TGF alpha is an extremely potent mitogen for BALB/MK cells.
 However, retroviral expression of TGF alpha in BALB/MK cells failed to relieve dependence on exogenously added EGF (or TGF alpha) for cell growth.
 These results suggest that overexpression of TGF alpha does not, by itself, transform rodent fibroblasts or keratinocytes.
",22
3632,"DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion: identification of four novel mutations in factor IX gene.
 Three hemophilia B patients with anti-factor IX antibodies who had no detectable gross deletion of the factor IX gene by Southern blotting analysis were investigated at the molecular level.
 All eight exons, accompanied by their splicing junction sites and presumptive promoter regions of the factor IX gene in these patients (total 5.5 kb in length) were amplified with the use of the polymerase chain reaction, followed by complete nucleotide sequence analysis.
 Three different types of novel single base substitutions and a 2 base-pair nucleotide deletion were identified.
 Patient HB-5 had two point mutations in his factor IX gene.
 One was located at the promoter region at nucleotide -793 and the other (C-to-T transition) was found in exon VI of the gene changing Gln-191 to a stop codon.
 Patient HB-6 had a point mutation (G-to-A) in the splice acceptor site, which interrupted the normal splicing of the last intron G.
 A small two-nucleotide deletion in exon III was detected in patient HB-7 and yielded frameshifted amino acids and terminated by a stop codon.
 These resuslts suggest that not only the gross gene deletion of factor IX gene but also the point mutations or small nucleotide deletion that may cause the interruption of coding informations for mature protein synthesis is predisposed to development of anti-factor IX inhibitors in patients with hemophilia B.
",22
3633,"Use of ektacytometry to determine red cell susceptibility to oxidative stress.
 To define a more sensitive and reliable method to determine changes in the overall cellular characteristics of erythrocytes after oxidative damage, we used a viscodiffractometric method (ektacytometry) to measure the effect of oxidative stress.
 Erythrocytes were incubated in the presence of hydrogen peroxide, t-butyl hydroperoxide, or cumene hydroperoxide in phosphate buffer.
 This treatment resulted in decreased cellular deformability of the intact erythrocytes.
 In addition, deformability and fragility measurements of the erythrocyte ghost membranes indicated an increased membrane dynamic rigidity and altered-mechanical stability as a consequence of oxidant stress.
 These changes were observed before the onset of hemolysis.
 The observed decrease in deformability was accompanied by oxidation of hemoglobin, alterations of membrane proteins, and lipid peroxidation.
 To continuously measure the time course of the decrease in deformability in intact erythrocytes under oxidative stress, a new ektacytometric method was developed.
 Erythrocytes were oxidatively challenged within the viscometer at a constant osmolality and shear stress.
 The change in deformability was monitored and a typical range was defined for erythrocytes from normal individuals.
 Comparison of erythrocytes from patients with sickle cell disease with those from normal individuals demonstrated a higher susceptibility of sickle red cells toward oxidative stress.
",22
3634,"Assessing the clinical effectiveness of preventive maneuvers: analytic principles and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination.
 This paper examines a process for evaluating clinical effectiveness and developing recommendations in which systematic methods are used to review evidence from published clinical research and to reach sound conclusions about appropriate medical policy.
 The methodology addresses four important components of the analytic process: (1) the criteria that must be satisfied for a clinical practice to be considered effective; (2) proper methods for reviewing evidence from published clinical research to determine whether a clinical practice meets these criteria (including methods for performing comprehensive literature reviews, for judging the quality of individual studies, and for synthesizing or pooling the results of multiple studies); (3) theoretical and practical concerns in translating the results of the scientific review into sound clinical practice recommendations; and (4) the importance of documentation, guidelines, and other safeguards to minimize the effect the reviewers themselves have on the objectivity and consistency of the analytic methods.
",22
3635,"Effects of inflammation and copper intake on rat liver and erythrocyte Cu-Zn superoxide dismutase activity levels.
 Stress such as inflammation produces an acute phase response that includes elevated levels of ceruloplasmin, the main copper component of plasma.
 Inflammatory effects on cellular copper enzyme activity levels are largely unknown.
 Cu-Zn superoxide dismutase (SOD) activities in liver, the main site of ceruloplasmin secretion, decreased with turpentine-induced inflammation (0.1 mL, intramuscular, leg) in rats fed any of three copper levels (adequate = 6 mg/kg, marginal = 2.5 mg/kg and deficient less than 0.5 mg/kg).
 Ceruloplasmin activities rose significantly with inflammation in the adequate and marginal groups but not in the deficient animals.
 Hepatic Cu-Zn SOD immunoreactive protein levels were unaffected by copper status or inflammatory state.
 Erythrocyte Cu-Zn SOD activities were influenced by dietary copper but not inflammation.
 An additional group of rats fed 15 mg copper/kg did not show a turpentine-induced decrease in liver Cu-Zn activity levels.
 Inflammatory effects on other copper enzyme activities did occur as evidenced by increases in ceruloplasmin and decreases in serum extracellular SOD.
 In conclusion, an acute phase response in rats increased the amount of dietary copper required to maintain hepatic Cu-Zn SOD activity at levels equal to those of nonstressed, copper-adequate rats.
 Rat erythrocyte Cu-Zn SOD activities provided a blood measurement reflective of copper intake with or without stress, but these values did not reflect decreases in liver Cu-Zn SOD activities after 3 d of inflammation.
",22
3636,"A prospective evaluation of the effectiveness of temporomandibular joint arthroscopy.
 This is a prospective study to evaluate therapeutic arthroscopy for internal derangement of the temporomandibular joint (TMJ).
 Fifty-nine patients with 76 abnormal joints were evaluated preoperatively for pain, noise, maximal incisal opening (MIO), and deviation on opening.
 Preoperative and postoperative magnetic resonance imaging (MRI) scans were obtained for 29 joints.
 Patients were treated by superior joint arthroscopy, lysis of adhesions, lavage, and steroid injection, along with preoperative and postoperative splint and physiotherapy.
 Pain, noise, and motion were evaluated at three time periods: 1) early (10 to 30 days); 2) intermediate (1 to 6 months); and 3) late (greater than 6 months).
 At early, intermediate, and late follow-up, increase in MIO was statistically significant (P less than .05).
 Noise did not return in the majority of patients.
 Disc position, evaluated by MRI, did not appear to change in 25 of 29 joints and did not correlate with clinical outcome.
 The results of this study indicate that TMJ arthroscopy is effective in reducing pain and increasing motion in patients with TMJ internal derangement.
",22
3637,"An improved technique for development of the pectoralis major myocutaneous flap.
 The pectoralis major myocutaneous flap is the most commonly employed muscle skin transfer used in soft-tissue reconstruction of defects of the upper neck and jaw region.
 This article presents conceptual and technical changes in the development of the pectoralis major myocutaneous flap that preserve a greater vascular pedicle and enhance the flap's arc of rotation.
 Data from 54 consecutive cases using this modified approach show a reduction in complications, a greater range of use, and consistent healing in radiated and nonradiated tissues without requiring sectioning or removing the clavicle or causing significant chest deformities.
 These modifications have produced a more predictable transfer compared with other reported techniques.
",22
3638,"The importance of routine surveillance of distal bypass grafts with duplex scanning: a study of 379 reversed vein grafts.
 To assess the utility of routine duplex surveillance, 379 infrainguinal reversed vein grafts performed at two independent teaching hospitals were prospectively entered into a surveillance protocol from March 1986 through August 1989.
 An average of 3.2 postoperative duplex graft flow velocity (GFV) measurements per graft was obtained during a mean follow-up interval of 21 1/2 months.
 Only 2.1% of 280 grafts with GFV measurements greater than 45 cm/sec failed within 6 months of a normal surveillance examination.
 GFV measurements less than 45 cm/sec in 99 grafts led to arteriography in 75 grafts, identifying 50 stenotic lesions in 48 bypasses (12.6% of series).
 Inflow lesions were present in 5%, outflow stenoses in 2%, and intrinsic graft stenoses in only 6% of bypasses.
 Only 29% of grafts identified as failing by duplex scan were associated with a reduction in ankle-brachial index of greater than 0.15.
 Secondary reconstructions were performed in 48 grafts based on detection of a reduced GFV measurement; all such reconstructions are patent after a mean follow-up of 5 months.
 Duplex surveillance is more reliable in identification of failing vein grafts than is determination of ankle-brachial index.
",22
3639,"Surgical procedures in the management of Takayasu's arteritis.
 Takayasu's arteritis is an inflammatory arteriopathy that often progresses to obliteration of multiple large arteries.
 Variable results have been reported after medical and surgical management.
 Twenty female patients with Takayasu's arteritis were treated from 1973 to 1989.
 Eleven (55%) patients had hypertension.
 Upper or lower extremity ischemia was present in 12 (60%) patients and cerebrovascular insufficiency in seven (35%).
 Nine patients initially managed with corticosteroids had no improvement in signs or symptoms of arterial insufficiency.
 Eleven patients had 16 vascular procedures for the following indications: renovascular hypertension (6), extremity ischemia (5), cerebrovascular insufficiency (2), dilation ascending aorta with aortic insufficiency (1), thoracic aortic aneurysm (1), abdominal aortic aneurysm (1).
 Procedures included aortorenal bypass (5), carotid-subclavian, axillary, or brachial bypass (4), aorto-carotid bypass (2), aneurysm resection (2), supra-celiac aorto-femoral bypass (1), ascending aorta/aortic valve replacement (1), and nephrectomy (1).
 Clinical improvement occurred in all patients.
 There were no operative deaths.
 All are alive at a mean follow-up of 5.75 years (6 months to 16 years).
 Revision of the initial reconstruction has been required for recurrent renovascular hypertension in one patient and extremity ischemia in another.
 The other nine patients remain symptomatically improved.
 Symptomatic Takayasu's arteritis frequently requires arterial reconstruction.
 Symptomatic improvement and excellent long-term graft patency can be expected after arterial reconstruction.
",22
3640,"Prediction of risk in noncardiac operations after cardiac operations.
 To determine the preoperative variables affecting the mortality rate and the development of severe complications in patients who have had myocardial revascularization or a valve replacement and who then undergo a noncardiac operation, we retrospectively studied data from 120 such patients over the 5 years from 1982 through 1986.
 Thirty-six percent of patients had a noncardiac operation during the first month after the cardiac operation.
 The mortality rate was 11%, and the morbidity rate was 56%.
 The statistical comparison of the predictive accuracy of postoperative complications of three simple, widely used classifications (American Society of Anesthesiologists physical status, New York Heart Association classification, Massachusetts General Hospital cardiac risk index) demonstrated the superiority of the simplified three-class cardiac risk index (Massachusetts General Hospital-cardiac risk index; predictive accuracy of 84%).
 In a multivariate discriminant analysis of 21 variables in this population, five variables (myocardial infarction in previous 6 months, S3 gallop or jugular vein distention, arrhythmia on last preoperative electrocardiogram, emergency operation, delay between cardiac and noncardiac operation) were identified as being the most predictive of a postoperative complication.
 When these variables were used in the function (DF3) obtained by linear discriminant analysis, the prediction accuracy of a postoperative complication reached 83%.
 Performance of the new models in a prospective validation population remained satisfactory (75% for Massachusetts General Hospital-cardiac risk index three-class index and 72% for DF3).
 Extensive statistical analysis of our data tested by a validation study provided simple predictive models based on clinical variables easily available even in emergency situations.
",22
3641,"The location of the maxillary os and its importance to the endoscopic sinus surgeon.
 As functional endoscopic sinus surgery continues to gain popularity and support, the necessity for a clear and accurate understanding of the anatomy of the ostiomeatal complex becomes essential.
 To clarify this anatomy, serial cadaver dissections were performed and the anatomy of the ostiomeatal complex was detailed in three dimensions, with an emphasis on precise localization of the internal os of the maxillary sinus as it relates to the orbit, natural antronasal canal, and ethmoid infundibulum.
 Measurements of the position of the internal os relative to the position of the anterior and posterior walls of the maxillary sinus and the position of the orbit were taken.
 The dimensions and configuration of the antronasal canal and its relationship to the infundibulum were also detailed.
 These measurements and relationships must be understood for an endoscopic sinus surgeon to locate the natural ostia without injuring the orbit.
",22
3642,"The role of the facial nerve latency test in the prognosis of Bell's palsy.
 Eighty patients with idiopathic facial nerve palsy were evaluated by the facial nerve latency test.
 Depending on the latency time, the patients were classified into the following four groups: group A patients had normal latency times (3.25 msec); group B patients had slightly extended latency times (4 to 7 msec) and a mean of 5.6 msec; group C patients had extended latency times (10 to 14 msec) and a mean of 10.2 msec; and group D patients displayed complete disappearance of evoked compound muscle action potential (no responses).
 Under the same therapeutic regimen, it was determined that, when the latency time was normal or close to normal, the functional recovery of the nerve was complete or almost complete, and the recovery time was short.
 When the latency time was extended or there was no response, the functional recovery of the nerve was either incomplete or absent.
",22
3643,"Non-ossicle homograft bone prostheses in the middle ear.
 This thesis proposes the use of human cadaver non-ossicle temporal homograft bone as middle ear reconstructive material.
 Bone obtained from the otic capsule histologically resembles that of the ossicles more so than any other bone in the body.
 The otic capsule, due to its proximity to the middle ear, can be harvested with the middle ear structures when bone cores are obtained, making it easily accessible.
 These prostheses are cost effective because multiple prostheses can be sculptured from one temporal bone core.
 This paper further proposes the use and introduction of non-ossicle homografts in primary stapedectomy, as well as in selected cases to bypass the incus and the superstructure of the stapes.
 Audiological data is provided.
 Some of the grafts have been in the middle ear for up to 5 years.
 There have been no extrusions and no complications.
 The method of harvesting, preservation, and sterilization is presented, as well as a pictorial illustration of the finished product and its relation to the natural ossicles.
 One histological specimen is presented.
 On the basis of the audiologic results, as well as the fact that no ossicles have extruded and none have been resorbed, it is proposed that non-ossicle temporal bone homografts have a place in transplantation surgery.
",22
3644,"Pediatric behavioral neurology: an update on the neurologic aspects of depression, hyperactivity, and learning disabilities [published erratum appears in Neurol Clin 1991 Feb;9(1):viii]
 The high incidence of poor social adjustment in long-term follow-up studies of depressed children seems to relate to the inadequacy of the pharmacotherapy necessary to sustain long-lasting remission or possibly to repetitive inappropriate stresses.
 Insufficient antidepressant therapy with resultant intermittent depression-induced dysfunction of the socialization functions performed by the right cerebral hemisphere would not permit the child to develop appropriate interpersonal skills (causing failure in most social situations), and associated cognitive difficulties would complicate academic performance.
 Repeated school failure and chronic social ineptitude preclude development of the skills necessary for successful independent living in society.
 Thus, if symptoms of depression are found, it is imperative that the learning-disabled or behaviorally disturbed child or adolescent receive adequate antidepressant therapy to ensure complete long-term remission of the depression.
 In addition, learning-disabled individuals, even without apparent diagnosable depressive illness, must be offered appropriate methods for learning and communication which reduce stress.
 When such appropriate educational strategies are offered and poor performance still ensues (or continues), a trial of antidepressant therapy should be considered.
 Recognition of the depressive nature of symptoms may not be possible until treatment-induced improvement has occurred and depression-associated learning disability has resolved.
 Improvement in academic performance associated with improved cognitive function after treatment-induced remission of a depressive episode can be dramatic, with resolution of apparent learning disability.
 Poor educational achievement associated with chronic learning difficulties ultimately affects adult social functioning, and untreated or improperly treated chronic depression may result in the development of later personality disturbances.
 Therefore, before attributing school problems in children to untreatable conditions, depressive disorder must be excluded, and appropriate antidepressant therapy (along with removal of all apparent inappropriate stress, including inappropriate demands on brain function) should be provided to children and adolescents with evidence of depression.
",22
3645,"Cortical tremor: a variant of cortical reflex myoclonus.
 Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture.
 Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor.
 However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method.
 Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs.
 We call this involuntary movement ""cortical tremor,"" which is in fact a variant of cortical reflex myoclonus.
",22
3646,"Topographic mapping of electrophysiologic measures in patients with homonymous hemianopia 
 We analyzed electroencephalographic (EEG) activity and spatial distribution of the pattern-reversal visual evoked potential (PVEP) in 20 patients with unilateral lesions in the retrochiasmal visual pathways.
 Focal abnormalities that were consistent with lesion location were present in the topographically analyzed EEG or VEP of 85% of the patients, compared with a 70% detection rate for conventional analysis techniques.
 Quantitative analysis of spectrally analyzed EEG revealed focal abnormality in 7 patients whose conventional EEG was interpreted as either normal or diffusely slow.
 However, focal paroxysmal spikes present in the EEG of 1 patient were missed by EEG mapping, and a false localization of quantitative EEG abnormality contralateral to the lesion occurred in 1 patient.
 Topographic analysis of the PVEP was no more sensitive to retrochiasmatic lesions than conventional analysis of 2 lateral occipital electrodes.
 We conclude that topographic mapping is a valid technique in the detection of localized cerebral lesions.
",22
3647,"Control of immediate postoperative pain with topical bupivacaine hydrochloride for laparoscopic Falope ring tubal ligation.
 Conflicting reports exist in the literature on the effectiveness of topical local anesthetic applied to the serosal surface of the fallopian tubes for the control of immediate postoperative pain after mechanical (band or clip) tubal ligation.
 Sixty-four patients were studied prospectively during outpatient laparoscopic Falope ring tubal ligation using the modified McGill Present Pain Intensity Scale.
 Patients randomly assigned to four groups received topical bupivacaine hydrochloride on both fallopian tubes, the right tube only, or the left tube only, or received none (controls).
 A unique study design was incorporated which allowed the untreated fallopian tube to serve as a within-subject control for each patient receiving unilateral treatment.
 Statistical analysis confirmed significant benefit when both fallopian tubes were treated as compared with no treatment (P less than .05).
 There was also consistent evidence of decreased immediate postoperative pain perception on the treated side for patients receiving unilateral treatment.
 The value of topical bupivacaine was demonstrated by both subjective patient response (McGill Pain Scale) and reduced need for pain medication before outpatient discharge.
 Our data support the value of topical bupivacaine applied to the serosal surface of the fallopian tubes for the reduction of postoperative pain after outpatient laparoscopic mechanical (band or clip) tubal ligation.
",22
3648,"Quality assurance indicators and short-term outcome of hysterectomy.
 Fifteen gynecologic quality assurance indicators recently published by The American College of Obstetricians and Gynecologists were applied to a previously reported hysterectomy data base.
 Chart reviews were performed for the most recent 257 cases in the data base, representing an 18-month interval.
 The indicators were divided into two groups: those intended to identify morbidity and mortality and those intended to screen for appropriateness of care.
 Rates of actual morbidity and cases that failed to meet published criteria sets for hysterectomy were determined by chart review regardless of the presence of a quality assurance indicator.
 A total of 135 indicators were identified in 114 (44%) of the 257 cases, including 64 patients (25%) with morbidity indicators and 50 (19%) with appropriateness indicators.
 Actual morbidity was correctly identified in all 64 cases in which morbidity indicators were present.
 Three cases with significant morbidity were identified by chart review but not identified by the indicators, yielding positive and negative predictive values of 100 and 98%, respectively, and an overall accuracy of 99% for morbidity indicators.
 By contrast, 14 of the 50 cases in which appropriateness indicators were present actually failed to meet published criteria sets.
 An additional seven cases failing to meet criteria sets were identified by chart review and not identified by the indicators, yielding a positive predictive value of 28%, a negative predictive value of 97%, and an overall accuracy of 83% for appropriateness indicators.
",22
3649,"Primary mass closure of midline incisions with a continuous polyglyconate monofilament absorbable suture.
 Mass closure of midline incisions with a running large-bore permanent monofilament polypropylene suture has been used in general surgery and gynecology patients with a reported small incidence of fascial dehiscence.
 Late-occurring wound sinus formation is one problem reported with the use of this permanent suture material.
 Over a 22-month period, 285 patients had midline incisions closed with a continuous, running no.
 1 polyglyconate monofilament delayed absorbable suture.
 Closely spaced bites (about 1.5 cm apart) were taken and placed 2 cm lateral to the fascial edge.
 Over 60% of the patients had surgery because of gynecologic cancer.
 Other high-risk factors included obesity in 62%, diabetes in 19%, and previous irradiation or chemotherapy in 22%.
 An ovarian cancer staging procedure was done in 16% of the patients.
 Of the remaining patients, almost half had extensive operative procedures that ranged from exenterations to hysterectomies with lymph node dissection.
 Wound complications were noted in nine patients (3.2%).
 Seven had superficial infections, one had an evisceration, and one developed a ventral hernia.
 Wound sinuses did not occur.
 The closure technique is safe and expedient and distributes tension equally over a continuous line.
 It has the additional advantage of eventual absorption of the suture material, thereby avoiding the wound sinus problems occasionally reported with large-bore permanent sutures.
",22
3650,"Clomiphene citrate stimulation as an adjunct in locating ovarian tissue in ovarian remnant syndrome.
 Ovarian remnant syndrome results from residual ovarian tissue after bilateral oophorectomy.
 The syndrome is associated with chronic pelvic pain and is suspected when premenopausal levels of FSH and LH are present in a patient with documented bilateral oophorectomy.
 Histologic demonstration of ovarian tissue at operation confirms the diagnosis.
 We treated a patient with ovarian remnant syndrome with a 10-day course of clomiphene citrate, 100 mg daily, to stimulate the residual ovarian tissue and facilitate localization.
 Preoperative ultrasound revealed a 5.0 x 3.5 x 6.2-cm cystic mass in the right adnexal region.
 Exploratory laparotomy easily localized the mass, and it was removed intact.
 Histologic slides demonstrated normal ovarian tissue with multiple follicles in various stages of development and a corpus luteum cyst.
 Clomiphene citrate is capable of stimulating an ovarian remnant, producing an enlarged, cystic structure easily localized by ultrasound.
 The increased size and preoperative knowledge of the location facilitated surgical removal.
",22
3651,"Umbilical cord hematoma following diagnostic funipuncture.
 Major complications associated with funipuncture have been reported but are rare.
 This is a report of a diagnostic funipuncture performed on a 29-week fetus with a single umbilical artery and multiple malformations.
 Immediately after the procedure, a voluminous hematoma developed at the site of needle insertion in association with a severe fetal bradycardia.
 Fetal death was confirmed within 5 minutes of needle insertion.
 It is hypothesized that the risk of complications of funipuncture may vary according to the clinical indication for the procedure and may be increased in the presence of certain fetal malformations.
 The rapid evolution of complications, as occurred in the present case, underlines the importance of having a clear plan of management in the event of mishap and discussing this plan with the parents before undertaking diagnostic funipuncture.
",22
3652,"Dental patient reaction to electrocardiogram screening.
 Ninety-one patients receiving routine dental treatment at the University of Minnesota School of Dentistry participated in an electrocardiogram screening study.
 The purpose of the study was to evaluate patient reaction to electrocardiogram screening in a dental school clinic.
 The vast majority of patients indicated the test was easy and did not intrude on the dental appointment.
 Most of the patients reported that the test was a valuable service and should be available in the dental office.
 None of the patients indicated that the tests should not be performed in the dental office.
 Few patients expressed any significant concern or anxiety about the test either before or after it was completed.
 Twenty-six percent (24/91) of the patients were found to have a cardiac arrhythmia; however, most of these were nonserious arrhythmias (18/24) and would not have had an impact on planned dental procedures.
 Six patients were identified with arrhythmias that required medical referral before dental treatment was started.
",22
3653,"Rapid sequence anesthesia induction for emergency intubation.
 Emergency intubations are done for a variety of reasons in the emergency department (ED).
 In some patients, a rapid, controlled induction of anesthesia is useful to facilitate intubation and to reduce the complications of intubation.
 This is referred to a rapid sequence induction (RSI) in the anesthesia literature.
 Atropine, thiopental, fentanyl, diazepam, ketamine, vecuronium, succinylcholine, other drugs and their applications for RSI are described.
 The purpose of this article is to describe the use of RSI in the airway management of ED patients.
 Nineteen pediatric patients requiring emergency intubation were intubated using RSI with vecuronium and thiopental.
 Actual intubation difficulty using RSI was significantly less than the anticipated intubation difficulty without RSI.
 There were no complications caused by intubation or RSI that had a significant impact on patient outcome.
 We feel that a sedative in combination with vecuronium represents the most optimal means of achieving RSI in the ED setting.
 Although the induction of general anesthesia is best done by anesthesiologists, emergency physicians are often the most experienced physicians immediately available to manage an airway in a critical emergency.
 An objective protocol such as that described will make it easier for emergency physicians to perform this procedure when needed.
",22
3654,"Bell's palsy. Ensuring the best possible outcome.
 Bell's palsy is thought to be an idiopathic polyneuritis and must be distinguished from other disorders that cause facial weakness.
 In most cases, differentiation can be accomplished on the basis of the history, physical examination, and clinical course.
 Routine follow-up care ensures that recovery is occurring.
 Electrodiagnostic testing often helps to assess prognosis.
 Eye care and corticosteroid therapy are recommended.
",22
3655,"The infant with a reddish diaper.
 The infant with a reddish diaper presents a diagnostic challenge to the primary care physician.
 As described by Dr Baumgardner, the cause may be benign, but more ominous disorders must be ruled out.
",22
3656,"Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells.
 A human cDNA library obtained from cultured normal mammary epithelial cells (HMECs) was searched by subtractive hybridization for genes whose decrease in expression might be relevant to epithelial transformation.
 One clone identified by this procedure corresponded to a 1.4-kilobase mRNA, designated NB-1, whose expression was decreased greater than 50-fold in HMECs tumorigenically transformed in vitro after exposure to benzo[a]pyrene and Kirsten sarcoma virus.
 Sequence analysis of NB-1 cDNA revealed an open reading frame with a high degree of homology to calmodulin.
 NB-1 expression could be demonstrated by polymerase chain reaction amplification in normal breast, prostate, cervix, and epidermal tissues.
 The presence of NB-1 transcripts was variable in primary breast carcinoma tissues and undetectable in tumor-derived cell lines of breast, prostate, or other origins.
 NB-1 mRNA expression could be down-regulated in cultured HMECs by exposure to reconstituted extracellular matrix material, while exposure to transforming growth factor type beta increased its relative abundance.
 The protein encoded by NB-1 may have Ca2+ binding properties and perform functions similar to those of authentic calmodulin.
 Its possible roles in differentiation and/or suppression of tumorigenicity in epithelial tissues remain to be examined.
",22
3657,"Tumorigenic 3T3 cells maintain an alkaline intracellular pH under physiological conditions.
 One of the earliest events in the response of mammalian cells to mitogens is activation of Na+/H+ exchange, which increases intracellular pH (pHin) in the absence of HCO3- or at external pH values below 7.2.
 The proliferative response can be blocked by preventing the pHin increase; yet, the proliferative response cannot be stimulated by artificially raising pHin with weak bases or high medium pH.
 These observations support the hypothesis that optimal pHin is a necessary, but not sufficient, component of the proliferative-response sequence.
 This hypothesis has recently been challenged by the observation that transfection of NIH 3T3 cells with yeast H(+)-ATPase renders them tumorigenic.
 Although previous measurements indicated that these transfected cells maintain a higher pHin in the absence of HCO3-, whether H(+)-ATPase transfection raised the pHin under physiologically relevant conditions was not known.
 The current report shows that these transfected cells do maintain a higher pHin than control cells in the presence of HCO3-, supporting the possibility that elevated pHin is a proliferative trigger in situ.
 We also show that these cells are serum-independent for growth and that they glycolyze much more rapidly than phenotypically normal cells.
",22
3658,"Simian virus 40 small tumor antigen and an amino-terminal domain of large tumor antigen share a common transforming function.
 The 82-residue amino-terminal sequences of simian virus 40 large tumor antigen (TAg) and small tumor antigen (tAg) are identical.
 Genetic analysis of TAg lacking amino acids 1-82 revealed that it was transformation-defective, as revealed by the agar growth assay, except when introduced in the presence of tAg.
 Since the latter, alone, lacks overt transforming activity, it would appear that the function of the sequence common to TAg and tAg is necessary, but not sufficient, for TAg transforming activity and that tAg can provide that function or its equivalent in trans.
 Thus, tAg may, in part, be viewed as a ""portable"" copy of a TAg functional domain.
",22
3659,"Identification and characterization of a regulated promoter element in the epidermal growth factor receptor gene.
 We have identified a 36-base-pair proximal element (-112 to -77 relative to the AUG translation initiation codon) in the epidermal growth factor receptor 5' region that functions as a promoter; mediates inductive responses to epidermal growth factor, phorbol 12-myristate 13-acetate, and cyclic AMP; and acts in an orientation-independent manner.
 This region functions as an enhancer when transferred to a heterologous promoter containing a TATA box.
 Mutations within the 36-base-pair region alter function as assayed by reporter gene expression in recipient cells.
 A protein has been identified that demonstrates appropriate binding specificity to mutant DNA sequences that correlates with promoter activity observed in vivo.
 On the basis of DNA binding characteristics and size, the identified protein appears distinct from several previously identified transcription factors known to bind to G+C-rich regions.
",22
3660,"Identification and preliminary characterization of protein-cysteine farnesyltransferase.
 Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to exert their biological activity.
 Previous studies indicate that an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group.
 Inhibition of mevalonate synthesis reverts the abnormal phenotypes induced by the mutant RAS2Val-19 gene in Saccharomyces cerevisiae and blocks the maturation of Xenopus oocytes induced by an oncogenic Ras p21 protein of human origin.
 These results have raised the possibility of using inhibitors of the mevalonate pathway to block the transforming properties of ras oncogenes.
 Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol.
 In this study, we describe an enzymatic activity(ies) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro at the correct (Cys-186) residue.
 This farnesylating activity is heat-labile, requires Mg2+ or Mn2+ ions, is linear with time and with enzyme concentration, and is present in all mammalian cell lines and tissues tested.
 Gel filtration analysis of a partially purified preparation of protein farnesyltransferase revealed two peaks of activity at 250-350 kDa and 80-130 kDa.
 Availability of an in vitro protein farnesyltransferase assay should be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.
",22
3661,"U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced.
 rev-regulated expression of HIV-1 envelope proteins from a simian virus 40 late replacement vector was found to be dependent on the presence of a 5' splice site in the env mRNA in spite of the fact that this mRNA remains unspliced.
 When the 5' splice site upstream of the env open reading frame was deleted or mutated, expression of envelope protein was lost.
 RNA analysis of cells transfected with 5' splice-site mutants showed a dramatic reduction in the steady-state levels of env mRNA whether or not rev was present.
 Envelope expression could be restored in one of the 5' splice-site mutants by cotransfection with a plasmid expressing a suppressor U1 small nuclear RNA containing a compensatory mutation.
 These experiments show that U1 small nuclear RNA plays a direct and essential role in the formation of an unspliced RNA that is subject to regulation by rev.
",22
3662,"Identification of three related human GRO genes encoding cytokine functions.
 The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity.
 We have identified two additional genes, GRO beta and GRO gamma, that share 90% and 86% identity at the deduced amino acid level with the original GRO alpha isolate.
 One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation.
 Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability.
 A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation.
 DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes.
 Only one chromosomal locus has been identified, at 4q21, by using a GRO alpha cDNA clone that hybridized to all three genes.
 Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide.
",22
3663,"Retro-orbicularis oculus fat (ROOF) resection in aesthetic blepharoplasty: a 6-year study in 63 patients 
 Sixty-three nonconsecutive patients have undergone resection of the retro-orbicularis oculus fat (ROOF) in conjunction with aesthetic blepharoplasty.
 In these patients, a consistent and useful ability to soften and flatten heaviness and bulkiness in the lateral upper orbital region was seen.
 Two patients developed postoperative hematoma, and two different patients had transient dry-eye symptoms following blepharoplasty.
 Twenty percent of patients had a transient degree of numbness in the lateral supraorbital nerve region, and all patients noted some transient numbness over the lateral upper brow region.
 No patient demonstrated significant paralysis of the orbicularis oculus or corrugator muscle.
 From this experience, retro-orbicularis oculus fat resection would appear to be a useful adjunct to standard blepharoplasty techniques in selected patients.
",22
3664,"Augmentation mammaplasty by means of the transrectus route.
 A new operative technique has been developed for augmentation mammaplasty.
 Through an inframammary incision, the anterior rectus sheath is entered, and the pocket is dissected in an entirely submuscular plane.
 We have performed this procedure in 112 patients to date.
 Complications have been few.
 The capsular contracture rate in 90 patients followed for greater than 1 year is 7 percent.
 The inframammary crease can be lowered using this technique, making mastopexy unnecessary in most patients with moderate ptosis.
",22
3665,"Comparison of lymphatic and venous interpositional autografts in experimental microsurgery of the canine lymphatics.
 In mongrel dogs, 56 autologous lymphatic and vein grafts were interpositioned to bridge a defect in the femoral collecting lymphatics.
 In one group, 26 lymphatic autografts were interpositioned with good results.
 No obstruction was observed over 6 months.
 In another group, 20 venous autografts were interpositioned after irrigation with heparinized saline and another 10 autografts were interpositioned without irrigation.
 After 1 week, four irrigated grafts were partially occluded with a red thrombus; after 6 months, all grafts were totally occluded.
 In a third group, 15 lymphaticolymphatic anastomoses were enveloped by a silicone sheet to provoke prolonged devascularization.
 None of the vessels was patent.
 Anastomotic patency was inspected in vivo postoperatively.
 The specimens were studied with light microscopy and scanning and transmission electron microscopy.
 Prolonged devascularization damaged the endothelial cells.
 The results show that the lymphatic vessel autograft is the best choice for an interpositional autografting to bridge a defect in lymphatic vessels.
",22
3666,"Intracerebral hematoma complicating split calvarial bone-graft harvesting.
 A case is reported of an intracerebral hematoma following the harvest of split calvarial bone.
 Full recovery by the patient occurred.
 Complications following calvarial bone graft harvest are reviewed.
 Potential devastating complications warrant serious consideration of alternative sources of bone, especially in the purely elective surgical candidate.
",22
3667,"New treatment for frontal sinus hypertrophy 
 A new treatment of frontal sinus hypertrophy is described.
 The anterior wall is removed, inverted, and attached again.
 The resulting depression is filled with bone dust.
 Details are discussed, and a case is presented.
",22
3668,"An angiographic technique for three-dimensional determination of arterial supply patterns in cadaver soft tissue.
 A method for arterial tree mapping that can be used in cadaver soft tissue is presented.
 In situ angiograms and photographs are supplemented with profile angiograms of relatively narrow bands of tissue from the removed specimen.
 The described method was better suited for mapping the course and supply patterns of a soft-tissue arterial network than either in situ angiograms or dissection.
 While practical problems were encountered with most of the solutions used for providing radiopacity or structural support to the vessels, pure barium sulfate was found to be suitable because it filled the vascular tree to the capillary level without leakage during excision of the specimen.
",22
3669,"Pinch-off syndrome: a complication of implantable subclavian venous access devices.
 Implantable central venous access devices placed via the subclavian vein may become obstructed by thrombosis, impingement against a vein wall, or compression between the clavicle and first rib.
 The latter has been termed pinch-off syndrome (POS).
 Eleven patients with POS were studied, including one whose catheter had fractured and one whose catheter had fragmented.
 They were compared with 22 matched control patients and 100 consecutive routine clinic patients.
 Each catheter was graded: 0 = normal, 1 = abrupt change in course with no luminal narrowing, 2 = luminal narrowing, and 3 = complete catheter fracture.
 POS was present in most (eight of 11) cases within 3 weeks after placement.
 A grade 1 catheter was common (33%) among control subjects, but grades 2 and 3 were uncommon (1%).
 Catheter fracture or fragmentation was seen in two of five cases with long-term (greater than 3 weeks) pinching (grade 2 catheter).
 The following conclusions were reached: Grade 2 represents significant catheter compression and the potential for serious complications.
 Grade 1 is of uncertain clinical significance, due to its high prevalence in control subjects.
",22
3670,"Mitral valve prolapse: comparison of diagnosis by physical examination and echocardiography 
 To determine how well physical examination findings suggestive of mitral valve prolapse (MVP) correlate with echocardiographic evidence of MVP, we retrospectively reviewed the charts of 104 patients referred to an Air Force Cardiology Clinic for echocardiography to rule out MVP.
 In each case, the referring physician's specialty and his findings on cardiac physical examination were recorded.
 All patients had M-mode echocardiography, and half of the patients had two-dimensional echocardiography.
 Sensitivities, specificities, and likelihood ratios for the physical examination were calculated using echocardiography as the comparison standard.
 The combination of a systolic click and a systolic murmur was the physical examination finding most predictive of echocardiographic MVP, with a positive likelihood ratio of 2.43.
 Other combinations of physical findings yielded likelihood ratios close to 1.
 No differences were found based on the specialty of the examining physician.
 We conclude that when practicing physicians find a systolic click and murmur, MVP is likely to be present on echocardiography, though one third of the patients will have normal echocardiograms.
 Other combinations of physical findings are of little help in predicting echocardiographic MVP.
",22
3671,"Selected measures of health status for Mexican-American, mainland Puerto Rican, and Cuban-American children.
 The 1987 National Vital Statistics System and the Hispanic Health and Nutrition Examination Survey (1982 through 1984) were used to assess the health status of Mexican-American, mainland Puerto Rican, and Cuban-American children by examining the prevalences of pregnancy outcomes and chronic medical conditions.
 The low-birth-weight rate among Hispanics (7.0%) compared favorably with that of non-Hispanic whites (7.1%) despite the greater poverty and lower levels of education among Hispanics.
 When examined by Hispanic subgroup, however, significant differences were present, with mainland Puerto Ricans having the highest prevalences of low-birth-weight infants.
 Premature births were more common among all three Hispanic subgroups than among non-Hispanic whites.
 Mexican-American and Cuban-American children had a similar prevalence of (3.9% and 2.5%, respectively) chronic medical conditions compared with non-Hispanic white children; Puerto Rican children had a higher prevalence of chronic medical conditions (6.2%).
 When assessed by these health status indicators, Hispanic children seem to have a health status similar to non-Hispanic white children.
 However, mainland Puerto Rican children seem at greater risk for poor health, reflecting the US Hispanic population's heterogeneity.
 Health programs targeted at US Hispanics should appropriately consider these group differences.
",22
3672,"A strategy to reduce infant mortality.
 Using maternal mortality reviews as an historic model, fetal and infant mortality reviews are proposed to reduce infant mortality in the United States.
 The national program has three elements: 1) guidelines and direction from a national multidisciplinary steering panel and staff, 2) a technical advisory capacity to translate guidelines and to work with local and regional review committees, and 3) local review committees.
 A special emphasis, lacking in the limited efforts of previous infant mortality reviews, would be given to fetal mortality.
 The plan proposes a broad classification of potential contributing causes of mortality, from those related strictly to medical care, to the health system, and to individual patient factors.
 This will allow different and more effective targeted responses to factors identified locally.
 Critical impetus will be gained with The American College of Obstetricians and Gynecologists leading the effort from the private medical sector in partnership with national, state, and local public health agencies and other national medical societies.
",22
3673,"Poloxamer 407 as an intraperitoneal barrier material for the prevention of postsurgical adhesion formation and reformation in rodent models for reproductive surgery.
 Comtemporary adhesion-prevention regimens for infertility surgery emphasize the use of barrier materials to effect physical separation of injured surfaces before reperitonealization.
 Poloxamer 407 is a biocompatible polymer that displays reverse thermal gelation characteristics; that is, the material exists as a liquid at room temperature and as a solid at body temperature.
 These properties make it an ideal material for use in laparoscopic surgery.
 The antiadhesion properties of poloxamer 407 were evaluated in two models.
 In the first experiment, Golden hamsters were subjected to a standardized adhesion-producing lesion in the left uterine horn.
 Poloxamer solutions in concentrations ranging from 15-35% were applied to the injured horn.
 Location, thickness, and extent of adhesion formation were assessed 14 days later.
 Significant reduction in post-traumatic adhesion formation was observed following treatment with the 30-35% solutions.
 The second experiment was designed as a paradigm of the typical situation encountered in infertility surgery: prevention of adhesion reformation after lysis of established adhesions.
 New Zealand White rabbits were subjected to three laparotomies at 14-day intervals for placement of the adhesion-producing lesion, evaluation (prescore) and surgical lysis of induced adhesions, and subsequent evaluation of adhesion reformation (post-score).
 The effect of applying poloxamer 407 after adhesiotomy was compared with controls (no treatment).
 Adhesion reformation (post-score) was markedly reduced by poloxamer-407 treatment.
 Further trials of this material in the clinical setting are indicated.
",22
3674,"Effects of topical glaucoma drugs on fistulized rabbit conjunctiva.
 Conjunctival fibroblastic proliferation with contracting scar formation has been implicated as a possible cause of glaucoma filtering surgery failure.
 The effects of glaucoma medications on bulbar conjunctiva were evaluated in both eyes of 20 pigmented rabbits, with 5 rabbits per group each receiving singular topically applied daily doses of either 0.5% timolol, 1% epinephrine, 4% pilocarpine, or artificial tears in a masked fashion for 4 months.
 Posterior lip sclerectomies were performed in 16 rabbits--4 from each treatment group.
 The remaining four rabbits served as nonsurgical controls.
 Four additional rabbits, which had not received eye drops, were included as a nonmedicated control group, with one rabbit serving as a nonsurgical control.
 Immunostaining was performed to identify the presence of myofibroblasts in fistulized conjunctiva.
 Treated surgical eyes, regardless of medication, had higher myofibroblastic cell proliferation than treated nonsurgical eyes.
 Among fistulized eyes, all medications increased cell proliferation, with pilocarpine eliciting the most dramatic increase compared with all other groups.
",22
3675,"Increase in skin-flap survival by the vasoactive drug buflomedil.
 The effect of buflomedil to protect skin tissue from ischemia and necrosis was studied in random cutaneous flaps.
 Measurements were performed by intravital microscopy on the microcirculatory level of capillary perfusion in a flap model in the hairless mouse.
 In 30 hairless mice, single-pedicle flaps measuring 6 x 16 mm were raised perpendicular to the spine of the animal.
 This flap develops a reliable amount of necrosis at its distal edge over a period of 7 days.
 A group of 10 mice received intravenous injections of buflomedil in doses of 3 mg/kg per day diluted in 0.1 ml normal saline beginning 4 hours before flap elevation and for 6 consecutive days postoperatively.
 In addition, 10 further animals received the same treatment except that it was started 5 minutes after flap elevation.
 In 10 mice serving as controls, normal saline in equal volumes as in the experimental groups was applied.
 By means of intravital microscopy, functional vessel density (FVD) was determined in 2.5-mm increments from the flap's base to its distal edge at 1, 6, and 24 hours after elevation.
 Skin-flap survival was quantified by measuring the necrotic area on day 7 by means of digital planimetry.
 Functional vessel density was preserved in the distal flap of animals pretreated with buflomedil, revealing a higher functional vessel density at 10.0 mm (p less than 0.01), 12.5 mm (p less than 0.05), and 15.0 mm (p less than 0.001) from the flap's base as compared with controls.
",22
3676,"Abdominal wall reconstruction (the ""mutton chop"" flap).
 Reconstruction of full-thickness abdominal wall defects can be a difficult surgical challenge.
 Reconstructing the epigastrium may be especially vexing.
 The use of prosthetic mesh has significant drawbacks, and the use of pedicled myofascial and myocutaneous flaps should be advantageous.
 We present 15 consecutive cases demonstrating highly successful reconstructions of massive abdominal wall defects using myofascial and myocutaneous flaps without prosthetic mesh.
 The extended rectus femoris flap, or ""mutton chop"" flap, which is capable of resurfacing the epigastrium, is described.
 Complications were minimal, and use of myofascial units, particularly the rectus femoris, should be considered as the technique of choice for reconstruction of major abdominal wall deficits.
",22
3677,"Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PET data correction for atrophy. Part II. Aging and Alzheimer dementia 
 A new, computerized segmentation technique, in which magnetic resonance (MR) imaging produces accurate volumetric measurements of brain and cerebrospinal fluid (CSF) without the limitations of computed tomography, was used in a retrospective analysis of digitized T2-weighted MR images of 16 healthy elderly control subjects and 16 patients with Alzheimer dementia.
 Ventricular and extraventricular CSF was quantified, and the effects of aging were studied; in both groups, the atrophy measurement was used to correct metabolic values obtained with positron emission tomography.
 Patients with Alzheimer dementia had higher total CSF; extraventricular, total ventricular, and third ventricular CSF volumes (49%, 37%, 99%, and 74%, respectively); and 7% lower brain volumes than the control group.
 The patients also showed a more marked decline in brain volumes and a greater increase in CSF volumes with advancing age than the control group.
 They had a 25.0% increase in corrected whole-brain metabolic rates; the control group had only a 15.8% increase.
 The use of this technique may provide a basis for further studies of aging and dementia, including regional volume analysis.
",22
3678,"Disruption of the human SCL locus by ""illegitimate"" V-(D)-J recombinase activity.
 A fusion complementary DNA in the T cell line HSB-2 elucidates a provocative mechanism for the disruption of the putative hematopoietic transcription factor SCL.
 The fusion cDNA results from an interstitial deletion between a previously unknown locus, SIL (SCL interrupting locus), and the 5' untranslated region of SCL.
 Similar to 1;14 translocations, this deletion disrupts the SCL 5' regulatory region.
 This event is probably mediated by V-(D)-J recombinase activity, although neither locus is an immunoglobulin or a T cell receptor.
 Two other T cell lines, CEM and RPMI 8402, have essentially identical deletions.
 Thus, in lymphocytes, growth-affecting genes other than immune receptors risk rearrangements.
",22
3679,"Interpleural analgesia after thoracotomy.
 We examined the effects of the following variables on interpleural analgesia after thoracotomy: addition of epinephrine to local anesthetic, thoracostomy drainage, two-catheter placement, and location of catheter tips.
 Twenty patients were randomized to have one catheter (paravertebral tip location) or two catheters (paravertebral and lateral thoracic wall tip locations).
 Interpleural catheters were sutured to the parietal pleura by the surgeon at time of wound closure.
 Patients were then randomly assigned to receive 20 mL of 0.5% bupivacaine with 1:200,000 epinephrine through the single catheter or 10 mL of 0.5% bupivacaine with or without 1:200,000 epinephrine through each of the two catheters while supine.
 Bupivacaine concentrations in whole blood and in thoracostomy drainage fluid were assayed by gas chromatography.
 Actual content of bupivacaine in the drainage fluid was calculated.
 Degree of analgesia was assessed by verbal numerical pain scores over the first 4 h and opioid demand thereafter.
 Addition of epinephrine to bupivacaine did not influence the degree of analgesia.
 Approximately 30%-40% of any administered dose of bupivacaine was lost via the thoracostomy tube over a 4-h period.
 There was no correlation between the true initial dose (100 mg minus thoracostomy drainage) and Cmax.
 Use of two catheters resulted in significantly less opioid requirements after an initial 8-h period.
 Failure to achieve adequate interpleural analgesia in postthoracotomy patients may be related to loss of anesthetic via thoracostomy drainage, presence of extravasated blood and tissue fluid in the pleural space, and possibly sequestration and channeling of flow of local anesthetic by restricted motion of an operated lung.
",22
3680,"A blinded comparison of noninvasive, in vivo phosphorus nuclear magnetic resonance spectroscopy and the in vitro halothane/caffeine contracture test in the evaluation of malignant hyperthermia susceptibility.
 Malignant hyperthermia (MH) is a potentially fatal, anesthetic-induced syndrome.
 Currently, the only accurate means of diagnosing susceptibility to this syndrome is the testing of biopsied skeletal muscle for its contracture response to halothane and caffeine.
 A less invasive means of diagnosis is needed.
 The authors previously reported that MH-susceptible patients studied by in vivo phosphorus nuclear magnetic resonance (31P NMR) spectroscopy demonstrated a higher resting inorganic phosphate (Pi) to phosphocreatine (PCr) ratio in their skeletal muscle, as well as a slower postexercise recovery of PCr/Pi, when compared to normal controls.
 In the present blinded study, the authors compared in vivo 31P NMR determination of resting Pi/PCr and recovery rate of PCr/Pi in forearm muscles to in vitro halothane/caffeine contracture test results in 42 patients.
 Forty-three control subjects were studied to establish normal NMR values of resting Pi/PCr and recovery rate of PCr/Pi.
 Their findings were compared with those of 27 patients shown to be MH-susceptible and 15 patients MH-negative by contracture testing.
 The MH-susceptible group had a significantly (P less than 0.005) higher resting Pi/PCr value (0.202 +/- 0.044) than either the MH-negative (0.152 +/- 0.043) or the control (0.141 +/- 0.026) group.
 The MH-susceptible group also had a significantly (P less than 0.02) slower postexercise recovery rate of PCr/Pi (1.50 +/- 0.872 PCr.Pi-1.min-1) than either the MH-negative (2.11 +/- 1.07 PCr.Pi-1.min-1) or control (2.25 +/- 0.828 PCr.Pi-1.min-1) group.
 Twenty-six of the 27 MH-susceptible patients demonstrated abnormal NMR test results (a resting Pi/PCr greater than or equal to 0.18 or recovery rate less than 1.0 PCr.Pi-1.min-1), and 13 of the 15 MH-negative patients had normal NMR results.
 Although neither NMR parameter alone was diagnostically reliable, an NMR test utilizing both parameters was quite accurate.
 The NMR test and contracture test demonstrated an overall agreement of 93% with a copositivity of 96% and conegativity of 87%.
 The sensitivity and specificity of the NMR test is estimated to be 98.8% +/- 11.8% and 95.3% +/- 20.3%, respectively.
 The role of 31P NMR in the diagnosis of MH susceptibility and possible mechanisms underlying the observations are discussed.
",22
3681,"Effective doses of epidural morphine for relief of postcholecystectomy pain.
 Having previously established the effective dose of intrathecal morphine for relief of postcholecystectomy pain, we determined in this study the effective dose of epidural morphine for relief of postcholecystectomy pain in 154 patients given epidural injections of a placebo (group 1, n = 49), 2 mg morphine (group 2, n = 54), or 4 mg morphine (group 3, n = 51) intraoperatively mixed in 1.5% lidocaine.
 The percentage of patients who did not request an analgesic, 30 mg IM pentazocine, for relief of pain during the first 24 postoperative hours was significantly greater in groups 2 and 3 than in group 1.
 In patients who did need 30 mg IM pentazocine postoperatively, the number of times pentazocine was administered was also significantly greater in group 1 than in groups 2 and 3.
 The percentage of patients developing respiratory depression or vomiting in the first 48 postoperative hours was similar in the three groups.
 Based on the present data and those we previously reported for intrathecal morphine, we conclude that an epidural morphine dose of 2-4 mg and an intrathecal morphine dose of 0.06-0.12 mg are equipotent for relief of postcholecystectomy pain.
",22
3682,"Caffeine and cardiac arrhythmias.
 PURPOSE: To review the evidence supporting the belief that caffeine causes cardiac arrhythmias.
 DATA SOURCES: Studies published since 1982 identified through computerized searches of MEDLINE, TOXLINE, and Chemical Abstracts and a review of bibliographies of relevant articles on the subject of caffeine and cardiac arrhythmias.
 STUDY SELECTION: All clinical studies examining caffeine as a cause of cardiac arrhythmias and a selection of basic science experiments to illustrate caffeine's effects in vitro.
 DATA EXTRACTION: Study quality was assessed and all available clinical data pertaining to caffeine as a cause of arrhythmias were summarized.
 RESULTS OF DATA ANALYSIS: In one electrophysiologic study, caffeine was associated with an increased susceptibility to provoked cardiac arrhythmias.
 In five placebo-controlled trials, caffeine in doses up to 500 mg daily (equivalent to 5 to 6 cups of coffee) did not increase the frequency or severity of ventricular arrhythmias.
 One large epidemiologic study reported an increase in the frequency of ventricular extrasystoles in persons consuming 9 or more cups of coffee daily.
 CONCLUSION: Moderate ingestion of caffeine does not increase the frequency or severity of cardiac arrhythmias in normal persons, patients with ischemic heart disease, or those with pre-existing serious ventricular ectopy.
",22
3683,"Reperfusion inhibits elevated splanchnic prostanoid production after hemorrhagic shock [published erratum appears in Ann Surg 1991 Feb;213(2):91]
 The effect of reperfusion following hemorrhagic shock on splanchnic prostanoid release was studied.
 Anesthetized male rats were bled to a mean arterial blood pressure of 30 mmHg for 30 minutes and either killed or treated with shed blood for 60 minutes and then killed.
 The superior mesenteric arterial bed was cannulated and perfused in vitro with oxygenated Krebs.
 Collected venous effluent (up to 180 minutes) was analyzed for 6-keto-PGF1 alpha (PGI2 metabolite), PGE2, PGF2 alpha, and thromboxane B2 by radioimmunoassay in shock, shock plus reperfusion, and sham groups.
 The major prostanoid released was 6-keto-PGF1 alpha and was three times higher in the shock group compared to the sham group (p less than 0.05).
 Reperfusion of shed blood abolished the increase in 6-keto-PGF1 alpha found in the shock group (p less than 0.05).
 These data show that the attempt of the rat splanchnic bed to compensate for hemorrhagic shock by increasing release of PGI2 (potent vasodilator) was abolished during reperfusion of blood.
",22
3684,"cAMP mediates IL-1-induced lymphocyte penetration through endothelial monolayers.
 Endothelial cell incubated with IL-1 have been shown adhere more lymphocytes than nontreated endothelial cells.
 Here we demonstrate that IL-1 can also increase lymphocyte penetration through endothelial monolayers in vitro.
 IL-1 induced a transient increase in the number of lymphocytes penetrated through the endothelial monolayer into a filter in a time- and dose-dependent manner.
 This effect could be mimicked by increasing the cytosolic cAMP levels in the endothelial cells either by forskolin or dibutyryl-cAMP.
 Concomitantly we were able to show that IL-1 increased the cytosolic cAMP levels in endothelial cells.
 An inhibitor of adenylate cyclase, ddAdo, decreased both the IL-1-induced cAMP elevation and lymphocyte penetration.
 A protein kinase A inhibitor HA 1004 could inhibit the IL-1-induced lymphocyte penetration, where as protein kinase C (N-(2-guamidino-ethyl)-5-isoquinolinesyl foamide hydrocloride) and calcium-calmodulin (N-(6-aminohexyl)-5-chloro-1-naphthalensulfanamide) inhibitors had no effect.
 Adding dibutyryl-cGMP or calcium ionophore to the endothelial cells could not mimic IL-1-induced penetration and finally IL-1 did not induce PKC translocation in endothelial cells.
 These data support the view that IL-1 acts via cAMP as a second messenger in regard to lymphocyte penetration through endothelial cells.
 The above data demonstrate that IL-1-induced lymphocyte penetration through endothelial cells and that this IL-1-induced signal is transduced via cAMP in endothelial cells.
",22
3685,"Interferons and collagen production.
 The immunoregulatory, antiviral, and antiproliferative agents known as the interferons have profound effects on collagen synthesis.
 Interferons alpha, beta, and gamma suppress collagen synthesis by dermal fibroblasts.
 In addition, interferon gamma (IFN-gamma) inhibits the constitutively increased collagen synthesis characteristic of fibroblasts derived from lesions of patients with scleroderma.
 IFN-gamma also inhibits collagen synthesis by myofibroblasts and synovial fibroblast-like cells.
 Inhibition of collagen synthesis by IFN-gamma is associated with a coordinate inhibition of transcription for types I and III collagen.
 In addition, IFN-gamma suppresses levels of procollagen mRNA and type II collagen synthesis in human articular chondrocytes.
 In vivo studies in mice have demonstrated that IFN-gamma inhibits the collagen synthesis associated with the fibrotic response to an implanted foreign body, bleomycin-induced pulmonary fibrosis, and the healing response to cutaneous thermal burns.
 In the latter case, while collagen content of the wound scar was decreased, hyaluronic acid was increased in mice receiving IFN-gamma compared to controls.
 This is in accord with in vitro studies showing that, while interferons alpha and beta decrease production of glycosaminoglycans, IFN-gamma increases production of glycosaminoglycans.
 Of interest, acute inflammation at sites of thermal injury, or when elicited by proinflammatory agents in separate experiments, also was suppressed in mice treated with IFN-gamma.
 The means by which IFN-gamma inhibits collagen synthesis involves transcriptional regulation.
 There is a single report that interferon alpha can decrease the size of a keloid of recent onset in a human patient.
 Because the interferons can inhibit collagen synthesis in vivo, further studies may be warranted to evaluate the usefulness of these agents in the treatment of disease states characterized by abnormal fibrotic responses as well as their potential for altering the healing response associated with particular therapeutic interventions.
",22
3686,"Long-term outcome following anterior cerebral artery ligation for ruptured anterior communicating artery aneurysms.
 The long-term prognosis (15 years) was determined for 17 patients who had undergone anterior cerebral artery (ACA) ligation as the sole treatment for an anterior communicating artery aneurysm.
 The number of early and late rebleeds was lower than expected from previously ruptured aneurysms.
 Late ischemia was not a major complication while late postoperative epilepsy occurred in 19% of survivors.
 In a review of previously published series, ACA ligation appears to have significantly reduced the rates of both early and late rebleeding.
 This study helps to define the late results of ""conservative"" operations for ruptured aneurysms.
",22
3687,"Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase.
 Six patients with severe intraventricular hemorrhage were treated with direct intraventricular infusion of urokinase.
 In each case, hemorrhage extended into all ventricular chambers, and a cast formation and expansion of the third and fourth ventricles were found.
 Immediately after the therapy was started (within 7 days from onset of symptoms), reduction of intraventricular hematoma volume was observed on computerized tomography.
 On average, both the third and fourth ventricles became clear on the third day after hemorrhage; there was one exception, a case of ruptured aneurysm.
 Five of the six patients showed excellent or good outcome, although two developed delayed hydrocephalus.
 No infection or rebleeding was observed.
 The outcome in a retrospectively studied group of five patients not treated with urokinase is also reported.
 The authors conclude that this relatively easy method of treatment will greatly improve the prognosis of severe intraventricular hemorrhage.
",22
3688,"Continuous arteriovenous rewarming: experimental results and thermodynamic model simulation of treatment for hypothermia.
 We evaluated a technique for treating hypothermia that uses extracorporeal circulation but does not require heparin or pump assistance.
 Hypothermia to 29.5 degrees C was induced in eight anesthetized dogs, and thermistors placed in the pulmonary artery, liver, bladder, esophagus, rectum, muscle, and skin.
 Four experimental animals were rewarmed by creating a fistula which connected arterial and venous femoral lines to an interposed counter-current heat exchanger.
 External rewarming was used in four controls.
 Bleeding time (BT), coagulation profile (PT, PTT, TT), and cardiac output (CO) were measured during rewarming.
 Core temperature (T) rose significantly faster with CAVR (0.00001).
 Average time to rewarming was 45 min, vs.
 4 hrs in controls.
 Haptoglobin, platelet, fibrinogen, and fibrin split product levels were unaffected.
 Continuous arteriovenous rewarming (CAVR) improved T, CO, BT, and coagulation profile faster than any method yet reported not requiring heparin or cardiac bypass.
 The application of CAVR in post-traumatic hypothermia warrants further investigation.
",22
3689,"The morbidity and financial impact of colostomy closure in trauma patients.
 During a 10-year period, 87 patients who had undergone elective colostomy closure at Bellevue Hospital were retrospectively reviewed in order to evaluate the morbidity of colostomy closure after traumatic injury and its financial impact.
 Sixty-two per cent of the colostomies were in the left colon and 38% were right sided.
 The interval from the original injury to colostomy takedown varied from 20 to 465 days, with a mean of 144 days.
 The mean postoperative hospital stay for the entire group was 15.13 days at a cost of $13,995.
 There were no deaths and no anastomotic leaks in the entire series, but a morbidity rate of 25% ensued.
 Small bowel obstruction was the most frequent significant complication, occurring in ten patients (11.5%) and resulting in a prolongation of hospital stay by 7 days at an additional cost of $6,500 per patient.
 One additional patient developed a subphrenic abscess which required operative drainage, necessitating an additional 24 days in the hospital at an increased cost of $22,200.
 Other complications which did not prolong hospital stay included eight superficial wound infections, one transient respiratory failure, and two patients who returned at a later date with incisional hernias at the stoma site.
 The 25% morbidity encountered in this series suggests that colostomy closure is not a low-morbidity procedure and should be considered as an important factor favoring primary repair.
 Coupled with the significant financial impact of both colostomy formation and takedown, ample justification exists for greater efforts in avoiding colostomy formation whenever feasible.
",22
3690,"Hilger facial nerve stimulator: a 25-year update.
 Percutaneous nerve excitability testing using the Hilger facial nerve stimulator was introduced about 25 years ago.
 The test is reliable, easy to use, and inexpensive; it continues to be the most frequently used method for predicting prognosis of facial nerve disorders.
 Between 1966 and 1974, we recorded 10,243 nerve excitability tests on 865 patients with a mean of 3.29 tests for each peripheral branch and 3.43 for the trunk.
 Using a multiple regression model, we determined the effect on nerve stimulation values of age, sex, race, diabetes, hypertension, partial or complete clinical paralysis, diagnosis of herpes zoster, year of testing, and eventual facial paralysis recovery profile.
 We discuss statistical reliability, provide a table of interpretive results, and offer ""tips and traps"" invaluable to the practitioner.
 A prospective study of 25 patients with residual facial paralysis was evaluated by two separate otolaryngologists to determine intertester reliability.
",22
3691,"A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway 
 Major histocompatibility complex (MHC) class I molecules export peptides to the cell surface for surveillance by cytotoxic T lymphocytes.
 Intracellular peptide binding is critical for the proper assembly and transport of class I molecules.
 This mechanism is impaired as a result of a non-functional peptide supply factor gene (PSF) in several human mutant cell lines with genomic lesions in the MHC.
 We have now identified PSF in the MHC class II region by deletion mapping in mutants and chromosome-walking.
 PSF is homologous to mammalian and bacterial ATP-dependent transport proteins, suggesting that it operates in the intracellular transport of peptides.
",22
3692,"Median nerve somatosensory evoked potentials and the Glasgow Coma Scale as predictors of outcome in comatose patients with head injuries.
 Median nerve somatosensory evoked potential (SSEP) grades and Glasgow Coma Scale (GSC) scores were obtained from 51 patients with head injuries within 1 week after the injury to determine the relationship of these scores, both individually and combined, to outcome scores obtained more than 6 months after the injury.
 SSEP grading was based on the presence or absence of the cortical evoked potential, the amplitude of the early cortically generated P22 wave form, and the conduction time through the brain (P/N13-N20 interpeak latency).
 SSEP responses from both sides of the brain were combined and graded from 1 to 6.
 The GCS was graded without the verbal component (maximum score, 10), because all patients were intubated.
 All patients were unresponsive to commands.
 Median SSEP grades correlated better with Glasgow Outcome Scale and Barthel Index scores (R = 0.57 and 0.64, respectively; P less than 0.00001) than GCS scores did (R = 0.35 and 0.37, respectively, P less than 0.00001), and combining SSEP grades and GCS scores did not improve the predictive power of the model (R = 0.57 and 0.64, respectively; P less than 0.00001).
 All SSEP Grade 1 patients (n = 13) either died or remained in a vegetative state.
 In contrast, all SSEP Grade 6 patients (n = 7) had a moderate disability or good recovery.
 This study demonstrates the prognostic value of early quantitative median nerve SSEP grading for patients with head injuries who are unresponsive to commands within 1 week after the injury.
",22
3693,"Persistent primitive trigeminal artery-cavernous sinus fistulas: report of two cases.
 Two cases of persistent primitive trigeminal artery-cavernous sinus fistulas are presented.
 In one case, the fistula was treated by using a two-balloon tandem technique.
 This method was accomplished by introducing, inflating, and detaching a silicone balloon into the trigeminal artery, thus preserving the carotid and basilar blood flow.
 An unusual case of a similar fistula with only contralateral exophthalmos is also reported.
 The relationship between this type of fistula and the presence of aneurysms on the persistent primitive trigeminal artery and the relationship with traumatic events are discussed.
",22
3694,"Quantification of leakage pressures after durotomy repairs in the canine.
 This study was undertaken to investigate the relative strengths of dural repair using standard suture techniques, suture supplemented with tissue adhesive, and tissue adhesive alone.
 Uniform 2 mm dural defects were created in adult beagles, repaired, and then subjected to pressurization testing.
 Defects repaired with suture alone initially leaked within the range of physiologic pressurization, while those supplemented with tissue adhesive or repaired with tissue adhesive alone failed at higher pressurization levels.
 Histologic sections obtained from the dura treated with fibrin adhesive sealant demonstrated minimal inflammatory response not significantly different than those sections examined at sites repaired by suture alone.
 A new substance, fibrin adhesive sealant, appears to be useful in effecting dural repair due to its ability to withstand pressures greater than those obtained with suture alone.
",22
3695,"Capillary leakage in inflammation. A study by vascular labeling.
 The local injection of pure inflammatory mediators induces venular leakage.
 To test the effect of endogenous mediators from dying tissue on vascular leakage, the authors devised an experimental model simulating an infarct, whereby living vessels would be exposed to fragments of organs undergoing aseptic necrosis.
 Tissues from donor rats were implanted aseptically in the cremasteric sac.
 Control rats were implanted with materials deemed to be as close as possible to nonirritating: boiled tissues and spheres of Teflon or glass.
 At different points the rats were injected intravenously with carbon black and killed an hour later.
 Whole cremaster mounts showed that vascular labeling was strictly venular up to 8 hours, mixed with capillary labeling between 12 and 24 hours, and mainly or exclusively capillary at 48 hours.
 Histology showed an acute inflammatory infiltrate in the labeled areas.
 A similar but weaker labeling pattern accompanied by milder inflammation was seen in controls.
 These results indicate that the vascular leakage in aseptic inflammation is biphasic, first venular, then capillary; and that the capillary phase is induced by the inflammatory reaction itself, possibly through a form of diffuse angiogenesis.
",22
3696,"Childhood traumas: an outline and overview 
 Childhood psychic trauma appears to be a crucial etiological factor in the development of a number of serious disorders both in childhood and in adulthood.
 Like childhood rheumatic fever, psychic trauma sets a number of different problems into motion, any of which may lead to a definable mental condition.
 The author suggests four characteristics related to childhood trauma that appear to last for long periods of life, no matter what diagnosis the patient eventually receives.
 These are visualized or otherwise repeatedly perceived memories of the traumatic event, repetitive behaviors, trauma-specific fears, and changed attitudes about people, life, and the future.
 She divides childhood trauma into two basic types and defines the findings that can be used to characterize each of these types.
 Type I trauma includes full, detailed memories, ""omens,"" and misperceptions.
 Type II trauma includes denial and numbing, self-hypnosis and dissociation, and rage.
 Crossover conditions often occur after sudden, shocking deaths or accidents that leave children handicapped.
 In these instances, characteristics of both type I and type II childhood traumas exist side by side.
 There may be considerable sadness.
 Each finding of childhood trauma discussed by the author is illustrated with one or two case examples.
",22
3697,"Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia.
 OBJECTIVE: The authors sought to determine if an acute dose of dextroamphetamine might have positive effects on affect and cognition in schizophrenic patients maintained on a regimen of haloperidol and, if so, what variables might predict such improvements.
 METHOD: Twenty-one patients with chronic schizophrenia who were hospitalized on a research ward received a single oral dose of dextroamphetamine (0.25 mg/kg) in a double-blind, placebo-controlled, crossover study.
 All patients were receiving 0.4 mg/kg per day of haloperidol.
 Cognitive tests, motor tests, global ratings, mood ratings, and videotape ratings were used to determine the effect of the coadministration of these drugs.
 Ventricle-brain ratios derived from CT scans were used to predict response to the coadministration of these drugs.
 RESULTS: Amphetamine improved performance on a measure of concept formation on the Wisconsin Card Sorting Test but did not result in changes in performance on tests of memory or attention.
 As a group, the patients were more active and performed psychomotor tests more quickly while receiving amphetamine.
 Six patients were judged by clinical raters to have improved in terms of affect, cooperation, and engagement with the environment.
 Improvement was associated with enlarged cerebral ventricles and increases in blink rate from the placebo to the active drug condition.
 No patient unequivocally worsened.
 CONCLUSIONS: These results may be consistent with the theory that coadministration of amphetamine and haloperidol produces relatively selective enhancement of cortical dopaminergic activity.
 However, because of the acute nature of the trial and the specialized research environment in which it was conducted, the authors do not advocate amphetamine as a routine clinical treatment of schizophrenia.
",22
3698,"A prospective analysis of intramuscular meperidine, promethazine, and chlorpromazine in pediatric emergency department patients.
 STUDY OBJECTIVE: To examine physiologic responses and efficacy of 2, 1, and 1 mg/kg IM meperidine, promethazine, and chlorpromazine (MPC), respectively, in children.
 DESIGN: Prospective, unblinded trial.
 SETTING: A university and community emergency department.
 PATIENTS: Sixty-three hemodynamically and neurologically stable children.
 INTERVENTION: Single dose of IM MPC.
 MEASUREMENTS AND MAIN RESULTS: Serial respirations, heart rate, arterial systolic blood pressure, oxygen saturation, and Glasgow Coma Scale were measured at 30-minute intervals.
 Effectiveness was assessed by two independent observers using separate visual analog scales for cooperation and sedation.
 Times to sleep (27 +/- 24 minutes), sitting upright (103 +/- 87 minutes), ED discharge (4.7 +/- 2.4 hours), eating (11 +/- 7.9 hours), and normal behavior (19 +/- 15 hours) were acceptable.
 Minor, but statistically significant, changes in respiration rate (-1.9 +/- 0.4), heart rate (+4.5 +/- 1.8), oxygen saturation (-0.7 +/- 0.3%), and Glasgow Coma Scale (-2.5 +/- 0.6) occurred for 120 minutes after MPC.
 No serious complications or resuscitation were required.
 Mean visual analog scale scores were 5.0/10.4 or more in 71% of cases, with interobserver agreement very good (cooperation, r = .79; effectiveness, r = .80).
 Twenty-nine percent of children were judged insufficiently sedated.
 CONCLUSION: IM MPC is a safe and generally effective agent for ED procedures in selected children.
",22
3699,"Comparison of rectal, axillary, and tympanic membrane temperatures in infants and young children.
 STUDY OBJECTIVE: To evaluate the reliability of a tympanic membrane thermometer in detecting fever in young children presenting to the emergency department.
 SETTING: Pediatric emergency department in an urban teaching hospital, DESIGN/MEASUREMENT/PARTICIPANTS: Temperature measurements were obtained sequentially at three body sites in children less than 3 years old presenting to the pediatric ED.
 Axillary and rectal temperatures were obtained with an electronic thermistor probe (Diatek 500), and tympanic membrane temperatures were obtained with a noncontact, infrared sensing device (First TEMP).
 Patients were stratified by age, ear canal patency, presence of otitis media, and rectal temperature.
 RESULTS: Of 224 patients enrolled, 87 (39%) were febrile.
 Overall correlation of axillary and tympanic membrane measurements to rectal for all strata was .75 (P = .001) and .81 (P = .001), respectively.
 Sensitivity in detecting fever for axillary and tympanic membrane sites was .48 and .55, respectively.
 Otitis media and ear patency did not influence correlation of tympanic membrane measurements.
 Low tympanic membrane temperature sensitivity may be a result of probe configuration.
 CONCLUSION: Tympanic membrane and axillary temperatures should be viewed with caution in children less than 3 years old as neither can detect fever reliably.
",22
3700,"Core temperature measurement in hypovolemic resuscitation.
 STUDY OBJECTIVES: Accurate core temperature measurement in severely hypovolemic patients can be difficult to achieve.
 We used a dog model to determine both a convenient method of measuring core temperature and the relative accuracy of the multiple sites.
 DESIGN: Prospective laboratory (animal model) study.
 SETTING: Operating suites in the Animal Care Department.
 PARTICIPANTS: Eight adult, anesthetized greyhound dogs.
 INTERVENTIONS: Continuous temperature monitoring by thermistors placed in the brain, central vein, tympanic membrane, bladder, rectum, esophagus, and subcutaneous tissue.
 Hemorrhage to 65% initial intravascular volume and autologous transfusion of cooled blood, during which serial temperature measurements were recorded.
 MEASUREMENTS AND MAIN RESULTS: The readings were analyzed with Pearson's correlation coefficient.
 Brain temperature correlated very well with tympanic membrane temperature throughout the course (r = .869, P less than .0005).
 Rectum, bladder, and esophagus also correlated well with brain.
 Central venous temperature, however, correlated poorly with temperatures at all other sites, reflecting the marked swings in intravascular temperature caused by cold transfusion.
 These wide variations were damped at the other sites.
 The best correlation of central venous temperature was with brain and bladder, although tympanic membrane correlation was fair.
 CONCLUSIONS: Because intravascular hypothermia appears to be the source of the arrhythmias and hemostatic abnormalities often seen during the early resuscitation of hypovolemic patients, our results suggest bladder or tympanic membrane as the initial temperature site.
 After the initial resuscitation, end organ (eg, brain) temperature is the most important and is most accurately reflected by tympanic membrane temperature.
",22
3701,"Code 9: a systematic approach for responding to medical emergencies occurring in and around a hospital.
 Members of the public expect to receive efficient and appropriate medical care if they become acutely ill or injured while in or around a hospital.
 Our institution became aware of the need for an organized system to respond to such emergencies involving patients, visitors, local community residents, and hospital employees, both inside the hospital and on the grounds surrounding the building.
 A search of the literature did not provide information regarding such a response; a survey of surrounding hospitals revealed no such plan in effect in other institutions.
 We therefore designed a plan to be superimposed onto our existing system for responding to in-house cardiac and respiratory arrests (""codes"").
 The results after one and one-half years appear encouraging.
 We recommend the establishment of such an emergency response system in all health care institutions.
",22
3702,"A comparison of neurological, metabolic, structural, and genetic evaluations in persons at risk for Huntington's disease.
 We compared four diagnostic data sets for the assessment of individuals at risk for Huntington's disease.
 Fifty-four chorea-free persons were evaluated by neurological examination, positron emission tomography measurement of glucose metabolism, radiographic computerized tomographic measurement of caudate size, and genetic testing at the polymorphic DNA loci D4S10, D4S43, and D4S125.
 Twelve (22%) persons had abnormal caudate metabolism, 6 (11%) had subtle abnormalities of motor control, and 7 (13%) had computed tomographic evidence of caudate atrophy, compared with an expected gene frequency of 34% for this population.
 In 20 persons with unambiguous genetic test results or the subsequent phenotypic expression of Huntington's disease (chorea), there was a greater sensitivity of the positron emission tomographic measurement of caudate metabolism (75%) relative to computed tomography (33%) or the clinical examination (17%) for the determination of a subpopulation of probable Huntington's disease gene carriers.
 Hypometabolism of the putamen and globus pallidus, and hypermetabolism of the precentral gyrus were also associated with a high probability of carrying the Huntington's disease gene.
 The findings support the hypothesis that abnormalities of cerebral metabolism precede clinical or structural (computed tomographic) abnormalities in gene-positive individuals at risk for Huntington's disease.
",22
3703,"Quadriceps myopathy: forme fruste of Becker muscular dystrophy.
 We examined dystrophin, the protein product of the Duchenne muscular dystrophy gene, in muscle biopsy specimens from 4 male patients with quadriceps myopathy, all of whom showed a mild and slowly progressive myopathy confined to the quadriceps muscles.
 All 4 patients had clear abnormalities of dystrophin, and were diagnosed as having Becker muscular dystrophy by both immunofluorescence and immunoblot examinations; that is, dystrophin of an abnormal molecular mass was visualized in muscle cryosections as ""patchy"" or discontinuous immunostaining at the surface membrane of the muscle fibers.
 One patient had a brother who showed widespread myopathic changes consistent with typical Becker muscular dystrophy.
 We conclude that the syndrome called quadriceps myopathy includes a group of forme fruste Becker muscular dystrophy.
",22
3704,"Dystrophin analysis in Duchenne and Becker muscular dystrophy carriers: correlation with intracellular calcium and albumin.
 Immunocytochemical localization and immunoblot analysis of dystrophin in muscle fibers of 11 obligate and probable, and 7 possible carriers of Duchenne and Becker muscular dystrophy revealed an abnormal expression of the protein in 3 of them.
 Localization of calcium and albumin, as endogenous markers of extracellular fluid penetration, showed the presence of both molecules inside some fibers lacking dystrophin.
 Our morphological studies show that the initial stages leading to fiber necrosis in Duchenne muscular dystrophy are present in carriers with mosaicism.
 Comparison of dystrophin studies with restriction fragment length polymorphism analysis and creatine kinase levels showed that neither immunocytochemical nor immunoblot techniques for dystrophin are sensitive enough to provide a basis for genetic counseling.
",22
3705,"Suicide in twins.
 Suicide appears to cluster in families, suggesting that genetic factors may play a role in this behavior.
 We studied 176 twin pairs in which one or both twins had committed suicide.
 Seven of the 62 monozygotic twin pairs were concordant for suicide compared with two of the 114 dizygotic twin pairs (11.3% vs 1.8%).
 The presence of psychiatric disorder in the twins and their families was examined in a subsample of 11 twin pairs, two of whom were concordant for suicide.
 Eleven of these 13 twin suicide victims had been treated for psychiatric disorder, as had eight of their nine surviving cotwins.
 In addition, twins in 10 pairs had other first- or second-degree relatives who had been treated for psychiatric disorder.
 Thus, these twin data suggest that genetic factors related to suicide may largely represent a genetic predisposition for the psychiatric disorders associated with suicide.
 However, they leave open the question of whether there may be an independent genetic component for suicide.
",22
3706,"Valproate in the treatment of acute mania. A placebo-controlled study.
 We conducted a placebo-controlled, double-blind study of valproate, a drug originally developed as an antiepileptic, in 36 patients with acute manic episodes who had previously failed to respond to or to tolerate lithium carbonate.
 Treatment duration was 7 to 21 days, with no other psychotropic medications permitted except lorazepam up to 4 mg/d during the first 10 days of treatment.
 Serum valproate concentrations were measured three times weekly; an unblinded investigator then adjusted dosage to produce serum concentrations between 50 and 100 mg/L.
 Valproate proved superior to placebo in alleviating manic symptoms.
 The 17 patients randomized to active drug demonstrated a median 54% decrease in scores on the Young Mania Rating Scale as compared with a median 5.0% decrease among the 19 patients receiving placebo.
 On the 100-point Global Assessment Scale of overall psychiatric functioning, patients receiving valproate improved by a median of 20 points as compared with a zero-point change with placebo.
 Significant differences also emerged on the Brief Psychiatric Rating Scale and in the number of supplemental doses of lorazepam required by the patients in each group.
 Substantial antimanic effects appeared within 1 to 4 days of achieving therapeutic serum valproate concentrations.
 Adverse effects were infrequent, with no adverse effect appearing significantly more frequently with valproate than with placebo.
 We conclude that valproate represents a useful new drug for the treatment of manic patients.
",22
3707,"Carbamazepine maintenance treatment in outpatient schizophrenics.
 A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study.
 Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered.
 Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening.
 Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating.
 Corroborating descriptive findings in the second phase were available for 14 of these patients.
 There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena.
",22
3708,"Reactions of first-year medical students to their initial encounter with a cadaver in the dissecting room.
 This study reports the results of a 1986 questionnaire survey of 100 first-year medical students regarding their preparation for and reactions to their first encounter with a human cadaver in the dissecting room.
 The students were aware of psychological and physical reactions to this experience, and although they felt adequately prepared prior to the class, expressed a desire for greater preparation afterwards, particularly through more discussion of the experience with the anatomy staff.
 A surprising number of the students (62) had had prior exposure to a dead human body, which was a significant influence upon their reactions.
 The results of this study suggest a need for improving both the preparation for coping with dissection and the follow-up opportunities for dealing with professional and emotional issues raised during human dissection.
",22
3709,"Hemoglobin Montreal: a new variant with an extended beta chain due to a deletion of Asp, Gly, Leu at positions 73, 74, and 75, and an insertion of Ala, Arg, Cys, Gln at the same location.
 The unstable hemoglobin Montreal with a deletion of three amino acid residues (Asp, Gly, Leu) at positions 73, 74, and 75 of the beta chain and an insertion of four residues (Ala, Arg, Cys, Gln) at the same location was observed in a 7-year-old Canadian boy suffering from a moderate hemolytic anemia.
 The introduction of an extra amino acid residue and of other changes in the crevice where the heme group is located is the likely cause of the instability of this hemoglobin variant.
 The above listed changes were detected through analyses of tryptic peptides of the beta-Montreal chain, sequencing of amplified DNA, and hybridization of amplified DNA with appropriate, 32P-labeled, oligonucleotide probes.
 It is suggested that a mispairing involving the AGTG sequences at codons 66 and 67 and at codons 72 and 73 of the normal beta gene caused a repetition of a 16-bp segment, while a deletion of 10 nucleotides due to recombination or slippage followed by a second short deletion during DNA repair resulted in the modified sequence of the beta-Montreal gene.
",22
3710,"Somatosensory-evoked potential monitored during total hip arthroplasty.
 One hundred consecutive patients were monitored using somatosensory-evoked potential (SEP) monitoring to detect intraoperative sciatic nerve compromise during total hip arthroplasty.
 The peroneal nerve was stimulated using the contralateral extremity to rule out systemic influences on the SEP tracings.
 Loss of amplitude or an increase in latency of greater than 10% was considered significant.
 Of the 18 patients who exhibited changes that met these criteria, 16 were female.
 Two patients had loss of amplitude of the tracings at the time of closure, and both of these patients exhibited postoperative sciatic nerve palsies.
 There were no false negatives.
 Femoral reaming and reduction are the surgical events most commonly associated with nerve reactions.
 Patients who have had prior hip procedures appear to be at higher risk.
 There was no correlation with intraoperative SEP changes and age, weight, surgical approach, or leg lengthening.
 Compared with unmonitored patients, there was no reduction in the incidence of sciatic palsy.
",22
3711,"The effects of smoking on the signal-averaged electrocardiogram in normal subjects.
 Tobacco smoking increases the risk of sudden cardiac death, possibly by altering the substrate for propagation or sustainment of ventricular tachyarrhythmias.
 To test this hypothesis, 15 long-term smokers without known coronary artery disease abstained from tobacco smoking for 12 h, after which they underwent SAECG before, 15 min after and 30 min after smoking two cigarettes.
 Other than minor lengthening of filtered QRS duration, no significant change in time-domain SAECG parameters was noted.
 We conclude that late potentials are not produced by cigarette smoking and that ventricular arrhythmia substrate as measured by SAECG variables is not worsened in long-term smokers without evidence of coronary artery disease.
",22
3712,"Snoring (I). Daytime sleepiness in regular heavy snorers.
 Fifteen men, mean (means) age 44 years, were investigated.
 Their means body mass index was 21.9 kg/m2, and all of them had a respiratory disturbance index below 5 and had good nocturnal oxygen saturation.
 The subjects were monitored several nights both with and without the following devices: a tight-fitting facial mask, a pneumotachometer, and an esophageal balloon.
 They were also monitored with and without nasal continuous positive airway pressure.
 The Multiple Sleep Latency Test was administered after three of the experimental nights (after the baseline nights and after the second nasal CPAP night).
 Determination of short EEG arousals during nocturnal sleep, which lasted 2 to 10 s, was performed.
 The relationship between short EEG arousals, the esophageal pressure nadir, and airflow decrease was investigated.
 We also determined the relationship between clinical reporting of decrease in daytime alertness and MSLT results, and the relationship between MSLT results and the frequency of EEG arousals.
 The monitoring indicated that heavy snorers may present significant increase in Pes nadir with abrupt decrease in flow leading to EEG arousals.
 The frequency at which EEG arousals occur has an impact on MSLT scores.
 Nasal CPAP improves MSLT scores and eliminates these respiration-related EEG arousals.
 Some heavy snorers without obstructive sleep apnea syndrome may be at risk of having a decrease in daytime alertness.
",22
3713,"Pharyngeal volume in asymptomatic snorers compared with nonsnoring volunteers.
 STUDY OBJECTIVE: to determine if asymptomatic snorers have smaller pharyngeal volumes than age- and height-matched nonsnorers.
 DESIGN: we recruited asymptomatic heavy snorers and nonsnorers for a study.
 Each snorer was matched by age (+/- 3 years) and height (+/- 2 inches) with a nonsnorer.
 The nonsnorers were required to be near ideal body weight.
 All volunteers underwent overnight polysomnography, pulmonary function testing, and magnetic resonance imaging of the pharynx while awake.
 The volume of the pharynx was determined by a computer with data input from a digitizing instrument.
 SETTING: Veterans Administration Hospital and University of Florida Teaching Hospital PARTICIPANTS: Nine volunteers were recruited for both the snorer and nonsnorer groups.
 Each participant was paid $50.
 There were no interventions.
 MEASUREMENTS and RESULTS: There were no differences in sleep variables between the two groups.
 There was also no significant difference between pharyngeal volumes for the two groups.
 CONCLUSIONS: The volume of the pharynx in asymptomatic snorers is similar to the volume in age- and height-matched nonsnorers.
",22
3714,"Polyamines and ornithine decarboxylase during repair of duodenal mucosa after stress in rats.
 This investigation shows whether polyamines and ornithine decarboxylase have a role in duodenal mucosal repair following stress-induced microscopic damage.
 Rats were fasted for 22 hours, placed in restraint cages, and immersed in water to the xiphoid process for 6 hours.
 Animals were killed either immediately after the period of stress or at 2-hour intervals up to 24 hours thereafter.
 Duodenal mucosa was examined histologically, and ornithine decarboxylase and polyamine levels were measured.
 Ornithine decarboxylase activity was increased significantly up to 6 hours following stress, peaking at 4 hours at a level 10 times the prestress control.
 By 8 hours, enzyme activity had returned to near normal.
 Increases in mucosal putrescine, spermidine, and spermine content paralleled the changes in ornithine decarboxylase activity and peaked 4 hours after stress.
 Stress resulted in microscopic damage evidenced by a nearly complete absence of villi.
 Significant macroscopic lesions were not present following stress.
 Mucosal repair was evident 12 hours after stress and almost complete by 24 hours, although the restituted villi were short and blunted.
 The decreases in mucosal DNA, RNA, and protein content caused by stress were restored and reached near-normal levels 12 hours after the period of stress.
 In animals given the specific inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine, increases in duodenal mucosal ornithine decarboxylase activity and polyamine levels were inhibited and mucosal repair was almost completely prevented following stress.
 alpha-Difluoromethylornithine also prevented the recovery of DNA, RNA, and protein content of the duodenal mucosa.
 These results indicate that duodenal mucosal damage following stress is repaired rapidly; the repair process is accompanied by significant increases in ornithine decarboxylase activity and polyamine levels; and the increases in ornithine decarboxylase and polyamines are absolutely required for the normal repair of the mucosa.
",22
3715,"Respiratory input impedance in anesthetized paralyzed patients.
 Respiratory impedance (Zrs) was measured between 0.25 and 32 Hz in seven anesthetized and paralyzed patients by applying forced oscillation of low amplitude at the inlet of the endotracheal tube.
 Effective respiratory resistance (Rrs; in cmH2O.l-1.s) fell sharply from 6.2 +/- 2.1 (SD) at 0.25 Hz to 2.3 +/- 0.6 at 2 Hz.
 From then on, Rrs decreased slightly with frequency down to 1.5 +/- 0.5 at 32 Hz.
 Respiratory reactance (Xrs; in cmH2O.l-1.s) was -22.2 +/- 5.9 at 0.25 Hz and reached zero at approximately 14 Hz and 2.3 +/- 0.8 at 32 Hz.
 Effective respiratory elastance (Ers = -2pi x frequency x Xrs; in cmH2O/1) was 34.8 +/- 9.2 at 0.25 Hz and increased markedly with frequency up to 44.2 +/- 8.6 at 2 Hz.
 We interpreted Zrs data in terms of a T network mechanical model.
 We represented the proximal branch by central airway resistance and inertance.
 The shunt pathway accounted for bronchial distensibility and alveolar gas compressibility.
 The distal branch included a Newtonian resistance component for tissues and peripheral airways and a viscoelastic component for tissues.
 When the viscoelastic component was represented by a Kelvin body as in the model of Bates et al.
 (J.
 Appl.
 Physiol.
 61: 873-880, 1986), a good fit was obtained over the entire frequency range, and reasonable values of parameters were estimated.
 The strong frequency dependence of Rrs and Ers observed below 2 Hz in our anesthetized paralyzed patients could be mainly interpreted in terms of tissue viscoelasticity.
 Nevertheless, the high Ers we found with low volume excursions suggests that tissues also exhibit plasticlike properties.
",22
3716,"Theophylline minimally alters contractile properties of canine diaphragm in vitro.
 We examined the effects of theophylline on contractile properties and high-frequency fatigue of canine diaphragm in vitro.
 Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline.
 These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm.
 No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed.
 Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%.
 A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior.
 High-frequency fatigue was similar in control and theophylline-treated bundles.
 We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies.
 This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical.
 Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations.
",22
3717,"Ventilatory effect of acute pulmonary hypothermia.
 The isolated effect of cooling the pulmonary circulation on ventilation was quantified in nine anesthetized dogs.
 The right pulmonary artery (RPA) was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the RPA between, but not during, periods of cooling.
 Cooled blood boluses were injected into the RPA under conditions in which either bolus temperature (5-35 degrees C) or volume (0-1.5 ml/kg body wt) varied.
 Inspiratory time (TI), expiratory time (TE), breath duration (TT), and peak integrated activity (PEAK) were determined from diaphragm EMG.
 Results for five postinjection breaths were converted to a percent of the values from five preinjection breaths.
 There was a linear relationship between bolus temperature and TI [r = 0.61, slope (x) = 0.59%/degrees C, P less than 0.001), TE (r = 0.73, x = 1.43%/degrees C, P less than 0.001] as well as TT (r = 0.74, x = 1.10%/degrees C, P less than 0.001), whereas PEAK was unaffected (n = 9).
 When injection temperature was 5 degrees C, an inverse linear relationship existed between bolus volume and TI (r = 0.75, x = -15.2%.ml-1.kg-1, P less than 0.001) and TE (r = 0.78, x = -23.4%.ml-1.kg-1, P less than 0.001) (n = 4).
 In two dogs tested the effect of bolus injection was minimal at residual volume and progressively increased with lung volume.
 The effect of cold bolus injection was eliminated after right vagotomy in three dogs.
 Results indicate that cooling of some vagal receptor in the lung increases breathing frequency primarily by shortening TE.
",22
3718,"The validity of canine platelet aggregometry in predicting vascular graft patency.
 Several laboratories have found canine platelet aggregometry predictive of thrombotic potential in vascular grafts.
 Adenosine diphosphate (ADP) is a frequently used agonist, often at unspecified or differing concentrations.
 This study was designed to evaluate the predictive value of ADP-induced platelet aggregometry and the validity of the methodology.
 Platelet aggregometry in response to 2 x 10(-5) M ADP was assayed in 70 dogs.
 Twenty-six percent were aggregators, 51% were non-aggregators, and 20% were indeterminant.
 All dogs were then treated with aspirin and dipyridamole.
 Vascular prostheses were implanted bilaterally (aorto-iliac) and anti-platelet therapy continued for two weeks.
 Dose-response to ADP was studied at three concentrations in 20 dogs.
 At 2 x 10(-5) 1/20 aggregated, at 4 x 10(-5) 3/19 aggregated and at 2 x 10(-4) 15/20 aggregated.
 Time between samples and study was evaluated in 11 dogs, with 2/11 changing from non-aggregator to aggregator at two or three hours.
 Daily reproducibility was studied in 70 dogs, 14 of which changed aggregation status between days.
 Patency was 58/68 (85%) for non-aggregators, 23/34 (68%) for aggregators (p = 0.038).
 Platelet aggregometry has significant predictive value for graft patency but methodology must be specified and standardized.
",22
3719,"Ultrastructural evidence of the effects of shear stress variation on intimal thickening in dogs with arterially transplanted autologous vein grafts.
 Based on our findings that changes in wall shear stress, not the rate of blood flow, were the main hemodynamic factor related to intimal hyperplasia of autologous vein grafts, we further investigated the effect of wall shear stress variation on sequential ultrastructural changes in the intimal hyperplasia of arterially transplanted autovein grafts, using canine models.
 As noted, wall shear stress variation (tau-variation) could be defined by the variation in wall shear stress within a cardiac cycle, using a desktop flow waveform analyzer.
 In Group I, which had a high flow rate of 78.4 +/- 4.6 ml/min and low tau-variation of 36.1 +/- 2.2 dynes/cm2, intimal hyperplasia was significant.
 Ultrastructurally, there was a marked transformation of intimal smooth muscle cells to secretory cells 2 to 4 weeks after implantation.
 The surface of the intima was lined with modified smooth muscle cells at 2 weeks after implantation.
 In Group II, which had a low flow rate of 5.6 +/- 2.2 ml/min and normal tau-variation value (174.6 +/- 13.0 dynes/cm2), intimal hyperplasia was minimal, and there were several layers of contractile type smooth muscle cells, with characteristic myofibrillae.
 The surface of the intima was lined with endothelial cells at 2 weeks after implantation.
 These findings suggest that, in regions of low wall shear stress variation, intimal smooth muscle cells of autovein grafts may well become secretory cells, and enhanced platelet adherence could occur during early intimal repair, causing intimal hyperplasia to develop.
",22
3720,"Clip repair of peripheral side-to-side arteriovenous fistulas. Evaluation of a method in dogs and preliminary results in humans.
 A simple technique for repair of peripheral arteriovenous fistula by clip application is presented.
 This procedure is rapid and effective, it minimizes the extent of dissection, and it eliminates the need for application of vascular clamps on the vessels and for anticoagulation.
 The safety of the procedure was confirmed in dog experiments and clinically applied successfully in four patients.
 It is suitable for simple, uncomplicated side-to-side fistulas amenable to this procedure.
",22
3721,"Spherical connective tissue inclusions in epithelial hyperplasia of the breast (""collagenous spherulosis"").
 Partial myoepithelial differentiation is common in simple epithelial hyperplasia (epitheliosis) of the breast but functional myoepithelial differentiation with basement membrane production is exceedingly rare.
 A peculiar change of hyaline globules within benign epithelial hyperplasia has been recognised before as ""collagenous spherulosis"" and type IV collagen has been shown by immunohistochemistry.
 Another seven cases are described which show the presence of laminin and collagens IV and III within the proliferation.
 Electron microscopy examination of two cases using material retrieved from the wax block showed varying degrees of myoepithelial differentiation of the cells immediately surrounding the spherules and basal lamina material, including mature collagen fibrils in one case.
 The degree of myoepithelial differentiation of the cells surrounding the spherules seemed to correlate with the differing types and amounts of extracellular matrix in the spherule.
 Histopathologists should be aware of this rare change as it may be misinterpreted as in situ carcinoma.
",22
3722,"Fluorometric determination of pseudocholinesterase activity in postmortem blood samples.
 A fluorometric assay using 3-(p-hydroxyphenyl) propionic acid (HPPA) was conducted to determine the activity of pseudocholinesterase (ChE) [Enzyme Commission (EC) No.
 3.1.1.8] in postmortem blood samples so as to test for organophosphate poisoning.
 By the enzymatic reaction of ChE, its substrate, benzoylcholine, produces choline, which is oxidized by choline oxidase to generate hydrogen peroxide.
 HPPA is oxidized by hydrogen peroxide and peroxidase to become the fluorogenic dimer whose concentration is measured fluorometrically at an excitation emission wavelength of 320 nm and an elimination emission wavelength of 404 nm.
 The selectivity and sensitivity of the present method were found to be superior to those of conventional pH and spectrophotometric methods.
",22
3723,"Brain markers and suicide: can a relationship be found?
 Recent work suggests that some persons who commit suicide have altered neurochemistry in their brains.
 It remains unclear which of the many reported abnormalities are most reliably present and whether they reflect a specific psychiatric disorder or a disposition to violent impulsivity.
 A number of technical and interpretive problems must be clarified, but a postmortem test indicating that a subject was at high risk for suicide may eventually emerge.
 This approach would not be useful for ruling out suicide, since altered neurochemistry is not likely to be involved in every case.
",22
3724,"Sudden cardiac death during exercise in a weight lifter using anabolic androgenic steroids: pathological and toxicological findings.
 A 21-year-old, previously healthy weight lifter collapsed during a bench press workout.
 He had taken anabolic androgenic steroids parenterally for the previous several months.
 Pertinent autopsy findings included marked cardiac and renal hypertrophy and hepatosplenomegaly, with regional myocardial fibrosis and focal myocardial necrosis.
 Nandrolone (19-nor-testosterone) metabolites were identified in postmortem urine.
 The possible etiologies of the cardiac findings are discussed.
",22
3725,"Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance.
 The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated.
 In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis.
 In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy.
 Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals.
 In each experiment a 2 X 2 factorial design was used.
 Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet.
 The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt.
 Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model.
 These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade.
",22
3726,"Pharmacological characterization of LY233053: a structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action.
 This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist.
 LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM).
 No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM).
 In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs.
 40 microM NMDA).
 LY233053 was effective after in vivo systemic administration in a number of animal models.
 In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr).
 In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA.
 However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons.
 In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.).
 Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p.
 doses of LY233053.
 In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity.
 The relatively short duration of action of LY233053 may make this compound particularly advantageous as a neuroprotective agent in the treatment of acute conditions such as cerebral ischemia.
",22
3727,"New biological properties of pyrroloquinoline quinone and its related compounds: inhibition of chemiluminescence, lipid peroxidation and rat paw edema.
 Pyrroloquinoline quinone (PQQ) inhibited the chemiluminescence (CL) from mouse peritoneal cells initiated by zymosan, carrageenin and N-formyl-methionyl-leucyl-phenylalanine and CL generated by the xanthine-xanthine oxidase reaction and the lipid peroxidation in the rat brain homogenate.
 The inhibitory activity of PQQ was more potent than that of idebenone, alpha-tocopherol and ascorbic acid in all the three assay systems.
 In the xanthine-xanthine oxidase reaction, PQQ had no effect on the formation of uric acid at the concentration of CL inhibition.
 These results suggest that PQQ might have a radical scavenger-like activity.
 Structure-activity relationship of PQQ and its six related compounds showed that the 7- and 9-carboxyl groups of PQQ as well as the orthoquinone structure are responsible for the radical scavenger-like activity.
 In addition, the -NH group in the pyrrole ring of PQQ seemed to be essential for the antilipid peroxidative activity in the rat brain homogenate.
 When administered i.p., PQQ inhibited the development of 0.1% carrageenin-induced paw edema in rats.
 These results suggest that PQQ might have therapeutic effects on various diseases, of which development or exacerbation has been known to be associated with radical oxygens.
",22
3728,"Application of pulsed and continuous wave 1.32 and 1.06 microns wavelengths of the Nd:YAG laser in the canine tracheobronchial tree: a comparative study.
 Previous investigations have shown good clinical potential for the use of the 1.32 microns wavelength Nd:YAG laser because its soft tissue absorption is better than that of the 1.06 microns wavelength Nd:YAG laser.
 The 1.32 microns wavelength Nd:YAG laser has an absorption coefficient in water that is 10 times higher than the 1.06 microns wavelength Nd:YAG laser.
 A comparative in vivo study of laser soft tissue effects was performed by using the 1.32 microns wavelength and the 1.06 microns wavelength Nd:YAG lasers in a pulsed wave (PW) mode and continuous wave (CW) mode using a non-contact endoscopic delivery system.
 A standard 5 mm mucosal lesion was made in the canine tracheobronchial tree down to the level of the perichondrium.
 Soft tissue and cartilage effects were examined by light and scanning electron microscopy, acutely, 1 week and 2 weeks after operation, and a comparison was made between the different laser modalities.
 To create similar lesions, higher energy was required when using the 1.06 microns wavelength Nd:YAG laser.
 Soft tissue injury was greater with the 1.06 microns wavelength in CW mode, and no cartilage damage occurred in the PW mode.
 Soft tissue and cartilage repair after 1 and 2 weeks was better with the 1.32 microns wavelength laser.
 In comparison, the CO2 laser and the contact Nd:YAG laser proved to be more precise cutting tools than the 1.32 microns wavelength or the 1.06 microns wavelength Nd:YAG lasers.
 Both Nd:YAG laser wavelengths were useful for coagulation and vaporization of tissues and blood vessels.
 More studies are needed to determine the effect of the new 1.32 microns wavelengths on endotracheal tumors.
",22
3729,"Trans-scleral application of a semiconductor diode laser.
 We used a diode laser with an output power of 1 W through a fiberoptic light pipe (200 microns diameter) to deliver laser energy through the sclera of pigmented rabbits.
 Ciliary body destruction occurred with energy levels of 300-400 mW and exposure time of 0.5 sec.
 Retinal photocoagulation was achieved with energy levels of 200-500 mW in 0.5 sec.
 Histologic examination of acute lesions demonstrated thermal destruction of ciliary body processes and retina.
 Chorioretinal scar formation was observed clinically and histologically within 2-3 weeks.
 Our data indicate that the transscleral diode laser may be used for destruction of the ciliary body processes or peripheral retinal coagulation in pigmented eyes.
",22
3730,"CO2-welded venous anastomosis: enhancement of weld strength with heterologous fibrin glue.
 The milliwatt CO2 laser was used to perform end-to-end anastomoses in canine jugular veins.
 There was a high disruption rate (50%) in laser-welded veins (n = 10).
 Fibrin glue (n = 17), formed from human fresh-frozen plasma, enhanced the weld strength decreasing the disruption rate (18%), resulting in an 82% patency which nearly equaled the contralateral sutured vein patency (93%).
 The bursting strength was improved with fibrin glue.
 Transmural necrosis was present initially in all groups but extended for a longer distance in the vessel wall in laser-welded anastomoses.
 Sutured anastomoses exhibited a greater inflammatory response.
 In laser-welded anastomoses endothelial cells were not as confluent as in sutured anastomoses by six weeks.
 Carbon dioxide laser-welded end-to-end vein anastomoses appear to be impractical because they disrupt too easily.
 However, the addition of heterologous fibrin glue to the weld results in a reasonably strong anastomosis with histologic properties that may be beneficial in vein bypass grafts.
",22
3731,"Decreased osmotic stability of dystrophin-less muscle cells from the mdx mouse 
 Human X-linked Duchenne and Becker muscular dystrophies are due to defects in dystrophin, the product of an exceptionally large gene.
 Although dystrophin has been characterized as a spectrin-like submembranous cytoskeletal protein, there is no experimental evidence for its function in the structural maintenance of muscle.
 Current hypotheses attribute necrosis of dystrophin-less fibres in situ to mechanical weakening of the outer membrane, to an excessive influx of Ca2+ ions, or to a combination of these two mechanism, possibly mediated by stretch-sensitive ion channels.
 Using hypo-osmotic shock to determine stress resistance and a mouse model (mdx) for the human disease, we show that functional dystrophin contributes to the stability of both cultured myotubes and isolated mature muscle fibres.
",22
3732,"The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus.
 T-associated maternal effect (Tme) is the only known maternal-effect mutation in the mouse.
 The defect is nuclear-encoded and embryos that inherit a deletion of the Tme locus from their mother die at day 15 of gestation.
 There are many genomically imprinted regions known in the mouse genome but so far no imprinted genes have been cloned.
 The Tme locus is absent in two chromosome-17 deletion mutants, Thp and the tLub2, and its position has been localized using these deletions to a 1-cM region.
 We report here that the genes for insulin-like growth factor type-2 receptor (Igf2r) and mitochondrial superoxide dismutase-2 (Sod-2) are absent from both deletions.
 Probes for these genes and for plasminogen (Plg) and T-complex peptide 1 (Tcp-1) were used in pulsed-field gel mapping to show that Tme must lie within a region of 800-1,100 kb.
 We also demonstrate that embryos express Igf2r only from the maternal chromosome, and that Tcp-1, Plg and Sod-2 are expressed from both chromosomes.
 Therefore Igf2r is imprinted and closely linked or identical to Tme.
",22
3733,"Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease 
 The brains of patients with Alzheimer's disease (AD) invariably exhibit neuropathology in the hippocampus and entorhinal cortex when examined postmortem.
 Magnetic resonance imaging (MRI) offers a noninvasive, high-resolution method for quantifying volumetric changes in the AD brain antemortem.
 Eight patients diagnosed with probable AD and 7 age-matched controls had MRI scans and were tested on a battery of cognitive and olfactory tests.
 The hippocampus and entorhinal cortex (parahippocampal gyrus) showed significant atrophy, with over 40% reduction in size.
 Areas of the brain that are not highly involved in the degenerative state of AD, such as the striatum, did not show significant volumetric changes.
 Hippocampal and parahippocampal gyrus volumes had the highest correlation with scores on the Mini-Mental State Examination (r = 0.89), with lower correlations for a smell identification test (r = 0.65), odor match-to-sample test (r = 0.72), and a visual match-to-sample test (r = 0.26).
",22
3734,"Recurrent peripheral facial nerve palsy after dental procedures.
 Peripheral facial palsy is an uncommon complication of dental procedures.
 Most cases begin immediately after dental anesthesia and resolve within 12 hours.
 No report of recurrent facial palsy with dental manipulations has previously been described.
 We report a patient with two episodes of peripheral facial palsy, 2 years apart, developing within 24 hours of dental procedures.
 A third episode of contralateral facial weakness developed 3 years after the second event.
 This event was not related to dental manipulations.
 Although the exact mechanism is not known, dental manipulations may rarely result in precipitation of recurrent Bell's palsy.
",22
3735,"Physiological induction and reversal of focus formation and tumorigenicity in NIH 3T3 cells [published erratum appears in Proc Natl Acad Sci U S A 1991 Apr 15;88(8):3510]
 NIH 3T3 cells undergo morphological transformation in response to conditions of constrained growth, such as occur in low serum concentrations or at confluence.
 Transformation is expressed in a small fraction of the cells by the appearance of discrete foci of multiplying cells on a confluent monolayer of quiescent cells.
 We isolated and expanded cell populations from three dense and three light foci.
 Cells from each of these populations efficiently reproduced foci of the same morphotype when grown on a background of nontransformed NIH 3T3 cells.
 Using cultures derived from one of the dense foci (subline D/2), we found that the number of focus-forming units was stable and the cells remained tumorigenic when they were subjected to repeated thrice-weekly passage in 2% calf serum.
 However, equivalent passage in 10% calf serum eventually rendered the cells incapable of both focus production and tumor formation.
 The results show that the capacity to produce tumors as well as morphological transformation are produced as a response to physiological constraints of growth and/or metabolism in the absence of carcinogens and that both properties can be reversed by lifting the constraints.
 This behavior is typical of an adaptational response and, taken together with other supporting evidence, shows that tumorigenesis does not require conventional genetic alteration.
",22
3736,"Cation-dependent mannose 6-phosphate receptor contains two internalization signals in its cytoplasmic domain [published erratum appears in Proc Natl Acad Sci U S A 1991 Feb 15;88(4):1591]
 The signals required for rapid internalization of the bovine cation-dependent mannose 6-phosphate receptor have been localized to two distinct regions of the 67-amino acid cytoplasmic domain.
 One signal includes phenylalanine 13 and phenylalanine 18, while the other involves tyrosine 45.
 The former signal is more potent than the latter, but both must be present for the maximal rate of receptor internalization.
 Each signal shares similarities with the known internalization signals of other recycling receptors.
",22
3737,"A long terminal repeat-containing retrotransposon is mobilized during hybrid dysgenesis in Drosophila virilis.
 A hybrid dysgenesis syndrome similar to those described in Drosophila melanogaster occurs in Drosophila virilis when a laboratory stock is crossed to a wild strain collected in the Batumi region of Georgia (U.S.S.R).
 Mutations in various loci obtained during these crosses are presumably induced by the insertion of DNA sequences.
 We have cloned an induced white mutation and characterized the insertion sequence responsible for the mutant phenotype.
 This sequence is a 10.6-kilobase (kb) transposable element we have named Ulysses.
 This element is flanked by unusually large 2.1-kb long terminal repeats.
 Ulysses also contains other landmarks characteristic of the retrotransposon family, such as a tRNA-binding site adjacent to the 5' long terminal repeat and open reading frames encoding putative products with homology to the reverse transcriptase, protease, and integrase domains typical of proteins encoded by vertebrate retroviruses.
 Some of the mutations obtained do not contain a copy of the Ulysses element at the mutant locus, suggesting that a different transposable element may be responsible for the mutation.
 Therefore, Ulysses may not be the primary cause of the entire dysgenic syndrome, and its mobilization may be the result of activation by an independent mobile element.
",22
3738,"Repair of O6-ethylguanine in DNA protects rat 208F cells from tumorigenic conversion by N-ethyl-N-nitrosourea.
 O6-Ethylguanine (O6-EtGua) is one of about a dozen different alkylation products formed in the DNA of cells exposed to the alkylating N-nitroso carcinogen N-ethyl-N-nitrosourea (EtNU).
 We have evaluated selectively the relative capacity of cells for the specific enzymatic repair of O6-EtGua as a determinant for the probability of malignant conversion.
 Eleven O6-EtGua-repair-proficient (R+) variant subclones were isolated from the O6-EtGua-repair-deficient (R-) clonal rat fibroblast line 208F by selection for resistance to 1,3-bis-(2-chloroethyl)-1-nitrosourea (frequency, approximately equal to 10(-5).
 Contrary to the 208F wild-type cells, all variants expressed O6-methylguanine-DNA methyltransferase activity, while both kinds of cells were deficient for repair of the DNA ethylation products O2- and O4-ethylthymine.
 After exposure to EtNU (less than or equal to 500 micrograms/ml; 20 min), cells were analyzed for the formation of piled-up foci in monolayer culture and of anchorage-independent colonies in semisolid agar medium.
 Depending on the EtNU concentration, the frequencies of piled-up foci and agar colonies, respectively, in the R+ variants were as low as 1/28th and 1/56th of those in the R- wild type.
 Contrasting with the cells from R+ variant-derived agar colonies, cells from 208F (R-) agar colonies gave rise to highly malignant tumors when implanted subcutaneously into syngeneic rats.
 No significant differences in the frequencies of piled-up foci were found between wild-type and variant cells after exposure to the major reactive metabolite of benzo[a]pyrene, (+)-7 beta, 8 alpha-dihydroxy-9,10 alpha-epoxy-7,8,9,10 alpha-tetrahydrobenzo[a] pyrene, for which stable binding to guanine O6 in cellular DNA has not been observed.
 The relative capacity of cells for repair of O6-alkylguanine is, therefore, a critical determinant for their risk of malignant conversion by N-nitroso carcinogens.
",22
3739,"Ligamentous laxity across C0-C1-C2 complex. Axial torque-rotation characteristics until failure.
 The axial torque until failure of the ligamentous occipito-atlanto-axial complex (C0-C1-C2) subjected to axial angular rotation (theta) was characterized using a biaxial MTS system.
 A special fixture and gearbox that permitted right axial rotation of the specimen until failure without imposing any additional constraints were designed to obtain the data.
 The average values for the axial rotation and torque at the point of maximum resistance were, respectively, 68.1 degrees and 13.6 N-m.
 The specimens offered minimal resistance (approximately 0.5 N-m), up to an average axial rotation of 21 degrees across the complex.
 The torque-angular rotation (T-theta) curve can be divided into four regions: regions of least and steadily increasing resistances, a transition zone that connects these two regions, and the increasing resistance region to the point of maximum resistance.
 The regions of least and steadily increasing resistances may be represented by two straight lines with average slopes of 0.028 and 0.383 N-m/degree, respectively.
 Post-test dissection of the specimens disclosed the following.
 The point of maximum resistance corresponded roughly to the value of axial rotation at which complete bilateral rotary dislocation of the C1-C2 facets occurred.
 The types of injuries observed were related to the magnitude of axial rotation imposed on a specimen during testing.
 Soft-tissue injuries alone (like stretch/rupture of the capsular ligaments, subluxation of the C1-C2 facets, etc.) were confined to specimens rotated up to or close to the point of maximum resistance.
 The specimens that were subjected to rotations up to the point of maximum resistance of the curve spontaneously reduced completely on removal from the testing apparatus.
 Spontaneous reduction was not possible for specimens tested slightly beyond their points of maximum resistance.
",22
3740,"Perinatal grief and mourning.
 The grief and mourning that parents experience following a perinatal loss is as devastating as the loss of an older loved one.
 The pattern of mourning can be anticipated and interventions can be implemented.
 With proper help, the parents can pass through this catastrophic time in their lives with a minimum of scars.
 If the physician stops, reaches out, listens, and supports the parents, he or she can have a dramatic effect on the lives of these parents.
 In the same manner in which we started this paper, we close with a quotation from another parent who suffered a loss: Daughters may die, But why? For even daughters can't live with half a heart.
 Three days isn't much a life.
 But long enough to remember thin blue lips, uneven gasps in incubators, Racking breaths that cause a pain to those who watched.
 Long enough to remember I never held her Or felt her softness Or counted her toes.
 I didn't even know the color of her eyes.
 Dead paled hands not quite covered by the gown she Was to go home in.
 Moist earth smell.
 One small casket.
 And the tears.
 You see, I hold in my hand but souvenirs of an occasion.
 A sheet of paper filled with statistics, A certificate with smudged footprints, A tiny bracelet engraved ""Girl, Smith."" You say that you are sorry That you know how I feel.
 But you can't know because I don't feel.
 Not yet.
",22
3741,"Study on the genesis of the double potential recorded in the high right atrium in atrial flutter and its role in the reentry circuit of atrial flutter.
 To investigate the genesis of the double potential (DP), which is two separate waves, and its role in the reentry circuit of atrial flutter (AF), we performed overdrive pacing (ODP) from the high right atrium (HRA) in six cases of spontaneous AF in which the DP was recorded in the HRA.
 In four of the six cases, when the DP was arbitrarily designated D1 and D2, D1 and D2 showed progressive fusion during ODP.
 In addition, the D1 return cycle, immediately after the termination of ODP, corresponded to the AF cycle, and the D2 return cycle corresponded to the pacing cycle.
 This may indicate that the DP is caused by the collision of two directional waves.
 Furthermore, it is suggested that the HRA plays an important role in preventing a possible shortcutting of reentry waves and in stabilizing the reentry circuit of AF.
",22
3742,"Echographic diagnosis of dural carotid-cavernous sinus fistulas.
 I used standardized ophthalmic echography to identify specific abnormalities in four patients with low-pressure, low-flow dural arteriovenous malformations.
 In all of the patients, B-scan ultrasonography showed engorgement of the ipsilateral vertical vein.
 A-scan ultrasonography dynamically imaged rapid blood flow through the superior ophthalmic vein and enlargement of the culpable ocular muscles in patients with restrictive ophthalmopathy.
 The 30-degree test distinguished between venous engorgement of the optic nerve sheath and apical compression of the optic nerve by enlarged ocular muscles.
",22
3743,"Leukotriene synthesis inhibition and receptor blockade do not inhibit hypoxic pulmonary vasoconstriction in sheep.
 Several lines of evidence suggest that leukotrienes may be mediators of hypoxic pulmonary vasoconstriction (HPV).
 However, the effect of leukotriene inhibition on HPV remains controversial.
 The present study investigated the effect of leukotriene synthesis inhibition and receptor blockade on HPV in the halothane-anesthetized sheep.
 After initial baseline measurements, the pulmonary pressor response to 15 min of global hypoxia (FIO2 = 0.13) was measured.
 A second set of baseline measurements was obtained and the sheep then received the combined cyclooxygenase/lipoxygenase inhibitor BW755C, the selective lipoxygenase inhibitor U60257, or the leukotriene receptor antagonist LY171883.
 Hemodynamic measurements were obtained after drug administration and during a subsequent hypoxic challenge (FIO2 = 0.13).
 Initial hypoxic challenge increased pulmonary artery pressure 68% and increased pulmonary vascular resistance 104%.
 Pulmonary hemodynamics after recovery from hypoxia were similar to initial baseline values.
 Drug administration had no significant hemodynamic effect.
 Hypoxic challenge after drug administration resulted in a pulmonary pressor response identical to the initial hypoxic challenge.
 Because leukotriene synthesis inhibition and receptor blockade did not alter the response to hypoxia, we conclude that leukotrienes are not obligatory mediators of HPV.
 A critical review of the literature supports a modulatory rather than an obligatory role for leukotrienes in HPV.
",22
3744,"Effects of neuroleptic agents on rat skeletal muscle contracture in vitro.
 The purpose of this investigation was to examine and compare the effects of both in vivo pretreatment and in vitro treatment with the neuroleptic agents droperidol, haloperidol, and trifluoperazine on skeletal muscle contracture using an in vitro model.
 Strips of normal rat diaphragm were challenged with succinylcholine and halothane (halothane: 1% and 3%) subsequent to either in vitro administration (10-100 microM) or in vivo pretreatment (0.35-2.80 mg/kg) with droperidol, haloperidol, or trifluoperazine.
 After equilibration, maximum increases in tension were recorded and mean data analyzed by analysis of variance (P less than 0.05).
 When either droperidol or trifluoperazine was administered in vivo, contracture values after exposure to succinylcholine and halothane were significantly decreased.
 After in vivo pretreatment with haloperidol or in vitro administration of droperidol, succinylcholine-induced contractures were significantly reduced; contractures subsequently induced by halothane did not significantly differ from that of controls.
 In vitro treatment with haloperidol and trifluoperazine, however, produced significant increases in tension in muscles exposed to succinylcholine and halothane.
 This study provides evidence that droperidol may be considered a safe anesthetic adjunct in malignant hyperthermia-susceptible patients, and, additionally, that caution should be exercised when interpreting results from studies in which contracture testing is performed on muscle from patients treated with neuroleptic agents.
",22
3745,"Simultaneous superior oblique sheathectomy and inferior oblique tuck in congenital Brown's syndrome.
 Since Harold Brown, in 1950, described the superior oblique tendon sheath syndrome, numerous surgical techniques have been explored to treat this condition.
 Tenectomy of the homolateral superior oblique, alone or in combination with a weakening procedure on the homolateral inferior oblique, has been the technique most advocated.
 However, good functional results are rarely achieved in a single procedure, and delayed complications are frequent.
 Taking advantage of the improved dissection and reduced trauma afforded by the use of a surgical microscope, one of the techniques first recommended and later abandoned by Brown was reappraised.
 The technique consists of dissection of the sheath and attachments of the superior oblique, while preserving its tendon, combined with a 10mm tuck of the homolateral inferior oblique.
 Both a typical and a severe atypical congenital case, according to the classification of Brown, were treated in this fashion.
 Full correction was achieved in both.
",22
3746,"Effects of hyaluronic acid fractions in the rabbit eye.
 Two fractions of hyaluronic acid with different molecular weight (Ial, molecular weight 500,000-730,000 and Healon, molecular weight 750,000) were injected intracamerally or intravitreously in the rabbit eye.
 Although the fraction with higher molecular weight caused an increase in intraocular pressure, no change of this parameter was found after administration of the fraction with the lower molecular weight.
 Furthermore, various inflammatory reactions in ocular tissues were observed during slit-lamp biomicroscopy after administration of Healon but not of Ial.
 No inflammatory reaction was found after subchronic instillation of the compounds.
",22
3747,"Pleural anesthetics given through an epidural catheter secured inside a chest tube.
 Pain management after thoracic surgical procedures is a difficult clinical problem.
 A variety of pain management methods are used with variable efficacy.
 This paper presents an effective method of pleural anesthetic administration using a pleural catheter inserted through a chest tube.
",22
3748,"Intraoperative coronary angiography using fluorescein.
 Intraoperative coronary angiography using fluorescein was applied to evaluate the patency of saphenous vein grafts just after completion of the distal anastomosis.
 By this technique, the area of the revascularized myocardium was well estimated in real time.
 This intraoperative direct-vision examination gives us more timely and precise information during coronary artery bypass grafting.
",22
3749,"Delayed chest wall pain due to sternal wire sutures.
 This report describes 18 patients with disabling chest wall pain due to one or more sternal wire sutures.
 The pain occurred from 2 to 84 months after a median sternotomy.
 The pain was described either as sharp and stabbing or as a deep-seated ache.
 The involved wires had an exaggerated fibrous tissue reaction surrounding the twisted portion.
 The adjacent noninvolved wires had minimal reaction.
 In the last 7 patients, serial sections of the fibrous tissue revealed entrapment of one or more sensory nerve fibers.
 In 6 of the 7 electrical potentials were measured and found to be elevated, indicating wire damage during twisting.
 Ferroxyl tests confirmed the collection of iron ions at this anodic point as a result of corrosion.
 Removal of the involved wires and the fibrous tissue surrounding this anodic point relieved the symptoms of pain and tenderness resulting from entrapped sensory nerves.
",22
3750,"Might free arterial grafts fail due to spasm?
 The rat femoral artery was used as a free graft and was studied after 2, 7, 14, 30, and 60 days.
 The patency of the grafts was 100% (2 days, n = 6), 78% (7 days, n = 9), 63% (14 days, n = 8), 33% (30 days, n = 12), and 18% (60 days, n = 11).
 Histology showed an intimal thickening after 14 days and the media, which in the controls consisted of eight to ten layers of myocytes, was reduced to six to eight cell layers.
 During the first 2 weeks the graft segments had an impaired contraction when exposed to Krebs solution with 124 mmol/L K+, whereas after 1 month and later the graft segments approached the controls or had even higher contractile force.
 The thromboxane mimic U-46619 elicited full contractile force at all times whereas the potency was significantly lower during the first 14 days.
 Noradrenaline was unable to induce contraction in the graft segments during the first 14 days, but at 30 and 60 days it had regained full contractile force and was significantly more potent (approximately 60 times) in the graft segments compared with the controls.
 This study suggests that intimal thickening and hypercontractility might be a problem in free muscular arterial grafts.
",22
3751,"Primary care patients who refuse specialized mental health services.
 The charts of 65 patients who completed mental health care referrals were compared with those of 65 patients who failed to complete such referrals.
 In the year before referral, the noncompliant patients made 37% more medical visits than the compliant patients.
 As compared with the compliant patients, a significantly greater proportion of the noncompliant patients' medical visits were for difficult-to-explain somatic symptoms.
 Mental health referrals from some physicians were much more successful than referrals from other physicians.
 By attending to their patients' pattern of health care utilization, primary care physicians may be able to identify patients at high risk for noncompliance with mental health referrals.
",22
3752,"Suicide attempts by the old and the very old.
 Attempted suicide by the elderly is a major psychiatric problem.
 Ninety-five patients between 60 and 90 years of age were evaluated by a psychiatric consultation service after a suicide attempt.
 Characteristics of this group included (1) a high degree of premeditation, (2) a tendency toward firearm use and wounds to the head, (3) male sex, (4) coexisting medical problems, (5) serious intent that increased by decade, (6) solitary living arrangements, (7) presence or history of a major psychiatric illness, and (8) ill health reported as a precipitant to suicidality.
 Major depression was the most common psychiatric diagnosis, with congestive heart failure and chronic obstructive pulmonary disease the most frequently noted physical ailments.
 This elderly population of attempters resembled older persons who actually completed suicide and differed significantly from 1630 persons aged 16 to 59 years who attempted suicide.
 Heightened investigation of depressive features, treatment of alcohol abuse, early referral for psychiatric care, limited access to firearms, and strategies aimed at decreasing social isolation are recommended to decrease the likelihood of completed suicide in the elderly.
",22
3753,"The relationship between hypochondriasis and medical illness.
 Forty-one Diagnostic and Statistical Manual of Mental Disorders-III-Revised hypochondriacs were accrued from a primary care practice.
 Seventy-five control subjects were selected at random from among the remainder of the patients in the same clinic.
 All subjects completed a structured diagnostic interview and standardized self-report questionnaires.
 Medical morbidity was assessed with a medical record audit and with primary physicians' ratings.
 The hypochondriacal and comparison samples did not differ in aggregate medical morbidity, although the hypochondriacal sample had more undiagnosed complaints and nonspecific findings in their medical records.
 Within the comparison sample, higher levels of medical morbidity were associated with higher levels of hypochondriacal symptoms.
 This occurred primarily because the most serious medical disorders were associated with more bodily preoccupation, disease conviction, and somatization.
 Within the hypochondriacal sample, no correlation was found between the degree of hypochondriasis and the extent of medical morbidity.
",22
3754,"Preoperative aspirin therapy and reoperation for bleeding after coronary artery bypass surgery.
 We performed a case-control study to estimate the relative risk of reoperation for bleeding in coronary artery bypass graft patients who had taken aspirin within the 7 days preceding surgery.
 Comparison of 90 cases of reoperation with 180 matched control subjects gave an estimated odds ratio for reoperation of 1.82 (95% confidence interval, 1.23 to 3.32).
 Although their preoperative coagulation values were similar, cases used significantly more whole blood (cases, 9.5 +/- 5.2 units; control subjects, 3.0 +/- 2.0 units; median +/- interquartile range), packed red blood cells (cases, 2.1 +/- 4.0 units; control subjects, 0.9 +/- 2.0 units), and platelets (cases, 12.2 +/- 12.0 units; control subjects, 2.9 +/- 4.0 units) than control subjects.
 Cases had intensive care unit stays of 4.7 +/- 5.7 days (mean +/- SD) vs 2.1 +/- 1.9 days for control subjects and postoperative hospitalizations of 10.9 +/- 8.2 days vs 7.0 +/- 3.2 days for control subjects.
 We conclude that aspirin exposure within 7 days before coronary bypass surgery is associated with an increased rate of reoperation for bleeding and that reoperation is associated with large increases in transfusion requirements and intensive care unit and hospital stays.
",22
3755,"Use of the calcium agonist BAY K 8644 for in vitro diagnosis of susceptibility to malignant hyperthermia.
 We have studied the effects of the calcium agonist BAY K 8644 on the in vitro halothane test in 10 malignant hyperthermia-susceptible (MHS), 12 MH ""equivocal"" to halothane (MHEh), 30 MH non-susceptible (MHN) and 10 control patients.
 BAY K 8644 potentiated the halothane-induced contracture in muscle strips from both MHS and MHEh patients.
 The drug produced a more obvious difference in contracture responses between the MHEh group compared with the MHN and control groups.
",22
3756,"Regulatory control of the terminal complement proteins at the surface of human endothelial cells: neutralization of a C5b-9 inhibitor by antibody to CD59.
 Functionally inhibitory antibody to the plasma membrane complement inhibitor CD59 has been used to investigate control of the terminal complement proteins at the endothelial cell surface.
 Antibodies against purified human erythrocyte CD59 (polyclonal anti-CD59 and monoclonal antibodies [MoAbs] 1F1 and 1F5) were found to bind specifically to monolayers of cultured human umbilical vein endothelial cells, and by Western blotting to recognize an 18- to 21-Kd endothelial protein.
 When bound to the endothelial monolayer, anti-CD59 (immunoglobulin G or Fab fragment) potentiated membrane pore formation induced upon C9 binding to C5b-8, and augmented the C5b-9-induced cellular responses, including stimulated secretion of von Willebrand factor and expression of catalytic surface for the prothrombinase enzyme complex.
 Although potentiating endothelial responses to the terminal complement proteins, anti-CD59 had no effect on the response of these cells to stimulation by histamine.
 Taken together, these data suggest that human endothelial cells express the CD59 cell surface inhibitor of the terminal complement proteins, which serves to protect these cells from pore-forming and cell-stimulatory effects of the C5b-9 complex.
 These data also suggest that the inactivation or deletion of this cell surface regulatory molecule would increase the likelihood for procoagulant changes in endothelium exposed to complement activation in plasma.
",22
3757,"Regulatory elements of the erythropoietin gene.
 Because the human hepatoma cell line Hep3B produces erythropoietin (Epo) in a regulated fashion, it can be used to investigate the cis-acting regulatory elements of the Epo gene.
 Comparison of primate and mouse sequences shows strong homology not only in the coding sequence but also within the 5' flanking region, the first intron, and the 3' flanking region.
 These portions of the Epo gene were inserted 5' and 3' to a reporter gene, human growth hormone (GH).
 5A is a 1,192-base pair (bp) HindIII-Xbal fragment that extends from 378 bp 5' to the cap site through the first intron.
 To obviate the problem of false initiation of translation from the Epo ATG start codon, this site was changed to TAG by site-directed mutagenesis.
 3A is a 255-bp Accl-BglII fragment that extends 67 bp upstream from the Epo termination codon and covers most of the 3' noncoding region of homology.
 The plasmid DNAs were transfected by electroporation into Hep3B cells with RSVCAT as an internal standard to correct for transfection efficiency.
 One aliquot of cells was exposed to 50 mumol/L CoCl2 or to 1% O2.
 At the end of the incubations, GH and Epo were measured in the cell media and the cell pellet was assayed for CAT.
 Production of GH was stimulated 1.7-fold by cobalt or hypoxia.
 Furthermore, addition of 3A to the GH gene, irrespective of orientation, stimulated GH production 2.6-fold with CoCl2 and 2.3-fold with hypoxia.
 Stable cell lines were produced by cotransfection of the above constructions, along with the selectable marker pSV-Neo.
 In two clones, exposure to hypoxia resulted in much more marked (16-fold) induction of GH.
 Stimulus of both GH and Epo production by hypoxia was partially abrogated by carbon monoxide.
 These results demonstrate the presence of promoter and enhancer elements within the human Epo gene that are appropriately responsive to hypoxia and cobalt.
",22
3758,"Does ethamsylate reduce haemorrhage in transurethral prostatectomy?
 A double-blind, randomised trial of 44 consecutive patients undergoing transurethral prostatectomy demonstrated that ethamsylate (Dicynene) did not reduce blood loss during either the operative or the post- operative periods.
",22
3759,"Acceleration of luteinizing hormone pulse frequency in functional hypothalamic amenorrhea by dopaminergic blockade.
 A constellation of neuroendocrine secretory aberrations, including reduced LH pulse frequency and PRL concentrations, has been documented in women with functional hypothalamic amenorrhea (FHA).
 As pituitary function was preserved, these aberrations were attributed to an alteration in hypothalamic neuromodulation.
 To investigate the participation of the dopaminergic system in the genesis of the reduced LH pulse frequency and suppressed PRL levels in FHA, we studied six women with FHA and six cyclic women in the early follicular phase by obtaining blood samples at 15-min intervals for 48 h during sequential 24-h infusions of saline and a dopamine receptor blocker, metoclopramide (MCP).
 A hypothalamic vs.
 pituitary site of action was inferred from the pulsatility characteristics.
 MCP consistently elicited an increase in the LH pulse frequency in the women with FHA [7.3 +/- 1.2 (+/- SE) to 10.5 +/- 1.3 pulses/24 h; P less than 0.005].
 In contrast, the eumenorrheic women did not show a significant change in LH pulse frequency in response to MCP (15.2 +/- 1.0 to 14.3 +/- 0.9 pulses/24 h).
 While the PRL concentrations were significantly lower in the FHA group during the infusion of saline (P less than 0.001) and MCP (P less than 0.005), the relative increases in PRL during MCP were similar in both groups.
 The acceleration of LH pulse frequency by blockade of dopamine receptors implies that there is increased hypothalamic dopaminergic inhibition of GnRH pulse frequency in women with FHA.
",22
3760,"A simple stress test for the evaluation of hypothalamic-pituitary-adrenal axis during the first 6 months of life.
 In 33 normal infants, divided into 3 age groups (less than 1 month, 1-3 months, and 3-6 months) plasma cortisol was measured at 2230, 2300, and 2330 h.
 Baseline plasma cortisol at 2230 h.
 was, as expected, low in all infants, with mean +/- SEM values of 41 +/- 5, 72 +/- 14, and 97 +/- 17 nmol/L in each group, respectively.
 Thirty and 60 min after the painful stimulus of the venipuncture, plasma cortisol increased significantly (P less than 0.0005), reaching a maximum increase up to 458 +/- 50, 392 +/- 66, and 455 +/- 97 nmol/L in each age group, respectively.
 We conclude that in these infants the hypothalamic-pituitary-adrenal axis was functionally intact and responded to the painful stimulus of the venipuncture by a significant increase in plasma cortisol.
 This test may be used as a simple procedure for the evaluation of the integrity of the hypothalamic-pituitary-adrenal axis without the administration of pharmacological agents.
 Its usefulness, however, should be validated with patients having a disorder of the system.
",22
3761,"How stressful is retirement? Findings from the Normative Aging Study.
 The stressfulness of retirement both as a transitional event experienced during the past year and as a life stage was investigated.
 Transitional stress was assessed using a life events approach, and stage stress using a ""hassles"" approach.
 Respondents were 1,516 male participants in the Normative Aging Study, 45% of whom were retired.
 Among those retiring in the past year, respondents' own and spouse's retirement were rated the least stressful from a list of 31 possible events.
 Only 30% found retirement stressful.
 Retirement hassles were also less frequently reported and were rated less stressful than the work hassles of men still in the labor force.
 The only consistent predictors of both transitional and stage retirement stress were poor health and family finances; personality did not predict retirement stress.
",22
3762,"Living arrangements and sources of caregiving.
 This study examined both the prevalence of different types of caregivers (in terms of the relation to the individual), and whether living with someone is more important for caregiving than the relation of an elder to an individual.
 Caregiving is examined in terms of IADL and emotional support.
 Analyses are conducted using three separate random samples of those who are married and living with a spouse, those who live alone, and those who live with nonspousal others in Winnipeg, Manitoba, Canada.
 The results confirm previous research pointing out that married people tend to receive assistance from their spouse.
 Among nonmarrieds, children are named most frequently as the primary caregiver.
 After children, however, those who live alone tend to receive assistance from friends, and those who live with nonspousal others receive assistance from siblings.
 The data further document the importance of the structural characteristic of living with someone, rather than marital status, for assistance with IADL.
",22
3763,"Social networks, health, and emotional well-being among the oldest old in London.
 A survey of the health and social circumstances of 662 people aged 85 and over, living at home in inner London, was conducted in 1987.
 A primary aim was to analyze the structure of social support networks of the sample in relation to respondents' emotional well-being and met and unmet needs for practical help.
 The conceptual and methodological framework that was applied to the study was derived from the theory of social networks.
 In confirmation of the common assumption that people aged 85+ are different from younger elderly people, as they are the ""survivors,"" high levels of social support and informal help were given to most respondents.
 Although associations were found between social network variables and the provision of informal help, multifactorial analysis showed that health status explained more of the variation in emotional well-being.
",22
3764,"Coumadin-induced gastrointestinal hemorrhage associated with an ileal duplication.
 A 31-year-old man had recurrent gastrointestinal hemorrhage after aortic valve replacement and initiation of anticoagulation therapy with coumadin.
 Radionuclide bleeding scan and subsequent contrast angiogram demonstrated a site of hemorrhage in the distal ileum, and at surgery a 1.8-cm spherical duplication was found.
 On histologic examination, the duplication was lined with normal ileal mucosa, and near the mouth of the duplication an inflammatory ulceration proved to be the site of hemorrhage.
 In a young patient with anticoagulation-associated gastrointestinal hemorrhage, alimentary tract duplication should be considered.
",22
3765,"Large telangiectatic focal nodular hyperplasia presenting with normal radionuclide studies: case report.
 A 9 cm-lesion of telangiectatic focal nodular hyperplasia was incidentally identified in a 31-yr-old female.
 Despite a typical appearance by X-ray computed tomography and ultrasonography, scintigraphy with technetium-99m-(99mTc) colloid, 99mTc-diethyliminodiacetic acid, and 99mTc-labeled red cells failed to demonstrate any abnormalities.
 These findings are felt to reflect the relative lack of architectural disruption that histologically characterizes this particular lesion.
 The present report described the imaging characteristics of the telangiectatic form of focal nodular hyperplasia.
",22
3766,"Techniques of emergency ventilation: a model to evaluate tidal volume, airway pressure, and gastric insufflation.
 We designed a model to evaluate the effectiveness of various noninvasive methods of ventilation.
 The upper airway was simulated with the head of a Resusci-Annie which was attached to a test lung.
 The esophagus and stomach were simulated with a Penrose drain connected to a rolling seal spirometer via a PEEP valve.
 Fifteen paramedic volunteers ventilated the model utilizing mouth-to-mouth, mouth-to-mask, bag-valve-mask, or portable field ventilator (Impact or HARV).
 Recording of tidal volume, gastric volume, and proximal and distal airway pressure was completed at three different levels of compliance.
 At normal compliance, all methods except the HARV met or exceeded American Heart Association standards.
 As compliance decreased, tidal volume fell and gastric insufflation increased.
 At a compliance of 0.02 L/cm H2O all methods failed to meet AHA standards and gastric insufflation volume equalled delivered tidal volumes for mouth-to-mouth and mouth-to-mask techniques.
 Mouth-to-mouth and mouth-to-mask techniques generated the largest tidal volumes but also created the largest volume of gastric insufflation.
 The Impact ventilator provided an acceptable tidal volume with minimal gastric insufflation.
 Our results suggest that mouth-to-mask ventilation with supplemental oxygen enrichment is the most efficient technique for non-invasive airway management.
",22
3767,"Prostaglandin F1 alpha levels during and after neonatal extracorporeal membrane oxygenation.
 Infants receiving extracorporeal membrane oxygenation therapy undergo long-term cardiopulmonary bypass, are systemically heparinized, and frequently receive platelet transfusions.
 Prostacyclin is a powerful inhibitor of platelet aggregation as well as a potent vasodilator.
 The levels of its stable metabolite prostaglandin F1 alpha increase significantly in children undergoing cardiopulmonary bypass during heart operations but decrease to preoperative levels after bypass.
 To determine the effect of long-term bypass on prostacyclin levels, multiple plasma samples were analyzed in 10 human neonates both during extracorporeal membrane oxygenation therapy and within 24 hours after extracorporeal membrane oxygenation.
 Prostaglandin F1 alpha, the stable metabolite of prostacyclin, was quantitated by radioimmunoassay in picograms per milliliter.
 Prostaglandin F1 alpha levels were elevated while the patients received extracorporeal membrane oxygenation therapy but decreased with duration of extracorporeal membrane oxygenation.
 In most infants, prostaglandin F1 alpha levels rose again during weaning from extracorporeal membrane oxygenation and remained elevated for 24 hours after extracorporeal membrane oxygenation.
 Extracorporeal membrane oxygenation course influenced circulating prostaglandin F1 alpha levels.
 Fluctuating prostaglandin F1 alpha levels are of clinical significance in the management of vasomotor tone and platelet function, common problems in the care and the prevention of hemorrhage in these critically ill infants.
",22
3768,"A reevaluation of heparin requirements for cardiopulmonary bypass.
 We wished to determine if reduction in the standard heparin administration for cardiopulmonary bypass could be accomplished safely with the use of membrane oxygenators.
 An experimental study was designed to evaluate two different heparin administration protocols for cardiopulmonary bypass with hollow-fiber membrane oxygenators.
 Two groups of six pigs were submitted to hypothermic cardiopulmonary bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed after 1 hour.
 In group I (control) heparin was administered to maintain the activated clotting time in excess of 450 seconds; in group II activated clotting time was maintained between 250 and 300 seconds.
 The mean total heparin administered was 41,000 units in group I and 25,000 units in group II.
 Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet count were determined before, during, and 1 hour after bypass.
 No significant difference in any of these coagulation parameters was observed between the groups.
 The performance of the oxygenators was similar in both groups, with no evidence of thrombosis.
 Thus reduced heparin administration, enough to keep activated clotting time between 250 and 300 seconds, was not related either to major coagulation factors and platelet consumption or to derangements in the oxygenator's performance.
",22
3769,"Analysis of the Medtronic Intact bioprosthetic valve. Effects of ""zero-pressure"" fixation.
 The long-term performance of current-design porcine xenograft valves has not been satisfactory.
 These valves are generally fixed at ""low pressures"" of about 3 to 5 mm Hg.
 The Medtronic Intact (Medtronic, Inc., Minneapolis, Minn.) valve is fixed at ""zero pressure"" and is proposed as a better alternative to existing xenograft valves.
 A mechanical analysis of this valve has been carried out to determine if the Intact valve differs significantly from the low-pressure fixed xenograft.
 Twelve circumferential strips of tissue 5 mm wide were cut from the leaflets of four clinical-grade Intact valves.
 Their stress/strain, stress relaxation, and flexural behavior were examined mechanically and histologically.
 The Intact valve was more extensible than the low-pressure fixed xenograft (22% versus 12% strain, p less than 0.001), relaxed faster (p less than 0.001), and was more pliable than the xenograft (p less than 0.05).
 It did not, however, buckle less than did the low-pressure fixed xenograft during enforced bending, and it buckled significantly more than did fresh porcine aortic valve tissue (p less than 0.001).
 The Intact valve also relaxed significantly more slowly than did the fresh tissue (p less than 0.05).
 Its bending stiffness had a stronger dependence on leaflet thickness than the bending thickness of fresh tissue had (p less than 0.001) but a weaker dependence than the bending thickness of the low-pressure fixed xenograft material had (p less than 0.001).
 The Intact valve demonstrated a very large variability in extensibility, bending stiffness, and buckling behavior, with little correlation between these parameters.
 Some valves appeared to have wrinkled leaflets; others were likely fixed at different pressures.
 The shrinkage of the leaflet material at these low fixation pressures is likely important, since it can modify the elastic behavior of the valve cusps.
 Overall, the Intact valve had a more ""natural"" elastic behavior than had low-pressure fixed xenograft, and it should therefore experience lower stresses during normal valve function.
 It can be concluded that zero-pressure fixation does preserve many of the desirable stress-reducing properties of aortic valve tissue.
",22
3770,"Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera.
 Neutrophil-mediated inflammation is involved in a number of human clinical manifestations, including the adult respiratory distress syndrome, multi-organ failure and reperfusion injury.
 One way of inhibiting this type of inflammatory response would be to block competitively the adhesive interactions between neutrophils and the endothelium adjacent to the inflamed region.
 The lectin-containing murine adhesion molecule gp90MEL, the homing receptor, is found on all leukocytic cells, including neutrophils.
 MEL 14, a monoclonal antibody directed against this adhesion molecule, blocks lymphocyte traffic to lymph nodes and extravasation of neutrophils from blood to inflammatory sites.
 Here we show that administration to mice of a soluble immunoglobulin chimaera containing the murine homing receptor extracellular domain significantly decreases the number of neutrophils that migrate to the peritoneum in response to the inflammatory irritant thioglycollate.
 These results indicate that soluble forms of a single type of adhesion molecule, the homing receptor, could be clinically effective compounds for the inhibition of neutrophil-mediated inflammation.
",22
3771,"The Ams (altered mRNA stability) protein and ribonuclease E are encoded by the same structural gene of Escherichia coli.
 The in vitro and in vivo analysis of the ribonuclease E-deficient (rne-) and the altered mRNA stability protein-deficient (ams-) strains of Escherichia coli has demonstrated that they carry mutations in the same structural gene.
 Strains encoding either thermolabile RNase E (rne-3071) or Ams protein (ams-1) are defective in both rRNA processing and mRNA turnover.
 Immediately after a shift to the nonpermissive temperature, the chemical decay rate of bulk mRNA is slowed 2- to 3-fold, and within 70 min, precursors to 5S rRNA begin to accumulate.
 In addition, all of the phenotypes associated with either the rne-3071 or the ams-1 alleles were complemented by a recombinant plasmid carrying ams+.
 When taken together with previous genetic studies, these results suggest that the role of ribonuclease E in mRNA turnover involves endonucleolytic cleavages at the proposed ACAG(A/U)AUUUG consensus sequence.
",22
3772,"Nerve growth factor binding domain of the nerve growth factor receptor.
 A structural analysis of the rat low-affinity nerve growth factor (NGF) receptor was undertaken to define the NGF binding domain.
 Mutant NGF receptor DNA constructs were expressed in mouse fibroblasts or COS cells, and the ability of the mutant receptor to bind NGF was assayed.
 In the first mutant, all but 16 amino acid residues of the intracellular domain of the receptor were removed.
 This receptor bound NGF with a Kd comparable to that of the wild-type receptor.
 A second mutant contained only the four cysteine-rich sequences from the extracellular portion of the protein.
 This mutant was expressed in COS cells and the resultant protein was a secreted soluble form of the receptor that was able to bind NGF.
 Two N-terminal deletions, in which either the first cysteine-rich sequence of the first and part of the second cysteine-rich sequences were removed, bound NGF.
 However, a mutant lacking all four cysteine-rich sequences was unable to bind NGF.
 These results show that the four cysteine-rich sequences of the NGF receptor contain the NGF binding domain.
",22
3773,"Molecular evolution of inversions in Drosophila pseudoobscura: the amylase gene region.
 The amylase region of the third chromosome of Drosophila pseudoobscura has been cloned and localized to cytological band 73A.
 It is contained within a series of highly polymorphic inversions and serves as a convenient tool for a molecular evolutionary analysis of the inverted gene arrangements.
 Amylase in D.
 pseudoobscura is a family of three genes, and some chromosomes have deletions for one or two of them.
 Two overlapping clones covering 26 kilobases were isolated and used as probes to survey DNA restriction map polymorphism among 28 lines, representing five of the major inversion types found in natural populations, as well as single chromosomes from the closely related species Drosophila persimilis and Drosophila miranda.
 Restriction-site differences are considerably greater among the various gene arrangements than among chromosomes with the same gene arrangement.
 Clustering the restriction map haplotypes yielded a dendrogram concordant with the phylogeny generated independently from cytogenetic considerations.
 The inversion polymorphism is estimated to be about 2 million years old.
",22
3774,"Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation.
 Platelet-derived growth factor receptors are composed of two subunits (alpha and beta) that associate with one another to form three functionally active dimeric receptor species.
 The two subunits are encoded by separate loci in humans and other species.
 In this study, we used conventional interspecific backcross mapping and an analysis of a deletional mutation to establish close linkage between the alpha-subunit gene (Pdgfra) and the dominant spotting (W) locus on mouse chromosome 5.
 Further, by analyzing the restriction fragment length polymorphisms in interspecific F1 hybrids, we were able to demonstrate that the closely associated patch (Ph) locus carries a deletion in Pdgfra.
 This observation was confirmed by both DNA and RNA analysis of 10.5-day fetuses produced from crosses between Ph heterozygotes.
 Out of 16 fetuses analyzed, Pdgfra genomic sequences were absent and no mRNA for the receptor was detected in 6 fetuses that were developmentally abnormal (the presumptive Ph homozygotes).
 We also determined that the deletion associated with the Ph mutation does not extend into the coding sequences of the adjacent Kit gene, by analysis of the genomic DNA from both the interspecific F1 hybrids and the presumptive Ph homozygotes.
 The absence of Pdgfra genomic sequences and the lack of detectable message associated with the Ph mutation should make this mutant a valuable asset for understanding the role of the receptor alpha subunit during mammalian development.
",22
3775,"The role of the iliolumbar ligament in the lumbosacral junction.
 The biomechanical function of the iliolumbar ligament in the human lumbosacral junction was investigated by analyzing the three-dimensional movements of the whole lumbar and lumbo-sacral-ilium specimens.
 The experiment was repeated in the following three conditions: 1) intact iliolumbar ligament, 2) right iliolumbar ligament transected, and 3) bilateral iliolumbar ligaments transected.
 The representative values of the increased motions, compared with intact, after transection of the bilateral iliolumbar ligaments were 1.7 degrees (23%) in flexion, 1.1 degrees (20%) in extension, 0.3 degrees (18%) in axial rotation, and 1.2 degrees (29%) in lateral bending.
 The most restricted motion governed by the iliolumbar ligament in the lumbosacral junction was lateral bending.
 The bilateral iliolumbar ligament specimen could restrict flexion and extension of the lumbosacral junction, but the unilateral iliolumbar ligament preparation alone could not restrict these motions.
 The iliolumbar ligament also had the function of restricting the rotational movement of the lumbosacral junction.
",22
3776,"Biomechanical evaluation of lumbar spinal stability after graded facetectomies.
 In an in vitro experiment using fresh human lumbar functional spinal units, the effects of the division of the posterior ligaments (consisting of the supraspinous/interspinous ligaments) and graded facetectomies were investigated.
 The graded facetectomies consisted of unilateral and bilateral medial facetectomies, and unilateral and bilateral total facetectomies.
 Six kinds of moments were applied and ranges of motion (ROM) and neutral zones (NZ) were determined three-dimensionally by stereophotogrammetric methods.
 Range of motion was not affected by the division of the supraspinous/interspinous ligaments for all load modes.
 In flexion, ROM increased slightly after unilateral medial facetectomy.
 In right axial rotation, ROM increased after left unilateral total facetectomy.
 Range of motion was not affected, even by bilateral total facetectomies, in extension and lateral bendings.
 This study suggested that medial facetectomy does not affect lumbar spinal stability, and conversely, total facetectomy, even created unilaterally, makes the lumbar spine unstable.
",22
3777,"Red cell antibodies arising from solid organ transplants.
 RBC antibodies arising from transplanted organs and directed against recipient RBCs represent a well-established immunohematologic complication of solid organ transplantation.
 In ABO-unmatched organs, the frequency and severity of graft antibodies and hemolysis generally increase with the size (lymphoid content) of the organ, from kidney to liver to heart-lung transplants.
 In the cases reviewed here, the frequency of hemolysis increased in cyclosporine-treated kidney transplant recipients and O-to-A liver transplant recipients and decreased in group AB liver transplant recipients and kidney transplant recipients receiving azathioprine or low-dose postoperative graft irradiation.
 Available data cannot otherwise distinguish which cyclosporine-treated recipients of ABO-unmatched kidneys and livers (30-40% of total) will develop graft antibody.
 There has been no conclusive effect to date of the age, race, or gender of the donor or the recipient, of cadaver versus living kidney donors, or of patients' A2 or secretor status.
 In a few cases of living-donor kidney grafts, the donor was the patient's mother or wife who had been exposed to the recipient's RBC antigens via pregnancy.
 The ABO antibodies are typically IgG, appear 7 to 10 days after transplantation, and last for about a month.
 If immediate-spin crossmatching is done routinely, DATs are recommended in compatibility testing after ABO-unmatched transplants.
 Changes in the immunosuppressive regimen, such as a change from cyclosporine therapy, have not affected the duration of these antibodies.
 Most patients require only transfusions for this self-limited process, but six cases of hemolysis-induced acute renal failure have been reported, and one death was attributed to complications of hemolysis.
 RBC or plasma exchange has been performed in a few fulminant cases.
 RBCs of the donor's blood type are given when antibody appears.
 Some workers recommend such transfusion as prophylaxis at the time of surgery, although in liver transplants, the plasma accompanying a large amount of group O RBCs given perioperatively might be problematic.
 In several other centers, ABO-unmatched liver transplants have equivalent overall graft survivals, but the Pittsburgh adult patients with hemolysis have had reduced early graft survival.
 In the cases reviewed here, nine IgG Rh antibodies from kidney grafts directed against recipient RBCs have been observed, usually beginning 2 to 3 weeks after a cyclosporine-treated transplant, lasting for 2 to 6 months after operation, and causing mild hemolysis.
 One case represented a primary immune response from a previously unsensitized donor.(ABSTRACT TRUNCATED AT 400 WORDS).
",22
3778,"Association between hypothermia and mortality rate of premature infants--revisited.
 The incidence of hypothermia (axillary temperature less than 35 degrees C) on admission of an infant to a neonatal intensive care unit was retrospectively analyzed in 559 very-low-birth-weight (less than 1500 gm) newborn infants.
 The smaller infants were at greater risk of hypothermia.
 Only in the larger neonates was mortality related to hypothermia, which suggests that this known association bears little cause-effect relationship.
",22
3779,"Myocardial epinephrine sensitization with subanesthetic concentrations of halothane in dogs.
 The authors investigated myocardial epinephrine sensitization by subanesthetic concentrations of halothane.
 The dose-response relationship for the action of halothane was examined with etomidate plus varying subanesthetic concentrations of halothane in dogs.
 The arrhythmogenic threshold of epinephrine was decreased in a dose-dependent manner at end-tidal concentrations of halothane between 0.1 and 0.3%.
 At end-tidal halothane is greater than 0.3%, and no further reduction of arrhythmogenic threshold of epinephrine occurred.
 The plasma concentrations of epinephrine producing four or more premature ventricular contractions in 15 s were 201.3 +/- 34.3, 98.1 +/- 13.9, 60.3 +/- 8.63, 57.9 +/- 12.8, 54.5 +/- 8.61, and 53.9 +/- 4.86 ng/ml (mean +/- SEM), at 0, 0.1, 0.3, 0.5, 1.0, and 1.5% of halothane at end-tidal concentrations, respectively.
 The results suggest that in the presence of etomidate, halothane produces myocardial sensitization to epinephrine at subanesthetic concentrations as low as 0.1%.
 Increasing halothane to 0.3% produces a further reduction in the arrhythmogenic dose of epinephrine.
",22
3780,"Endothelium-derived relaxing factor inhibits hypoxic pulmonary vasoconstriction in rats.
 The hypothesis that endothelium-derived relaxing factor (EDRF) modulates hypoxic pulmonary vasoconstriction (HPV) was tested in isolated, blood-perfused rat lungs ventilated with gas mixtures of 21% O2-5% CO2-74% N2 (normoxia) or of 3% O2-5% CO2-92% N2 (hypoxia); 30 microM NG-monomethyl-L-arginine (L-NMMA), an inhibitor of EDRF production, caused a reduction in the endothelium-dependent relaxant response to acetylcholine (ACh) from 62 +/- 7, 88 +/- 4, and 100 +/- 4% to 26 +/- 8, 49 +/- 12, and 75 +/- 7% at ACh concentrations of 1, 10, and 100 microM, respectively (p less than 0.05 at all concentrations), indicating that L-NMMA acts via the inhibition of EDRF production.
 L-NMMA induced a concentration-related augmentation in HPV of 20 +/- 5, 32 +/- 8, and 34 +/- 8% at concentrations of 30, 300, and 1,000 microM (p less than 0.05, compared with a vehicle control group at all concentrations).
 The pressor response to a dose of angiotensin II (A-II), which produced the same increase in pulmonary artery pressure as that induced by hypoxia, was also significantly augmented (2 +/- 0.6%), but to a lesser extent.
 The augmentation of HPV by 30 microM L-NMMA was completely reversed by 1 mM L-arginine (a precursor of EDRF), but not by D-arginine (an isomer of L-arginine).
 One and 6 mM L-arginine, but not 6 mM D-arginine caused a significant inhibition of HPV by 20 +/- 2 and 47 +/- 12% (p less than 0.05, compared with the vehicle control group) and a small but not significant reduction in A-II-mediated contraction.
",22
3781,"The neural substrate of memory impairment demonstrated by the intracarotid amobarbital procedure.
 The intracarotid amobarbital sodium (Amytal) procedure (IAP) was performed for 46 patients with temporal lobe epilepsy (21 with left seizure foci; 25 with right seizure foci).
 After anteromedial temporal lobectomy, neuronal densities were established for hippocampal subfields CA1, CA2, and CA3; the hilum; and the dentate granule cell layer.
 Intracarotid amobarbital procedure memory results were related to CA3 neuronal loss only.
 Patients who did not demonstrate memory after injection contralateral to the seizure focus had significantly fewer cells in CA3 than patients who did.
 Additionally, a significant correlation was observed between the intracarotid amobarbital procedure memory examination raw score after injection contralateral to the seizure focus and CA3 cell density.
 Using chi 2 analysis, significant differences were documented in the frequency with which memory was demonstrated after injection contralateral to the seizure focus for groups of patients classified by degree of CA3 neuronal loss.
 This finding supports prior research showing subfield specificity in some memory processes.
",22
3782,"Memory complaints in older adults. Fact or fiction?
 Complaints of poor memory by patients may be an early symptom of a pathologic process like Alzheimer's disease.
 It is therefore important to determine if patients' complaints of memory impairments are an accurate reflection of real memory disturbance.
 The relationship between memory complaints (metamemory) and objective memory performance, mood, age, verbal intelligence, and sex was examined in a group of 199 healthy, community dwelling adults (39 to 89 years old).
 Memory complaints demonstrated a stronger association with depressed mood than with performance on memory tests.
 Increasing reports of depressive symptoms were associated with more overall memory complaints.
 Verbal intelligence, age, and sex also contributed to memory complaints.
 Patients with higher verbal intelligence reported fewer complaints and placed less emphasis on forgetting.
 Older individuals reported greater frequency of forgetting and greater frequency of using memory techniques.
 Specific types of memory complaints, seriousness of forgetting, and types of memory aids employed are also described.
 These results showed that self-rating of memory disturbance by older adults may be related more to depressed mood than to poor performance on memory tests.
",22
3783,"Clinical choices for circulatory assist devices.
 Approximately 1.0% of open heart surgery patients become unweanable from cardiac bypass during the surgical procedure.
 In addition, nearly 20% of patients accepted for cardiac transplantation die while waiting for a donor heart.
 Pulsatile pneumatic ventricular assist devices (VADs) provide a realistic solution to these dilemmas.
 Currently, there are five manufacturers who are competing for the major market share in the clinical use of these devices.
 Novacor, Thermetics, Thoratec, Symbion, and Abiomed all have competitive VAD systems.
 Because no one system is optimal for all patients, the limitations, similarities, and strengths of each system should be known to enhance the patient's outcome when using these devices.
 Successful use of VAD systems, either as a bridge to transplantation or to ventricular recovery, is best approached by adherence to strict patient selection.
 Once instituted, VAD management centers on detailed attention to anticoagulation and prompt diagnosis and treatment of various complications.
",22
3784,"The deoxyribonucleic acid regions involved in the hormonal regulation of thyroglobulin gene expression.
 Transcription of the thyroglobulin (TG) gene is stimulated by TSH via cAMP.
 We have characterized the sequence elements responsible for the hormone-dependent expression of TG gene in rat thyroid FRTL-5 cells using internal deletion and linker-scanning mutants of the minimal TG promoter (-170 basepairs) fused with the bacterial chloramphenicol acetyltransferase reporter gene.
 The TG gene is regulated by at least two regions located between -165 and -140 bp (TG-III) and between -95 and -65 bp (TG-I) from the transcription initiation site.
 The intervening region can be deleted without significant effect on the promoter activity.
 Either of the two regions alone does not promote hormone-dependent transcription.
 A DNase footprinting assay showed that TG-I and TG-III are the principal protein-binding sites and that the proteins interacting with these two regions are induced by TSH or cAMP.
 These results suggest that the hormone-dependent expression of TG gene may be achieved by cooperative interaction of the proteins bound to TG-I and TG-III.
",22
3785,"The effect of surgical stress on the in vitro metabolism of thyroxine by rat liver, kidney, and brain.
 In man, acute stress, like extensive surgery, leads to a rapid and prolonged decrease in serum T3 concentrations.
 The present study was carried out to investigate the mechanisms that underly the abrupt decrease in T3-neogenesis that occurs in response to acute surgical stress.
 Male Sprague-Dawley rats, surgically thyroidectomized, and treated with 1.2 micrograms T4/100 g BW/day, underwent wide vertical and horizontal incisions extending into the abdominal cavity while receiving light ether anesthesia.
 Different dietary manipulations were performed to investigate the superimposed influence of reduced carbohydrate and caloric intake on T3-neogenesis.
 The metabolism of 125I T4 labeled in its outer (phenolic) ring was investigated in liver, kidney, and brain homogenates of animals killed 48 h after surgery.
 In liver, values for the proportion of T4 degraded and the percent generation of T3 and iodide were unaffected by laparotomy.
 The percent T3 generation in experiments with 25 nM T4 concentration was 3.7 +/- 1.24% (mean +/- SD) in fed control animals given free access to 5% glucose, 3.4 +/- 0.67% in unoperated controls given a restricted amount of chow and 5% glucose, and 3.8 +/- 0.67% in operated animals given free access to chow and 5% glucose.
 As expected, T3 neogenesis in livers from unoperated animals was significantly reduced in rats fasted for 48 h and this reduction was similar in laparotomized rats fasted for 48 h after surgery.
 As in the liver, no effect of laparotomy on T4 metabolism in kidney and brain homogenates was observed.
 Finally, serum total T4 and T3 concentrations were not affected by surgery.
 It is concluded that acute surgical stress in thyroidectomized T4 replaced rats does not influence T4 metabolism in liver, kidney, and brain homogenates or affect the serum T4 and T3 concentrations.
 Since thyroid secretion of T4 (and T3) was eliminated and careful attention was paid to caloric intake in this rat model, previously reported abnormalities in serum thyroid hormone concentrations and T3-neogenesis in various states of nonthyroidal illness in man and rat, including surgery, are probably contributed to by thyroid secretion of T4 (and T3) and caloric deprivation, especially carbohydrate.
",22
3786,"The rat glucagon gene is regulated by a protein kinase A-dependent pathway in pancreatic islet cells.
 A cAMP response element (CRE) has been identified in the proximal 5'-flanking region of the rat glucagon gene, and activation of the cAMP-dependent pathway in fetal rat intestinal cells leads to an increase in the levels of glucagon mRNA transcripts.
 In contrast, the human glucagon gene does not contain a similar CRE, and the results of studies using immortalized rat and hamster islet cell lines have suggested that glucagon gene expression may not be regulated by cAMP.
 To reconcile these observations, we have studied the control of glucagon gene expression.
 Incubation of primary rat islet cell cultures with forskolin in the presence of low (0.5 g/liter) or high (2.0 g/L) glucose resulted in a 2- to 3-fold increase in the levels of glucagon mRNA transcripts.
 Forskolin also stimulated the secretion and synthesis of immunoreactive glucagon.
 The importance of the protein kinase-A-dependent pathway in the regulation of glucagon gene expression was also examined in hamster islet InR1-G9 cells.
 Cotransfection of a glucagon-chloramphenicol acetyltransferase (CAT) fusion gene containing the glucagon CRE and a cDNA encoding the catalytic subunit of protein kinase-A resulted in stimulation of glucagon-CAT activity in hamster islet cells.
 Catalytic subunit cotransfection also activated somatostatin-CAT, but no activation of RSVCAT was detected.
 The results of these experiments suggest that the rat glucagon gene is regulated by a protein kinase-A-dependent pathway in the endocrine pancreas.
",22
3787,"Sympathetic neural adjustments to stress in physically trained and untrained humans.
 The purpose of this study was to determine if the state of physical training influences sympathetic neural activation during acute stress in humans.
 We recorded muscle sympathetic nerve activity (microneurography of the peroneal nerve), arterial blood pressure, and heart rate in 12 highly trained, endurance athletes (25 +/- 1 years, mean +/- SEM) and 12 untrained subjects (27 +/- 1 years) before (supine rest control) and during: 1) lower body negative pressure at -5, -10, -15, and -20 mm Hg (orthostatic stress); 2) isometric handgrip at 30% of maximum (exercise stress); and 3) hand immersion in ice water, that is, the cold pressor test (thermal stress).
 Body weight was not different in the two groups, but the athletes had a lower body fat content (8.9 +/- 1.3% versus 16.1 +/- 2.0%, p less than 0.05).
 During supine rest, muscle sympathetic nerve burst frequency (24 +/- 3 versus 24 +/- 2 bursts/min, athletes versus untrained subjects) and burst incidence (36 +/- 3 versus 44 +/- 4 bursts/100 heart beats) and arterial blood pressure were not different in the two groups, but heart rate was lower in the athletes (54 +/- 2 versus 67 +/- 3 beats/min, p less than 0.05).
",22
3788,"Electrophysiologic findings after Fontan repair of functional single ventricle.
 Cardiac arrhythmias are well recognized sequelae of the Fontan operation for complex congenital anomalies.
 In this study the electrophysiologic effects of the Fontan procedure were evaluated in 30 patients who underwent cardiac catheterization with electrophysiologic study 1.9 +/- 1.3 years (mean +/- SD) after modified Fontan repair for functional single ventricle.
 Abnormalities of sinus node or ectopic pacemaker automaticity were detected in 50% (15 patients) by determination of a prolonged corrected sinus node or pacemaker recovery time.
 Total sinoatrial conduction time was prolonged in 50% of the patients with normal sinus rhythm.
 Sinus node or ectopic atrial pacemaker function was entirely normal in only 43% of patients.
 The predominant atrial rhythm was normal sinus in 70% and ectopic atrial or junctional in 30%.
 Abnormalities of atrial effective and functional refractory periods were noted in 43% of patients and were most pronounced at faster paced cycle lengths.
 Atrial endocardial catheter mapping revealed intraatrial conduction delays between adjacent sites in 76% of the patients tested and in eight of nine patients with inducible intraatrial reentry.
 Programmed atrial stimulation induced nonsustained supraventricular arrhythmias in 10% of the 30 patients and sustained arrhythmias in 27%.
 Intraatrial reentry was the most common inducible arrhythmia and was present in seven of the eight patients with sustained and two of the three patients with nonsustained atrial arrhythmias.
 Atrioventricular conduction abnormalities were noted in 10% (three patients).
 No patient had inducible ventricular arrhythmias with programmed ventricular stimulation.
 The electrophysiologic findings after Fontan repair include abnormal sinus node function, prolonged atrial refractoriness, delayed intraatrial conduction and inducible atrial arrhythmias.
",22
3789,"Patients in a persistent vegetative state attitudes and reactions of family members.
 Patients in a persistent vegetative state (PVS) constituted approximately 3% of the population in four Milwaukee nursing homes.
 In order to understand family members' attitudes and reactions toward such patients, 33 (92%) of 36 family members of patients in PVS contacted were studied.
 The age of the patients ranged from 19 to 95 with a mean age of 73.4 +/- 17.2 years, and family members' ages ranged from 41 to 89 with a mean age of 61.8 +/- 3.3 years.
 The etiology of the PVS varied from dementia to cerebral trauma.
 The mean duration of the PVS was 54 +/- 8.4 months (range 12 to 204).
 Family members reported that they visited patients 260 times during the first year following the onset of the PVS and were still visiting at a rate of 209 visits yearly at the time of the interview.
 There was no significant correlation between the frequency of the family members visits and the duration of the PVS, the patient's or family member's age, or the family member's relationship to the patient.
 Ninety percent of patients were considered by family members to have some awareness of pain, light or darkness, environment, taste, verbal conversation, or the family member's presence.
 Most family members thought they understood the patient's medical condition, and the majority did not expect the patient to improve.
 Nevertheless, the majority of family members wanted the patient to undergo therapeutic interventions, including transfer to the acute hospital and surgery.
",22
3790,"Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex.
 Saponins were purified from Quillaja saponaria Molina bark by silica and reverse phase chromatography.
 The resulting purified saponins were tested for adjuvant activity in mice.
 Several distinct saponins, designated QS-7, QS-17, QS-18, and QS-21, were demonstrated to boost antibody levels by 100-fold or more when used in mouse immunizations with the Ag BSA and beef liver cytochrome b5.
 These purified saponins increased titers in all major IgG subclasses.
 To determine optimal dose in mice for adjuvant response, QS-7 and QS-21 were tested in a dose-response study in intradermal immunization with BSA in mice; for both of these purified saponins, adjuvant response (determined by stimulation of ELISA titers to BSA) neared maximum at doses of 5 micrograms and was shown to plateau up to the highest dose tested, 80 micrograms.
 These purified saponins vary considerably in their toxicity, as assessed by lethality in mice; the main component, QS-18, being the most toxic.
 Saponins QS-7 and QS-21 showed no or very low toxicity in mice, respectively.
 None of these saponins stimulated production of reaginic antibodies.
 The monosaccharide composition of these saponins showed similar but distinct compositions with all four containing fucose, xylose, galactose and glucuronic acid.
 Predominant differences were observed in the quantities of rhamnose, arabinose, and glucose.
 Monomer m.w.
 (determined by size exclusion HPLC) were determined to range from 1800 to 2200.
",22
3791,"Effects of site-specific mutations on biologic activities of recombinant human IL-6.
 To examine structure-activity relationships of human IL-6, we have determined the effects of specific mutations on the biologic activity of a human rIL-6 expressed in bacteria.
 Three types of mutants were examined: 1) a variant that contains serines in place of the four naturally occurring cysteines; 2) a series of cysteine-containing deletion mutants, each having a single internal 20 amino acid deletion; and 3) a cysteine-free variant containing a single 20 amino acid deletion.
 The mutants of the second type constitute a set of nonoverlapping, adjacent deletions spanning amino acids 4 through 183 of the 184 amino acids in natural human IL-6.
 All of the mutants were expressed, along with the full length, cysteine-containing analogue, in Escherichia coli as fusion proteins, joined to beta-galactosidase through a collagen linker.
 This system allows microgram quantities of the rIL-6 variants to be partially purified from small bacterial cultures without chromatographic or refolding steps.
 Each of the rIL-6 variants was released from the beta-galactosidase fusion protein with collagenase, and the recovered rIL-6 was quantitated by laser densitometry of Coomassie-stained, SDS polyacrylamide gels.
 The sp.
 ac.
 of each of the rIL-6 variants was determined using four assays: induction of IgM secretion from an EBV transformed human B cell line, induction of fibrinogen secretion from a human hepatoma cell line, induction of fibrinogen secretion from a rat hepatoma cell line, and induction of proliferation of a murine hybridoma cell line.
 Replacement of cysteines with serines reduced activity relative to cysteine-containing rIL-6 to about 20% in the rat hepatoma assay and about 3% in the mouse hybridoma assay, whereas activity in both of the human cell lines was reduced to less than 0.1%.
 These data suggest that the murine and rat cell lines are less selective than the human cell lines in their requirements for recognition of biologically active IL-6.
 Each of the deletions, except that of amino acids 4 through 23, resulted in loss of activity in all four assays.
 These results suggest that the information necessary for activity is not contained within any one portion of the IL-6 molecule, but rather that multiple segments of the protein are required for each of the biologic activities that we tested.
",22
3792,"Chronic hypomagnesemia caused by cisplatin: effect of calcitriol.
 A group of six patients with hypomagnesemia (serum magnesium less than or equal to 0.5 mmol/L), previously given treatment with cisplatin for ovarian or testicular cancer, received calcitriol at a dose of 0.5 to 1.0 microgram/day for a period of 4 weeks to determine whether treatment with this vitamin D metabolite could improve their hypomagnesemia.
 In response to treatment, the serum magnesium concentration fell progressively in association with a rise in serum and urinary calcium levels and a decrease in parathyroid hormone level.
 In a single previous report, active vitamin D metabolites markedly improved renal magnesium wasting.
 However, in the present study, increases in serum and urinary calcium levels and suppression of parathyroid hormone, factors known to decrease magnesium reabsorption, presumably overwhelmed any direct effect calcitriol may have had to enhance magnesium reabsorption, so that the net effect was a marked exacerbation of the renal magnesium wasting.
",22
3793,"Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.
 To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely.
 Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI).
 Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene.
 Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS).
 Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years.
 Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole.
 The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43).
 On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004).
 Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.
",22
3794,"Prospective, randomized comparison of ringed and nonringed polytetrafluoroethylene femoropopliteal bypass grafts: a preliminary report.
 Kinking and compression with knee flexion are thought to be one cause of failure of below-knee polytetrafluoroethylene femoropopliteal bypass.
 To prevent this problem polytetrafluoroethylene grafts externally supported with rigid rings have been developed.
 The present randomized, prospective study compared ringed and nonringed polytetrafluoroethylene grafts in 122 patients who underwent femoropopliteal bypass for severe limb ischemia.
 Patients were well matched for surgical indications and risk factors.
 There was no significant difference in the 3-year graft patency rate of ringed versus nonringed polytetrafluoroethylene femoropopliteal bypasses (74% vs 68%, p = 0.5).
 Similarly, no significant differences were found in the 3-year graft patency rates of ringed versus non-ringed above-knee (82% vs 74%, p = 0.5) or below-knee polytetrafluoroethylene femoropopliteal bypasses (68% vs 59%, p = 0.5).
 The 3-year graft patency rate of all above-knee polytetrafluoroethylene femoropopliteal bypasses was slightly greater than that of below-knee polytetrafluoroethylene femoropopliteal bypasses (76% vs 62%), but this difference was not statistically significant (p = 0.25).
 The 3-year limb salvage rate with ringed polytetrafluoroethylene grafts was 92% compared with 79% for nonringed polytetrafluoroethylene grafts, but this difference was not statistically significant (p = 0.25).
 Data to date from this study fail to support the recommendation that ringed polytetrafluoroethylene grafts be used preferentially over conventional polytetrafluoroethylene grafts in patients who require femoropopliteal bypass with a synthetic graft.
",22
3795,"Glucose-induced exertional fatigue in muscle phosphofructokinase deficiency 
 BACKGROUND.
 The exercise capacity of patients with muscle phosphofructokinase deficiency is low and fluctuates from day to day.
 The basis of this variable exercise tolerance is unknown, but our patients with this disorder report that fatigue of active muscles is more rapid after a high-carbohydrate meal.
 METHODS AND RESULTS.
 To determine the effect of carbohydrate on exercise performance, we asked four patients with muscle phosphofructokinase deficiency to perform cycle exercise under conditions of differing availability of substrate--i.e., after an overnight fast, and during an infusion of glucose or triglyceride (with 10 U of heparin per kilogram of body weight) after an overnight fast.
 As compared with fasting and the infusion of triglyceride with heparin, the glucose infusion lowered plasma levels of free fatty acids and ketones, reduced maximal work capacity by 60 to 70 percent, and lowered maximal oxygen consumption by 30 to 40 percent.
 Glucose also increased the relative intensity of submaximal exercise, as indicated by a higher heart rate at a given workload during exercise.
 The maximal cardiac output (i.e., oxygen delivery) was not affected by varying substrate availability, but the maximal systemic arteriovenous oxygen difference was significantly lower during glucose infusion (mean +/- SE, 5.5 +/- 0.3 ml per deciliter) than after fasting (7.6 +/- 0.4 ml per deciliter, P less than 0.05) or during the infusion of triglyceride with heparin (8.9 +/- 1.3 ml per deciliter, P less than 0.05).
 CONCLUSIONS.
 In muscle phosphofructokinase deficiency, the oxidative capacity of muscle and the capacity for aerobic exercise vary according to the availability of blood-borne fuels.
 We believe that glucose infusion lowers exercise tolerance by inhibiting lipolysis and thus depriving muscle of oxidative substrate (plasma free fatty acids and ketones); this impairs the capacity of working muscle to extract oxygen and lowers maximal oxygen consumption.
",22
3796,"Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I 
 BACKGROUND.
 As part of an interdisciplinary study of medical injury and malpractice litigation, we estimated the incidence of adverse events, defined as injuries caused by medical management, and of the subgroup of such injuries that resulted from negligent or substandard care.
 METHODS.
 We reviewed 30,121 randomly selected records from 51 randomly selected acute care, nonpsychiatric hospitals in New York State in 1984.
 We then developed population estimates of injuries and computed rates according to the age and sex of the patients as well as the specialties of the physicians.
 RESULTS.
 Adverse events occurred in 3.7 percent of the hospitalizations (95 percent confidence interval, 3.2 to 4.2), and 27.6 percent of the adverse events were due to negligence (95 percent confidence interval, 22.5 to 32.6).
 Although 70.5 percent of the adverse events gave rise to disability lasting less than six months, 2.6 percent caused permanently disabling injuries and 13.6 percent led to death.
 The percentage of adverse events attributable to negligence increased in the categories of more severe injuries (Wald test chi 2 = 21.04, P less than 0.0001).
 Using weighted totals, we estimated that among the 2,671,863 patients discharged from New York hospitals in 1984 there were 98,609 adverse events and 27,179 adverse events involving negligence.
 Rates of adverse events rose with age (P less than 0.0001).
 The percentage of adverse events due to negligence was markedly higher among the elderly (P less than 0.01).
 There were significant differences in rates of adverse events among categories of clinical specialties (P less than 0.0001), but no differences in the percentage due to negligence.
 CONCLUSIONS.
 There is a substantial amount of injury to patients from medical management, and many injuries are the result of substandard care.
",22
3797,"Psychometric and descriptive perspectives of illness impact over the life span.
 This article describes the development of an instrument that quantifies illness over the course of life.
 The sample was comprised of 308 women, aged 50 to 70, who were alumnae of a master's program in nursing.
 Each submitted information concerning illness experienced during each decade of life.
 Each time period was then rated multidimensionally (Duration, Discomfort, Interference, Threat to Life) to reflect the impact of the various conditions and the means by decade (Decade Impact) were computed.
 In general, after the first two decades, magnitude of ratings increased with age, indicating greater disease impact.
 Interrater reliability and internal consistency reliability of the scale were high.
 Evidence for construct validity included substantial differences between those with and without specific illness conditions, as well as correlations with hospitalization history and health self-ratings.
 In cluster analysis of patterns across decades, five distinct patterns emerged into which subjects were grouped.
",22
3798,"Benign biliary strictures: treatment with percutaneous cholangioplasty.
 Results of percutaneous balloon cholangioplasty of 17 patients with 28 benign biliary strictures were compared with those of published radiologic and surgical series to determine whether stricture location was related to therapeutic success and whether a patient should undergo percutaneous or surgical therapy.
 Treatment was considered successful if there was no anatomic evidence of recurrent stricture or need for surgery (mean follow-up, 32 months).
 Treatment was successful in all nine (100%) intrahepatic (zone 1) strictures, 11 of 12 (92%) extrahepatic-extrapancreatic (zone 2) strictures, one of three (33%) intrapancreatic (zone 3) strictures, and three of four (75%) bilienteric anastomotic (zone 4) strictures.
 Restenosis occurred in five patients; cholangioplasty was ultimately successful in two of those patients after redilation and stent placement.
 On the basis of these results and those of published radiologic and surgical series, the authors believe that cholangioplasty is the treatment of choice for zone 1 strictures and is as effective as surgery for zone 2 and 4 strictures.
 Patients with zone 2 and 4 strictures with concomitant portal hypertension or a history of multiple previous biliary surgical procedures should be considered good candidates for cholangioplasty.
 Zone 3 strictures may be better treated surgically than percutaneously.
",22
3799,"Dominant negative regulation of the mouse alpha-fetoprotein gene in adult liver.
 Transcription of the mouse alpha-fetoprotein gene is activated in the developing fetal liver and gut and repressed in both tissues shortly after birth.
 With germline transformation in mice, a cis-acting element was identified upstream of the transcription initiation site of the alpha-fetoprotein gene that was responsible for repression of the gene in adult liver.
 This negative element acts as a repressor in a position-dependent manner.
",22
3800,"Hot spots for growth hormone gene deletions in homologous regions outside of Alu repeats.
 Familial growth hormone deficiency type 1A is an autosomal recessive disease caused by deletion of both growth hormone-1 (GH1) alleles.
 Ten patients from heterogeneous geographic origins showed differences in restriction fragment length polymorphism haplotypes in nondeleted regions that flanked GH1, suggesting that these deletions arose from independent unequal recombination events.
 Deoxyribonucleic acid (DNA) samples from nine of ten patients showed that crossovers occurred within 99% homologous, 594-base pair (bp) segments that flanked GH1.
 A DNA sample from one patient indicated that the crossover occurred within 454-bp segments that flanked GH1 and contained 274-bp repeats that are 98% homologous.
 Although Alu repeats, which are frequent sites of recombination, are adjacent to GH1, they were not involved in any of the recombination events studied.
 These results suggest that length and degree of DNA sequence homology are important in defining recombination sites that resulted in GH1 deletions.
",22
3801,"Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region.
 The function of the c-Myc oncoprotein and its role in cell growth control is unclear.
 A basic region of c-Myc is structurally related to the basic motifs of helix-loop-helix (HLH) and leucine zipper proteins, which provide sequence-specific DNA binding function.
 The c-Myc basic region was tested for its ability to bind DNA by attaching it to the HLH dimerization interface of the E12 enhancer binding factor.
 Dimers of the chimeric protein, termed E6, specifically bound an E box element (GGCCACGTGACC) recognized by other HLH proteins in a manner dependent on the integrity of the c-Myc basic motif.
 Methylation of the core CpG in the E box recognition site specifically inhibited binding by E6, but not by two other HLH proteins.
 Expression of E6 (but not an E6 DNA binding mutant) suppressed the ability of c-myc to cooperate with H-ras in a rat embryo fibroblast transformation assay, suggesting that the DNA recognition specificity of E6 is related to that of c-Myc in vivo.
",22
3802,"Death and functional outcome after spontaneous intracerebral hemorrhage. A prospective study of 166 cases using multivariate analysis 
 Using death and functional status as end points, we prospectively analyzed the outcome 6 months after spontaneous intracerebral hemorrhage in 166 patients admitted to an acute-care stroke unit on the first day of their stroke.
 Seventy-one patients (43%) died, 69 (42%) had a satisfactory outcome, and 26 (16%) had a poor functional outcome.
 Early (30-day) survival was correlated with morphologic parameters on the initial computed tomogram (hemorrhage size, midline shift, and intraventricular spread of the hemorrhage), while later (6-month) survival was correlated with age.
 Using logistic regression, we found five independent predictors of satisfactory outcome at 6 months: age, hemorrhage size, intraventricular spread of the hemorrhage, limb paresis, and communication disorders.
 Of these, age was the most important predictor by far.
",22
3803,"Mild hypothermic intervention after graded ischemic stress in rats.
 We investigated the effect of mild (34 degrees C) postischemic hypothermia on hippocampal neuronal damage in 43 rats as a function of the duration of forebrain ischemia.
 Two temperatures and two durations were investigated.
 In two normothermic groups ischemia lasted 8 (n = 15) and 12 (n = 10) minutes, respectively.
 In two hypothermic groups ischemia lasted 8 (n = 9) and 12 (n = 9) minutes, respectively, and was followed immediately by the lowering and maintenance of rectal temperature to 34 degrees C for 2 hours.
 Seven days after the ischemic insult, the rats were sacrificed and the brains were prepared for histologic analysis; the percentage of necrotic neurons among the total neuronal population in selected CA1/2 sectors of the hippocampus was determined.
 There was a significant decrease in the percentage of necrotic neurons in the central (77.5% versus 55.5%, p = 0.006) and lateral (62.5% versus 38.9%, p=0.005) areas and in the overall CA1/2 sector of the hippocampus (71.8% versus 52.2%, p = 0.008) for the 8-minute hypothermic group compared with the 8-minute normothermic group.
 In contrast, no differences were detected in any area of the hippocampus between the 12-minute normothermic and the 12-minute hypothermic groups (p = 0.29-0.49).
 Our data indicate that mild postischemic whole-body hypothermia ameliorates neuronal survival when ischemia lasts 8 minutes but not 12 minutes.
",22
3804,"Increased microvascular permeability in vivo in response to intradermal injection of neutrophil-activating protein (NAP-2) in rabbit skin.
 Neutrophil-activating protein-2 (NAP-2), an NH2-terminally processed form of the platelet-release product beta thromboglobulin (beta TG), was purified to homogeneity from stimulated human blood leukocytes.
 In the presence of a vasodilator substance (PGE2, CGRP) picomolar (pmol/l) amounts of NAP-2 induced neutrophil accumulation and plasma leakage on intradermal injection in rabbit skin, whereas the longer forms, beta TG itself and connective tissue-activating peptide III (CTAP-III), had no such effect.
 NAP-2-induced increased in microvascular permeability was neutrophil dependent and fast in onset, with a half-life of 65 to 75 minutes, comparable to that previously reported for the structural-related neutrophil-activating protein-1/interleukin-8 (NAP-1/IL-8).
 However NAP-2 showed a lower potency in that more protein was needed to provoke skin reactivity.
 Nevertheless the finding that a platelet release product can elicit neutrophil-mediated inflammation further narrows the gap between thrombotic events and inflammatory disorders.
",22
3805,"Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats.
 Post-resectional hyperplasia is the phenomenon in which residual small bowel increases in size and absorptive capacity after segmental enterectomy.
 This experiment studied the effect of somatostatin analogue therapy on the development of two structural parameters of post-resectional hyperplasia in rats subjected to 40% proximal small bowel resection.
 Octreotide acetate-treated rats failed to develop increased villus height (902 +/- 50 microns) relative to saline-treated rats (1,103 +/- 98 microns).
 Augmentation of residual intestinal weight was also significantly impaired in analogue-treated rats (92 +/- 3 versus 118 +/- 5 mg/cm).
 We conclude that somatostatin analogue treatment during the early postoperative period does impair the growth of residual bowel in rats.
 These findings raise concern regarding the use of this drug for postoperative patients who have undergone massive small bowel resection in whom the process of post-resectional adaptation may be critical to allow sustenance with enteral nutrition.
",22
3806,"Prospective, randomized trial of the biofragmentable anastomosis ring. The BAR Investigational Group.
 A randomized trial was undertaken to compare the biofragmental anastomotic ring (BAR) with conventional intraperitoneal colorectal anastomotic techniques.
 Patients were randomized into one of two schemes: BAR versus sutured or BAR versus stapled anastomosis.
 There were 782 patients entered into the study and 283 patients (36%) had a sutured anastomosis, 104 patients (13%) had a stapled anastomosis, and 395 (51%) had the BAR.
 Comparison of the BAR with combined suture and stapled controls revealed no significant differences in wound complication, abscess rate, bleeding, anastomotic leaks, ileus, obstruction, or deaths.
 There were no differences in return of bowel function, return to normal diet, or hospital stay.
 Intraoperative difficulties occurred in 46 BAR patients (17%), and this was significantly higher (p less than 0.001) than for sutured (3%) but not for stapled anastomoses (11%).
 The occurrence of these problems did not adversely effect the outcome.
 The data suggest that the BAR is a safe, satisfactory alternative to sutured or stapled colorectal anastomoses.
",22
3807,"Laparoscopic guided cholecystectomy.
 Cholecystectomy remains the most effective form of therapy for patients with symptomatic cholelithiasis.
 An alternative method of gallbladder removal, laparoscopic guided cholecystectomy, was attempted in 100 patients.
 Five patients required conversion of the laparoscopic procedure to an open laparotomy for the following reasons: discovery of a pancreatic malignancy in one patient, extensive adhesions in one, presence of an aberrant accessory right hepatic duct in one, common hepatic duct injury in one, and avulsion of the cystic duct in one.
 Both ductal injuries occurred during the early phase of the clinical program.
 In those patients undergoing laparoscopic cholecystectomy, 93 were discharged within 24 hours of surgery and 94 returned to normal activity within 1 week.
 Laparoscopic guided cholecystectomy appears to offer a number of advantages in patient care as well as a significant reduction in health care expenses for gallbladder disease.
 Appropriate training in laparoscopic surgery is necessary in order to avoid operative complications.
",22
3808,"A 27-year experience with splenectomy for Gaucher's disease.
 Gaucher's disease is an inherited metabolic disorder caused by the defective activity of acid beta-glucosidase and the resultant accumulation of glucosyl ceramide-laden macrophages in the liver, bone, and spleen.
 Splenectomy is the preferred treatment for patients with Gaucher's disease who develop massive splenomegaly with accompanying hypersplenism and/or mechanical pressure symptoms.
 The charts of 48 patients with Gaucher's disease undergoing splenectomy at our institution between January 1963 and December 1989 were analyzed to determine the short- and long-term results of this procedure.
 Thirty-five (73%) patients had total splenectomy, whereas 13 (27%) patients had partial splenectomy.
 There was one postoperative death (after total splenectomy), and 13 patients (27%) had postoperative complications.
 Eleven patients (23%) presented with accelerated bone disease after total splenectomy (mean follow-up: 96 months).
 No patients having partial splenectomy (mean follow-up: 25 months) developed progressive bone disease.
 Eight patients have died since surgery.
 All four deaths due to malignant disease occurred in patients after total splenectomy.
 The results of this largest-ever reported series of splenectomy for Gaucher's disease confirm that while either total or partial splenectomy can be performed with minimal morbidity and mortality, total splenectomy is accompanied by more aggressive bone disease and a predisposition to malignancy.
 Prospective, randomized trials are needed to substantiate whether partial splenectomy is indeed the treatment of choice for splenomegaly associated with Gaucher's disease.
",22
3809,"Growth velocity before sudden infant death.
 Weight velocities of 136 infants who died from sudden infant death syndrome (SIDS) were compared with those of 136 controls matched for sex, birth weight, and type of feeding.
 It was found that the SIDS infants gained weight more slowly overall and that the differences were significantly different for infants who were not breast fed in the last two weeks in which it was possible to estimate their growth velocity.
 Breast fed infants had more periods of growth below the 25th centile than expected.
 These differences are unlikely to be useful in the prediction of which babies are likely to die from SIDS as there are frequent episodes of poor growth in infants who do not die.
",22
3810,"Are measurements of height made by health visitors sufficiently accurate for routine screening of growth?
 To find out whether measurements of height made by health visitors are sufficiently accurate for use in routine screening of children we carried out an interobserver and intraobserver reliability study.
 Height measurements were made on a group of 10 children aged 3 years old and 10 aged 4.5 years old by two sets of four health visitors.
 They used a Microtoise or wall chart and the measurements were compared with those made by a trained auxologist with a Harpenden stadiometer.
 For a single assessment of height both pieces of equipment gave reasonably accurate results.
 In a child aged 3 years, with height measured on the Microtoise as 100 cm, the true height could be expected--with 95% probability--to lie between 99.2 cm-101.8 cm.
 At the age of 4.5 years, if the measurement was 110 cm, the child's true height could be expected to lie between 108.9 cm and 111.9 cm.
 The narrowest confidence interval for the growth rate from 3 to 4.5 years was achieved with the Microtoise, taking the mean of three measurements.
 We conclude that measurements made by health visitors are sufficiently accurate for routine screening of height, and the use of such measurements for the calculation of height velocity could be improved by more structured training.
",22
3811,"Nocturnal faecal soiling and anal masturbation.
 Two cases of late onset faecal soiling as a result of anal masturbation in children who were neither mentally handicapped nor psychotic were studied.
 The role of soiling in aiding the young person and his family to avoid separating and maturing is highlighted.
 We suggest that the association of anal masturbation and resistant nocturnal soiling may be unrecognised.
",22
3812,"Systemic idiopathic fibrosis with T-cell receptor gene rearrangement.
 A case of systemic idiopathic fibrosis was analyzed by Southern blotting with probes to the immunoglobulin heavy chain and T-cell receptor genes.
 A 45-year-old man presented with bilateral neck swelling.
 He later developed lower back pain, and findings on a computed tomographic scan were consistent with idiopathic retroperitoneal fibrosis.
 A biopsy specimen of a neck lesion showed morphologic characteristics typical of idiopathic fibrosing cervicitis.
 Immunophenotyping of the lesion revealed a polymorphic lymphoid population.
 Molecular analysis with the use of probes to the immunoglobulin and T-cell receptor genes disclosed a germline DNA pattern for the immunoglobulin gene and a rearranged pattern for the T-cell receptor gene.
",22
3813,"Persistence of chronic constipation in children after biofeedback treatment.
 We investigated the efficacy of biofeedback treatment and evaluated anorectal factors that might be responsible for persistence of chronic constipation with or without encopresis in a group of 38 children with abnormal contraction of the pelvic floor during straining and persistence of chronic constipation with encopresis after conventional treatment.
 Nine children were unsuccessful in learning to relax the pelvic floor during straining with biofeedback treatment, and one patient had contraction of the pelvic floor on follow-up despite successful biofeedback treatment; none recovered.
 Twenty-eight children were able to relax the pelvic floor on follow-up; 14 recovered and 14 did not recover from chronic constipation.
 Nonrecovered patients who learned to relax the pelvic floor had significantly decreased rectal and anal responsiveness to rectal distension as compared to recovered patients during the initial and follow-up anorectal manometric study.
 Psychological factors such as social competence and behavior problems did not appear to be responsible for recovery or nonrecovery from chronic constipation and encopresis.
",22
3814,"Clinical and physiological study of anal sphincter and ileal J pouch before preileostomy closure and 6 and 12 months after closure of loop ileostomy.
 Spontaneous evolution of pouch and anal function, and absorption features has been assessed in 15 patients who underwent proctocolectomy with J ileal pouch anastomosis without conservation of a rectal muscular cuff.
 All the patients were studied before preileostomy closure and six and 12 months after the closure of the protection loop ileostomy.
 Stool frequency was identical at six and 12 months (mean +/- SEM: 5.0 +/- 0.4 and 5.3 +/- 0.5/day, respectively).
 Sixty-six percent of patients at six months and 40% of patients at 12 months need to defecate at least one time during night.
 Stool weight as well as steatorrhea decreased significantly six months after the closure of loop ileostomy (P less than 0.05).
 Mean resting anal pressure remained unchanged six and 12 months after closure of the loop ileostomy (41 +/- 6 and 45 +/- 5 cm H2O, respectively).
 Maximum squeeze anal pressures increased significantly at six (P less than 0.05) and 12 months (P less than 0.05).
 The rectoanal inhibitory reflex was always absent at the same period.
 The maximum pouch capacity increased significantly during the first six months (P less than 0.01) from 142 +/- 17 to 279 +/- 27 ml.
 The maximum infused volume during a saline continence test was not significantly different at six and 12 months; the percentage of evacuation of the reservoir and the volume at which the first ileal contraction appeared in the reservoir increased significantly (P less than 0.05) at six and 12 months.
 In conclusion, in patients with ileoanal anastomosis and pouch reservoir, the closure of the loop ileostomy is associated with spontaneous modifications of the anal and pouch parameters.
",22
3815,"Kupffer cell activation and endothelial cell damage after storage of rat livers: effects of reperfusion.
 Reperfusion injury characterized by loss of endothelial cell viability occurs after cold ischemic storage of livers for transplantation surgery.
 Here, ultrastructural changes in stored rat livers were examined by scanning and transmission electron microscopy.
 With increasing times of storage in Euro-Collins solution (4 to 24 hr) followed by 15 min of reperfusion at 37 degrees C, a sequence of structural alterations was observed involving endothelial and Kupffer cells.
 Widening of endothelial fenestrations occurred after 4 hr and progressed over 8 to 24 hr to retraction of cellular processes, ball-like rounding, sinusoidal denudation and ultrastructural derangements consistent with loss of cell viability.
 Kupffer cells exhibited progressive rounding, ruffling of the cell surface, polarization, appearance of wormlike densities, vacuolization and degranulation over a similar time course.
 By contrast, the structures of parenchymal and fat-storing cells were relatively undisturbed by cold storage and reperfusion.
 Alterations to endothelial and Kupffer cells were also studied as a function of time of reperfusion.
 After 24 hr of storage, endothelial cells showed retraction of cytoplasm before reperfusion that progressed quickly to loss of viability and denudation during reperfusion.
 Kupffer cell activation (ruffling, degranulation) during reperfusion was slower and occurred after deterioration of endothelial cells.
 Livers stored in Euro-Collins solution were also compared with livers stored in University of Wisconsin cold storage solution, an improved preservation medium for transplantation.
 University of Wisconsin solution provided better preservation of endothelial structure and markedly reduced parenchymal cell blebbing and swelling before reperfusion.
 University of Wisconsin solution also reduced Kupffer cell activation and release of lysosomal enzymes.
 In conclusion, endothelial cell deterioration followed by Kupffer cell activation occurred after increasing times of cold ischemic storage and reperfusion of rat livers.
 Both changes may contribute to the pathophysiology of graft failure caused by reperfusion-mediated storage injury.
",22
3816,"Interpleural analgesia [published erratum appears in Heart Lung 1991 Jul;20(4):413]
 Postoperative pain relief is necessary not only for patient comfort, but also to facilitate ventilation and ambulation.
 The use of opioid analgesia, either intravenously, intramuscularly, or intraspinally, may be ineffective and can cause respiratory depression.
 The administration of local anesthetics into the pleural space is a technique of providing analgesia of rapid onset and long duration.
 This analgesia is accomplished without causing the respiratory depression or sedation associated with the use of opioids.
 Because innovative analgesic methods are often selected for critically ill patients presenting after surgery in the intensive care setting, critical care nurses may encounter patients receiving local anesthetics administered via interpleural catheter.
",22
3817,"Development of a special care unit for chronically critically ill patients.
 Intensive care units (ICUs) are recognized as one of the most expensive services provided by hospitals.
 Within these ICUs are a growing population of patients whose stays are extensively prolonged because of complications or underlying chronic health conditions that are exacerbated by a critical illness.
 These patients can be described as ""chronically critically ill"" and are costly to hospitals both in terms of actual dollars and in terms of the burden of care to nurses and physicians.
 This article describes the creation of a special care unit (SCU) designed specifically to meet the needs of chronically critically ill patients.
 The SCU environment is composed of a physical design that accommodates limited technology and care aimed at family involvement and rehabilitation, a case management practice model, and a shared governance management model.
 This structure is in contrast to traditional ICU environments, which include physical layouts that allow for high technology and close monitoring of patients, a primary nursing delivery system, and a bureaucratic management model.
 A research project to compare the effects of the SCU with the effects of the traditional ICUs on nurse and patient outcomes is described.
",22
3818,"Treatment strategies in shock: use of oxygen transport measurements.
 Shock has traditionally been categorized according to its cause.
 Shock can result from hemorrhage, primary cardiac failure, central nervous system failure, trauma, or sepsis.
 Therapeutic principles have been developed for each etiologic type.
 End points for such therapy have included optimization of pulmonary capillary wedge pressure, cardiac output, blood pressure, and urine output.
 Recent investigators agree that the common denominator in each of the shock syndromes is a reduction in the amount of oxygen consumed by the cell.
 The logical therapeutic approach would be to increase oxygen delivery to support the increased metabolic demand of the cells.
 The end point of resuscitation should be optimization of oxygen delivery and oxygen consumption.
 These variables are easily calculated by using data obtained from pulmonary artery catheter and laboratory measurements.
 The physician or nurse caring for critical ill patients should have a thorough understanding of the rationale for the use of oxygen transport calculations and the methods of manipulating oxygen delivery.
 A simple explanation of these principles including the importance of hemoglobin, cardiac index, and percent saturation of hemoglobin and suggested treatment strategies are presented.
",22
3819,"Flow-volume characteristics in the pulmonary circulation.
 Isolated ferret and canine lungs were used to validate a method for assessing determinants of vascular volume in the pulmonary circulation.
 With left atrial pressure (Pla) constant at 5 mmHg, flow (Q) was raised in steps over a physiological range.
 Changes in vascular volume (delta V) with each increment in Q were determined as the opposite of changes in perfusion system reservoir weight or from the increase in lung weight.
 At each level of Q, the pulmonary arterial and left atrial cannulas were simultaneously occluded, allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation before occlusion.
 Hypoxia (inspired PO2 25 Torr) in ferret lungs, which causes intense constriction in arterial extra-alveolar vessels, had no effect on the slope of the Ps-Q relationship, interpreted to represent the resistance downstream from compliance (control 0.025 +/- 0.006 mmHg.ml-1.min, hypoxia 0.030 +/- 0.013).
 The Ps-axis intercept increased from 8.94 +/- 0.50 to 13.43 +/- 1.52 mmHg, indicating a modest increase in the effective back-pressure to flow downstream from compliant regions.
 The compliance of the circulation, obtained from the slope of the relationship between delta V and Ps, was unaffected by hypoxia (control 0.52 +/- 0.08 ml/mmHg, hypoxia 0.56 +/- 0.08).
 In contrast, histamine in canine lungs, which causes constriction in veins, caused the slope of the Ps-Q relationship to increase from 0.013 +/- 0.007 to 0.032 +/- 0.006 mmHg.ml-1.min (P less than 0.05) and the compliance to decrease from 3.51 +/- 0.56 to 1.68 +/- 0.37 ml/mmHg (P less than 0.05).
",22
3820,"Regional H2O2 concentration in rat brain after hyperoxic convulsions.
 O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2.
 In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO).
 H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3-amino-1,2,4-triazole.
 Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively.
 In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values.
 The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures.
 Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values.
 These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity.
",22
3821,"Transfection and stable transformation of adult mouse Schwann cells with SV-40 large T antigen gene.
 Cultured Schwann cells derived from adult mouse dorsal root ganglia and peripheral nerves were transfected with a plasmid containing SV-40 large T antigen gene, and 25 colonies of stable transformants were obtained, one of which was expanded and recloned.
 This transfected cell line, designated MS1, expressed SV-40 large T antigen and showed continuous cell growth with a doubling time of 27 hours.
 The MS1 cells had distinct Schwann cell phenotypes such as S-100 protein, laminin, 2',3'-cyclic nucleotide 3'-phosphodiesterase and P0 protein, as shown by immunofluorescence microscopy.
 When MS1 cells were exposed to dibutyryl cyclic adenosine-3',5'-monophosphate (dbc AMP), they extended long bipolar processes two- to ten-fold longer than those of untreated MS1 cells and frequently formed whorl-like alignments similar to palisade formations or organoid patterns observed in human Schwannomas and neurofibromas.
 These results suggest that transformed Schwann cells can be a useful model for analyzing regulatory mechanisms of Schwann cells, neuron-Schwann cell interactions and experimental Schwann cell neoplasms in vitro.
",22
3822,"Acute experimental allergic encephalomyelitis in SJL/J mice induced by a synthetic peptide of myelin proteolipid protein.
 Clinical, histologic, and ultrastructural characteristics of acute experimental allergic encephalomyelitis (EAE) induced by sensitization with a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 139-151 HCLGKWLGHPDKF were studied in SJL/J mice.
 Groups of mice were immunized with 20, 50, or 100 nmol of the peptide and were killed from seven to 28 days after sensitization or when they were moribund.
 Beginning on Day 9, the mice showed signs of EAE and the disease progressed rapidly to paralysis.
 Central nervous system (CNS) inflammation, edema, gliosis, and demyelination were found in all mice killed between Days 10 and 28 and white matter lesion areas correlated with clinical score at the time the mice were killed.
 Peripheral nerve roots and the cauda equina did not have lesions.
 Within the range studied, the severity of clinical or histologic disease was the same regardless of the PLP peptide dose.
 Two of ten mice immunized with 100 nmol and none of 14 mice given smaller doses of a synthetic peptide of mouse myelin basic protein (MBP) showed clinical EAE.
 These mice had small numbers of CNS lesions that were indistinguishable from those in PLP peptide-sensitized mice.
 These findings demonstrate that immunization of SJL/J mice with PLP peptide 139-151 produces a disease with the clinical and morphologic features of CNS tissue-, whole PLP-, whole MBP-, and MBP peptide-induced acute EAE.
 Thus, PLP is a major encephalitogen and immune reactions to epitopes of different myelin proteins may induce identical patterns of injury in the CNS.
",22
3823,"Reliability of the clinical and electromyographic examination of tendon reflexes.
 The reliability of clinical examination of the tendon reflexes was examined by studying inter-observer agreement.
 Twenty patients were examined by three neurologists.
 The briskness of the tendon reflexes in arms and legs was scored on a nine-point scale.
 In 28% of the 160 examined reflexes the observations disagreed 2 scale units or more.
 Disagreement on the presence of asymmetry occurred in 45% of the 80 reflex pairs.
 In 15% one observer judged a reflex pair to be symmetrical while another observer found asymmetry of at least 2 scale units.
 In a second experiment clinical observation of apparently asymmetrical quadriceps reflexes was compared with measurement by surface electromyography.
 A significant, semi-logarithmic relationship was found between clinical scores and measured reflex amplitudes.
 Measured reflex asymmetry always agreed with clinical asymmetry, and the magnitudes of right-left amplitude differences were correlated with the magnitude of clinically observed asymmetry.
 The bedside examination of tendon reflexes is subject to considerable inter-observer disagreement.
",22
3824,"Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment.
 In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter.
 Five patients had stage IIB disease, and 44 had stage III or IV disease.
 Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy.
 Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy.
 Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission).
 Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%.
 A subset of 10 patients received mantle radiation therapy after maximal response to MOPP.
 One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed.
 In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536).
 Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment.
 The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055).
 However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment.
",22
3825,"A variant of arteriovenous fistulas within the wall of dural sinuses. Results of combined surgical and endovascular therapy.
 Dural arteriovenous (AV) fistulas are thought to be acquired lesions that form in an area of thrombosis within a sinus.
 If the sinus remains completely thrombosed, venous drainage from these lesions occurs through cortical veins, or, if the sinus is open, venous drainage is usually into the involved sinus.
 Among 105 patients with dural AV fistulas evaluated over the the past 5 years, seven had a unique type of dural AV fistula in the superior sagittal, transverse, or straight sinus in which only cortical venous drainage occurred despite a patent involved sinus; the fistula was located within the wall of a patent dural sinus, but outflow was not into the involved sinus.
 This variant of dural AV fistulas puts the patient at serious risk for hemorrhage or neurological dysfunction caused by venous hypertension.
 Three patients presented with hemorrhage, one with progressive neurological dysfunction, one with seizures, and two with bruit and headaches.
 A combination of surgical and endovascular techniques was used to close the fistula while preserving flow through the sinus.
",22
3826,"Management of hemorrhagic complications from preoperative embolization of arteriovenous malformations.
 Endovascular embolization procedures have undergone dramatic evolution and improvement in recent years.
 Despite these advances, controversy remains regarding the optimal role of these procedures in treating cerebral arteriovenous malformations (AVM's) and whether their purpose should be as a presurgical adjunct or as primary therapy.
 This controversy risks fragmentation between disciplines in the broader efforts to improve management of cerebrovascular disorders.
 The authors report seven cases of life-threatening hemorrhages that occurred during staged invasive therapy for AVM's which illustrate the value of a unified team approach to optimize patient care.
 Each patient underwent at least one embolization procedure using polyvinyl alcohol particles, followed in two cases by the occlusion of proximal feeding vessels by platinum microcoils and in one case by the attempted detachment of an endovascular balloon.
 In three patients, catheter penetration into the subarachnoid space resulted in subarachnoid hemorrhage.
 One patient suffered rupture of a large feeding vessel during balloon inflation.
 The final three patients sustained intracranial hemorrhage 2 hours, 8 hours, and 5 days, respectively, following embolization.
 All but two patients underwent emergency craniotomy at the time of the complication.
 These cases underscore the advantages of interdisciplinary management optimizing decision-making and providing expeditious care when life-threatening complications develop.
",22
3827,"Dorsal root ganglionectomy for failed back surgery syndrome: a 5-year follow-up study.
 Dorsal root ganglionectomy has been suggested as a method for the treatment of chronic intractable radicular pain, with theoretical advantages over dorsal rhizotomy, which does not interrupt ventral root afferents.
 The indications for these procedures in patients with persistent pain following lumbosacral spine surgery are not well established.
 Long-term results have been reported infrequently, and no published series has a mean follow-up period of more than 30 months.
 The authors have reviewed their experience with a series of 13 patients with failed back surgery syndrome, in whom dorsal root ganglionectomy was performed.
 Patients were selected on the basis of clinical presentation and diagnostic root blocks suggesting a monoradicular pain syndrome.
 Follow-up data were obtained at a mean of 5.5 years following dorsal root ganglionectomy.
 Follow-up interviews to assess outcome were conducted by a disinterested third party.
 Treatment ""success"" (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in two patients at 2 years after surgery and in none at 5.5 years.
 Equivocal success (at least 50% relief, without clearcut patient satisfaction) was recorded in one patient at 2 and at 5.5 years postoperatively.
 Improvements in activities of daily living were recorded in a minority of patients.
 Loss of sensory and motor function was reported frequently by patients.
 A minority of patients had reduced or eliminated analgesic intake.
 These results suggest that dorsal root ganglionectomy has a limited role in the management of failed back surgery syndrome, and that methods to select patients to receive this procedure should be refined or alternative approaches should be considered.
",22
3828,"Intraoperative monitoring of the facial nerve during decompressive surgery for hemifacial spasm.
 In 11 consecutive patients, intraoperative electromyographic (EMG) recordings were made from the facial muscles during microvascular decompression for hemifacial spasm.
 In one patient, recordings could not be obtained for technical reasons, and two patients had no abnormality.
 In the remaining eight patients, the abnormal response resolved before decompression in two, resolved immediately at the time of decompression in five, and failed to resolve in one.
 All patients were relieved of their hemifacial spasm.
 In the five patients whose abnormalities resolved at the time of decompression, there was a precise intraoperative correlation between decompression of the nerve and disappearance of the abnormal EMG response.
 In three cases, this was a useful guide to the need to decompress more than one vessel.
 These results confirm the findings of Moller and Jannetta, support the use of this technique for intraoperative monitoring of facial nerve decompression procedures, and provide strong circumstantial evidence that vascular cross-compression is an important etiological factor in hemifacial spasm.
",22
3829,"The no-scalpel vasectomy.
 A refined method of delivering the vas deferens for vasectomy has been developed and used in China since 1974.
 This method eliminates the scalpel, results in fewer hematomas and infections, and leaves a smaller wound than conventional techniques.
 An extracutaneous fixation ring clamp encircles and firmly secures the vas without penetrating the skin.
 A sharp curved hemostat punctures and dilates the scrotal skin and vas sheath.
 The vas is delivered, cleaned and occluded by the surgeon's preferred technique.
 The contralateral vas is delivered through the same opening.
 The puncture wound contracts to about 2 mm., is not visible to the man and requires no sutures for closure.
 The reported incidence of hematoma in 179,741 men followed in China was 0.09%.
 No hematomas or infections were identified in the first 273 procedures performed by a surgeon in the United States.
 The operating time in China and for the last 50 United States procedures has ranged from 5 to 11 minutes.
 The disadvantage of the technique is the hand-on training and number of cases necessary to gain proficiency.
 However, the advantages for surgeons and patients should enhance the popularity of vasectomy.
",22
3830,"Elevation of the petrous bone caused by hyperplasia of the occipital bone presenting as hemifacial spasm: diagnostic values of magnetic resonance imaging and three-dimensional computed tomographic images in a bone anomaly.
 A case of elevation of the petrous bone due to hyperplasia of the occipital bone presenting as hemifacial spasm is reported.
 A 44-year-old man sought treatment for twitching of the buccal muscles on the right side that progressed rapidly in severity within 2 weeks of the onset.
 The anatomical details of the petrous and occipital bones were delineated clearly by computed tomographic scans of a bone window level.
 Details of the brain stem were shown by magnetic resonance images.
 The bone anomaly was displayed more realistically by three-dimensional computed tomographic reconstructions.
 The faithful representation of structures with these radiological studies should be mandatory, to prepare the surgical planning of such a complicated bone anomaly.
",22
3831,"Saccular aneurysms of the distal anterior cerebral artery.
 We report a series of 42 consecutive patients with aneurysms of the distal anterior cerebral artery (ACA).
 Of these, 36 patients had one aneurysm, 5 had two aneurysms, and one had three aneurysms.
 Thirty patients had a ruptured distal ACA aneurysm; among these patients, the size of the aneurysm was less than 5 mm in diameter in 20, 6 to 10 mm in 7, and larger than 11 mm in 3.
 Eighteen patients (42.9%) had multiple aneurysms, and distal ACA aneurysms were responsible for a subarachnoid hemorrhage in 10.
 Thirty-four patients underwent direct surgery, and 30 of these had excellent outcomes 3 months after surgery.
 The treatment of patients with distal ACA aneurysms is often technically difficult, because of their broad neck configuration and the coexistence of other aneurysms.
 Nevertheless, the present study emphasizes that distal ACA aneurysms tend to bleed, irrespective of their size, and that excellent outcomes are obtainable by direct surgery.
",22
3832,"Peritoneal closure or non-closure at cesarean.
 The value of peritoneal closure at the time of cesarean birth was evaluated prospectively.
 Two hundred forty-eight women undergoing low transverse cesarean through a Pfannenstiel skin incision were assigned to one of two groups: peritoneum open (N = 127) or peritoneum closed (N = 121).
 The mean (+/- SEM) surgical time in the open group (48.1 +/- 1.2 minutes) was significantly less than for the closed group (53.2 +/- 1.4 minutes) (P less than .005).
 There were no postoperative differences between the groups in the incidence of wound infection, dehiscence, endometritis, ileus, and length of hospital stay.
 Our study suggests that leaving the parietal peritoneum unsutured is an acceptable way to manage patients at cesarean delivery.
",22
3833,"Calmodulins with deletions in the central helix functionally replace the native protein in yeast cells.
 Deletion of Glu-84, Glu-83 and Glu-84, or Ser-Glu-Glu-Glu (residues 81-84) from the central helix of mammalian calmodulin is known to result in a 5-7 times decrease in its apparent in vitro affinities for three calmodulin-dependent enzymes.
 However, based on in vitro experiments, it is difficult to estimate how these deletions might affect in vivo cellular function.
 The yeast Saccharomyces cerevisiae, which requires calmodulin for growth, provides an excellent system to evaluate these deletion proteins in vivo.
 Based on its ability to restore normal growth characteristics to yeast cells, mammalian calmodulin is functionally identical to the yeast protein; herein we evaluate the effect of deleting residues 84, 83 and 84, or 81-84 from the central helix.
 Sequences encoding the deletion proteins and an unaltered control sequence were introduced by means of a yeast shuttle vector and were expressed under control of the yeast calmodulin promoter.
 The deletion and control calmodulins are produced at levels similar to that observed for the yeast protein, and they completely restore normal growth characteristics.
 This result suggests that the regions deleted from the central helix are not critical for activation of any yeast calmodulin target normally required for cell growth or division.
 It is likely that there are twisting and shortening motions associated with the deletions from the central helix that alter significantly the spatial relationship between the two lobes of calmodulin.
 The abilities of the deletion calmodulins to restore completely normal growth characteristics to yeast cells suggest that the lobes of all the deletion proteins can still be appropriately positioned in calmodulin-target complexes.
 This is consistent with the hypothesis that the central helix of calmodulin is analogous to a flexible tether rather than to a rigid connector between the two lobes of the molecule.
",22
3834,"The noncatalytic src homology region 2 segment of abl tyrosine kinase binds to tyrosine-phosphorylated cellular proteins with high affinity.
 Several proteins implicated in the regulation of cell proliferation contain a common noncatalytic domain, src homology region 2 (SH2).
 We have used the bacterially expressed SH2 domain of abl protein-tyrosine kinase to evaluate the ability of this domain to bind to cellular proteins.
 ablSH2 specifically bound to a number of tyrosine-phosphorylated proteins from cells transformed by tyrosine kinase oncogenes in a filter-binding assay and to a subset of those proteins in solution.
 The SH2 probe bound almost exclusively to tyrosine-phosphorylated proteins, and binding was eliminated by dephosphorylation of cell proteins.
 Free phosphotyrosine could partially disrupt SH2 binding, suggesting that phosphotyrosine is directly involved in the binding interaction.
 These results demonstrate that an SH2 domain is sufficient to confer direct, high-affinity phosphotyrosine-dependent binding to proteins and suggest a general role for SH2 domains in cellular signaling pathways.
",22
3835,"Nasal augmentation with split calvarial grafts in Orientals.
 This study reports on my experience with autogenous split calvarial grafts in nasal augmentation in 62 Orientals.
 In 78 percent of patients, the procedure was performed under local anesthesia in an outpatient setting.
 Total operating time for harvesting of split calvarial grafts ranged from 20 to 55 minutes, with a mean of 32 minutes.
 Patients ranged in age from 16 to 48 years, with a mean of 27 years.
 Follow-up was from 6 months to 8 years, with an average of 3.1 years.
 Intraoperative discomfort was uniformly low and well tolerated when local anesthesia was used.
 The complication rate was 8.0 percent, with three cases of minor seroma-hematoma formation at the bone-graft donor site.
 These were treated with aspiration.
 There were two recipient-site complications, with one case of complete bone resorption that occurred in a densely fibrotic nose with preexisting septal perforation and a case of overcorrection that was successfully rasped 1 year later.
 Because of their easy accessibility beneath the scalp, split calvarial grafts to the nose are useful in various types of nasal augmentation, and the technique is offered as a practical alternative to the use of alloplastic materials.
",22
3836,"Donor seropositivity and prednisolone therapy as risk factors for cytomegalovirus infection and disease in cyclosporin-treated renal allograft recipients.
 We attempted to assess the importance of blood transfusion, donor seropositivity, and prednisolone therapy as risk factors for cytomegalovirus infection in cyclosporin-treated renal allograft recipients.
 Primary infection was diagnosed in 27 of 86 patients (31 per cent) and recurrent infection in 27 of 79 patients (34 per cent).
 Receipt of banked blood from unselected donors after transplantation did not increase the incidence of primary infection in the few transfused patients.
 Kidney donor seropositivity and maintenance prednisolone in addition to cyclosporin were associated with increases in the incidence of primary or recurrent infection, respectively.
 Cytomegalovirus infection was clinically mild.
 Presumed bacterial pneumonias occurred in three patients with recurrent cytomegalovirus infection.
 The absence of severe cytomegalovirus disease probably reflected the minimal use of prednisolone.
 Matching of seronegative donors with seronegative recipients seemed unjustifiable in cyclosporin-treated renal transplant patients.
",22
3837,"Abdominal wall considerations and complications in reoperative surgery.
 The abdominal wall is the source of significant problems for patients undergoing multiple abdominal operations.
 The orientation of sequential incisions must be carefully considered to avoid compromise of the abdominal wall blood supply, which may result in either acute (dehiscence) or delayed (ventral hernia) complications.
 Infections are the most serious problems of the multiply operated on abdominal wall.
 These complications may range from simple wound infection to necrotizing fasciitis.
 Management may require only simple drainage of the infection or may entail extensive debridement for the necrotizing processes.
 Regardless of the cause, the multiply operated on abdominal wall may require reconstruction because of lost fascia.
 Polypropylene mesh can be employed safely and effectively for this purpose.
",22
3838,"Reoperation for biliary strictures.
 Benign bile duct strictures most often follow intraoperative injury not recognized until later.
 The ideal reconstruction entails a mucosa-to-mucosa anastomosis without tension, usually with a stent tube to maintain patency in the immediate postoperative period.
 The mortality rate for reoperation and bile duct reconstruction in patients who are not cirrhotic is approximately 2%, and success rates average 85%.
 Prevention of operative injuries by the use of cholangiography, careful dissection, and removal of the gallbladder from the fundus downward is the best treatment.
",22
3839,"Reoperation for intra-abdominal abscess.
 Reoperative procedures for patients with abscess and other septic complications remain among the most difficult management problems in general surgery.
 The diagnosis of intra-abdominal septic complications has been greatly enhanced within the last 10 years but remains imperfect and requires clinical judgment that transcends objective methods.
 Surgical drainage remains the mainstay of care for patients with postoperative intraabdominal abscess.
",22
3840,"Performance of cesarean section using absorbable staples.
 Although stapling techniques have gained wide acceptance in general surgery, they are still not commonly used in obstetrics.
 U.S.
 Surgical Corporation has introduced a stapling device suitable for use in cesarean sections.
 The copolymer staples (a blend of polylactic and polyglycolic acids) maintain their tensile strength until healing occurs and absorb without producing granulation tissue.
 The benefits include minimal trauma to tissue and reduced operating time, blood loss and postoperative morbidity.
 From July 1988 to February 1989, all patients undergoing low transverse cervical cesarean sections were randomized to either group 1 with the uterine incision performed in a routine manner or group 2 with the uterine incision cut and stapled using the Stapler.
 The preoperative management, intraoperative technique and postoperative surveillance were similar for both groups.
 The uterine incision was assessed by pelvic sonography during the postpartum period.
 Statistical analysis was performed using Fisher's exact test and chi-square analysis.
 Both groups were comparable for age, race, parity, gestational age and primary diagnosis.
 The length of the operative procedure was significantly shorter (p less than 0.05) in the stapled group.
 These patients also had a statistically significantly decreased incidence of uterine incisions and lacerations.
 All other parameters were not significantly different in the two groups.
 The stapled uterine incisions were visible by ultrasonography in more patients in the stapled group throughout the postpartum period than in the sutured group.
 Thus, stapling of the uterine incision was an acceptable alternative to traditional suturing techniques and it was possible to visualize clearly these incisions during the postpartum period.
",22
3841,"Correlation of APACHE II score, drainage technique and outcome in postoperative intra-abdominal abscess.
 The APACHE II Score was used to stratify retrospectively severity of illness in 91 patients postoperatively undergoing drainage of intra-abdominal abscesses.
 The method of initial abscess drainage (percutaneous or operative) was selected by the attending physician.
 The two groups of patients, those whose initial drainage was performed percutaneously versus operatively were similar with respect to age, sex, abscess location and, most importantly, severity of illness as assessed by the APACHE II score calculated on the day of their abscess drainage.
 Over-all, the mortality rate was 29 per cent (26 of 91 patients).
 Only 1.7 per cent of the patients with an APACHE II score of less than 15 died compared with 78 per cent when APACHE II was equal to or more than 15 (p less than 0.0001).
 Only 8 per cent of patients with APACHE II equal to or more than 15 undergoing percutaneous drainage survived compared with 30 per cent of patients who underwent surgical drainage procedures.
 While chi-square analysis demonstrated independence between outcome and drainage technique, outcome was dependent upon severity of illness (p less than 0.0005).
 Paradoxically, despite the attractiveness of a percutaneous technique for abscess drainage in the most ill patients, in this series, a better, although not statistically improved, chance for survival was noted with surgical treatment.
 We recommend that an objective severity scoring system be used whenever assessing results of treatment of intraabdominal infection and that surgical treatment not be avoided because the patient is considered to be too ill.
",22
3842,"Death by smothering and its investigation.
 This case report provides details from an extensive death investigation, the results of which led to the certification of suicidal manner of death by means of smothering in a pillow, without additional assistance from other persons or mechanical devices.
 This was the death of a chronically mentally ill person who was under currently approved professional treatment.
 Major investigative aspects of this case were the death-scene observations of the body, elimination of the possibility of homicide, and the study and analysis of the subject's psychiatric illness.
 Reasons for the uncommonness of reported deaths in this category are discussed.
",22
3843,"Death notification.
 Family notification in sudden, unexpected, and violent death is a major responsibility of law enforcement, medical examiner, and coroner offices.
 This report reviews and discusses the process and procedures utilized in death notification and provides suggestions to accomplish this difficult task more effectively.
",22
3844,"Long-term results of Ionescu-Shiley valve in the tricuspid position.
 A retrospective analysis of the long-term results of using the Ionescu-Shiley pericardial bioprosthesis in the tricuspid position was carried out on 73 patients (8 men, 65 women).
 Of these procedures, ten were tricuspid valve replacement alone and the remainder were in combination with other valve procedures.
 The mean follow-up was 9.6 years (range, 4 to 18 years).
 The mean age of the patients was 53 years (range, 27 to 78 years).
 Seventy-one of the patients suffered tricuspid valve dysfunction from rheumatic heart disease.
 There were 13 postoperative deaths (within 30 days), giving a mortality rate of 17.8%.
 The actuarial survival at 10 years was 71% +/- 4.2%.
 Of the survivors, 49 (79.6%) were in functional class I or II.
 Primary tissue valve failure in the tricuspid position occurred in 1 patient 12 years after implantation and required reoperation.
 In another patient bioprosthetic tricuspid valve endocarditis developed.
 There was no incidence of thromboembolic complications.
 We conclude that the Ionescu-Shiley pericardial bioprosthesis was a satisfactory prosthesis in the tricuspid position in patients with acquired valvar dysfunction.
",22
3845,"Dosage of haloperidol for schizophrenia.
 Eighty-seven newly admitted inpatients with schizophrenia were randomized to receive 10, 30, or 80 mg/d of oral haloperidol.
 They were treated under double-blind conditions for 6 weeks, less if their acute symptoms remitted sooner.
 Survival analysis showed no differences among the three treatments.
 Side effects were minimal in all three treatment groups, and there were no differences in side effects among the groups.
 These results suggest that dosages higher than 10 mg/d of haloperidol for most patients have no additional beneficial effect in the treatment of acute or exacerbated schizophrenia.
",22
3846,"Disordered colorectal motility in intractable constipation following hysterectomy.
 Colorectal and anal sphincter motility and electrophysiology were investigated in 14 women with profound constipation following hysterectomy and compared with an asymptomatic group of control subjects.
 Twelve patients complained of significant urinary symptoms.
 No differences in the motor function of the anal sphincters were detectable.
 The latency of the pudendoanal reflex was unchanged after hysterectomy.
 Proctometrograms demonstrated significantly increased rectal volumes and compliance in the hysterectomy group together with deficits of rectal sensory function.
 In the basal state a significant proximal-to-distal sigmoid colon motility gradient existed only in the control group.
 Following stimulation with Prostigmin, this gradient was enhanced in the control group but paradoxically reversed in the hysterectomized patients, thus constituting a functional obstruction.
 Denervation supersensitivity was demonstrable in two patients tested with carbachol provocation but not in control subjects.
 These findings suggest dysfunction in the autonomic innervation of the hindgut in some patients who had undergone hysterectomy, resulting in severe constipation.
",22
3847,"Emergent saphenous vein graft stenting for acute occlusion during percutaneous transluminal coronary angioplasty.
 This report describes the initial use in the United States of emergency intravascular stenting for the treatment of acute coronary occlusion complicating elective saphenous vein graft angioplasty.
 This case adds further support to the role of the balloon expandable stent as an effective ""bail out"" device for failed angioplasty.
",22
3848,"An alternative oxygen delivery system for infants and children in the post-anaesthesia care unit.
 This randomized controlled trial compared the compliance of a blow-by oxygen method with the standard face mask by children recovering from anaesthesia.
 The rate at which a face mask was rejected when applied to infants and children in PACU was compared with that of a proposed ""hose"" method.
 The efficacy of the ""hose"" as a method of oxygen supplementation in children at low and high risk for developing postoperative hypoxaemia was also compared with the face mask.
 Using a Nellcor N-200 pulse oximeter, 66 infants and children (mean age 2.3 yr, range 2 mo-6 yr) were continuously monitored for 30 min upon arrival in the PACU.
 Patients were randomized to receive oxygen supplementation with either the face mask or the proposed ""hose"" method.
 The results showed a greater than 80 per cent rejection of the face mask in contrast to 100 per cent compliance with the ""hose"" method.
 The SaO2 measurements following 5, 15 and 30 min of O2 supplementation with the hose were all significantly higher than the SaO2 measurements obtained on room air upon arrival to the PACU.
 Patients with pre-existing cardiopulmonary disease had a 20 per cent incidence of arterial oxygen desaturation upon arrival to the PACU versus 2.1 per cent of patients with no pre-existing disease.
 It is concluded that the ""hose"" is associated with high patient compliance and is effective in the PACU in increasing the SaO2 in children at low or high risk of developing postoperative hypoxaemia.
",22
3849,"Oxygen debt and metabolic acidemia as quantitative predictors of mortality and the severity of the ischemic insult in hemorrhagic shock.
 BACKGROUND AND METHODS: An experimental canine model of hemorrhagic, hypovolemic shock is described that uses oxygen debt and its metabolic consequences of lactic acidemia and metabolic base deficit as independent variables for the prediction of probability of death.
 RESULTS: Lactic acidemia and metabolic base deficit are compared with the conventional hemodynamic variables of BP and cardiac output (Qt) as predictors of outcome and are shown to be superior using a modified Kaplan-Meier probability statistic.
 The LD50 for oxygen debt is shown to be 113.5 mL/kg, 12.9 mmol/L for lactate, and -18.8 mmol/L for base excess (BE).
 Comparison is made between the ability of Qt, BP, shed blood, BE, and lactate to predict oxygen debt.
 CONCLUSIONS: Of the single-variable predictors, BE shows the highest explained variability.
 However, a combined prediction from both lactate and BE appears superior to the use of either alone.
 Using this regression to compute the oxygen debt, it is possible to estimate accurately the actual level of oxygen debt from the BE and lactate values obtained during hemorrhagic hypovolemia.
 From serial determinations over time of the increase in these biochemical variables above the oxygen debt baseline, it is possible to estimate the rate of oxygen debt accumulation and the time remaining until the LD50 will be reached as indicators of the severity of the total body ischemia resulting from hemorrhagic shock.
",22
3850,"Long-term postthoracotomy pain.
 We used a pain questionnaire to evaluate the prevalence and functional significance of long-term postthoracotomy pain.
 Data on 56 patients who were at least 2 months postsurgery were analyzed.
 Thirty patients (54 percent) with a median follow-up of 19.5 months had persistent pain; 26 others were pain free at a median of 30.5 months postthoracotomy.
 Pain was reported in 24 of 44 patients (55 percent) who were more than one year after surgery, 13 of 29 patients (45 percent) more than two years, six of 16 (38 percent) more than three years, and three of ten patients (30 percent) greater than four years postthoracotomy.
 Pain intensity was low, but 13 patients stated that pain ""slightly"" or ""moderately"" interfered with their lives.
 Five of 56 patients had sufficiently severe chronic pain to require either daily analgesic use, nerve blocks, relaxation therapy, acupuncture, or referral to a pain clinic.
 We conclude that long-term chest wall pain is common postthoracotomy.
 It is generally not severe, but a small proportion of patients may experience persistent, moderately disabling pain.
",22
3851,"Stress-induced adrenocorticotropin secretion: diurnal responses and decreases during stress in the evening are not dependent on corticosterone.
 To test whether the diurnal rhythm in stress responsiveness is dependent on corticosterone (B)-mediated negative feedback, the responses of intact (SHAM) and adrenalectomized (ADX) rats to restraint for 3-90 minutes or ip injection with saline in the morning (AM) and the evening (PM) were compared.
 In both SHAM and ADX rats, ACTH responses to restraint stress were larger in the AM.
 In intact rats, this could have resulted from both fast negative feedback, due to the rate of rise of B during the stress in the PM, and delayed negative feedback, due to the high basal concentrations of B before the stress in the PM.
 However, this diurnal pattern of stress responsiveness was not dependent on B, as the same relative responses to restraint and ip injection were found in ADX rats.
 To determine whether the lack of response of ADX rats in the PM to stress was due to a loss of sensitivity to endogenous secretagogues, ADX rats were given CRF + arginine vasopressin (AVP) while anesthetized with ether after 30 min of restraint.
 In both the AM and the PM, the pituitaries were able to respond to exogenous secretagogues.
 A second novel finding was that in the PM, but not the AM, plasma ACTH concentrations in the ADX rats decreased substantially during the period of restraint, despite the lack of B-mediated negative feedback.
 In the AM and the PM, ADX rats were restrained for 30 min and then stressed with ether for 6 min.
 The ACTH concentrations were not different before and after ether, suggesting that, although the pituitaries of ADX rats are able to respond to exogenous CRF + AVP after stress, an additional stress of ether exposure no longer stimulates endogenous CRF and AVP release after 30 min of restraint at either time of day.
 After 90 min of restraint in the AM and the PM, the relationship between ACTH and B was positive, not negative, providing no evidence of ongoing B-mediated negative feedback in the SHAM rats.
 Therefore, the same mechanism responsible for the decrease in ACTH secretion in ADX rats may occur in SHAM rats as well.
 From these results, we conclude that the diurnal rhythm in stress responsiveness and, in the PM in the ADX rats, the decrease in plasma ACTH during stress, are largely independent of B.
",22
3852,"The ""military family syndrome"" revisited: ""by the numbers"".
 Because concerns have been raised about high levels of psychopathology in military children, the authors used standardized psychopathology rating scales to survey 213 six-to twelve-year-old children of military parents and their parents.
 Results from children's symptom self-reports, as well as from teachers' ratings of children, indicated that children's symptom levels were at levels consistent with national norms.
 In contrast, parents' (especially mothers') ratings of children were significantly higher than national norms, as were parents' ratings of their own symptoms.
 Also, parents' own symptom reports showed somewhat stronger relationships with life stressors presumably affecting the child than did the children's and teachers' reports.
 Results suggest that parents' reports of children's symptoms may be mediated by the effects of military life stressors on the parents, but these stressors do not necessarily result in higher symptoms in the children.
 Overall results do not support the notion that levels of psychopathology are greatly increased in children of military parents.
 Further studies of military families should address the effects of rank and socioeconomic status, housing, and the current impact of life stressors on the parents as well as the children in order to avoid drawing erroneous conclusions about parts or all of the military community.
",22
3853,"Outpatient orthognathic surgery: criteria and a review of cases.
 Over a 9-year period, 87 orthognathic procedures were performed in an outpatient environment.
 Procedures performed included horizontal mandibular osteotomies, rapid palatal expansions, bilateral sagittal split osteotomies, posterior and anterior maxillary osteotomies, and Le Fort I osteotomies.
 Fourteen of these patients were subsequently admitted to a hospital for either observation or full inpatient care.
 The rates of admission varied for each of the procedures, with length of anesthesia statistically related to the frequency of admission.
 Patient selection criteria and facilities used are reviewed.
",22
3854,"Mechanisms of vein graft atherosclerosis: LDL metabolism and endothelial actin reorganization.
 We have explored the effect of arterial hemodynamics on endothelial cell morphology and low-density lipoprotein metabolism in human saphenous vein segments harvested from tissue donors.
 An arterial pulsatile perfusion system was used to impose physiologic pressures and flows for 20 hours on saphenous vein and companion (control) femoral artery segments.
 A venous perfusion apparatus was also employed for the perfusion of a second (control) saphenous vein segment for the same period of time.
 Calculations of fluid shearing and wall tensile stresses were performed and related to induced changes in endothelial cell geometry and cytoskeletal actin organization and the incorporation, degradation, and localization of intact low-density lipoprotein within the vessel wall.
 Our results indicate that, compared with native arteries and veins, a 20-hour exposure of test saphenous veins to arterial hemodynamics induced (1) a significant increase in endothelial cell luminal surface area and perimeter independent of alignment with flow, (2) disassembly of the dense peripheral band of actin with a concomitant assembly of stress fibers, and (3) a two- to fourfold elevation in the undegraded low-density lipoprotein content, localized primarily within the subendothelial intima.
 Although the exact mechanisms underlying these results are uncertain, the focal accumulation of intramural low-density lipoprotein may be related to the loss of normal barrier function during endothelial cell enlargement, which is accompanied by transient cytoskeletal reorganization during the adaptation to arterial flow.
",22
3855,"Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control.
 Transfer of a normal Chinese hamster X chromosome (carried in a mouse A9 donor cell line) to a nickel-transformed Chinese hamster cell line with an Xq chromosome deletion resulted in senescense of these previously immortal cells.
 At early passages of the A9/CX donor cells, the hamster X chromosome was highly active, inducing senescence in 100% of the colonies obtained after its transfer into the nickel-transformed cells.
 However, senescence was reduced to 50% when Chinese hamster X chromosomes were transferred from later passage A9 cells.
 Full senescing activity of the intact hamster X chromosome was restored by treatment of the donor mouse cells with 5-azacytidine, which induced demethylation of DNA.
 These results suggest that a senescence gene or genes, which may be located on the Chinese hamster X chromosome, can be regulated by DNA methylation, and that escape from senescence and possibly loss of tumor suppressor gene activity can occur by epigenetic mechanisms.
",22
3856,"Laparoscopic cholecystectomy: report of 82 cases.
 In our initial experience with 82 patients, laparoscopic cholecystectomy has shown numerous advantages over open cholecystectomy.
 Both intraoperative blood loss and postoperative need for pain medication have been minimal.
 Most patients were discharged within 24 to 36 hours and resumed normal activities within 3 to 5 days.
 The aesthetic aspect is also an obvious advantage, since the laparoscopic procedure avoids disfiguring abdominal scars.
 Previous abdominal surgery is not a contraindication to attempting this procedure.
 Based on our experience, laparoscopic cholecystectomy can be done safely on most patients who are candidates for open cholecystectomy, including the elderly, the obese, and those with acute gangrenous cholecystitis.
",22
3857,"Study of the influence of left bundle branch block on the signal-averaged electrocardiogram: a qualitative and quantitative analysis.
 To study the influence of left bundle branch block (LBBB) on the signal-averaged electrocardiogram (SAECG), quantitative and qualitative analyses of SAECG parameters were undertaken in 48 patients with electrocardiographic evidence of intrinsic LBBB and in 39 patients with a ""normal"" surface QRS duration (less than 120 msec) who underwent right ventricular pacing-induced LBBB.
 We assumed pacing of the right ventricular apex to be a suitable model of this conduction defect.
 Sustained monomorphic ventricular tachycardia (SMVT) was inducible in 16 of 48 patients with intrinsic LBBB and in 23 of 39 patients with pacing-induced LBBB.
 Utilizing a filter setting of 25 to 250 Hz, late potentials were defined as a total filtered QRS duration greater than or equal to 120 msec, a root mean square voltage in the terminal 40 msec (RMS 40) of less than or equal to 25 microV, and the duration of signals less than 40 microV (LAS 40) of greater than or equal to 38 msec.
 Only RMS 40 and LAS 40 criteria were used in patients with LBBB.
 Prolongation of LAS 40 and fragmentation of signals in the terminal portion of the filtered QRS were characteristic of all patients with LBBB aberration.
 Of those patients with intrinsic LBBB, the mean total filtered QRS duration, RMS 40, and LAS 40 for inducible and noninducible patients were significantly different (170 +/- 28, 16 +/- 10, 55 +/- 24, and 153 +/- 18 msec, 25 +/- 10 microV, 33 +/- 16.9 msec; p = 0.04, 0.009, and 0.007, respectively).
 Noninducible patients with a normal QRS duration demonstrated a 60% decrement in the mean RMS 40 value during pacing-induced LBBB.
 These changes resulted in a 59% false positive incidence of late potentials during pacing-induced LBBB.
 This correlated with a similarly low mean RMS 40 value in patients with intrinsic LBBB and no inducible SMVT, hence giving rise to a false positive incidence of late potentials of 63%.
 Since ""standard"" RMS 40 and LAS 40 criteria resulted in low specificity and positive predictive value, new parameters were selected and analyzed.
 The combination of RMS 40 less than or equal to 17 microV plus LAS 40 greater than or equal to 55 msec yielded the best overall statistical result, with a sensitivity, specificity, and total predictive accuracy of 69%, 81%, and 77%, respectively.
 In conclusion: (1) A reduction of RMS 40, prolongation of LAS 40, and fragmentation of signals in the terminal portion of the filtered QRS are characteristics of LBBB.(ABSTRACT TRUNCATED AT 400 WORDS).
",22
3858,"Short-term variability of ventricular arrhythmia and rapid assessment of drug efficacy.
 Statistical criteria for suppression and aggravation of ventricular arrhythmia were defined by means of 50 short-term drug tests performed in 24 patients.
 Each patient's spontaneous variability (SV) was evaluated by linear regression analysis of hour-to-hour changes in ectopy during 24- to 48-hour Holter monitoring.
 The response to a single oral dose of disopyramide, 300 mg, flecainide, 200 mg, and propafenone, 450 mg, was measured during a trial lasting 4 hours.
 Lidocaine was administered intravenously in incremental doses of up to 4 mg/min and was evaluated over 3 hours.
 Threshold values of ventricular arrhythmia corresponding to 95% confidence limits were calculated from baseline recordings and were used to ascertain the likelihood of a true drug effect.
 The minimum decrease in hourly ectopy indicating arrhythmia suppression averaged 90.9%, while an increase of at least 947% was required for a proarrhythmic effect.
 When these efficacy criteria were applied, 16 of 50 short-term tests revealed no drug effect.
 In contrast, when a 70% threshold derived from studies of daily variability was employed, only 7 of 50 trials were negative.
 Thus individual determination of hourly arrhythmia variability yields more stringent criteria than extrapolation from day-to-day spontaneous variation.
",22
3859,"Prosthetic valves in children and adolescents.
 The purpose of this paper is to present the short- and long-term results of prosthetic valve replacement in children.
 During a 7-year period that ended in April 1985, 186 children, ages 1 to 20 years, underwent valve replacement; there were 55 (30%) aortic valve replacements, 95 (51%) mitral valve replacements, and 36 (19%) multiple valve replacements.
 Ninety-four percent of the lesions were rheumatic in origin, 4% were congenital, and 2% were infectious.
 Of 223 valves replaced, 175 (78%) were mechanical valves and 48 (22%) were heterografts; the latter were in the mitral position in all but three patients.
 Surgical mortality rates were 3.6%, 4.2%, and 19.4% respectively for aortic valve, mitral valve, and multiple valve replacements.
 Five-year actuarial survival was 91% for aortic valve replacement, 82% for mitral valve replacement and 60% for multiple valve replacement.
 Major events included reoperation in 34 (with three deaths), progressive myocardial failure that led to death in 10, sudden unexpected death in two, thromboembolic complications in 19 (death in five), subacute bacterial endocarditis in five (two deaths), and bleeding that required transfusion in two patients.
 Five-year complication-free actuarial survival rates were 83% for aortic valve replacement, 63% for mitral valve replacement, and 57% for multiple valve replacement.
 The respective five-year complication-free survival rates were 83%, 48%, and 43%.
 Significant morbidity and mortality rates are associated with valve replacement.
 Therefore every effort should be made to preserve the native valve by plastic reparative procedures.
 When prosthetic replacement of mitral valve is contemplated, our data would suggest that heterografts should not be inserted in children 15 years of age or younger, although heterografts may be used in children over 15 years of age with the expectation of valve survival comparable to that of mechanical valves.
 When complications that are associated with anticoagulant therapy were reviewed, platelet inhibiting drugs seem quite satisfactory in patients with aortic valve replacement; patients with mitral valve replacement seem to require warfarin therapy, and warfarin must be used in patients with multiple valve replacement to reduce the risk of thromboembolic complications.
",22
3860,"Improved molecular diagnostics for ornithine transcarbamylase deficiency.
 Since the cloning of the cDNA for X-linked ornithine transcarbamylase (OTC) in 1984, diagnostic accuracy of OTC deficiency for prenatal and carrier detection has been greatly improved by the use of linkage analysis.
 However, the use of RFLP-based diagnosis is limited in this and in other new mutation diseases.
 Here we report both the use of direct mutation detection by new PCR-based techniques and our experience with linkage-based diagnosis in 18 families.
 We have previously reported the use of chemical mismatch cleavage to detect mutations first in amplified mRNA and then in genomic DNA of patients.
 This technique has now been utilized for prenatal diagnosis.
 Primers for specific amplification of OTC exons 1, 3, 5, 9, and 10 have been developed and been employed to map deletions of the OTC gene in two families.
 These primers also have been used to detect alterations in the TaqI sites found in exons 1, 3, 5, and 9.
 Four novel mutations of the OTC gene leading to abolition of a TaqI site in the OTC cDNA were discovered.
 One of these mutations is in exon 1; two lie in exon 3; and one is in exon 9.
 In addition, we have used the PCR products as probes to identify the exon-specific bands seen on Southern blots and to map the polymorphic BamHI and MspI sites, which are commonly used for linkage analysis.
 This information will facilitate the interpretation of altered band patterns seen in deletion cases and in cases of point mutations affecting restriction sites.
 Utilization of the appropriate combination of these molecular techniques permitted accurate diagnostic evaluations in 17 of 18 families.
",22
3861,"New approaches to the diagnosis, prevention, and treatment of cytomegalovirus infection after transplantation.
 Infection occurring after solid organ transplantation continues to exert a considerable detrimental effect upon patient and allograft survival.
 While the search for better targeted immunosuppressive regimens continues, we must seek to improve our ability to both diagnose and treat those infections that do occur after transplantation.
 Viral infections in general, and cytomegalovirus (CMV) infections in particular, represent an area in which substantial progress is being made.
 Improvement in diagnostic modalities has allowed more rapid and precise identification of CMV infection and disease, and the use of antiviral agents that possess activity against CMV has allowed both prophylaxis and treatment of this frequently life-threatening disease.
 The prophylactic use of presently available agents in combination and the development of less toxic, more potent anti-CMV agents should serve to further lessen the impact of CMV disease upon the field of solid organ transplantation.
",22
3862,"Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat.
 Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation.
 Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models.
 To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment.
 Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria.
 Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin.
 Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy.
",22
3863,"Arterial oxygen saturation during induction of anaesthesia 
 Three groups of 10 ASA 1 patients were studied to determine the incidence of hypoxaemia (oxygen saturation less than or equal to 90%) using pulse oximetry during induction of 'mask' anaesthesia, and whether simple oxygenation techniques could prevent its occurrence.
 We also surveyed all anaesthetists in three major hospitals to ascertain their techniques for this method of anaesthesia.
 Anaesthesia was induced in all patients with thiopentone and maintained with nitrous oxide and isoflurane.
 The first group received 33% oxygen in nitrous oxide as carrier gases, a second group a few normal breaths of 100% oxygen during thiopentone administration followed by 33% oxygen in nitrous oxide, while a third group received 100% oxygen after loss of eyelash reflex until spontaneous breathing was established.
 No patient received positive pressure ventilation before spontaneous breathing was established.
 Six of the 10 patients in the first group became hypoxaemic compared to none in the second group, and three patients became hypoxaemic in the third group.
 Thirty-seven percent of anaesthetists who responded to the survey either did not apply positive pressure ventilation before establishment of spontaneous breathing, or only did so if apnoea was prolonged.
 Only one anaesthetist fully pre-oxygenated patients lungs.
 We conclude that to avoid the likely occurrence of hypoxaemia during induction of mask anaesthesia, a minimum of a few breaths pre-oxygenation is necessary.
",22
3864,"A randomised double-blind study of interpleural analgesia after cholecystectomy.
 Continuous interpleural analgesia provided by 4 hourly injections of 20 ml bupivacaine 0.5% with adrenaline 5 micrograms/ml was compared with placebo in a randomised, double-blind study after cholecystectomy.
 All patients self-administered intravenous morphine using a patient-controlled analgesia device.
 There was a highly significant difference in mean morphine consumption between the groups (72 mg as compared with 22 mg).
 Visual analogue pain scores tended to be lower in the bupivacaine group throughout and this was significant at 2 hours.
 Respiratory function measurements were not significantly different between the groups.
 The mean peak venous plasma bupivacaine concentration after the sixth dose was 3.03 micrograms/ml and no symptoms suggestive of local anaesthetic toxicity occurred.
 It is concluded that this regimen can provide effective and continuous analgesia after cholecystectomy and that combined administration of interpleural bupivacaine and systemic morphine is more effective than morphine alone in the immediate postoperative period.
 The doses of bupivacaine required for optimal use of the technique lead to significant total plasma bupivacaine concentrations within 24 hours.
",22
3865,"Patients' expectations of patient-controlled analgesia.
 Patient-controlled analgesia is an increasingly popular method of postoperative pain relief.
 However, patients often worry about new therapies.
 Eighty ASA 1 and 2 patients aged 18-65 years were asked to list the advantages and disadvantages of using patient-controlled analgesia.
 The most important advantage as perceived by patients was the reduced time spent by nurses in giving medication, but there was concern that direct personal contact would also be lessened.
 Preservation of self control, autonomy, rapid onset of analgesia, ability to titrate analgesia and lack of injections were seen as an advantage.
 Addiction and machine faults were seen as minimal problems.
 Preservation of patient-nurse contact is of great importance to ensure success of postoperative analgesia.
",22
3866,"Patient-controlled analgesia in children.
 We report our experience in introducing patient-controlled analgesia at the Royal Hospital for Sick Children, Glasgow.
 Twenty-five children used the technique after orthopaedic or general surgery using the Graseby system.
 The pump was loaded with 1 mg/kg morphine sulphate in 50 ml.
 A bolus dose of 0.02 mg/kg (1 ml) and a lockout interval of 10 minutes were the initial settings.
 The dose used, pain and sedation scores, respiratory rate and arterial oxygen saturation were recorded.
 Ages ranged from 5-15 years (mean 9.6) and the method was used for a mean of 48 hours after operation.
 Morphine requirements averaged 26 (micrograms/kg)/hour (SD 10.6).
 Pain control was good and sedation minimal.
 Adverse effects were few and minor.
 Education of patients, parents and nurses is essential for its success and safety.
 The technique is an effective and safe means of providing good quality analgesia in school age children.
",22
3867,"Clinical efficacy of oral-transdermal clonidine combinations during the perioperative period.
 In an attempt to maintain stable levels of an alpha 2-adrenergic agonist throughout the perioperative period, two different oral-transdermal clonidine dosage regimens were administered according to a randomized, double-blind, placebo-controlled study in patients undergoing abdominal surgery.
 We determined the clinical efficacy of a high- and a low-dose clonidine regimen on sedation, hemodynamic parameters, anesthesia, and analgesia.
 The low-dose clonidine group of patients (n = 14) received a 7-cm2 clonidine transdermal patch (Catapres-TTS #2), which was supplemented with oral doses of clonidine approximately 3 micrograms.kg-1 on the evening prior to surgery and on the morning of surgery.
 The high-dose clonidine group (n = 14) received a 10.5-cm2 clonidine transdermal patch (Catapres-TTS #3) with oral clonidine approximately 4.5 micrograms.kg-1 at bedtime and 6.0 micrograms.kg-1 on the morning of surgery.
 Placebo-treated (control) patients received the same occlusive patch without active ingredient and oral placebo tablets at bedtime and on the morning of surgery.
 Preanesthetic medication included midazolam 50 micrograms.kg-1 intramuscularly (im).
 Anesthesia was induced with alfentanil 30 micrograms.kg-1 intravenously (iv), thiopental 3 mg.kg-1 iv, and vecuronium 0.1 mg.kg-1 iv, and was maintained with 70% nitrous oxide in oxygen and a continuous infusion of alfentanil 0.5 microgram.kg-1.min-1.
 Isoflurane was added when the blood pressure exceeded 110% of the patient's prestudy value.
 For pain relief postoperatively, the patients received morphine, 1-2-mg iv boluses, via a patient-controlled analgesia pump.
 The low-dose clonidine patient group had mean plasma clonidine concentrations that varied from 1.47 ng.ml-1 (preoperative) to 1.32 ng.ml-1 (postoperative day 2).
",22
3868,"Beneficial effect of upper thoracic epidural anesthesia in experimental hemorrhagic shock in dogs: influence of circulating catecholamines.
 The question as to whether reduction of plasma catecholamine concentration contributes to the beneficial effects of upper thoracic epidural anesthesia on survival during hemorrhagic shock was examined.
 Twenty-six dogs were anesthetized with halothane and nitrous oxide, and blood was withdrawn to reduce the mean arterial blood pressure (MAP) to 40 mmHg.
 The 12 dogs in group A received both upper thoracic epidural anesthesia before the hemorrhage and intravenous infusion of epinephrine (450 ng.kg-1.min-1) and norepinephrine (150 ng.kg-1.min-1) during hemorrhage.
 The 14 dogs in group B received none of these.
 At 20 min after the start of the bleeding, plasma catecholamine concentrations were increased in both groups more than ten-fold.
 There were no significant intergroup differences with respect to these concentrations at any point during the experimental period.
 During the 100-min period of hemorrhage, 1 of the 12 animals in group A and 10 of the 14 in group B died.
 A significant difference in survival was seen between the two groups over the 100-min hypotensive period (P less than 0.01 by the generalized Wilcoxon test).
 These results suggest that the survival benefit of upper thoracic epidural anesthesia cannot be explained simply by differences in the level of catecholamines in the plasma, and that perhaps differences in the level of catecholamines at the nerve endings or other factors may be more important.
",22
3869,"Memory retraining to support educational reintegration.
 A memory retraining package specifically designed to facilitate reintegration of head injured patients into an educational environment is described.
 Two adolescent patients who had severe head injuries were administered the memory retraining package approximately three months postinjury.
 A single case study and multiple baseline design was used to evaluate the efficacy of the memory retraining program.
 The results suggested that this is a promising avenue for improving memory functioning and facilitating educational reintegration, but only where moderate rather than severe memory deficits are involved.
 Studies involving groups of patients and the collection of data on generalization are required to confirm usefulness.
",22
3870,"Interleukin-6 and its receptor are expressed by human megakaryocytes: in vitro effects on proliferation and endoreplication.
 Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in the megakaryocytic differentiation.
 Recently, we have observed that IL-6 is synthesized by several human cell lines with megakaryocytic features.
 In this study, we have investigated whether a similar phenomenon occurs during normal megakaryocytic differentiation.
 Human megakaryocytes (MK) were obtained by culturing normal marrow in liquid culture with aplastic plasma (AP).
 First, an IL-6 secretion in bone marrow culture enriched in MK as well as in purified MK populations was demonstrated by a biologic assay.
 Second, IL-6 mRNA was detected in a purified population of MK by the polymerase chain reaction and dot blot analysis.
 IL-6 mRNA and protein were undetectable in platelets.
 Third, in situ hybridization procedure demonstrated the presence of IL-6 mRNA in individual immature MK.
 Fourth, IL-6 protein was detected in MK at the unicellular level by an immunoalkaline phosphatase technique using a monoclonal antibody against IL-6.
 Furthermore, the presence of IL-6 receptor (IL-6-R) on MK was demonstrated by in situ hybridization using an IL-6-R probe and in situ autoradiography after binding with [125I]-labeled recombinant IL-6.
 The IL-6 endogenously produced in liquid cultures containing normal human plasma or AP was subsequently neutralized.
 This resulted in a 50% decrease of the MK growth with a minor shift in the ploidy distribution toward lower values.
 In semisolid cultures the addition of anti-IL-6 antibodies led to a 42% decrease in colony number in cultures stimulated by IL-3 but not in other conditions of culture.
 These results suggest that normal human megakaryocytopoiesis might be regulated in part by an IL-6 autocrine loop.
",22
3871,"Molecular characterization of erythrocyte glycophorin C variants.
 Human erythrocyte glycophorin C plays a functionally important role in maintaining erythrocyte shape and regulating membrane mechanical stability.
 Immunochemical and serologic studies have identified a number of glycophorin C variants that include the Yus, Gerbich, and Webb phenotypes.
 We report here the molecular characterization of these variants.
 Amplification of glycophorin C mRNA from the Yus phenotype, using two oligonucleotide primers that span the coding domain, generated a 338-bp fragment compared with a 395-bp fragment generated by amplification of normal glycophorin C mRNA.
 Sequencing of the mutant 338-bp fragment identified a 57-bp deletion that corresponds to exon 2 of the glycophorin C gene.
 Similar analysis showed deletion of 84-bp exon 3 in the Gerbich phenotype.
 In contrast to the generation of shorter than normal DNA fragments from mRNA amplification in the Yus and Gerbich phenotypes, amplification of mRNA from the Webb phenotype generated a normal-sized fragment.
 Sequencing of this DNA fragment showed an A----G substitution at nucleotide 23 of the coding sequence, resulting in the substitution of asparagine by serine.
 This modification accounts for the altered glycosylation of glycophorin C seen in this phenotype.
 These results have enabled us to characterize glycophorin C variants in three different phenotypes that involve deletions of exons 2 and 3 of the glycophorin C gene, as well as a point mutation in exon 1 that results in altered glycosylation of this protein.
",22
3872,"Metastatic tumors of unknown origin.
 The clinical appearance of metastatic lesions without an obvious primary source for the tumor is a common event.
 Tumor Registry figures and epidemiologic data grossly understate the actual frequency of unknown primaries, because primary sites are often ""assigned"" to patients on a best-guess basis without positive proof of a tumor's origin.
 In the majority of patients whose primary tumors have continued to elude detection, the extensive use of diagnostic imaging studies fails to produce information that alters the patients' clinical course.
 Rare exceptions will be cited, but these exceptions prove the general rule.
 Imaging studies should therefore be targeted for selected patients with disseminated malignancies in whom identification of their primary tumors could benefit quality of life or length of survival.
",22
3873,"Conditioning prepulse of biphasic defibrillator waveforms enhances refractoriness to fibrillation wavefronts.
 The mechanism of biphasic waveform defibrillation threshold reduction is unknown.
 We tested the hypothesis that, during refractory period stimulation, sarcolemmal hyperpolarization by the first pulse of biphasic waveforms facilitates excitation channel recovery, which enhances graded responses produced by the second depolarizing pulse.
 This prolongs cellular refractoriness to fibrillation wavefronts when compared with a monophasic depolarizing stimulus.
 Monophasic (10 msec, rectangular wave) or symmetrical biphasic (10 msec, each pulse) current injection S2 stimuli at 1.5 and two times S1 threshold were used to scan the S1 action potential refractory period (S1 cycle length, 600 msec) in myocardial cell aggregates.
 S2 waveforms were delivered with normal and reversed polarity to test the hyperpolarizing action of biphasic waveforms.
 Responses to an S3 stimulus, which simulated a potential incoming fibrillation wavefront, were also determined.
 Results showed that biphasic S2 waveforms produced longer graded responses during and immediately after the S1 refractory period than did corresponding monophasic S2 waveforms.
 The maximum difference in response duration produced by the biphasic and monophasic waveforms was 58.6 +/- 10.0 msec (p less than 0.001).
 This maximum difference occurred 10 msec before the end of the S1 refractory period.
 The longer response durations produced by biphasic S2 also produced longer refractoriness to the S3 stimulus.
 The maximum difference in total refractoriness to S3 of 51.8 +/- 2.8 msec (p less than 0.002) occurred at the same S1S2 coupling interval as the maximum difference in S2 response duration.
 Prolonged refractoriness may protect ventricular cells from refibrillation wavefronts and act as the cellular basis for greater biphasic waveform defibrillation efficacy.
",22
3874,"Endothelium-dependent responses in long-term human coronary artery bypass grafts.
 In the present study, responses of long-term human coronary artery bypass grafts (CABGs) to known endothelium-dependent vasodilators, acetylcholine, calcium ionophore A23187, thrombin, and histamine, as well as authentic nitric oxide, the putative endothelium-derived relaxing factor, were studied.
 Sixteen CAGBs were isolated within 1-2 hours from hearts of 14 patients receiving a cardiac transplant.
 A total of 109 ring segments were prepared from these CABGs and studied in vitro.
 The duration of the CABGs ranged from 7 months to 12 years.
 Addition of acetylcholine (0.01-10 microM), calcium ionophore A23187 (0.01-1.0 microM), thrombin (0.01-1.0 unit/ml), and histamine (0.01-1.0 microM) consistently produced a dose- and endothelium-dependent relaxation, reaching a maximum of -35.3 +/- 3.3%, -45.3 +/- 5.5%, -26.9 +/- 4.8%, and -17.8 +/- 2.5% (mean +/- SEM), respectively.
 No significant difference was observed among the CABGs with different duration of transplantation, whereas the relaxant responses of different segments along the entire length of a CABG were markedly different.
 These latter differences in the endothelium-dependent responses appear to correlate inversely with the development of intimal proliferative lesions in these CABGs.
 Addition of nitric oxide (0.01-10 microM) produced a potent dose- and endothelium-independent relaxation, which was also slightly depressed in CABGs with severe intimal proliferation.
 These results demonstrate that long-term transplanted human saphenous vein grafts retain their endothelium-dependent responses and that development of severe intimal proliferative lesions, rather than the duration of the grafts, result in marked alterations in the reactivity of these transplanted CABGs.
",22
3875,"Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model.
 The effect of long-term oral administration of antiarrhythmic drugs on defibrillation energy requirements is not well understood.
 We examined the effect of clofilium, a drug that prolongs cardiac action potential duration without slowing cardiac conduction, on defibrillation energy requirements and ventricular effective refractory periods in a canine model during a 3-week period.
 Epicardial patch electrodes were implanted in 12 dogs, and baseline testing was conducted under fentanyl anesthesia on day 7.
 An oral clofilium (100 mg/day) regimen was started on day 8.
 Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery.
 Truncated trapezoidal shocks were given repeatedly at various stored energies in random order; delivered current and impedance were measured; and delivered energy was calculated.
 The energy and current for 50% success in defibrillation (E50 and I50, respectively) were determined.
 For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%, and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28, respectively.
 In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%, 24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively.
 Mean current requirements (I50) remained relatively stable compared with baseline in control animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28, respectively).
 After clofilium administration I50 decreased by 36 +/- 22%, 32 +/- 17%, and 33 +/- 17% on days 14, 21, and 28, respectively.
",22
3876,"Life table analysis of fecundity in intravenously gonadotropin-releasing hormone-treated patients with normogonadotropic and hypogonadotropic amenorrhea.
 The success of pulsatile intravenous (IV) gonadotropin-releasing hormone (GnRH) treatment in patients with normogonadotropic and hypogonadotropic amenorrhea was studied retrospectively using life table analysis.
 Two hundred forty-four ovulatory cycles in 48 normogonadotropic and hypogonadotropic patients were evaluated.
 The cumulative conception rate after 12 cycles was 93%, with a mean conception rate of 22.5% per cycle.
 Comparing cycles 1 to 6 with cycles 7 to 12, no significant difference in conception rate was observed.
 Subdivisions were made relative to the presence of additional infertility factors, history of weight loss, actual weight, estrogenic status, and primary versus secondary amenorrhea.
 The life table curves of patients either with or without other infertility factors were significantly different.
 No statistically significant differences were found in the other subdivisions.
 It is concluded that IV GnRH therapy is highly successful in patients with normogonadotropic and hypogonadotropic amenorrhea, especially if no other infertility factors are present.
",22
3877,"Response of plasma endorphins, corticotropin, cortisol, and luteinizing hormone in the corticotropin-releasing hormone stimulation test in eumenorrheic and amenorrheic athletes.
 We compared pituitary response in the corticotropin-releasing hormone (CRH) test between 9 eumenorrheic and 10 amenorrheic endurance athletes.
 The maximal oxygen capacity (VO2max), determined using an exercise test on a bicycle ergometer, was larger in amenorrheic (62.7 +/- 1.0 SE mL/min per kg) than in eumenorrheic (54.7 +/- 2.3 mL/min per kg) athletes.
 A 100 micrograms bolus of human CRH was administered intravenously, and blood samples were collected at -15, 0, 30, 60, 90, and 120 minutes.
 The mean basal concentrations of endorphins, adrenocorticotropic hormone (ACTH), and cortisol did not show significant differences between the groups.
 The cumulative response of ACTH in the CRH test was larger in eumenorrheic (7.7 +/- 1.3 pmol/L) than in amenorrheic (3.6 +/- 0.6 pmol/L) athletes, but the response of endorphins and cortisol did not differ between the groups.
 A negative correlation was found between the VO2max and the ACTH response during the CRH test in the total group of athletes.
 These findings indicated changes in the function of hypothalamic-pituitary-adrenal axis in amenorrheic athletes that can be attributed to intensive training.
",22
3878,"Evaluation and therapy of breakthrough bleeding in women using a triphasic oral contraceptive.
 This study was designed to investigate the incidence and pattern of breakthrough bleeding (BTB) in 1,259 women who were prescribed for the first time a triphasic oral contraceptive (OC, 7-7-7) and to evaluate a hypothesis of management for BTB persisting after three cycles.
 The new users were compared with a control group of 696 women who had used various OCs for at least 6 months.
 The incidence of BTB in the control group was 16.8% and in the new users was 24.9%, 17.5%, and 15.3% in the first 3 months, respectively.
 Breakthrough bleeding occurred late in the 7-7-7 package in 58% and early or midway through the package in 17% and 25%, respectively.
 We hypothesized that late-package BTB would improve if the patient was switched to a monophasic pill similar to the relatively estrogenic formulation of the beginning of the package and vice versa for early or midpackage BTB.
 Seventy women with BTB at 3 months were randomly given 0.5/35 or 1/35 for a further 3 months.
 Breakthrough bleeding was more likely (P less than 0.05) to improve in women switched to 1/35 compared with 0.5/35 regardless of where in the package BTB occurred.
",22
3879,"Steroid hormone abnormalities in women with severe idiopathic constipation.
 Patients with severe idiopathic constipation are almost exclusively women of reproductive age.
 To investigate the possibility of a sex hormone abnormality in this condition, we have compared a range of sex hormones during the follicular and luteal phases of the menstrual cycle in 23 healthy women (mean age 33 years) with those in 26 patients with severe idiopathic constipation (mean age 32 years, spontaneous bowel frequency less than one per week).
 In the patients there was a reduction in the follicular phase of progesterone (4.5 v 4 nmol/l, p = 0.006, median value, controls v patients), 17 hydroxyprogesterone (9.7 v 5.8 nmol/l, p = 0.01), cortisol (387 v 245 nmol/l, p = 0.008), testosterone (2.3 v 1.8 nmol/l, p less than 0.001), androstenedione (10.3 v 8.4 nmol/l, p = 0.02), and dehydroepiandrosterone sulphate (5.1 v 3.0 mumol/l, p = 0.03).
 In the luteal phase there was a reduction of oestradiol (483 v 350 pmol/l, p = 0.015), cortisol (322 v 242 nmol/l, p = 0.047), and testosterone (2.4 v 1.7 nmol/l, p = 0.003).
 The concentrations of sex hormone binding globulin, prolactin, luteinising hormone, and follicle stimulating hormone were not significantly different in either phase of the cycle.
 Women with severe idiopathic constipation have a consistent reduction in steroid hormones.
",22
3880,"Fatigue failure of noncemented porous-coated implants. A retrieval study.
 The causes of mechanical failure of five noncemented porous-coated components were studied.
 There were two cobalt-chromium alloy and three titanium alloy implants which fractured after 12 to 48 months.
 The implants included one acetabular component, and one femoral condylar, one patellar and two tibial components.
 Examination of the fractured surfaces revealed fatigue to be the mechanism of failure in all cases.
 The porous coating and the processes required for its fabrication had resulted in weakening and reduction of substrate thickness.
 Additional factors were stress concentration due to limited, localised bone ingrowth, and some features of the design of the implants.
",22
3881,"Micromotion of cemented and uncemented femoral components.
 We evaluated the initial stability of cemented and uncemented femoral components within the femoral canals of cadaver femurs during simulated single limb stance and stair climbing.
 Both types were very stable in simulated single limb stance (maximum micromotion of 42 microns for cemented and 30 microns for uncemented components).
 However, in simulated stair climbing, the cemented components were much more stable than the uncemented components (76 microns as against 280 microns).
 There was also greater variation in the stability of uncemented components in simulated stair climbing, with two of the seven components moving 200 microns or more.
 Future implant designs should aim to improve the initial stability of cementless femoral components under torsional loads; this should improve the chances of bony ingrowth.
",22
3882,"Repair of cartilage lesions using biological implants. A comparative histological and biomechanical study in goats.
 We report the experimental use of three different biological implants to restore articular surface defects: glutaraldehyde-fixed bovine meniscal xenograft, glutaraldehyde-fixed bovine costal cartilage xenograft, and viable osteochondral allografts.
 The grafts were implanted in the knees of 19 goats who were allowed free-field activity and were studied for up to one year.
 The natural articular surfaces of meniscal fibrocartilage provided excellent articular surfaces at all times.
 Equally good articular surfaces were restored by host tissue growth covering costal cartilage grafts at six months, but by 12 months this surface had degenerated.
 The majority of the allografts survived and integrated with the host at six months, but many showed signs of failure at 12 months.
 Only three out of seven ungrafted defects healed completely at six months and the healed surfaces were degenerating at 12 months.
",22
3883,"Successful treatment of severe premenstrual syndrome by combined use of gonadotropin-releasing hormone agonist and estrogen/progestin 
 Although abolishment of ovarian cyclicity by the use of a long-acting GnRH agonist (GnRH-a) provides effective treatment for premenstrual syndrome (PMS), its use is limited by sequellae of the resultant hypoestrogenism.
 In this study the effects of estrogen/progestin replacement on the symptomatic improvement afforded by GnRH-a were evaluated in eight women with severe PMS.
 The 8-month study design included 2 months of control, 2 months of GnRH-a alone, and 4 further months in which the exogenous steroids were replaced in randomized, double blind, placebo-controlled cross-over fashion using 1 month each of 1) conjugated equine estrogen (CEE) on days 1-25, 2) 10 mg medroxyprogesterone acetate (MPA) on days 16-25, 3) CEE (days 1-25) plus MPA (days 16-25), and 4) placebo alone.
 Mood and physical symptoms were measured daily on a valid and reliable instrument, the Calendar of Premenstrual Experiences.
 As expected, administration of GnRH-a alone resulted in a 75% improvement in luteal phase symptom scores (17.8 +/- 4.8 vs.
 4.2 +/- 1.6; P less than 0.01).
 Combined sequential administration of CEE and MPA in addition to GnRH-a was effective in maintaining the reduced symptom scores seen after GnRH-a alone and was superior to the addition of CEE alone, MPA alone, or placebo.
 This combination of CEE and MPA resulted in a 60% improvement (P less than 0.05) compared to the luteal phase of control months in both behavioral (14.1 +/- 3.9 vs.
 4.2 +/- 0.8) and total (17.8 +/- 4.8 vs.
 6.5 +/- 1.8) symptoms.
 We conclude that the undesirable consequence of ovarian steroid deficiency in the treatment of PMS by GnRH-a can be overcome by the addition of sequential estrogen and progestogen replacements without significantly reducing the effectiveness of GnRH-a in this disorder.
",22
3884,"Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children.
 Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release.
 The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg).
 In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs.
 saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs.
 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs.
 ivGHRH, 1316 +/- 183.0 vs.
 644.9 +/- 154.5 micrograms/L.h; P less than 0.03).
 In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs.
 137.1 +/- 28.2 micrograms/L.h; P less than 0.03).
 Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs.
 inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone.
 In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally.
 Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.
",22
3885,"Screening of nineteen unrelated families with generalized resistance to thyroid hormone for known point mutations in the thyroid hormone receptor beta gene and the detection of a new mutation.
 Generalized resistance to thyroid hormone (GRTH) is a syndrome characterized by impaired tissue responsiveness to thyroid hormone.
 Two distinct point mutations in the hormone binding domain of the thyroid hormone receptor (TR) beta have recently been identified in two unrelated families with GRTH.
 One, Mf, involves a replacement of the normal glycine-345 for arginine in exon 7 and another, Mh, replaces the normal proline-453 for histidine in exon 8.
 To probe for the presence of the Mf and Mh defect in 19 unrelated families with GRTH, we applied separate polymerase chain reactions using allele-specific oligonucleotide primers containing the normal and each of the two mutant nucleotides at the 3'-position.
 A total of 24 affected subjects and 13 normal family members were studied.
 The mode of inheritance was dominant in 13 families, was unknown in 5 families, and was clearly recessive in 1 family in which only the consanguineous subjects were affected.
 Primers containing the substitutions specific for Mf and Mh amplified exons 7 and 8, respectively, only in affected members of each of the two index families.
 Primers containing the normal sequences amplified exons 7 and 8 of the TR beta gene in all subjects except affected members of one family.
 In this family with recessively inherited GRTH, neither exon could be amplified using any combinations of primers and DNA blot revealed absence of all coding exons.
 These results indicate a major deletion of the TR beta gene, including both DNA and hormone binding domains.
 Since heterozygous members of this family are not affected, the presence of a single normal allele is sufficient for normal function of the TR beta.
 These data also support the hypothesis that in the dominant mode of GRTH inheritance the presence of an abnormal TR beta interferes with the function of the normal TR beta.
 Distinct mutations are probably responsible for GRTH in unrelated families.
",22
3886,"Murine mast cells synthesize basement membrane components. A potential role in early fibrosis.
 Mast cells are resident in tissues, particularly in association with endothelial and epithelial cell basement membranes, and increase at sites of inflammation, injury, and fibrosis.
 Although mast cells are known to both release and generate proinflammatory molecules in response to inflammatory stimuli, little is known about their normal biologic function.
 Here we demonstrate that IL-3-dependent mouse PT18 mast cells, mouse bone marrow-derived mast cells, and rat basophilic leukemia cells express large amounts of mRNA for collagen IV, laminin, and heparan sulfate proteoglycan.
 Western blot analysis confirmed that mast cells synthesize and secrete significant amounts collagen IV and laminin B1 and B2 chains.
 These data suggest that mast cells may contribute to normal tissue repair and/or the early overproduction of basement membrane components seen in a variety of fibrotic conditions.
",22
3887,"Nursing home patients transferred by ambulance to a VA emergency department.
 Nursing home residents are frequently transferred to hospital emergency departments.
 Delayed transfer may lead to poor outcomes.
 However, inappropriate transfer of the frail elderly may cause social and financial problems.
 We prospectively evaluated 221 consecutive ambulance transfers from community nursing homes to a VA emergency department.
 The objectives of the study were to describe the process and outcomes of transferred patients and to determine if alternative interventions were feasible.
 The results indicate that the problems of nearly half the study group could have been treated at the nursing home by a visiting physician with minimal medical equipment.
 Those admitted to the hospital (52%) were seriously ill, had prolonged lengths of stay (23.6 days), and had a high mortality rate (11%).
 Complex issues of physician reimbursement, proprietary nursing home budgeting, and day-to-day expediency appear to be involved in decisions to transport patients by ambulance to VA emergency departments.
",22
3888,"Endothelial cell adhesiveness for human T lymphocytes is inhibited by transforming growth factor-beta 1.
 Recombinant human transforming growth factor-beta (TGF-beta) was found to inhibit the adhesive phenotype of human umbilical vein endothelial cells for human PBL, purified T lymphocytes, and PHA-activated lymphoblasts.
 TGF-beta inhibited lymphocyte attachment to resting human umbilical vein endothelial cells and also to endothelial monolayers stimulated with the pro-inflammatory cytokines TNF-alpha and IL-1 beta.
 Our investigations also show that the ability of endothelial cells to respond to TGF-beta by altering their adhesiveness is lost with prolonged culture of the cells.
 However, this loss is selective as TGF-beta inhibits cell proliferation in both early and late passage endothelial cells.
 These results suggest that in vivo TGF-beta may inhibit the adhesive phenotype of endothelial cells and also may limit the immunologic response occurring at the endothelial cell barrier.
",22
3889,"Cytokine release syndrome induced by the 145-2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisolone.
 The hamster mAb 145-2C11 specific for the CD3 complex of murine T lymphocytes shares many properties with OKT3, including the induction of T cell activation.
 In vivo, the injection of 145-2C11 entails a variety of pathologic changes in relation to the systemic release of cytokines.
 We tested the effects on this cytokine release syndrome of different doses of methylprednisolone (m-PDS) given at various intervals of time before the 145-2C11 mAb.
 The administration of high doses of m-PDS (50 mg/kg) 2 to 3 h before the mAb resulted in an almost complete inhibition of the systemic release of TNF-alpha, IL-2, and IL-6.
 As far as the pathologic changes are concerned, the hypothermia, the acute renal tubular necrosis, and the fatty infiltration of the liver were completely prevented whereas the hypoglycemia was only partially attenuated.
 The protective effect of m-PDS on the toxicity of 145-2C11 was confirmed by the reduction of the mortality rate among galactosamine-sensitized mice.
 The inhibition of the release of cytokines by m-PDS did not affect the immunosuppression triggered by 145-2C11 as assessed by the CTL activity against alloantigens measured 48 h after the injection of the mAb.
 We conclude that the administration of very high doses of glucocorticoids 2 to 3 h before 145-2C11 prevents the release of cytokines and attenuates the acute toxicity of the mAb.
 Similar protocols could allow mitigation of the cytokine-release syndrome induced by the OKT3 mAb in man.
",22
3890,"The lovastatin-treated rodent: a new model of barrier disruption and epidermal hyperplasia.
 Recent studies have linked epidermal cholesterol synthesis with maintenance of the permeability barrier.
 To assess directly the importance of cholesterol synthesis, we applied lovastatin, a potent inhibitor of cholesterol synthesis, to hairless mouse skin.
 Transepidermal water loss (TEWL) began to increase after four to six daily applications.
 Co-application of cholesterol blocked the expected increase in TEWL, demonstrating the importance of cholesterol for development of the lesion.
 The histology of lovastatin-treated skin revealed epidermal hyperplasia, accompanied by accelerated DNA synthesis.
 Whereas cholesterol synthesis initially was reduced in lovastatin-treated epidermis, with further treatment cholesterol synthesis normalized, while fatty acid synthesis accelerated greatly.
 Although the total free sterol content of lovastatin-treated epidermis remained normal, the fatty acid content increased coincident with barrier disruption.
 Finally, morphologic abnormalities of both lamellar body structure and their deposited, intercellular contents occurred coincident with the emerging biochemical abnormalities.
 Thus, the abnormal barrier function in this model can be ascribed to an initial inhibition of epidermal sterol synthesis followed by an alteration in cholesterol and fatty acid synthesis, leading to an imbalance in stratum corneum lipid composition and abnormal membrane bilayer structure.
",22
3891,"Secretion of a unique collagen by spontaneously transformed murine keratinocytes (PAM cells) in vitro.
 A spontaneously transformed murine keratinocyte cell line (PAM cell) was found to secrete two nondisulfide-linked collagenous polypeptides with apparent molecular weight (MW) 190-kd and 120-kd.
 Pulse-chase experiments indicated that the 190-kd polypeptide was secreted into the culture medium in 2 h and processed to the 120-kd collagen component within 4 h.
 This process was inhibited by EDTA.
 The 120-kd polypeptide was sensitive to pepsin, and a 50-kd fragment was produced by a mild pepsin treatment at 4 degrees C.
 A cyanogen bromide peptide map of the 120-kd polypeptide was distinct from that of types I, II, III, IV, and V collagens.
 These properties indicate similarities to the type VIII-related collagen produced by human astrocytoma cells.
 The secretion of the collagen rapidly reached a maximum level on the first day of culture and subsequently declined with cell proliferation.
 An accelerated processing to the 120-kd polypeptide was observed under culture conditions of high cell density.
 Similar collagens were also found to be produced by normal human keratinocytes.
 These results indicate that the 120-kd polypeptide is a potentially functional protein that may participate in the formation of the extracellular matrix of keratinocytes.
",22
3892,"Immunopathology of olfactory mucosa following injury to the olfactory bulb.
 Removal of the olfactory bulb was performed on rats in an attempt to elucidate the processes of olfactory dysfunction following head injury.
 Degeneration and regeneration of the olfactory mucosa were examined, histopathologically and immunohistochemically.
 We used antisera to olfactory marker protein (OMP) and neuron specific enolase (NSE) as a marker of the mature olfactory receptor neurons.
 Following rapid degeneration after bulbectomy, the olfactory receptor neurons regenerated.
 OMP and NSE containing cells re-appeared 49 days later.
 However, the cell population of the neuroepithelium did not revert to the numbers observed in the non-operated neuroepithelium, even three months later.
 The lack of a connection between regenerated axons and the olfactory bulb may result in immature neuronal replacement and reduce the number of olfactory receptor neurons.
",22
3893,"Enlarged adenoid and adenoidectomy in adults: endoscopic approach and histopathological study.
 Adenoid enlargement is uncommon in adults and because examination of the nasopharynx by indirect posterior rhinoscopy is inadequate, many cases of enlarged adenoid in adults are misdiagnosed and accordingly maltreated.
 This study was conducted on 35 cases of enlarged adenoid aged between 20 and 42 years.
 The nasal endoscope was utilized to identify the adenoid mass.
 Adenoidectomy under transnasal endoscopic control was performed and all the excised material was sent for histopathological examination.
 Adenoidectomy resulted in marked improvement in 94 per cent of cases without major complications.
 Histopathological examination revealed non-specific inflammatory reaction in 15 cases (43 per cent), pure reactive changes, predominantly follicular hyperplasia, in two cases (6 per cent) and mixed pattern in 18 cases (51 per cent).
 Endoscopic follow-up for an average 17 months identified recurrence in only two patients.
 It was concluded that enlarged adenoid tissue in adults has some histopathological differences from that in children and adenoidectomy under transnasal endoscopic control is safe and reliable.
",22
3894,"Delayed positive gastrointestinal bleeding studies with technetium-99m-red blood cells: utility of a second injection.
 Two patients studied with technetium-99m-labeled red blood cells (RBCs) for gastrointestinal bleeding had positive findings only on 24-hr delayed images, at which time the site of bleeding could not be ascertained.
 In each instance, when additional delayed images suggested that active bleeding was occurring, a second aliquot of RBCs was labeled and injected.
 Sites of active hemorrhage were identified following further imaging in both patients.
 When delayed GI bleeding images are positive, further views should be obtained to ascertain if the pattern of intraluminal activity changes.
 If renewed active hemorrhage is suspected, reinjection with a second dose of labeled RBCs may identify the bleeding site.
",22
3895,"Warm heart surgery.
 Hypothermia is widely acknowledged to be the fundamental component of myocardial protection during cardiac operations.
 Although it prolongs the period of ischemic arrest by reducing oxygen demands, hypothermia is associated with a number of major disadvantages, including its detrimental effects on enzymatic function, energy generation, and cellular integrity.
 We hypothesized that the ideal protected state of the heart would be electromechanically arrested and perfused with blood, that is, aerobic arrest.
 Under these conditions the fundamental need for hypothermia becomes questionable.
 We have developed a novel approach to myocardial protection during cardiac operations based on these concepts, in which the chemically arrested heart is perfused continuously with blood and maintained at 37 degrees C.
 In 121 consecutive coronary bypass procedures we have compared this approach with a historical cohort of 133 consecutive patients treated with hypothermic cardioplegia.
 Perioperative myocardial infarction was significantly less prevalent (1.7% versus 6.8%; p less than 0.05) in the warm cardioplegic group, as was the use of the intraaortic balloon pump (0.9% versus 9.0%; p less than 0.005) and the prevalence of low output syndrome (13.5% versus 3.3%; p less than 0.005).
 Cardiac output immediately after bypass was significantly higher than before bypass (3.1 +/- 0.9 versus 4.9 +/- 1.0 L/min; p less than 0.001) only in the warm cardioplegia group.
 Furthermore, the heartbeat in 99.2% of patients treated with continuous warm cardioplegia converted to normal sinus rhythm spontaneously after removal of the aortic crossclamp compared with only 10.5% of the hypothermic group.
 The time from removal of the aortic crossclamp to discontinuation of cardiopulmonary bypass (i.e., reperfusion time) was significantly shorter in the warm cardioplegia group (11 +/- 4.3 versus 27 +/- 5.6 minutes; p less than 0.001).
 Our results suggest that continuous normothermic blood cardioplegia is safe and effective.
 Conceptually, this represents a new approach to the problem of maintaining excellent myocardial preservation during cardiac operations.
",22
3896,"Studies of controlled reperfusion after ischemia. XX. Reperfusate composition: detrimental effects of initial asanguineous cardioplegic washout after acute coronary occlusion.
 This study tests whether initial asanguineous washout of potentially toxic substances that accumulate during ischemia improves recovery produced by blood cardioplegic reperfusion and evaluates the role of plasma versus whole blood cardioplegia.
 METHODS: Twenty-four dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 20 minutes of blood cardioplegic reperfusion on total vented bypass.
 In 13 dogs, a 5-minute infusion of either a crystalloid (n = 7) or plasma (n = 6) cardioplegic solution (containing the same pH, calcium potassium, and osmolarity as blood cardioplegia) was given immediately before reoxygenation with blood cardioplegia.
 Regional oxygen uptake and coronary vascular resistance were measured during controlled reperfusion, and segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed 1 hour after bypass was discontinued.
 RESULTS: Asanguineous cardioplegic washout before reoxygenation with blood cardioplegic solution resulted in a progressive (+42%) increase in coronary vascular resistances (from 123 to 176 units, p less than 0.05) and low oxygen utilization during 20 minutes of blood cardioplegic reperfusion (29 ml/100 gm, p less than 0.05); coronary vascular resistance remained low throughout blood cardioplegic reperfusion without washout (from 109 to 98 units), and oxygen utilization was 54 ml/100 gm (p less than 0.05).
 Neither plasma nor crystalloid washout restored substantial regional systolic shortening (3% systolic shortening versus 73% systolic shortening with blood cardioplegia), and asanguineous washout caused more myocardial edema (81.1% +/- 80.9% versus 79.5% water content, p less than 0.05) and produced extensive transmural triphenyltetrazolium chloride damage (48% +/- 41% versus 8% nonstaining in area at risk, p less than 0.05) than initial blood cardioplegic reperfusion.
 CONCLUSION: Asanguineous cardioplegic washout before blood cardioplegic reperfusion limits oxygen utilization during subsequent controlled reperfusion, restricts early recovery of systolic shortening, allows more myocardial edema, and produces extensive histochemical damage, which may be avoided by initial reoxygenation with blood cardioplegia.
 The red blood cells appear more important than the plasma components of blood cardioplegia.
",22
3897,"Studies of controlled reperfusion after ischemia. XXII. Reperfusate composition: effects of leukocyte depletion of blood and blood cardioplegic reperfusates after acute coronary occlusion.
 OBJECTIVES: This study evaluates the role of leukocyte depletion during initial reoxygenation with normal blood and blood cardioplegic reperfusates in limiting reperfusion damage.
 METHODS: Twenty-eight dogs underwent 2 hours of ligation of the left anterior descending coronary artery.
 The initial reperfusate (37 degrees C) was delivered on total vented bypass to the left anterior descending artery by a calibrated pump via an internal mammary artery graft at 50 mm Hg for 20 minutes.
 Eight dogs received normal (normokalemic, nonenriched) blood reperfusion (leukocyte count 8000/mm3) and six were reperfused with leukocyte-depleted normal blood (leukocyte count less than 100/mm3).
 Of 14 dogs reperfused with substrate-enriched (hyperkalemic) blood cardioplegic solution, six received a cardioplegic solution with a leukocyte count less than 100/mm3.
 RESULTS: Leukocyte depletion of normal blood reduced reperfusion-induced arrhythmias from 63% to 17% (p less than 0.05).
 Coronary vascular resistance at initial reperfusion was low and remained low during substrate-enriched blood cardioplegic reperfusion with both normal and reduced leukocyte counts.
 In contrast, coronary vascular resistance rose 63% with normal blood reperfusion, and this increase was avoided by leukocyte depletion (2.6 versus 4.0 mm Hg x ml/min, p less than 0.05).
 Coronary vascular resistance after 20 minutes was, however, higher than that with blood cardioplegia with normal or decreased leukocyte counts.
 Negligible functional recovery followed reperfusion with normal blood and leukocyte-depleted blood (12% and 6% of control systolic shortening).
 In contrast, substantial segmental recovery followed blood cardioplegic reperfusion (73% systolic shortening, p less than 0.05) but was not improved by leukopheresis (81% systolic shortening).
 Leukocyte depletion of normal blood reperfusate reduced histochemical damage from 53% to 38% (p less than 0.05), but the least histochemical damage followed blood cardioplegic reperfusion with a normal or reduced leukocyte count (8% or 11%, p less than 0.05).
 CONCLUSIONS: These findings suggest an important role for leukocytes in reperfusion damage, but reperfusate leukocyte filtration alone is inferior to blood cardioplegic reperfusion.
 Leukocyte depletion of blood cardioplegic solutions seems unnecessary after only 2 hours of ischemia.
",22
3898,"Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.
 The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor.
 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time.
 Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim.
 Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry.
 Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%).
 The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months).
 Adverse effects were mild and could be eradicated by reduction or cessation of stimulation.
 This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.
",22
3899,"Diaphragmatic fatigue produced by constant or modulated electric currents.
 In anesthetized rabbits the efficiency of phrenic nerve stimulation with trains of electric current was studied either when ventilation was effected entirely by bilateral nerve stimulation (electrophrenic ventilation) or during unilateral nerve stimulation when animals were ventilated with a pump and open chest.
 Trains of rectangular electric pulses (RPT) with constant amplitude and frequency or sine waves, both the amplitude and frequency of which were modulated and controlled by a computer (MSWT), were used with each animal.
 MSWT closely reproduced the physiological shape of transdiaphragmatic pressure waves.
 Diaphragm fatigue, as determined from the decrease in the maximal relaxation rate of twitches, occurred after 20 minutes of bilateral or unilateral nerve stimulation with RPT, but only after 60 min (unilateral stimulation) or 98 min (bilateral stimulation) with MSWT.
 These data show the importance of the motor signal pattern in long-lasting nerve stimulation.
",22
3900,"Raf-1 protein kinase is required for growth of induced NIH/3T3 cells.
 Many growth factors regulate the cytoplasmic Raf-1 protein kinase, consistent with its having a central role in transduction of growth signals.
 The kinase is ubiquitously expressed and can promote proliferation, presumably in a manner dependent on growth-factor receptors and membrane-associated oncogenes.
 We have now examined the dependence of serum- and TPA (12-O-tetradecanoylphorbol-13-acetate)-regulated NIH/3T3 cell growth on RAF-1 kinase to determine whether Raf-1 is essential for receptor signalling.
 We inhibited Raf-1 function by expressing c-raf-1 antisense RNA or kinase-defective c-raf-1 mutants.
 Antisense RNA for c-raf-1 interferes with proliferation of normal NIH/3T3 cells and reverts raf-transformed cells.
 In revertant cells, DNA replication induced by serum or TPA was eliminated or reduced proportionately to the reduction in Raf protein levels.
 Expression of a kinase-defective Raf-1 mutant (craf301) or a regulatory domain fragment (HCR) inhibited serum-induced NIH/3T3-cell proliferation and raf transformation even more efficiently.
 Inhibition by antisense RNA or craf301 blocked proliferation and transformation by Ki- and Ha-ras oncogenes.
 We conclude that raf functions as an essential signal transducer downstream of serum growth factor receptors, protein kinase C and ras.
",22
3901,"The effect of flunarizine on essential tremor.
 We investigated the effect of flunarizine treatment (10 mg/d) in 17 subjects with essential tremor in a double-blind placebo-controlled design.
 Tremor was assessed by clinical scoring, tremographic recordings, and subjective rating by subjects.
 Of the 15 subjects who completed the study, 13 showed improvement.
 We conclude that flunarizine is effective treatment for essential tremor.
",22
3902,"A case of myelinoclastic diffuse sclerosis in an adult.
 We report a case of rapidly progressive cerebral demyelinating disease in a previously healthy 40-year-old woman.
 This case satisfies the diagnostic criteria for myelinoclastic diffuse sclerosis (MDS), but is unusual in the age of onset.
 This is the 1st case of MDS in an adult with full documentation of clinical, biochemical, radiographic, and pathologic features.
",22
3903,"Full-thickness skin graft vaginoplasty for treatment of the stenotic or foreshortened vagina.
 Vaginal stenosis or foreshortening following surgery or radiation therapy can lead to dyspareunia.
 This report concerns the successful use of full-thickness skin grafts taken from the flank overlying the iliac crest to treat vaginal stenosis or foreshortening.
 The operation consists of incising the involved area and creating a space which will become the recipient site.
 An elliptical piece of full-thickness skin harvested from the area overlying the iliac crest is cleared of underlying fat, trimmed to fit the recipient site, and sutured in place.
 Vaginal packing is used to keep the graft against the recipient bed.
 Ten patients have been treated successfully with this technique, without significant complications or sequelae.
 Follow-up from 6 weeks to 42 months showed excellent postsurgical vaginal capacity in all patients.
 Similarly, excellent functional results were achieved in eight patients, with distinct improvement in the remaining two.
 This procedure is a useful addition to the gynecologic surgeon's armamentarium.
",22
3904,"GTPase-activating protein interactions with the viral and cellular Src kinases.
 GTPase-activating protein (GAP), which regulates the activities of Ras proteins, is implicated in mitogenic signal transduction by growth-factor receptors and oncoproteins with tyrosine kinase activity.
 Oncogenic viral Src (p60v-src) encoded in Rous sarcoma virus possesses elevated tyrosine kinase activity compared with its nononcogenic normal homolog, cellular Src (p60c-src).
 To examine molecular interactions between GAP and the two Src kinases, immunoprecipitates of Src or GAP prepared from cell lystates were resolved by gel electrophoresis and analyzed by an immunoblot procedure with antibodies to GAP or Src used as probes.
 Results suggest that p60c-src is associated with a complex containing GAP in immunoprecipitates from lysates of normal rat and chicken cells.
 However, GAP is not phosphorylated in p60c-src immunoprecipitates subjected to in vitro kinase reactions.
 By contrast, GAP undergoes tyrosyl phosphorylation in vitro when immunoprecipitates of p60v-src prepared from transformed cell lysates are incubated with ATP.
 Our findings suggest that p60v-src and p60c-src associate with complexes containing GAP and provide a biochemical link between both kinases and GAP/Ras signal transduction pathways.
 These results are consistent with the hypothesis that GAP has a role in mediating normal functions of p60c-src as well as oncogenic activities of p60v-src.
",22
3905,"Molecular basis of the activation of the tumorigenic potential of Gag-insulin receptor chimeras.
 A previous study showed that the human insulin receptor (IR) could be activated by insertion of a 3' portion of the cDNA encoding the beta subunit into a retrovirus genome to form a Gag-IR fusion protein.
 While capable of transforming cells in culture, this IR cDNA-containing virus, called UIR, was not able to induce tumors in animals.
 Subsequently, we isolated a spontaneous sarcomagenic variant called UIR19t from the parental UIR.
 UIR19t was molecularly cloned, sequenced, and found to harbor two mutations.
 A 44-amino acid deletion immediately upstream from the transmembrane domain of the Gag-IR fusion protein removes all the extracellular sequence of the IR remaining in the original UIR construct.
 In addition, a single nucleotide deletion at the 3' end results in truncation and replacement of the carboxyl-terminal 12 amino acids by 4 new amino acids.
 The specific kinase activity of UIR19t is 4- to 5-fold higher than that of the parental UIR.
 However, no new cellular substrates were detected in UIR19t-transformed cells as compared to UIR cells.
 Viruses containing either the 5' or the 3' deletion mutation were constructed and assessed for their biological function.
 Our data indicate that the 5' deletion alone is sufficient to confer tumorigenic ability.
 We conclude that sequence immediately upstream from the transmembrane domain imposes a negative effect on the transforming and tumorigenic potential of the Gag-IR fusion protein.
",22
3906,"The transcriptional transactivator of human foamy virus maps to the bel 1 genomic region.
 The human foamy virus (HFV) genome possesses three open reading frames (bel 1, 2, and 3) located between env and the 3' long terminal repeat.
 By analogy to other human retroviruses this region was selected as the most likely candidate to encode the viral transactivator.
 Results presented here confirmed this and showed further that a deletion introduced only into the bel 1 open reading frame of a plasmid derived from an infectious molecular clone of HFV abolished transactivation.
 In contrast, deletions in bel 2 and bel 3 had only minor effects on the ability to transactivate.
 The role of the bel 1 genomic region as a transactivator was further investigated by eukaryotic expression of a genome fragment of HFV spanning the bel 1 open reading frame.
 A construct expressing bel 1 under control of a heterologous promoter was found to transactivate the HFV long terminal repeat in a dose-dependent fashion.
 Furthermore, it is shown that the U3 region of the HFV long terminal repeat is sufficient to respond to the HFV transactivator.
",22
3907,"Transgenic mice susceptible to poliovirus.
 Poliovirus-sensitive transgenic mice were produced by introducing the human gene encoding cellular receptors for poliovirus into the mouse genome.
 Expression of the receptor mRNAs in tissues of the transgenic mice was analyzed by using RNA blot hybridization and the polymerase chain reaction.
 The human gene is expressed in many tissues of the transgenic mice just as in tissues of humans.
 The transgenic mice are susceptible to all three poliovirus serotypes, and the mice inoculated with poliovirus show clinical symptoms similar to those observed in humans and monkeys.
 Rabbit antipoliovirus serum detects the antigens mainly in motor neurons in the anterior horn of the spinal cord and in nerve cells in the medulla oblongata and pons of the paralyzed transgenic mice.
 Therefore, cell types sensitive to poliovirus in the central nervous system of the transgenic mice appear to be identical to those of humans and monkeys.
 Furthermore, many more doses of oral poliovirus vaccine strains than of the virulent strains are required to cause paralysis in the transgenic mice.
 This may reflect the observation that the virulent strain multiplies more efficiently in the central nervous system than the attenuated strain.
 Thus, the transgenic mice may become an excellent new animal model to study molecular mechanisms of pathogenesis of poliovirus and to assess oral poliovirus vaccines.
",22
3908,"Ability of the c-mos product to associate with and phosphorylate tubulin.
 The mos proto-oncogene product, pp39mos, is a protein kinase and has been equated with cytostatic factor (CSF), an activity in unfertilized eggs that is thought to be responsible for the arrest of meiosis at metaphase II.
 The biochemical properties and potential substrates of pp39mos were examined in unfertilized eggs and in transformed cells in order to study how the protein functions both as CSF and in transformation.
 The pp39mos protein associated with polymers under conditions that favor tubulin oligomerization and was present in an approximately 500-kilodalton ""core"" complex under conditions that favor depolymerization.
 beta-Tubulin was preferentially coprecipitated in pp39mos immunoprecipitates and was the major phosphorylated product in a pp39mos-dependent immune complex kinase assay.
 Immunofluorescence analysis of NIH 3T3 cells transformed with Xenopus c-mos showed that pp39mos colocalizes with tubulin in the spindle during metaphase and in the midbody and asters during telophase.
 Disruption of microtubules with nocodazole affected tubulin and pp39mos organization in the same way.
 It therefore appears that pp39mos is a tubulin-associated protein kinase and may thus participate in the modification of microtubules and contribute to the formation of the spindle.
 This activity expressed during interphase in somatic cells may be responsible for the transforming activity of pp39mos.
",22
3909,"Cauda equina anatomy. I: Intrathecal nerve root organization.
 The three-dimensional organization of the human cauda equina has not been described previously.
 This is partly due to the difficulties of dissecting individual, unfixed nerve roots.
 By the use of a newly developed in situ fixation and embedding technique on 15 fresh human cadavers, the cross-sectional anatomy of the cauda equina was defined from L2-L3 to L5-S1.
 A highly consistent cross-sectional pattern was observed in all specimens.
 The lower sacral (S2-S5) and coccygeal roots were located in the dorsal aspect of the thecal sac, whereas the lumbar and first sacral roots exhibited an oblique, layered pattern as they ascended.
 The motor bundle was situated anteromedial to its respective sensory bundle within each layer, Invaginations of arachnoid held the nerve roots in a fixed relationship to one another.
 This previously undescribed three-dimensional anatomy within the thecal sac may aid in the understanding and treatment of trauma, neurocompressive syndromes, and tumors of the cauda equina.
",22
3910,"1990 AcroMed Award in basic science. Cauda equina anatomy. II: Extrathecal nerve roots and dorsal root ganglia.
 Inconsistent data exist regarding the anatomy of the spinal nerve roots lateral to the thecal sac.
 A newly developed in situ technique was used to precisely define anatomic parameters on 20 fresh human cadavers.
 The take-off angle of the nerve roots from the thecal sac decreases from a mean of approximately 40 degrees from L1-L5 to 22 degrees at S1.
 The motor bundles are directly ventral to the sensory fibers within individual roots extrathecally.
 Dorsal root ganglia size varies with vertebral level.
 The majority of ganglia lie directly beneath the vertebral pedicles and one third overlie a portion of the lateral intervertebral disc.
 These previously undescribed relationships may aid in the understanding of lumbosacral neurocompressive disorders and are important to note during pedicle screw insertion, posterolateral decompression for spinal trauma, and paravertebral approaches for lateral disc herniations.
",22
3911,"A prospective study of patients with sciatica. A comparison between conservatively treated patients and patients who have undergone operation, Part I: Patient characteristics and differences between groups.
 Based on a prospective study on 342 sciatica patients examined with rhizography, the aim was to determine which factors others than the rhizography finding and the grade and duration of symptoms were related to the selection of patients to undergo operation.
 Compared with surgically treated patients, conservatively treated patients who did not undergo operation and who had pathologic rhizography findings had pessimistic attitudes to possible surgery, often expressed a desire to retire, and considered their work as physically stressful.
 The women in this group were older and had lower pain indices than women who underwent operation.
 Conservatively treated patients with negative rhizography had more severe occupational handicaps, minor expectations of possible surgery, physically more strenuous jobs requiring difficult physical positions, and lower indices for pain and ADL than did the operated patients.
 The social and ergonomic background problems are emphasized in sciatica patients conservatively treated after rhizography.
",22
3912,"A prospective study of patients with sciatica. A comparison between conservatively treated patients and patients who have undergone operation, Part II: Results after one year follow-up.
 The prospective study included 122 sciatica patients who had not undergone operation (NOPs) and 220 sciatica patients who had undergone operation (OPs); all had been examined by rhizography.
 The follow-up study was done on 110 (90%) of the NOPs and 212 (96%) of the OPs.
 The NOPs were divided into two groups: 30 patients with pathologic rhizography (PR) and 80 patients with negative rhizography (NR).
 Pain-, ADL-, and occupation-handicap indices showed that after the 1 year follow-up the OP group had the best result and the NR group the lowest result.
 The PR group had nearly as good a result as the OP group.
 Thus, sciatica patients are candidates for conservative therapy, even though they have pathologic findings in rhizography, if the symptoms are mild.
 To improve therapeutic outcome, more accurate diagnostic tools are needed to develop specific therapy especially for those sciatica patients with negative rhizography.
",22
3913,"A preliminary study of dye-enhanced laser photosclerosis.
 Laser ablation of veins after injection of wavelength-specific dyes to enhance and localize energy absorption could provide a useful adjunct to current treatment options.
 To enhance the absorption of diode laser energy at 808 nm, ear veins of 41 rabbits were infused with 2 to 3 ml of indocyanine green dye (maximum absorption, 805 nm) and exposed for 2 to 20 seconds.
 Animals were killed between 0 and 28 days after operation.
 Discrete time intervals of laser exposure exist during which various-sized vessels can be ablated without significant thermal injury to the overlying tissue.
 Small vessels (0.2 mm in diameter) blanch after 2 to 3 seconds of exposure, whereas medium-sized vessels (2 mm in diameter) require 8 to 10 seconds.
 Vessels can be ablated with a power density as low as 11.1 W/cm2.
 Specimens taken immediately after laser exposure show vessel wall thinning and a reirradiation effect, created as laser energy initially absorbed by dye is reemitted.
 By the seventh day after operation, a brisk inflammatory response and acanthosis of the overlying epidermal layer develop.
 The lumen is partially filled by thrombus with cellular invasion.
 By postoperative day 28, the epidermal thickening and inflammatory reaction have resolved; the vessel walls are fibrotic.
 The use of low-power, air-cooled diode lasers, in conjunction with wavelength-specific dyes, may provide a simple, viable, and cosmetically appealing alternative to the treatment of superficial varicosities of the extremities.
",22
3914,"Treatment of solitary arteriovenous fistulas.
 Four patients with a solitary arteriovenous fistula were treated by transvascular balloon embolization technique, which resulted in complete fistula closure in three patients and partial closure in one.
 There were two vertebral arteriovenous fistulas, one peroneal arteriovenous fistula, and one radial arteriovenous fistula.
 The first two fistulas were spontaneous, the other two were traumatic.
 The only partial occlusion of the peroneal fistula was, in our opinion, due to a technical failure, the balloon was inflated slightly proximal to the fistular orificium instead of in the orificium itself.
 There were no complications, and there was no morbidity.
 In our opinion transvascular balloon embolization technique is the treatment of choice for solitary arteriovenous fistulas.
",22
3915,"Munchausen syndrome by proxy documented by discrepant blood typing.
 The authors describe a case of Munchausen syndrome by proxy, a form of child abuse, documented by use of routine blood bank serologic procedures.
 While immunohematologic testing has been used in the legal arena to resolve issues of disputed paternity and to investigate instances of criminal acts, the authors believe this to be the first documented application to this clinical disorder.
",22
3916,"The analysis of erythrocyte morphologic characteristics in urine using a hematologic flow cytometer and microscopic methods.
 Three methods for the examination of erythrocyte morphology in urine are described: phase contrast microscopy, microscopy of cytocentrifuged and stained preparations, and erythrocyte analysis with the Technicon H1.
 Analysis with the H1 has not been described until now.
 All methods can be used to discriminate between dysmorphic and isomorphic erythrocytes.
 The red cell distribution width was the best H1 parameter for this discrimination.
 The authors have found a good correlation between the microscopic methods.
 The clinical impact of the three methods was studied with urine samples from patients with a confirmed diagnosis.
 The discrimination between renal and nonrenal hematuria is similar with phase contrast microscopy and cytocentrifuged preparations.
 The use of the H1 for this discrimination is not recommended.
",22
3917,"Small bowel enteroscopy and intraoperative enteroscopy for obscure gastrointestinal bleeding.
 Intraoperative endoscopy (IOE) is accepted as the ultimate diagnostic procedure for completely evaluating the small bowel in patients with obscure gastrointestinal (GI) bleeding.
 Small bowel enteroscopy (SBE) has been reported useful in the nonsurgical evaluation of the small intestine in these patients, but findings may be limited because of incomplete small bowel intubation and a lack of tip deflection.
 Twenty-three patients underwent 25 SBE exams and subsequently had 25 IOE exams during surgical exploration for continued bleeding.
 Patients' bleeding histories averaged 2 yr, with an average transfusion requirement of 27 units.
 Findings on IOE were the same as with SBE in 17/22 (77%) of examinations.
 We conclude that SBE and IOE are comparable in depth of insertion and ability to detect small vascular ectasias.
 Both procedures missed pathology due to limited visibility and the evanescent nature of ectasias.
 Long-term success in abolishing bleeding with these combined techniques can be expected in 55% of these patients.
 SBE should precede surgery, since the finding of diffuse ectasias precludes any benefit from operative intervention.
",22
3918,"Endoscopic management of postoperative biliary leaks: review of 77 cases and report of two cases with biloma formation.
 Biliary leaks are uncommon complications of abdominal surgery.
 Left untreated, they may result in significant morbidity and mortality.
 The traditional treatment has been surgical, but several authors have reported successful endoscopic management.
 We review 77 cases of endoscopically managed postoperative biliary leaks reported in the literature over the past 15 yr.
 Endoscopic treatment was technically successful in 95% of cases, and resulted in biliary leak healing in 82%.
 Cystic stump leaks had a better prognosis for healing compared with common bile duct or hepatic duct leaks.
 We also present two additional cases of postoperative biliary leaks with biloma formation successfully treated with endoscopic stent placement.
 Our experience lends additional support to endoscopic management as the preferred approach to postoperative biliary leaks.
",22
3919,"Heparin skin necrosis: delayed occurrence in a patient on hemodialysis.
 A case of skin necrosis in a patient receiving intravenous (IV) heparin during routine intermittent hemodialysis is reported.
 Multiple erythematous, tender lesions developed over the abdomen and thighs and rapidly became necrotic.
 Biopsies showed fibrin thrombi in the dermal venules and capillaries, but no cellular infiltrate.
 The patient was in her third month of regular hemodialysis.
 Skin necrosis associated with the use of heparin usually occurs within 2 weeks of beginning heparin therapy and has not been reported in patients receiving heparin with hemodialysis.
 Possible mechanisms, including acquired antithrombin III deficiency leading to heparin-induced skin necrosis, are discussed.
",22
3920,"Toxicities in rats with free versus liposomal encapsulated cisplatin.
 Wistar rats (five in each group) were given either 1 mg/kg of free cisplatin, 1 or 2 mg/kg of liposomal encapsulated cisplatin, or saline solution intraperitoneally biweekly for 15 injections.
 Rats in the free drug group showed significantly less weight gain; two rats died during the study.
 At necropsy, the free cisplatin--treated rats showed gross and microscopic evidence of peritoneal fibrosis that was not detected in any of the remaining groups.
 The free cisplatin--treated rats showed serum and histologic evidence of renal damage; all five rats had moderate or severe acute tubular necrosis.
 No renal abnormalities were detected in rats that received 1 mg/kg, and only focal or mild changes were found in rats that received 2 mg/kg of the liposomal preparation.
 Neurotoxicity, as determined by nerve conduction and inclined plane studies, developed in rats treated with free and liposomal cisplatin.
 These results are encouraging and warrant further investigation.
",22
3921,"Acetazolamide in the treatment of abnormal oculovestibular response.
 We treated seven patients with incapacitating vertigo elicited by walking down a grocery store aisle or driving a car.
 Results of neurologic, neuro-ophthalmic, and neuroradiologic examinations were normal.
 Episodic vertigo secondary to an abnormal oculovestibular response was diagnosed.
 Each patient was given a trial of 250 to 500 mg of acetazolamide daily.
 Symptoms resolved completely in four patients, two patients had near resolution of symptoms, and one patient had no relief.
 Carbonic anhydrase activity has been demonstrated in the inner ear, and acetazolamide has been shown to affect the ion balance of the inner ear fluids.
",22
3922,"Genetics and psychiatry: an unheralded window on the environment.
 Two recent reviews in the American Journal of Psychiatry and the British Journal of Psychiatry reported on progress in understanding the genetics of psychiatric disorder.
 Both reviews focused on this progress as a prelude to psychiatric diagnostics and therapeutics based on molecular biology.
 Neither review recognized that the latest data in behavioral genetics support environmental causes for abnormal development and psychopathology as much as they support genetic causes.
 Moreover, these genetic data point clearly to a type of environmental cause with central importance: the environment that is specific or unique to each sibling in a family.
",22
3923,"Nortriptyline treatment of depressed cardiac transplant recipients.
 The safety of tricyclic antidepressants in cardiac transplant recipients has not been established.
 The author used nortriptyline to treat major depressive episodes in eight cardiac transplant recipients.
 Nortriptyline therapy was associated with increased QRS interval and heart rate but did not significantly affect other hemodynamic or ECG variables or cyclosporine dose requirements.
 It appears that nortriptyline may be used safely in depressed cardiac transplant patients.
",22
3924,"Splenectomy for the massively enlarged spleen.
 The experience at the National Cancer Institute from 1955 to 1988 with 46 cases of splenectomy for massive splenomegaly (greater than or equal to 1,500 grams) was reviewed to assess the indications, pathology, operative, and postoperative course for this procedure.
 The median age was 51 years.
 Thirty-one splenectomies (67.4%) were performed for malignancy (chronic lymphocytic leukemia, 11; chronic myelogenous leukemia, 10; lymphoma, 9; hairy cell leukemia, 1), 11 for myeloid metaplasia, and four for other nonmalignant conditions.
 Indications for splenectomy included hypersplenism (32 patients), symptoms (6), diagnosis (3), and splenic rupture (3).
 A midline incision (30 patients) was most commonly used.
 Median operative time was 2 hours, 50 minutes.
 Median operative blood loss was 1,300 ml (range, 100 ml-60 units).
 The splenic artery was ligated initially in 16 patients (34.8%) but did not correlate with blood loss or operating time.
 The median splenic weight was 2,030 grams (range, 1500-5320 gm).
 The postoperative complication rate was 39.1 per cent (21 complications in 18 patients).
 This included infection in 10 patients, bleeding in six patients.
 Six patients required reoperation (bleeding, 4; abscess, 1; small bowel obstruction, 1 patient).
 The 30-day operative mortality was 19.6 per cent (9 patients).
 Excluding operative deaths, 35 patients were available for follow-up evaluation.
 Twenty-nine patients had improvement in parameters for which splenectomy was indicated.
 Six patients had no change in their course after splenectomy.
 These findings indicate that many patients with massive splenomegaly benefit from splenectomy, however, the procedure is associated with a high risk for postoperative morbidity and mortality.
",22
3925,"Erythrocyte sedimentation rate predicts early relapse and survival in early-stage Hodgkin disease. The EORTC Lymphoma Cooperative Group.
 OBJECTIVE: To assess the value of an elevated (greater than 30 mm/h) Westergren erythrocyte sedimentation rate (ESR) for predicting early relapse and survival after therapy in patients with clinical stage I or II Hodgkin disease.
 INTERVENTIONS: We studied 772 patients with early-stage Hodgkin disease who had participated in two separate multicenter clinical trials.
 Both trials used modern field radiotherapy and, in some patients, multi-agent chemotherapy.
 MAIN RESULTS: The ESR patterns were based on pretherapy and post-therapy assessments: pattern 1, always normal (n = 261); pattern 2, elevated before therapy but normal immediately after therapy (n = 121); pattern 3, elevated before therapy but normal within 3 months after therapy (n = 89); pattern 4, always elevated (n = 48); pattern 5, normal before therapy but oscillating between normal and elevated after therapy (n = 150); pattern 6, elevated before therapy but oscillating between normal and elevated after therapy (n = 130).
 By multivariate analysis, independent of whether or not patients received chemotherapy in the initial therapy protocol, ESR patterns 4, 5, and 6 were shown to be the best predictors for early relapse and survival when patients were stratified according to the type of chemotherapy received and the number of involved nodal areas.
 Patients with ESR pattern 4 had a relative risk for death seven times that of patients with patterns 1, 2, or 3.
 Early relapse was the second most important factor predicting death, irrespective of ESR; patients with early relapse and ESR patterns 1, 2, or 3 had a relative risk for death of 4.5, and those with early relapse and ESR patterns 4, 5, or 6 had a relative risk for death of 15.
 Whether or not chemotherapy was given initially did not change the relative risk, which shows that ESR, not initial therapy, was the predictor for early relapse and death due to Hodgkin disease.
 CONCLUSION: An unexplained elevated ESR after therapy, especially after modern radiotherapy, independent of other factors, strongly suggest the presence of aggressive and resistant Hodgkin disease.
 An elevated ESR is predictive of early relapse and poor prognosis; its presence justifies early aggressive therapy.
",22
3926,"Surgical complications with the cochlear multiple-channel intracochlear implant: experience at Hannover and Melbourne.
 The surgical complications for the first 153 multiple-channel cochlear implant operations carried out at the Medizinische Hochschule in Hannover and the first 100 operations at the University of Melbourne Clinic, The Royal Victorian Eye and Ear Hospital, are presented.
 In the Hannover experience the major complications were wound breakdown, wound infection, electrode tie erosion through the external auditory canal, electrode slippage, a persistent increase in tinnitus, and facial nerve stimulation.
 The incidence of wound breakdown requiring removal of the package was 0.6% in Hannover and 1.0% in Melbourne.
 The complications for the operation at both clinics were at acceptable levels.
 It was considered that wound breakdown requiring implant removal could be kept to a minimum by making a generous incision and suturing the flap without tension.
",22
3927,"The role of calcium ions and calcium channel entry blockers in experimental ischemia-reperfusion-induced liver injury.
 Verapamil administered before treatment, but not after treatment, had a beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury model.
 The possible activation of proteases converting the xanthine dehydrogenase to xanthine oxidase, the significant mitochondrial calcium loading during the ischemic period, and the potentiation of calcium and oxygen-derived free radicals to promote injury to mitochondria are mechanisms supported by this study, based on both histologic observations and on the pattern of enzyme leak after the acute ischemic event.
",22
3928,"Deleterious effects of criminal victimization on women's health and medical utilization.
 The long-term consequences of criminal victimization on physical health were examined among 390 adult women (74 nonvictims and 316 victims of crime).
 Data included health status self-ratings and objective service utilization.
 Findings indicated that severely victimized women, compared with nonvictims, reported more distress and less well-being, made physician visits twice as frequently in the index year, and had outpatient costs that were 2.5 times greater.
 Criminal victimization severity was the most powerful predictor of physician visits and outpatient costs.
 Utilization data across 5 years preceding and following crime were obtained from 15 rape victims, 26 physical assault victims, and 27 noncontact crime victims and were compared with five continuous years of utilization among 26 nonvictims.
 Victims' physician visits increased 15% to 24% during the year of the crime compared with less than 2% change among nonvictims.
 We conclude that these long-term deleterious effects suggest that criminally victimized women's needs for medical treatment transcend the traditional focus on emergency care and forensic evaluation.
",22
3929,"Reference ranges for lymphocyte subsets. A comparison of standard vs rapid whole-blood lysis techniques.
 Reference ranges for lymphocyte subsets may vary with processing techniques, monoclonal reagents, or analytic methods.
 We compared reference ranges obtained for T- and B-lymphocyte subsets by means of standard manual whole-blood lysis with a wash step vs a rapid, no-wash whole-blood lysis system.
 Both techniques demonstrated reference ranges similar to those in previous literature reports.
 The ranges established with standard and rapid lysis were similar when antibodies directed to the same cluster designation were used.
 Although slight statistical differences in relative percentages of CD2 and CD3 lymphocytes were observed, these differences were probably not clinically significant.
 These data indicate that the rapid technique provides a standardized method for enumerating T and B lymphocytes in peripheral blood.
",22
3930,"Anatomic, metabolic, neuropsychological, and molecular genetic studies of three pairs of identical twins discordant for dementia of the Alzheimer's type.
 Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years.
 Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests.
 The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin.
 DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins.
 Family pedigrees were negative for Alzheimer's disease.
 The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation.
",22
3931,"Anterior femoral cutaneous nerve injury following femoral artery reconstructive surgery.
 Two cases are presented exhibiting symptoms and signs of bilateral anterior femoral cutaneous nerve injury, clinically sparing femoral nerve branches to the saphenous nerve and quadriceps muscles.
 This occurred following surgical dissection in the femoral triangles associated with femoral artery reconstructive surgery.
 Anterior femoral cutaneous nerve injury should be considered when anterior medial thigh pain and numbness occur following aortofemoral bypass graft surgery and other types of femoral artery reconstructive surgery.
",22
3932,"Perinatal mortality rates in isolated general practitioner maternity units 
 OBJECTIVE--To determine the perinatal mortality rate among normally formed, singleton babies with birth weights greater than or equal to 2500 g in Bath health district based on the intended place of delivery at the time of onset of labour or at the time of diagnosis of intrauterine death.
 DESIGN--The numbers of live births and stillbirths were collected monthly returns from the maternity units concerned.
 Deaths of infants aged less than or equal to 1 week were collected in the same returns.
 The intended place of delivery was confirmed at the monthly perinatal mortality meeting, during which maternal and fetal factors were discussed.
 SETTING--A rural health district of 400,000 population where one third of all deliveries occurred in seven isolated general practitioner maternity units, 8% in the integrated general practitioner unit, and the remainder in the consultant unit.
 SUBJECTS--All babies of women whose deliveries were booked in the district before the onset of labour or the diagnosis of intrauterine death, excluding twins, babies with lethal congenital malformations, and those less than 2500 g.
 MAIN OUTCOME MEASURES--Outcome of all deliveries and parity of mothers.
 RESULTS--14,415 Deliveries were analysed.
 The perinatal mortality rate was 2.8/1000 births in the consultant unit (7950 deliveries), 4.8 in the isolated general practitioner units (5237 deliveries), and zero in the integrated general practitioner unit (1228 deliveries).
 Perinatal deaths attributable to asphyxia were more common in the isolated general practitioner units (1.5 per 1000) than the consultant unit (0.6 per 1000).
 The perinatal mortality rate among babies born to nulliparous women was 3.2/1000 births in the consultant unit and 5.7 in the isolated general practitioner units; for those born to multigravid women it was 2.4 and 4.2 respectively.
 CONCLUSIONS--The outcome of delivery was not influenced by parity.
 Both antenatal and intrapartum care were responsible for the higher perinatal mortality rate in the isolated general practitioner units.
 The integrated unit, which shared midwifery staff with the consultant unit, seemed to work well.
 Analysis by intended place of delivery at the time of onset of labour or diagnosis of intrauterine death suggested that the care given in isolated units needs to be improved, perhaps by better training of general practitioners and consultant supervision of antenatal care.
",22
3933,"The role of fistulography in fistula-in-ano. Report of five cases.
 A retrospective review of 27 patients undergoing anal fistulography is presented.
 The etiology of the 27 fistulas studied are as follows: cryptoglandular infection in 18, IBD in 7 (Crohn's 6, CUC 1), iatrogenic in 1, and foreign body perforation in 1.
 Twenty-six fistulograms revealed either direct communication with the anus or rectum, or abscess cavities/tracts, or both.
 Two fistulograms revealed no radiographic evidence of fistula (one patient had two fistulograms).
 In 13 of the 27 patients (48 percent) information obtained from the fistulograms revealed either unexpected pathology (n = 7) or directly altered surgical management (n = 6).
 We conclude that anal fistulography in properly selected patients may add useful information for the definitive management of fistula-in-ano.
",22
3934,"Chronic care needs to be a higher priority.
 Although acute care remains the focus of the U.S.
 health care delivery system, a shift is taking place toward chronic-illness mortality.
 Developing effective chronic-disease management processes is tough in the context of today's acute care orientation, according to William F.
 Henry, president of ForeSight Strategy Associates, St.
 Paul, MN.
",22
3935,"Revision total knee arthroplasty for failed unicompartmental replacement.
 The results in nineteen patients (twenty-one knees) who had a failed unicompartmental knee replacement followed by a revision total knee arthroplasty were evaluated.
 There were twelve excellent, four good, one fair, and two poor results.
 The interval between the unicompartmental replacement and the revision total knee arthroplasty ranged from eight months to eight years.
 At the time of the revision, a major osseous defect was found in sixteen knees (76 per cent).
 The duration of follow-up after the revision ranged from two to ten years.
 At the most recent follow-up examination, radiographs revealed at least one radiolucent line in thirteen knees (62 per cent).
 The technical difficulties associated with the revision operation are evidence that unicondylar arthroplasty is not a conservative procedure that allows a total knee arthroplasty to be done easily later.
 The results also do not support the argument that a revision performed after failure of a unicondylar arthroplasty is less technically demanding than one performed after a failed primary total knee arthroplasty.
",22
3936,"Cross-linked hemoglobin solution as a resuscitative fluid after hemorrhage in the rat.
 Intramolecularly (alpha-alpha) cross-linked hemoglobin has been reported to have oxygen transport properties similar to those of whole blood.
 The present study evaluated the efficacy of diaspirin alpha-alpha cross-linked hemoglobin solution as a resuscitation fluid, with heart rate, mean arterial pressure, and transcutaneous oxygen tension as the study parameters.
 Rats were bled and approximately one third of their total blood volume (20 ml/kg) was removed while they were anesthetized; they were then resuscitated with 14% hemoglobin solution.
 Animals that received either 10 mg/kg (n = 10) or 20 mg/kg (n = 10) of hemoglobin solution responded quickly and positively to the infusions: mean arterial pressure (which had dropped to less than 40% of prehemorrhage levels) returned to baseline within 2 minutes of initiating infusion; by 4 minutes, the mean arterial pressures of the hemoglobin-infused groups were significantly higher (p less than or equal to 0.05) than those in both the autologous shed blood (n = 8) and lactated Ringer's (n = 10) groups.
 The heart rate and transcutaneous oxygen tension responses in both the half-volume and full-volume replacement hemoglobin groups matched the response to autologous shed blood throughout the hour of observation.
 The favorable hemodynamic response to infusion of cross-linked hemoglobin solution after hemorrhage suggests that this material is comparable to autologous shed blood and superior to lactated Ringer's solution as a resuscitative fluid as assessed in this model.
",22
3937,"Slowly progressive aphasia: three cases with language, memory, CT and PET data.
 Three cases of slowly progressive speech and language disturbance were studied at various points post onset (three, five and 15 years respectively).
 Language, neuropsychological and brain imaging (computer tomography and positron emission tomography) evaluations were completed on all three patients.
 The data suggest that the syndrome of ""progressive aphasia"": 1) does not involve a uniform symptom complex; 2) does not necessarily develop into a full blown dementia syndrome; 3) varies greatly in rate of progression from case to case; 4) is associated with normal brain structure (on computer tomography); and 5) is associated with abnormal left temporal lobe metabolism as measured by fluorodeoxyglucose (FDG) positron emission tomography (PET).
 One patient had histological findings consistent with Alzheimer's disease at necropsy.
",22
3938,"Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs.
 The major side effects of racemic oxybutynin (OXY), which is used in the treatment of urinary incontinence are dry mouth (xerostomia) and blurred vision (mydriasis).
 Highly purified enantiomers of OXY [(R)OXY, (S)OXY] were compared with the racemate both in vitro in functional studies and in vivo in guinea pigs to evaluate their pharmacological action relative to their adverse effects.
 The affinity of (R)OXY and (S)OXY for different muscarinic receptor subtypes was determined using field stimulated rabbit vas deferens (M1) and guinea pig atria (M2) or bladder (M3) strips.
 Stereoselective antimuscarinic effects [(R)OXY greater than or equal to (R/S) OXY much greater than (S)OXY] were evident at all three receptor subtypes; the isomeric ratio [(S)OXY/(R)OXY] ranged from 12 to 88.
 Both (R)OXY and (R/S)OXY were slightly more selective (2-4-fold, P less than .01) for M1 and M3 relative to M2 muscarinic receptors.
 Stereoselectivity was also evident in vivo for volume-induced urinary bladder contractions as measured by cystometrogram parameters [(S)OXY/(R)OXY approximately 21], mydriasis [(S)OXY/(R)OXY approximately 136] and salivary gland secretory responses [(S)OXY/(R)OXY approximately 30].
 The absolute potencies of (R)OXY or (R/S)OXY for mydriasis and salivation were similar to those for inhibition of intravesical bladder pressure.
 Also, (R)OXY and (R/S)OXY equipotently antagonized cholinergic-mediated CNS effects in mice.
 Collectively, the data suggest that the activity of (R/S)OXY resides predominantly in the (R)-enantiomer.
 However, it appears that (R)OXY may offer no significant pharmacological advantage over (R/S)OXY in terms of its principal therapeutic and side effect profile.
",22
3939,"Evidence for intraluminal Ca++ regulatory site defect in sarcoplasmic reticulum from malignant hyperthermia pig muscle.
 Malignant hyperthermia (MH) is a pharmacogenetic disease of humans and various animal species that predisposes to a life-threatening, anesthetic agent-induced syndrome.
 MH is thought to be a consequence of abnormal, sustained increases in myoplasmic Ca++ and sarcoplasmic reticulum (SR) membranes from MH muscle have been shown to have a Ca++ release channel defect.
 In the present study we have tested a hypothesis that the abnormal Ca++ release mechanism in MH can be expressed when Ca++ is loaded in the presence of pyrophosphate.
 SR membrane vesicles isolated from normal and MH pig muscle were loaded with Ca++ in the presence and absence of pyrophosphate until Ca(++)-induced Ca++ release occurred.
 Under both circumstances the threshold amount of Ca++ loaded until Ca++ release occurred was lower in the SR from MH pig skeletal muscle.
 This difference in amount of Ca++ preload is not explained by results obtained comparing rates of Ca++ uptake, number of ryanodine binding sites or the amounts of calsequestrin among SR vesicles from MH and normal muscle.
 We conclude from this study that use of pyrophosphate for Ca++ loading does not ablate the abnormal Ca++ release in SR from MH muscle, suggesting the study can be done on small amounts of SR from biopsied human muscle.
 The data also suggest that abnormality in an intraluminal, low affinity Ca++ binding site regulating Ca++ release occurs in the SR membrane of MH pig muscle.
",22
3940,"Absorbable mesh splenorrhaphy for severe splenic injuries: functional studies in an animal model and an additional patient series.
 Polyglycolic acid mesh has been introduced as a method of controlling hemorrhage in severely damaged spleens.
 This study examines the effect of splenic wrapping on the immune function of the spleen, and also on its ability to control splenic bleeding in trauma patients.
 Thirty purebred beagle dogs were divided into three groups and subjected to sham operation (Group 1), splenectomy (Group 2), and splenic wrap (Group 3).
 Immunologic studies showed no difference between the wrapped group (Group 3) and those with their spleens intact (Group 1) in the induction of specific antibody-producing lymphocytes in splenic tissue after the injection of attenuated Pneumococci.
 All splenic injuries treated at Cook County Hospital between January 1985 and May 1988 were retrospectively analyzed.
 Of 60 patients with splenic injuries, 14 underwent mesh splenorrhaphy without mortality or serious complications.
 This study demonstrates that the immune function of spleen is preserved following mesh splenorrhapy, and that this technique can be used in a clinical setting with safe and efficacious results.
",22
3941,"Lumbar spinal nerves in the neural foramen: MR appearance.
 The appearance of the proximal lumbar spinal nerves at magnetic resonance (MR) imaging has not, to the authors' knowledge, been described.
 MR images and exactly corresponding sections obtained from four cadavers by means of a freezing microtome were correlated to characterize the MR appearance of the proximal spinal nerves.
 The junction of the dorsal and ventral rami with the dorsal and ventral roots consists of a group of six to 15 fascicles measuring 2-6 mm in length.
 These fascicles appear in MR images obtained with short repetition times as small foci of lower signal intensity than that of surrounding fat.
 The proximal spinal nerve and its relationship to the intervertebral disk and osseous margins of the neural foramen can be demonstrated effectively with MR imaging.
",22
3942,"The Dutch experience in percutaneous transluminal angioplasty of narrowed saphenous veins used for aortocoronary arterial bypass.
 Of 19,994 percutaneous transluminal coronary angioplasty procedures performed in The Netherlands between April 1980 and January 1989, the long-term follow-up of 454 patients who underwent angioplasty of greater than or equal to 1 saphenous vein bypass graft was reviewed.
 In 46% of patients single graft angioplasty was attempted, and in 54% of patients sequential graft angioplasty was attempted.
 The clinical primary success rate was 90%.
 In-hospital mortality was 0.7%, 2.8% of patients sustained a procedural myocardial infarction, and 1.3% of patients underwent emergency bypass surgery.
 After a follow-up period of 5 years, 74% of patients were alive, and 26% were alive and event-free (no myocardial infarction, no repeat bypass surgery or repeat angioplasty).
 In patients in whom the initial angioplasty attempt was unsuccessful, only 3% were event-free at 5 years, versus 27% of successfully dilated patients.
 The time interval between the angioplasty attempt and previous surgery was a significant predictor for 5-year event-free survival.
 The event-free survival rates for patients who had bypass surgery 1 year before, between 1 and 5 years, and 5 years before angioplasty, were 45, 25 and 19%, respectively.
 Less than one-third of patients with previous bypass surgery who had angioplasty of the graft remained event-free after 5 years.
 In patients needing angioplasty within 1 year after bypass surgery, better long-term results were achieved.
",22
3943,"Intraosseous infusion of dobutamine and isoproterenol.
 Intraosseous infusion has been advocated as an emergency route in sick infants and children when intravenous access is not readily obtainable.
 Dobutamine hydrochloride and isoproterenol hydrochloride are useful emergency drugs that have not been studied when administered into the bone marrow.
 In a swine model, we compared the physiologic responses (heart rate, arterial pressure, and cardiac output) of dobutamine and isoproterenol infusions delivered intravenously and intraosseously during 20-minute intervals.
 We observed statistically significant effects of both dobutamine and isoproterenol delivered by the intraosseous route.
 In addition, the effects resulting from intraosseous infusion were statistically similar to those resulting from intravenous administration of these drugs.
 We conclude that the intraosseous infusion of dobutamine and isoproterenol is an effective and useful method for emergency administration of these medications.
",22
3944,"Effectiveness of growth-promoting therapies. Comparison among growth hormone, clonidine, and levodopa.
 The ability of growth hormone, clonidine, and levodopa to stimulate growth was compared in short and slowly growing children randomly assigned to different treatment regimens for 6 months.
 There were 10 children in each group, and 10 additional subjects served as controls.
 Growth hormone improved mean height velocity, height velocity SD score, and height SD score.
 The mean height velocity and height velocity SD score were significantly increased by clonidine, while levodopa only enhanced the mean height velocity SD score of the treated children.
 Moreover, in nine patients (90%) receiving growth hormone, two (20%) receiving clonidine, and one (10%) receiving levodopa, the height velocity was raised by more than 2 cm/y.
 The increments in height velocity and height SD score were greatest in the growth hormone group.
 Clonidine induced an increase in height velocity significantly different from that in control children only.
 In the control group, there was a significant reduction of height SD score with time.
",22
3945,"Unsuspected cocaine exposure in young children.
 OBJECTIVE: To determine the prevalence of cocaine exposure among preschool children with clinically unsuspected signs and/or symptoms.
 DESIGN: Prevalence study.
 SETTING: Pediatric emergency department in an inner-city hospital.
 PARTICIPANTS: 250 children aged 2 weeks to 5 years who underwent urine assays for cocaine prior to discharge from the emergency department.
 INTERVENTIONS: None.
 MEASUREMENTS/MAIN RESULTS: Six (2.4%) of the 250 urine assays (95% confidence interval, 0.5% to 4.3%) were positive for benzoylecgonine, the major urinary cocaine metabolite.
 Four of the positive urine assays were from children younger than 1 year and all children with positive urine assays were younger than 24 months.
 None of these children presented with a complaint or was identified as having clinical problems currently associated with childhood exposure to cocaine.
 Possible exposure routes include breastfeeding, intentional administration, accidental ingestion of cocaine or cocaine-contaminated household dust via normal hand-to-mouth activity, and passive inhalation of ""crack"" vapors.
 CONCLUSION: Among the inner-city children served by this hospital, significant numbers of infants and young children are being exposed to cocaine, and this exposure occurs in a clinically unsuspected population.
",22
3946,"Role of experience in the response to simulated critical incidents.
 Eight experienced anesthesiologists (faculty or private practitioners) were presented with the same simulated critical incidents that had previously been presented to 19 anesthesia trainees.
 The detection and correction times for these incidents were measured, as was compliance with Advanced Cardiac Life Support (ACLS) guidelines during cardiac arrest, and the occurrence of unplanned incidents.
 Experienced personnel tended to react more rapidly than did trainees, but differences between second-year anesthesia residents (CA2) and experienced anesthesiologists were not statistically significant.
 There was a high variability in performance between incidents and within each group.
 Unplanned errors and management flaws still occurred with experience subjects.
 The response to incidents during anesthesia is a complex process that involves multiple levels of cognitive activity and is vulnerable to error regardless of experience.
 Most trainees seemed to acquire adequate response routines by the end of the CA2 year.
 Formal reasoning appeared to play a minor role in responding to intraoperative events, but the exact nature of the anesthesiologist's cognition remains to be thoroughly investigated.
",22
3947,"Low-dose bupivacaine does not improve postoperative epidural fentanyl analgesia in orthopedic patients [published erratum appears in Anesth Analg 1991 May;72(5):718]
 Epidural infusions of 10 micrograms/mL fentanyl combined with low-dose bupivacaine (0.1%) were compared with epidural infusions of fentanyl alone for postoperative analgesia after total knee joint replacement.
 There were no detectable differences between the two groups in analgesia (visual analogue scale ranging between 15 and 40 mm), infusion rates (which averaged 7-9 mL/h), or serum fentanyl levels (which reached 1-2 ng/mL).
 The incidence of side effects, including nausea, vomiting, and pruritus, was also similar.
 Of the patients receiving fentanyl and low-dose bupivacaine, one developed a transient unilateral motor and sensory loss, and one developed significant hypotension and respiratory depression.
 The addition of low-dose bupivacaine does not improve epidural fentanyl infusion analgesia after knee surgery and may increase morbidity.
",22
3948,"Patient flow in the emergency department: the chest pain patient.
 Prompt treatment of the chest pain patient in the emergency department (ED) is crucial.
 To ensure prompt treatment, identification of factors that delay flow of these patients through the department is essential.
 To identify factors that delay patient flow through the ED, the authors conducted a prospective study of all chest pain patients, using a time-flow analysis.
 Eighty-eight (36%) of 245 patients required critical unit admissions and had an average department stay of 3 1/2 hours.
 Flow differences were seen between critical and noncritical care patients.
 Three primary sources of delay were identified: critical unit bed availability, the registration process, and the role of the unit admitting resident.
 Additional findings confirmed the efficacy and role of the triage nurse in patient flow.
 Nursing and medical education and staffing needs were addressed.
 The use of the community's emergency medical services was examined by analyzing the disposition of patients arriving at the ED by ambulance.
",22
3949,"Immune functions during treatment of growth hormone-deficient children with biosynthetic human growth hormone.
 Immune functions, including cell surface markers, interleukin-2 receptor levels and responses of lymphocytes to mitogenic stimulation were evaluated in seven growth hormone deficient children ages 4-15 years, during treatment with biosynthetically derived human growth hormone.
 Treatment resulted in a decrease in % B cells and in % T total cells and also decreases in most individual patients' mitogen responses and interleukin-2 receptor levels.
 Most of the changes noted were transient and similar to those previously demonstrated during pituitary-derived human growth hormone treatment.
 Although not resulting in overt clinical manifestations in our patients, we think that potential interactions between growth hormone and immune functions need to be considered by physicians treating children with growth hormone.
",22
3950,"Oxygen desaturation during fiberoptic bronchoscopy in pediatric patients.
 STUDY OBJECTIVE: Pulse oximetry was used to measure arterial oxygen saturation and the extent of hypoxemia in pediatric patients undergoing FB.
 DESIGN: Arterial oxygen saturation was measured (1) prior to the procedure to provide a baseline value, (2) when the bronchoscope was positioned in the nasopharynx, and (3) when the bronchoscope was positioned in the mid-trachea.
 SETTING: Fiberoptic bronchoscopy was performed in the Pediatric Special Care Unit or in the Pediatric Pulmonary Laboratory using an Olympus BF3C4 fiberoptic bronchoscope with a 3.5-mm outer diameter.
 PATIENTS OR PARTICIPANTS: Thirty-six children who underwent diagnostic or therapeutic bronchoscopy for a variety of reasons were evaluated.
 They ranged in age from 6 to 142 months; 20 were male and 16 were female.
 INTERVENTIONS: There were no interventions.
 MEASUREMENTS AND RESULTS: Of the 36 patients, 29 experienced a fall in SaO2 levels exceeding 5 percent of baseline values.
 The youngest age group, 6 to 12 months, showed the greatest drop in saturation as compared with the other groups.
 Desaturation was significantly increased by midtracheal FB.
 CONCLUSIONS: A decline in arterial oxygen saturation that may be substantial in infants and children undergoing FB examination was frequently noted, especially in smaller infants and when the bronchoscope was positioned in the mid-trachea.
 Supplemental oxygen and a brisk procedure time will minimize the risk of dangerous hypoxia.
",22
3951,"Patterns of resource consumption in medical intensive care 
 Intensive care is being scrutinized as a major factor in increasing health care costs.
 We examined 404 consecutive admissions to the medical ICUs at a university medical center to study patterns of consumption of ICU resources and the proportion of resources used by patients admitted for monitoring only.
 We found a skewed distribution of ICU resource consumption, with the ""high-cost"" 8 percent using as many ICU resources as the ""low-cost"" 92 percent.
 Forty-one percent of admissions did not receive acute ICU treatments, but these admissions consumed less than 10 percent of ICU resources.
 Reducing the number of patients admitted for monitoring will have a relatively small impact on hospital charges.
 Since over 70 percent of the high-cost patients died, improved understanding of prognosis and better physician-patient communication may substantially reduce the proportion of critical care resources expended on futile treatment.
",22
3952,"Active vs passive rhythms as an explanation of bigeminal rhythm with similar P waves.
 We describe the criteria for differential diagnosis between 3:2 sinoatrial block from atrial bigeminy due to an ectopic focus in the sinus or parasinus zone.
 In the 3:2 sinoatrial block the RR interval of the basic rhythm is similar to the short R-R interval of the paired rhythm.
 In atrial bigeminy, the R-R interval of the basic rhythm is similar to the long R-R interval of the paired rhythm.
",22
3953,"Immunoglobulins A, G, and M to cytomegalovirus during recurrent infection in recipients of allogeneic bone marrow transplantation.
 Occurrence and significance of specific IgA and IgM to cytomegalovirus (CMV) in recurrent CMV infection was evaluated in 21 allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) recipients who had been previously CMV seropositive.
 Of 17 patients with CMV infection, viruria was detected in 94%, CMV-specific IgA in 88% and IgM in 76%, and a fourfold rise in IgG in 65%.
 The median time between BMT and detection of viruria was 69 days, of IgA 70, of IgM 62, and of IgG 88 days.
 The IgM and IgA responses lasted for 14 and 30 days (median time), whereas high IgG titers persisted.
 Twelve patients developed CMV disease; in these the appearance of viruria, IgA, and IgM preceded the rise of IgG (P less than .02).
 CMV-specific IgA and IgM are valuable diagnostic tools in BMT recipients with recurrent CMV infection.
",22
3954,"Operation Everest II: ventilatory adaptation during gradual decompression to extreme altitude.
 To assess the ventilatory adaptation during gradual ascent to extreme altitude, we studied seven healthy males as part of the 40 d simulated ascent of Mt.
 Everest in a hypobaric chamber.
 We measured resting ventilation (VE, l.min-1), arterial oxygen saturation (SaO2%), the ventilatory response to oxygen breathing, isocapnic hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) at sea level prior to the ascent (760 torr), 14,000 feet (428 torr), 24,000 feet (305 torr), and within 24 h of descent (765 torr).
 VE increased from 9.3 +/- 1.1 l.min-1 at 760 torr to 23.4 +/- 1.3 l.min-1 at 305 torr and remained elevated at 14.7 +/- 0.7 l.min-1 after descent.
 Oxygen breathing decreased VE by 9.6 +/- 1.3 l.min-1 at 305 torr.
 Isocapnic HVR (expressed as a positive slope of VE/SaO2, l.min-1.%SaO2(-1) increased from 0.18 +/- 0.07 at 760 torr to 0.34 +/- 0.11 and 0.38 +/- 0.5 at 428 torr and 305 torr (P less than 0.05) respectively.
 HVR was elevated further upon return to sea level (0.8 +/- 0.09, P less than 0.05).
 HCVR (S = VE/PETCO2, l.min-1.torr-1) increased from sea level (S = 4.4 +/- 0.09) to 305 torr (S = 18.7 +/- 3.5, P less than 0.01) and remained elevated upon return to sea level (S = 10.7 +/- 4.6, P less than 0.001).
 This study is the first to investigate the ventilatory response to such extreme altitude and so soon after descent and shows that hypoxic and hypercapnic responses increase during prolonged progressive hypoxic exposure and remain significantly elevated from pre-ascent levels immediately upon descent.
",22
3955,"Seismic communication in a blind subterranean mammal: a major somatosensory mechanism in adaptive evolution underground.
 Seismic communication, through low-frequency and patterned substrate-borne vibrations that are generated by head thumping, and which travel long distances underground, is important in the nonvisual communication of subterranean mole rats of the Spalax ehrenbergi superspecies (2n = 52, 54, 58, and 60) in Israel.
 This importance pertains both intraspecifically in adaptation and interspecifically in speciation.
 Neurophysiologic, behavioral, and anatomic findings in this study suggest that the mechanism of long-distance seismic communication is basically somatosensory and is independent of the auditory mechanism.
 Seismic communication thus appears to be a channel of communication important in the evolution of subterranean mammals that display major adaptation to life underground.
",22
3956,"Clustered tRNA genes in Schizosaccharomyces pombe centromeric DNA sequence repeats.
 The centromere-associated B' and B DNA sequence repeats of Schizosaccharomyces pombe chromosomes I and II have been found to contain clusters of tRNA genes.
 The centromere II region (cen2) includes at least 22 tRNA genes distributed among five copies of the B sequence repeat containing genes specifying tRNA(Ile), tRNA(Ala), and tRNA(Val).
 Individual B repeats are variously associated with other tRNA genes, including those specifying tRNA(Lys), tRNA(Arg), and tRNA(Glu2).
 The centromere I region (cen1) contains at least six tRNA genes in two copies of the B' repeated element, including genes specifying tRNA(Ile), tRNA(Ala), and tRNA(Glu3).
 Multiple tandemly arranged clusters of tRNA genes are presumably conserved due to restricted recombination frequencies in the centromere regions.
",22
3957,"Quantification of midline shift as a predictor of poor outcome following head injury.
 A retrospective study of patient outcome, based on admission computed tomography, was carried out in 75 consecutive patients with head injury.
 Computed tomography data collected included the type and extent of intracranial hemorrhage, the extent of midline shift, and the ratio of midline shift compared with the extent of intracranial hemorrhage.
 Midline shift was considered to be out of proportion to intracranial hemorrhage when the midline shift of the septum pellucidum exceeded the extent of the hemorrhage as measured radially from the inner table of the skull.
 When computed tomography data were analyzed by logistic regression, significant predictive factors for poor outcome were intracranial hemorrhage (34%), intracranial hemorrhage with midline shift (61%), and midline shift out of proportion to the extent of intracranial hemorrhage (88%).
 When patient outcome and mortality rates are considered, our study indicates that midline shift out of proportion to the extent of intracranial hemorrhage is a highly useful predictor of poor patient outcome following head injury.
",22
3958,"Ketamine as analgesic for total intravenous anaesthesia with propofol.
 A prospective study of 18 patients who underwent noncardiac surgery was performed to study the use of ketamine as an analgesic during total intravenous anaesthesia with propofol.
 A comparison was made with the combination propofol/fentanyl.
 The propofol/ketamine combination resulted in haemodynamically stable anaesthesia without the need for additional analgesics.
 Postoperative behaviour was normal in all patients and none of the patients reported dreaming during or after the operation.
 Propofol seems to be effective in eliminating side effects of a subanaesthetic dose of ketamine in humans.
 We recommend the propofol/ketamine combination for total intravenous anaesthesia for surgery when stable haemodynamics are required.
",22
3959,"Awareness during caesarean section.
 Between 1982 and 1989 over 3000 patients were questioned about recall and dreaming after general anaesthesia for Caesarean section.
 Some 28 (0.9%) patients were able to recall something of their operation and 189 (6.1%) reported dreams.
 There was uniform adherence to a rigid anaesthetic protocol up to and including 1985, but a much publicized incident reported from the courtroom stimulated a relaxation of this regimen.
 Consequently the incidence of awareness decreased from 1.3% to 0.4%, and the incidence of dreaming was also reduced.
 Recollections of surgery were confined to manipulations, noises and voices.
 None of our patients complained of pain at the time of interview, although one since has.
 The inadequacies of the initial protocol and an approach to informed consent are discussed.
",22
3960,"National Institute of Mental Health longitudinal study of chronic schizophrenia. Prognosis and predictors of outcome [published erratum appears in Arch Gen Psychiatry 1991 Jul;48(7):642]
 We performed a longitudinal study of chronic schizophrenic patients who were hospitalized for research purposes at the National Institute of Mental Health (NIMH) Intramural Program in the 1970s and early 1980s.
 We assessed present course, outcome and predictor data from the initial cohort of 58 young chronic schizophrenic patients who were followed up for 2 to 12 years following their NIMH index hospitalization.
 At follow-up, the sample showed substantial functional impairment and levels of symptoms with only about 20% of the sample demonstrating a good outcome.
 In addition, strong intercorrelation was noted among the symptom and functioning indexes at follow-up.
 Moreover, neuropsychologic tests of frontal cortical functioning were significantly correlated with outcome levels of negative symptoms and social functioning but not with levels of positive symptoms.
 During the period from the index hospitalization to the follow-up assessment, 78% of the sample suffered a relapse, 38% attempted suicide and 24% had episodes of major affective illness.
 Furthermore, levels of positive and negative symptoms ascertained when patients received optimal neuroleptic treatment during the index hospitalization significantly predicted outcome levels of symptoms and functioning and time spent hospitalized during the follow-up period.
 In contrast, levels of index positive and negative symptoms ascertained during the drug-free state did not predict outcome symptoms or functioning.
 These data suggest that treatment response is a critical predictor variable.
 We examined the implication of these data for the course of illness in schizophrenics.
",22
3961,"Posthospital course and outcome in schizophrenia.
 To study the early course of schizophrenia, we assessed 79 early phase, young, DSM-III schizophrenic patients at two successive posthospital follow-ups, 2.5 and 5.0 years after index hospitalization.
 More than 50% of the sample had poor overall outcome, with either severe impairment in functioning and symptoms, or suicide, in the follow-up period.
 Rehospitalization rates decreased significantly during the course of the two posthospital assessments, despite the sample showing persisting psychosis.
 Only a small group of schizophrenic patients showed complete remission: 10% at the first follow-up and 17% at the second follow-up, when patients who suicided are excluded from consideration.
 While progressive deterioration is not common in schizophrenia, our relatively negative findings challenge the conclusions of some other longitudinal studies.
 Implications of our data on schizophrenic course are discussed.
",22
3962,"Plasma concentrations of bupivacaine and two of its metabolites during continuous interscalene brachial plexus block.
 An interscalene brachial plexus block was performed via a catheter with 20-28 ml of 0.75% bupivacaine plus adrenaline for surgery of the shoulder region in 12 patients.
 Constant infusion of 0.25% bupivacaine 0.25 mg kg-1 h-1 was continued for 24 h.
 During surgery light general anaesthesia, without analgesics, was maintained.
 Plasma concentrations of total and unbound (free fraction) bupivacaine, desbutylbupivacaine (DBB), 4-hydroxybupivacaine (4-OHB) and alpha 1-acid glycoprotein (AAG) were measured at predetermined intervals during the continuous block.
 The greatest mean plasma concentrations of bupivacaine were measured at 30 min (1.63 (SD 0.55) micrograms ml-1) and 60 min (1.38 (0.48) micrograms ml-1).
 There was a small but statistically significant increase in the plasma concentration of bupivacaine between 12 and 24 h of infusion.
 The mean unbound concentration of bupivacaine in plasma decreased from 0.044 (0.015) microgram ml-1 (3.6 (1.1)% of total bupivacaine concentration) at 3 h to 0.023 (0.011) micrograms ml-1 (2.1 (1.0)%) at 24 h.
 The AAG concentration in plasma increased by 38% in 24 h.
 The metabolites DBB and 4-OHB were detectable in plasma from 30 min, with a gradual increase during infusion.
 At 24 h the mean concentrations of DBB and 4-OHB were 0.33 (0.22) micrograms ml-1 and 0.13 (0.04) micrograms ml-1, respectively.
 There were no toxic reactions during the blocks.
",22
3963,"Pharmacokinetics and clinical experience of 20-h infusions of methohexitone in intensive care patients with postoperative pyrexia.
 We have studied the pharmacokinetics of 20-h infusions of methohexitone in young patients with postoperative fever undergoing artificial ventilation of the lungs.
 The infusion rate was adjusted so that patients were unresponsive to vocal stimulation but reacted to tracheal suction.
 The mean steady state concentration of methohexitone required was 2.6 mg litre-1 (unbound 0.53 mg litre-1).
 The mean (SD) total clearance of methohexitone was 16.3 (4.2) ml min-1 kg-1, which is greater than that for volunteers or normal surgical patients.
 The unbound clearance correlated positively with body temperature during the infusion (r = 0.796, P = 0.017).
 The terminal half-life of methohexitone was 6.3 (3.8) h and that of the 4'-hydroxy metabolite 5.8 (2.1) h.
 There were no marked haemodynamic effects of the infusion, and no excessive sedation after the infusion.
 However, the clearance of methohexitone was high and variable, possibly as a direct effect of postoperative fever.
 Consequently, the need for individual titration of the rate of infusion is emphasized.
",22
3964,"Sciatic nerve monitoring during revision total hip arthroplasty.
 This study presents a simple method of intraoperative sciatic nerve monitoring during revision total hip arthroplasty (THA), utilizing intraoperative, somatosensory evoked potentials.
 Using this method, the sciatic nerve was protected when surgical correction of shortened limb length was necessary during revision THA.
 Twenty-three revision THAs were performed using intraoperative sciatic nerve monitoring.
 No postoperative peripheral nerve complications occurred, with an average increase of 18 mm in leg length, ranging from 6 mm to 43 mm.
",22
3965,"The importance of the GHQ in general practice.
 The relationship between General Health Questionnaire (GHQ) score and complaints presented at the general practitioners office was examined, and showed that the correlation between them is not as high as might be expected.
 Many patients who present psychosocial problems to their GP appear to have a low GHQ score; many patients with a high GHQ score exclusively present somatic complaints, which are also assessed by the GP as being purely somatic.
 Implications of the results are discussed.
",22
3966,"Morphological features of blood access stenosis and results of noninvasive angioplasty.
 We investigated a connection between the results of noninvasive angioplasty for the blood access stenosis and its morphological features in 37 dialysis cases.
 In 3 cases presenting stenosis in the original artery, the area could not be dilated by noninvasive techniques.
 In 4 cases with stenosis in the arterialized vein downstream of the needle insertion points for extracorporeal circulation, 3 showed long-term dilatation by the procedures.
 In 30 cases having stenosis upstream of the points, 16 showed long-term dilatation.
 In the unsuccessful cases, the angle formed between the axes of the stenosed portion and the normal vessel was over 39 degrees, and the distance between the anastomosis and the stenosed portion was less than 11 mm.
",22
3967,"Reliability of stimulated and spontaneous growth hormone (GH) levels for identifying the child with low GH secretion.
 The reliability of stimulated and spontaneous GH levels for identifying the child with low GH secretion has been the subject of debate.
 We compared the ability of GH concentrations after pharmacological stimulation with levodopa and clonidine and of spontaneous peak and 12-h pooled GH concentrations during sleep on a single night to estimate the maximum spontaneous GH secretion from 2 nights in 55 children, aged 5-16 yr, with heights below the 3rd percentile and/or height velocities below the 25th percentile for age, who had two consecutive overnight GH secretory profiles.
 Maximum stimulated GH concentrations correctly categorized 80% of children who had maximum spontaneous GH concentrations above and below 4 micrograms/L using a double monoclonal immunoradiometric assay for GH (Tandem-R HGH, Hybritech).
 The remaining 20% of children had stimulated GH concentrations below but spontaneous GH concentrations above 4 micrograms/L.
 Using this cut-off, the maximum GH concentrations from the first and second nights correctly categorized 98% and 95% of the children, respectively.
 Night to night variation in GH secretion was low in children who had low spontaneous GH secretion (maximum spontaneous peak and pool GH concentrations, less than 4 and less than or equal to 0.7 micrograms/L, respectively), and pooled GH concentrations from the 2 nights were concordant in 98% of the cases.
 We conclude that it is not uncommon for stimulated GH concentrations to underestimate spontaneous GH secretion.
 Even without acclimatization to the hospital setting, measurement of spontaneous GH secretion on a single night was more reliable for identifying the child with low endogenous GH secretion than was GH stimulation testing alone.
",22
3968,"Quality of life in elderly, chronically ill outpatients.
 Quality of life (QL) in elderly outpatients is poorly characterized.
 We interviewed 258 elderly outpatients from three health care settings to identify the attributes and events that affect self-assessment of QL.
 These outpatients rated their QL as acceptable, citing medical care, health, interpersonal relationships, financial status, and functional status as affecting their QL.
 Overall QL ratings were not strongly associated with objective indicators such as demographic characteristics and use of health care services.
 Subjective indicators, including patient perceptions of health, memory, and financial concerns, were correlated independently with global QL (sigma R2 = .35).
 We conclude that older, chronically ill patients generally consider their QL to be acceptable and affected by a variety of factors, including their perceptions of their emotional, socioeconomic, intellectual, and physical functioning.
 Furthermore, QL is poorly associated with objective indicators.
 Thus, in assessing the QL of elderly, chronically ill outpatients, physicians should elicit information regarding these perceptions.
",22
3969,"Value of combined assessment of physical health and functional status in community-dwelling aged: a prospective study in Florence, Italy.
 A survey of the health and social conditions of a representative sample of 967 persons aged 60 years and older from the city of Florence, Italy, was undertaken in 1980.
 In 1987, a follow-up survey of this cohort was performed.
 There were 391 documented deaths, 408 survivors, and 168 individuals who could not be located.
 Functional ability at baseline was assessed using a World Health Organization 14-item scale.
 Indicators of physical health status included chronic disease status, number of drugs, physician visits, and days of hospitalization.
 After adjustment for age and sex, both functional ability and indicators of physical health status were found to be independent, statistically significant predictors of mortality.
 The results of this study further support the view that biomedical and functional assessment are both necessary for a comprehensive evaluation of the older population.
",22
3970,"Decision criteria for pure-tone detection used by two age groups of normal-hearing and hearing-impaired listeners.
 Response criteria from a yes-no task and detection thresholds from two test procedures were measured for four groups of adults: younger normal-hearing, older normal-hearing, younger hearing-impaired, and older hearing-impaired.
 The two test procedures were an audiological procedure (which does not control for response bias) and a 21FC adaptive procedure (which does control for bias).
 The signal was a 500 or 4000 Hz tone presented in quiet.
 All four groups showed an equally conservative response bias in the yes-no task.
 In addition, neither age nor hearing loss affected the difference (6.5 dB) between the two threshold measures.
",22
3971,"The effects of rate, sequencing, and memory on auditory processing in the elderly.
 Auditory sequencing, rate, and memory were evaluated in three age groups with a series of subtests that require the identification of tones (Repetition Test; Tallal & Piercy, 1973).
 The older elderly group (M age = 80), but not the younger elderly group (M age = 70), performed significantly (p less than .05) poorer than the young adult group (M age = 25) when auditory memory of 4 and 5 tones was required and when the interstimulus interval was decreased.
 Performance was not related to hearing sensitivity, thus suggesting that changes in the auditory mechanism that occur with age may encompass more than a loss of hearing sensitivity.
 Moreover, performance on the Repetition Test did correlate with memory for digits, which indicates a relationship between auditory processing and higher cortical functions.
",22
3972,"Nonorganizational religious participation among elderly black adults.
 This study investigated rates of participation in nonorganizational religious activities of elderly Black adults.
 Four indicators of participation were examined: reading religious materials, watching or listening to religious programs, prayer, and requests for prayer.
 Demographic, religious denomination, and health disability factors influenced participation in these behaviors.
 The findings were discussed for their implications for the development of a multidimensional conceptualization of religiosity.
",22
3973,"Health perceptions and survival: do global evaluations of health status really predict mortality?
 Self-evaluations of health status have been shown to predict mortality, above and beyond the contribution to prediction made by indices based on the presence of health problems, physical disability, and biological or life-style risk factors.
 Several possible reasons for this association are discussed: (a) methodological shortcomings of previous studies render the association spurious; (b) other psychosocial influences on mortality are involved and explain the association; and (c) self-evaluations of health status have a direct and independent effect of their own.
 Four-year follow-up mortality data from the Yale Health and Aging Project (N = 2812) are used to explore these possibilities.
 The analysis controls for the contribution of numerous indicators of health problems, disability and risk factors, and also makes adjustments of standard errors for the complex sample design.
 The findings favor the third possibility, an independent effect, to the extent that the particular set of psychosocial factors examined did not explain the basic association, and to the extent that the control variables were an adequately comprehensive set.
",22
3974,"Population aging patterns: the expansion of mortality.
 We used the hypothesis of mortality compression as a framework to examine patterns of mortality from 1962 to 1984.
 Data from national vital statistics records were used for analysis of the changing age at death for percentiles of the population.
 Data from the Social Security Administration and the U.S.
 Census Bureau were used to calculate the force of mortality.
 The mean age at death for all percentiles, including the oldest groups, has risen during the interval.
 Examination of the coefficient of variation for the mean age at death suggests that there is a relative increase in the variability of age at death among the oldest old.
 The available data do not fit a hypothetical sequence of normal density distributions with an increasing mean and declining standard deviation.
 The force of mortality in those over 85 years appears to be decreasing in a pattern similar to that for those under 85 years.
 Current mortality patterns suggest an ""expansion,"" rather than compression, of mortality at the oldest ages.
 Further refinement of these observations, with improved data on mortality among the oldest old, will be helpful in delineating mortality patterns.
",22
3975,"Stressful events and life satisfaction among elderly men and women.
 The purpose of this study was to examine the interrelationships among stressful events, domain-specific assessments of life satisfaction, and global evaluations of life satisfaction.
 This research was guided by two competing theoretical formulations.
 According to bottom-up theory, older adults first assess feelings of satisfaction within specific life domains that are based in part on the experiences (i.e., stressors) they encounter in these areas.
 The domain-specific views are subsequently synthesized to form an overall sense of satisfaction with life as a whole.
 In contrast, the top-down theory suggests that a person's ongoing sense of satisfaction with life as a whole predisposes him or her to assess satisfaction with specific domains in ways that are congruent with his or her initial sense of global life satisfaction.
 Analysis of data provided by older participants in a nationwide survey tends to support the bottom-up perspective.
",22
3976,"Resting metabolic rate and energy balance in amenorrheic and eumenorrheic runners.
 This study investigated metabolic and nutritional factors in association with athletic menstrual dysfunction (AMD).
 Three groups of women were studied: amenorrheic runners (amenorrheic), eumenorrheic runners (eumenorrheic), and eumenorrheic sedentary controls (sedentary).
 Amenorrheic and eumenorrheic were similar in age, weight, percent body fat by hydrodensitometry, training pace and mileage, best 10 km race time, years running, and maximal oxygen consumption.
 When adjusted for body weight or for fat-free mass by analysis of covariance, RMR was significantly lower in amenorrheic than in eumenorrheic and sedentary.
 The daily caloric intakes of the groups did not differ significantly, but the amenorrheic scored significantly higher than the eumenorrheic and sedentary on a scale of aberrant eating patterns.
 Amenorrheic high mileage runners seem to have a less adequate diet than eumenorrheic runners but appear to maintain energy balance and stable weight through a reduction in RMR.
",22
3977,"Menstrual function and eating behavior in female recreational weight lifters and competitive body builders.
 A group of 103 female weight lifters (WL) and 92 control (C) women answered a survey concerning eating behavior and attitudes (including the Eating Disorder Inventory) and menstrual function.
 The incidence of menstrual dysfunction, defined as oligomenorrhea plus amenorrhea, was significantly higher for the WL (30%) than for the C (13%) not on contraceptive pills.
 Only 2% of the women had amenorrhea.
 The incidence of dysfunction was highest for the subset of 12 WL who had competed in at least one body building competition (COMP); 86% of the COMP not on birth control pills had menstrual dysfunction (P less than 0.05).
 More WL than C reported missing at least one menstrual period during the last year (P = 0.06).
 WL scored significantly higher than C on the Drive for Thinness subscale of the Eating Disorder Inventory (EDI).
 Fifteen percent of the WL and 9% of the C achieved the criteria on this subscale for being weight preoccupied (P greater than 0.05).
 Significantly more WL than C responded that they were terrified of becoming fat (WL 56%, C 38%), were obsessed with food (WL 47%, C 30%), used laxatives for weight control (WL 14%, C 1%), and claimed that they had been anorexic in the past (WL 17%, C 5%).
 Examination of the answers of COMP revealed several items that were significantly different from the remainder of the WL.
 For example, 42% used to be anorexic, 67% were terrified of becoming fat, and 50% experienced uncontrollable urges to eat.
",22
3978,"Skeletal muscle following tonic overload: functional and structural analysis.
 Functional overloading of skeletal muscle induces a compensatory hypertrophy as an adaptive response to increased functional demand.
 Overload of the extensor digitorum longus (EDL) muscle (129 ReJ strain male mouse) was induced by unilateral surgical removal of a synergistic muscle, tibialis anterior (TA).
 Response of the EDL to overload for 7, 21, and 42 d was analyzed for changes in 1) muscle weight, 2) myofiber type distribution, 3) myofiber cross-sectional area by fiber type, 4) speed of contraction and relaxation of the muscle, 5) force of contraction, and 6) myofiber morphologic integrity.
 The weight of the EDL significantly increased.
 The overload caused no impairment of muscle contractility and did not have a significant effect on isometric twitch contraction time to peak tension or the time to one-half relaxation of the twitch.
 Overloaded muscles demonstrated a transient shift in fiber type profile with preferential hypertrophy of Type IIA fibers that occurred in the early phase of overload while type IIB fibers were recruited by 42 d.
 No significant increase in myofiber number in overloaded muscles occurred.
 Some morphologic changes in over-loaded muscles parallel those found in patients with neurogenic muscular disorders.
 However, overloaded muscle did not exhibit a significant occurrence of fiber branching from controls in the midbelly region of the muscle.
",22
3979,"Oxygen uptake and heart rate responses during hypoxic exercise in children and adults.
 Control of ventilation and heart rate during exercise appears to undergo maturation, while aerobic metabolism (VO2) may not.
 Since we had previously found that hypoxia during exercise produced different ventilatory responses in children (C) compared to adults (A), we hypothesized that VO2 and heart rate kinetics during exercise would show similar maturational responses to hypoxia.
 To test this hypothesis, we examined the responses during progressive (ramp) and constant work rate tests in children and adults breathing either room air or hypoxic gas (FiO2 = 0.15).
 When corrected for body weight, children and adults had similar values for lactic acidosis threshold (LAT) (C: 29.1 +/- 5.0 ml.min-1.kg-1; A: 27.9 +/- 4.3) and VO2max (C: 40.7 +/- 8.6 ml.min-1.kg-1; A: 45.2 +/- 6.7) during normoxia.
 Hypoxia significantly lowered LAT (C: 27.5 +/- 5.4 ml.min-1.kg-1; A: 23.2 +/- 3.8; both P less than 0.05) and VO2max (C: 37.7 +/- 8.3 ml.min-1.kg-1; A: 40.1 +/- 5.3; both P less than 0.05) in both children and adults.
 Metabolic efficiency (delta VO2/delta work rate) and the VO2-heart rate relationship (delta VO2/delta HR/kg) were similar in the two groups and unaffected by hypoxia.
 During the constant work rate exercise, VO2 kinetics (time constant during phase 2 of the response (pi 1) and the O2 deficit) were similar between children and adults and were significantly slowed by hypoxia, consistent with current understanding of the control of oxidative metabolism.
 Finally, heart rate was increased at rest and during exercise with hypoxia, while the time to reach 75% of the end-exercise response was delayed significantly, in both groups.
",22
3980,"Video display terminals and the risk of spontaneous abortion.
 BACKGROUND.
 The relation between spontaneous abortion and the use of video display terminals (VDTs) is of great public health concern.
 Previous investigators of this issue have reported inconsistent findings.
 METHODS.
 To determine whether electromagnetic fields emitted by VDTs are associated with an increased risk of spontaneous abortion, a cohort of female telephone operators who used VDTs at work was compared with a cohort of operators who did not use VDTs.
 To obtain reliable estimates of exposure, we determined the number of hours of VDT use per week from company records and measured electromagnetic fields at VDT workstations and, for purposes of comparison, at workstations without VDTs.
 Operators who used VDTs had higher abdominal exposure to very-low-frequency (15 kHz) electromagnetic fields (workstations without VDTs did not emit very-low-frequency energy).
 Abdominal exposure to extremely-low-frequency fields (45 to 60 Hz) was similar for both operators who used VDTs and those who did not.
 Among 2430 women interviewed, there were 882 pregnancies that met our criteria for inclusion in the study.
 RESULTS.
 We found no excess risk of spontaneous abortion among women who used VDTs during the first trimester of pregnancy (odds ratio = 0.93; 95 percent confidence interval, 0.63 to 1.38), and no dose-response relation was apparent when we examined the women's hours of VDT use per week (odds ratio for 1 to 25 hours per week = 1.04; 95 percent confidence interval, 0.61 to 1.79; odds ratio for greater than 25 hours per week = 1.00; 95 percent confidence interval, 0.61 to 1.64).
 There continued to be no risk associated with the use of VDTs when we accounted for multiple pregnancies, conducted separate analyses of early abortion, late abortion, and all fetal losses, or limited our analyses to spontaneous abortions for which a physician was consulted.
 CONCLUSIONS.
 The use of VDTs and exposure to the accompanying electromagnetic fields were not associated with an increased risk of spontaneous abortion in this study.
",22
3981,"A comparison of three formulations of TAC (tetracaine, adrenalin, cocaine) for anesthesia of minor lacerations in children.
 A randomized, prospective, double-blind study comparing three formulations of the topical anesthetic solution TAC for laceration repair was undertaken in 250 children.
 The children's wounds were anesthetized with either TAC I (original formulation--0.5% tetracaine, 1:2000 Adrenalin, 11.8% cocaine), TAC II (1.0% tetracaine, 1:4000 Adrenalin, 7.0% cocaine), or TAC III (1.0% tetracaine, 1:4000 Adrenalin, 4.0% cocaine) prior to repair.
 The solutions were compared with respect to efficacy, acceptability, wound complications, and side effects.
 We found comparable efficacy of the three formulations, with similar efficacy to 1% lidocaine infiltration for facial and scalp wounds.
 Anesthesia for extremity wounds was adequate in only 39.9% of cases, regardless of TAC strength.
 Wound complications and side effects were within expected and acceptable limits.
 Our findings support use of TAC for face and scalp lacerations and a change to a less concentrated TAC preparation, such as our ""TAC III,"" which is presumably safer for widespread use.
",22
3982,"Experience with 50 free TRAM flap breast reconstructions.
 The data from the first 50 patients undergoing free TRAM flap breast reconstruction in two units were examined.
 Average patient age was 42 years, and average weight was 62 kg.
 Forty percent of patients were chronic smokers, and 26 percent had low abdominal scars.
 Twelve percent exercised their abdominal muscles regularly.
 Eighteen percent had undergone radical mastectomy, whereas 76 percent had undergone modified radical mastectomy and 6 percent had undergone subcutaneous mastectomy.
 Postoperative radiotherapy had been given in 16 percent of patients, and 54 percent had received postoperative chemotherapy.
 The average time from mastectomy was 32 months, whereas six breasts were reconstructed immediately.
 Average operating time was 5.6 hours, and average blood loss was 2.4 units.
 Average hospital stay was 11.2 days.
 Complications included three total flap losses (6 percent) and two partial flap losses (4 percent).
 Abdominal hernia occurred in two patients (4 percent).
",22
3983,"Methyl prednisolone in double-lumen gel-saline submuscular mammary prostheses: a double-blind, prospective, controlled clinical trial.
 At the time of immediate breast reconstruction with submuscular implants, 76 consecutive patients (89 breasts) were randomized into two groups.
 One received a gel-saline, double-lumen implant with 40 cc of saline added to the outer lumen, while the other received the same implant plus 40 cc of saline and 16 mg methyl prednisolone (40 mg%).
 Patients were followed for a minimum of 3 years.
 The groups, which were matched for patient age and implant size, were evaluated at 3, 12, 24, and 36 months for capsular contracture, steroid atrophy, and other complications.
 With completion of the double-blind study, the patients with submuscular gel-saline implants with only saline added had an overall capsular contracture rate of 38 percent at 3 months, 38 percent at 12 months, and 44 percent at 24 and 36 months.
 Those with methyl prednisolone had an overall capsular contracture rate of 14 percent at 3 months, and this remained unchanged through the end of the study.
 The rates of all other complications were comparable.
 Methyl prednisolone in a dose of 16 mg in 40 cc saline (concentration 40 mg%), when used in the outer lumen of a double-lumen gel-saline implant in a submuscular pocket, is both safe and efficacious in reducing the risk of capsular contracture for a minimum of 3 years in patients undergoing immediate breast reconstruction with submuscular mammary implants.
",22
3984,"Radiographic manifestations of congenital anomalies of the spine.
 Although the foregoing review of embryologic development and congenital anomalies of the spine in infants and children is necessarily brief, the most commonly encountered abnormalities have been reviewed, and when possible, an attempt has been made to cite the stage of embryologic development at which the various abnormalities originate.
 As noted, congenital abnormalities of the spine are relatively uncommon but may be of profound clinical significance.
 During the past decade, the most significant developments in the diagnosis and treatment of these abnormalities have been ultrasonography, CT scanning, and MR imaging.
 In the neonate, the spinal cord and neural outflow can be evaluated by ultrasonography until the osseous elements begin to fuse.
 Thereafter, MR imaging is the procedure of choice because it permits evaluation of the spine and spinal cord in all planes of imaging and provides detailed evaluation of the effect of osseous abnormalities on neural structures.
 Finally, plain radiographs of the spine for evaluation of neonates who have any of a spectrum of sacral dimples are rarely helpful, and in the presence of significant cutaneous or subcutaneous abnormalities, ultrasonography is the preferred modality for evaluation.
",22
3985,"Characteristics of accessory pathways exhibiting decremental conduction.
 The prevalence, electrophysiologic characteristics and functional significance of decremental conduction over an accessory pathway were examined in this retrospective study of 653 patients who had an accessory pathway demonstrated at electrophysiologic study.
 Decremental conduction was identified in 50 patients (7.6%).
 In 15 patients with anterograde decremental conduction, the accessory pathway was right parietal or septal in 14 patients and left parietal in 1 patient.
 In the 40 patients with retrograde decrement, the accessory pathway was left parietal in 19, posteroseptal in 13, right parietal in 2 and right anteroseptal in 6 patients.
 Anterograde conduction over the accessory pathway was absent in 11 of the 40 patients with retrograde decrement.
 Retrograde conduction over the accessory pathway was absent in 9 patients with anterograde decrement.
 There was no significant difference in the accessory pathway effective refractory period, or shortest cycle length with 1:1 conduction over the accessory pathway in anterograde and retrograde directions.
 The shortest RR interval in atrial fibrillation between 2 preexcited QRS complexes was longer in patients with anterograde decremental conduction than in a control group of patients with anterograde-conducting accessory pathways without decremental properties.
 These data demonstrate that decremental conduction over accessory pathways is uncommon.
 Anterograde decremental conduction usually occurs in right-sided or septal pathways that often do not conduct in the retrograde direction.
",22
3986,"Usefulness of d, I sotalol for suppression of chronic ventricular arrhythmias.
 Sotalol is a unique beta-blocking drug, possessing significant class III antiarrhythmic activity.
 The efficacy and safety of 2 doses of sotalol (320 and 640 mg/day, divided in 2 doses) were compared to placebo in a 6-week randomized, double-blind, multicenter study of 114 patients with chronic ventricular premature complexes (VPCs) at frequencies of greater than or equal to 30/hour.
 Sotalol significantly reduced VPCs in patients receiving both low (n = 38) and high (n = 39) doses, compared with patients (n = 37) receiving placebo (by 75 and 88%, respectively, vs 10%; p less than 0.001, sotalol vs placebo; p less than 0.05, high vs low dose).
 The individual efficacy criterion (greater than or equal to 75% VPC reduction) was achieved in 34% of low-dose and 71% of high-dose sotalol versus 6% of placebo-treated patients (p less than 0.003, sotalol vs placebo; p = 0.007, high vs low dose).
 Repetitive beats were suppressed 25% by placebo (difference not significant), 80% by low-dose (p less than 0.003) and 78% by high-dose sotalol (p less than 0.005).
 Sotalol decreased heart rate (by 24 to 25%, p less than 0.001) and increased PR (by 4 to 6%, p less than 0.001) and corrected JT intervals (by 12 to 13%, p less than 0.001), but did not change ejection fraction.
 Proarrhythmia (nonfatal) occurred in 3 sotalol and in 2 placebo patients.
 Nine discontinued therapy because of adverse effects (1 low dose and 8 high dose, p less than 0.02).
 In summary, sotalol is an efficacious antiarrhythmic drug for VPC suppression; in lower doses, it is somewhat less effective but better tolerated.
",22
3987,"The perception of life events and daily stress in nonulcer dyspepsia.
 Previous studies on the association of nonulcer dyspepsia with major life events were performed without emphasis on the perception of these events, and have yielded conflicting results.
 The present study examined the perception of life events and, in addition, the role of daily ""hassles"" (stressful events) in patients with nonulcer dyspepsia.
 Thirty-three dyspeptic patients as defined by normal endoscopy and ultrasonogram and 33 controls of comparable sex, age, and social class were recruited for study.
 Both groups were asked to select from 56 major life events those they had experienced and to give a rating on how they perceived them.
 They were further asked to select similarly from 117 items of daily stress and to rate the severity of each item.
 The results demonstrated that the number of positive and negative events and the positive score were similar in both dyspeptic patients and controls, but dyspeptic patients had a higher perceived magnitude of negative events and a higher score of total life change as given by the summation of magnitude of positive and negative events (both p less than 0.05).
 The ""hassles"" scores were not significantly different between dyspeptic patients and controls.
 Analysis of individual life events revealed that dyspeptic patients had significantly (p less than 0.05) higher scores than controls in items of minor law violations, major change in closeness of family members, and major personal illness or injury.
 We conclude that patients with nonulcer dyspepsia have higher negative perception of major life events, which indicates that psychological factors may play a role in the pathogenesis of nonulcer dyspepsia.
",22
3988,"Clinical and molecular diagnosis of Miller-Dieker syndrome.
 We report results of clinical, cytogenetic, and molecular studies in 27 patients with Miller-Dieker syndrome (MDS) from 25 families.
 All had severe type I lissencephaly with grossly normal cerebellum and a distinctive facial appearance consisting of prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw.
 Several other abnormalities, especially growth deficiency, were frequent but not constant.
 Chromosome analysis showed deletion of band 17p13 in 14 of 25 MDS probands.
 RFLP and somatic cell hybrid studies using probes from the 17p13.3 region including pYNZ22 (D17S5), pYNH37 (D17S28), and p144-D6 (D17S34) detected deletions in 19 of 25 probands tested including seven in whom chromosome analysis was normal.
 When the cytogenetic and molecular data are combined, deletions were detected in 21 of 25 probands.
 Parental origin of de novo deletions was determined in 11 patients.
 Paternal origin occurred in seven and maternal origin in four.
 Our demonstration of cytogenetic or molecular deletions in 21 of 25 MDS probands proves that deletion of a ""critical region"" comprising two or more genetic loci within band 17p13.3 is the cause of the MDS phenotype.
 We suspect that the remaining patients have smaller deletions involving the proposed critical region which are not detected with currently available probes.
",22
3989,"Blockade of prostaglandin production increases cachectin synthesis and prevents depression of macrophage functions after hemorrhagic shock.
 Although hemorrhage severely depresses macrophage functions, it is not known whether the increased TNF-alpha or PGE2 production is responsible for it.
 To study this C3H/HeN mice were bled to mean blood pressure of 35 mmHg for 60 minutes, resuscitated, and treated with either ibuprofen (1.0 mg/kg body weight) or vehicle (saline).
 Hemorrhage increased plasma prostaglandin E2 (PGE2) levels by 151.7% +/- 40.0% (p less than 0.05) and significantly decreased peritoneal macrophage (pM phi) antigen presentation (AP) by 60.5% +/- 7.3%, Ia expression by 52.3% +/- 7.6%, and interleukin-1 (IL-1) synthesis by 60.5% +/- 12.3% compared to shams.
 However ibuprofen treatment reduced PGE2 plasma levels by 61.3% +/- 12.1% and significantly increased AP (+237.0% +/- 95.3%), Ia expression (+72.8% +/- 27.5%), IL-1 synthesis (+235.7% +/- 134.7%), and cachectin synthesis (+485.8% +/- 209.0%) compared to vehicle-treated animals.
 These results indicate that prostaglandins but not cachectin are involved in the suppression of pM phi functions following hemorrhage because blockade of prostaglandin synthesis improved depressed macrophage functions despite enhanced cachectin synthesis.
",22
3990,"Site of action of continuous extrapleural intercostal nerve block.
 Continuous extrapleural intercostal nerve block has been shown in a randomized, controlled study to be effective in reducing postoperative pain after thoracotomy and in restoring pulmonary mechanics.
 To assess the extent of spread of bupivacaine infused through an extrapleurally placed cannula inserted at thoracotomy, iohexol (Omnipaque) was infused at 5 days postoperatively in 5 patients and computed tomography performed.
 The contrast medium was confined to the paravertebral space covering on average six intercostal spaces.
 This study demonstrated that anatomically, the site of action of the bupivacaine infused through an extrapleural cannula was primarily in the paravertebral space.
",22
3991,"Simplified hepatic resection with the use of prolonged vascular inflow occlusion.
 Ten consecutive patients scheduled to undergo liver resection were studied prospectively with the use of a standard protocol, which included routine vascular inflow occlusion to reduce blood loss and blood transfusion requirements.
 Fibrin sealant was sprayed on the raw liver surface, and abdominal drainage was not performed.
 No deaths occurred, and the postoperative course was remarkably smooth.
 The normothermic liver ischemic times of 30 to 122 minutes (mean, 73 minutes) were well tolerated.
 The amount of blood transfused was reduced to a mean of 2 U (range, 0 to 4 U).
 The occurrence of infected intraabdominal bile collections in two patients with preexisting biliary tract infection suggested that abdominal drainage should be performed in such patients.
 Vascular inflow occlusion is recommended for all liver resections.
",22
3992,"Babies born before arrival at hospital.
 OBJECTIVE--To establish the prevalence of babies born before arrival at two local hospitals.
 To identify women at risk of giving birth before arrival, and the morbidity and mortality associated with such births.
 DESIGN--A case control study.
 Each baby born before arrival and its mother were compared with the next born in the hospital (random control), and one matched for gestation and birthweight, together with their mothers.
 SETTING--Two maternity units serving East Birmingham and Solihull.
 SUBJECTS--All babies (and their mothers) born before arrival at these hospitals from January 1983 to December 1987.
 MAIN OUTCOME MEASURES--Perinatal mortality rates, patterns of perinatal morbidity, demographic, social and obstetric features of the mothers.
 RESULTS--137 (0.44%) of 31,140 consecutive births were before arrival at hospital (BBA group).
 The perinatal mortality rate in the BBA group was 58.4/1000 (8 deaths) compared with 10.1/1000 for all inborn babies (relative risk 5.8, 95% confidence interval 2.9-11.4).
 In the BBA group the mean birthweight of 3008 g was 212 g (95% CI 50-374 g) less than that in the random control group; the mean gestation of 266 days was 10 days less (95% CI 5.9-14.1 days) than in the random control group.
 Hypothermia was the commonest morbidity.
 Women delivered before arrival tended to be either multigravid inner city Asians living a long way from the hospital or unmarried unbooked younger white Europeans.
 CONCLUSIONS--The high perinatal mortality was related to immaturity and low birthweight, rather than to birth before arrival itself.
 Although groups of mothers at risk of delivery before arrival can be identified more information is needed to establish whether additional antenatal care would be beneficial for these women and their babies.
",22
3993,"Role of phenytoin in healing of large abscess cavities.
 The promotion of healing of large abscess cavities attained with topical phenytoin was evaluated in controlled studies of clinical and experimental wounds.
 In the clinical abscess cavities, phenytoin application in 20 patients compared with conventional treatment in 20 patients resulted in earlier separation of slough, decrease in oedema, control of pain and overall enhanced healing.
 The mean(s.d.) rate of reduction of wound area was 2.02(0.48) cm2/day in the phenytoin group versus 1.58(0.51) cm2/day in controls (P less than 0.05) on day 10, and 1.8(0.32) cm2/day versus 1.19(0.21) cm2/day (P less than 0.01) on day 20.
 The mean volume reduction rates at both the 10th and 20th day were 0.48(0.01) cm3/day for phenytoin versus 0.32(0.04) cm3/day for controls; (P less than 0.005).
 By day 20, 17 of the patients treated with phenytoin were rated as having healed completely, compared with only one of the controls.
 In a standardized guinea-pig model of the clinical abscess cavity, which included inoculation of the wound with Bacillus proteus and Klebsiella pneumoniae, an enhanced healing rate was also observed (at 7 days 0.40(0.05) cm2/day with phenytoin versus 0.21(0.08) cm2/day in controls; P less than 0.005).
 All eight of the animals treated with phenytoin healed by day 21, compared with one of the eight controls.
 Biopsies of wounds treated with phenytoin showed less inflammation, no necrosis, and enhanced neovascularization, collagen deposition and fibroblast proliferation compared to controls.
 Bacterial colonies also decreased more rapidly with the use of phenytoin.
",22
3994,"Effect of fibrin sealant on the healing colonic anastomosis in the rat.
 Fibrin adhesives have been advocated as a protective seal in colonic anastomosis to prevent leakage.
 In order to assess the effect of fibrin glue sealing we compared the healing of sutured colonic anastomosis in the rat (group 1) with the addition of human-derived fibrin sealant (group 2).
 As a control for a possible reaction to foreign protein, in group 3 the sutured anastomosis was sealed with specially prepared rat fibrin adhesive.
 On days 2, 4 and 7, ten animals in each group were killed.
 Adhesion formation was scored and the in situ bursting pressure was measured.
 The collagen concentration and degradation were estimated by measuring hydroxyproline.
 Adhesion formation was significantly increased in groups 2 and 3 compared with the control group.
 On days 2 and 7 the bursting pressure was not different between the groups.
 On day 4 the bursting pressure in groups 2 and 3 was significantly lower than in group 1 (P less than 0.001).
 These findings correspond with the results of collagen measurements.
 On day 4 the concentration of hydroxyproline was significantly reduced in groups 2 and 3.
 Histological examination showed infiltration of neutrophilic granulocytes into the sealant on days 2 and 4; on day 7 the sealant had vanished.
 From these results it is concluded that fibrin sealing of the colonic anastomosis in the rat does not improve healing, as demonstrated by bursting pressure and hydroxyproline concentration.
 On the contrary, it seems to have a negative influence.
",22
3995,"The mechanism of spastic muscle hypertonus. Variation in reflex gain over the time course of spasticity.
 The electromyographic (EMG) response of the initially passive biceps brachii muscle to imposed extension applied at the elbow was studied in 19 hemiparetic and 12 normal subjects.
 In relaxed normal subjects, the biceps muscle was found to respond only at displacement velocities above 175 deg/s, with a single early burst of activity in the biceps EMG.
 In contrast, the hemiparetic subjects, in addition to the early EMG activity, also showed considerable late activity, which persisted even with stretch velocities as low as 35 deg/s.
 This late activity is a stretch reflex, present in fully plegic arms.
 It was seen in all spastic subjects in whom the tone of the biceps had been clinically assessed to be raised, but was never observed in subjects with normal muscle tone.
 The mean level of this EMG response was highly correlated with displacement velocity and its duration to the duration of the applied displacement.
 It is suggested that this reflex EMG activity is the major factor in the genesis of spastic hypertonus in the arm and that it arises not from a reduction in the threshold of the stretch reflexes of the muscle, but from a pathological increase in stretch reflex gain.
 It is further shown that this activity is at a high level between the first and third months after the onset of spasticity and that the reflex gain is significantly reduced when spasticity is established for a year or more.
 It is concluded that, while changes in passive mechanical properties may play a role when spasticity has been established for more than a year, the major cause of spastic muscle hypertonus is a pathological increase in stretch reflex activity.
",22
3996,"Alterations in left ventricular diastolic twist mechanics during acute human cardiac allograft rejection.
 BACKGROUND.
 Contraction of obliquely oriented left ventricular (LV) fibers results in a twisting motion of the left ventricle.
 The purpose of this study was to assess the effects of acute human cardiac allograft rejection on LV twist pattern and the twist-volume relation.
 METHODS AND RESULTS.
 Tantalum markers were implanted into the LV midwall in 15 transplant recipients to measure time-varying, three-dimensional chamber twist using computer-assisted analysis of biplane cinefluoroscopic images.
 Twist was defined as the mean longitudinal gradient of circumferential rotation about the LV long axis.
 When plotted against normalized percent ejection fraction (%EF), the resulting twist-normalized %EF relation could be divided into three phases.
 In systole, LV twist was linearly related to ejection of blood.
 In contrast, diastolic untwist was characterized by early rapid recoil with little change in LV volume, followed by more gradual untwisting when the bulk of diastolic filling occurred.
 During 10 acute rejection episodes in 10 patients, maximum twist, peak systolic twist rate, and the slope of the systolic twist-normalized %EF relation did not change.
 In contrast, the slope of the early (first 15% of filling) diastolic twist-normalized %EF relation (M(early-dia)) decreased significantly (-0.194 +/- 0.062 [prerejection] versus -0.103 +/- 0.054 rad/cm [rejection], p = 0.0003), resulting in a prolonged tau 1/2 (time required to untwist by 50% [20 +/- 5% versus 28 +/- 5% of diastole], p = 0.0003) and decrease in percent untwisting at 15% diastolic LV filling (62 +/- 11% versus 36 +/- 13%, p = 0.0003).
 Therefore, a greater proportion of LV untwisting occurred later in diastole during rejection, as reflected by an increase in the slope (M(mid-dia)) of the middle to late (from 15 to 90% filling) diastolic twist-normalized %EF relation (-0.018 +/- 0.009 versus -0.030 +/- 0.010 rad/cm, p = 0.0015).
 Peak rate of untwist was not affected.
 With resolution of rejection, M(early-dia) and percent untwist during early diastole returned to baseline levels (p = NS versus baseline).
 There was also a trend for M(mid-dia) to return toward prerejection values (p = NS versus baseline), but this change did not reach statistical significance compared with rejection values.
 CONCLUSION.
 Acute cardiac allograft rejection is associated with altered diastolic twist mechanics in the absence of any demonstratable systolic abnormalities.
 During rejection, myocardial edema and other factors may result in intrinsic changes of the elastic properties of the myocardium, thereby leading to modification of recoil forces responsible for the early, rapid unwinding of the deformed ventricle.
",22
3997,"Small-volume resuscitation from hemorrhagic shock in dogs: effects on systemic hemodynamics and systemic blood flow.
 BACKGROUND AND METHODS: This study compared canine systemic hemodynamics and organ blood flow (radioactive microsphere technique) after resuscitation with 0.8% saline (Na+ 137 mEq/L), 7.2% hypertonic saline (Na+ 1233 mEq/L), 20% hydroxyethyl starch in 0.8% saline, or 20% hydroxyethyl starch in 7.2% saline, each in a volume approximating 15% of shed blood volume.
 Twenty-four endotracheally intubated mongrel dogs (18 to 24 kg) underwent a 30-min period of hemorrhagic shock, from time 0 to 30 min into the shock period, followed by fluid resuscitation.
 Data were collected at baseline, 15 min into the shock period, immediately after fluid infusion, 5 min after the beginning of resuscitation, and at 60-min intervals for 2 hr, (65 min after the beginning of resuscitation, and 125 min after the beginning of resuscitation).
 The animals received one of four randomly assigned iv resuscitation fluids: saline (54 mL/kg), hypertonic saline (6.0 mL/kg), hydroxyethel starch (6.0 mL/kg) or hypertonic saline/hydroxyethyl starch (6.0 mL/kg).
 RESULTS: Mean arterial pressure increased in all groups after resuscitation.
 Cardiac output increased with resuscitation in all groups, exceeding baseline in the saline and hypertonic saline/hydroxyethyl starch groups (p less than .05 compared with hypertonic saline or hydroxyethyl starch).
 Sixty-five minutes after the beginning of resuscitation, cardiac output was significantly (p less than .05) greater in either of the two colloid-containing groups than in the hypertonic saline group.
 After resuscitation, hypertonic saline and hydroxyethyl starch produced minimal improvements in hepatic arterial flow, hypertonic saline/hydroxyethyl starch increased hepatic arterial flow to near baseline levels, and saline markedly increased hepatic arterial flow to levels exceeding baseline (p less than .05, saline vs.
 hydroxyethyl starch).
 One hundred twenty-five minutes after the beginning of resuscitation, hepatic arterial flow had decreased in all groups; hepatic arterial flow in the hypertonic saline group had decreased to levels comparable with those during shock.
 Myocardial, renal, and brain blood flow were not significantly different between groups.
 CONCLUSIONS: Small-volume resuscitation with the combination of hypertonic saline/hydroxyethyl starch is comparable with much larger volumes of 0.8% saline, and is equal to hypertonic saline or hydroxyethyl starch in the ability to restore and sustain BP and improve organ blood flow after resuscitation from hemorrhagic shock.
",22
3998,"Corticotropin-releasing factor modulates the immune response to stress in the rat.
 We examined the role of CRF, a key mediator of the endocrine response to stress, in modulating immunosuppression during the subacute stress of intermittent electrical shock over 1 h.
 Administration of shock to intact rats resulted in a 74% decrement in T-lymphocyte proliferation and a 59% decrease in natural killer cytotoxicity.
 Similar suppression of these two parameters of immune function in response to shock was noted in adrenalectomized rats as well.
 The immunosuppressive effects of this shock were significantly and comparably blunted when both intact and adrenalectomized animals were pretreated 1) iv with either a highly potent polyclonal CRF antibody or a specific CRF antagonist or 2) intracerebroventricularly with either a high affinity monoclonal antibody to CRF or a specific CRF antagonist.
 An immunomodulatory role for CRF is further supported by the findings that administration of exogenous CRF, either iv (10 micrograms/animal) or intracerebroventricularly (1 microgram/animal), resulted in significant decrements in lymphocyte proliferation and natural killer cytotoxicity, similar to those seen with the stress paradigm.
 Our observations indicate that CRF plays a significant role in modulating the immune response to subacute stress, largely by adrenal-independent mechanisms.
",22
3999,"The pituitary-adrenocortical system of neonatal rats is responsive to stress throughout development in a time-dependent and stressor-specific fashion.
 The responsiveness of the neonatal hypothalamus-pituitary-adrenal (HPA) axis to stress has been thought to be impaired or diminished during the first 2 weeks of life.
 Although we previously found full responsiveness of the hypothalamus-pituitary unit to adrenalectomy in young rats [days (d) 5-10], we failed to measure a significant increase in ACTH 10 min after ether administration until d14 of age.
 These studies were, therefore, designed to test the functional activation of the HPA axis after a single or repeated exposures to stress.
 Both qualitative (time-course, stressor-specific, circadian) and quantitative changes in the ACTH and corticosterone (B) responses to various stressors were tested during the first 10 days of life.
 Exposure to 3 min of ether vapor increased ACTH and B secretion (P less than 0.05-0.01) in 1-, 5-, and 10-d-old rats, with an increasing amplitude of both ACTH and B responses as a function of age.
 Peak secretion of ACTH occurred 5 min after the onset of stress (122 +/- 3.8 to 359 +/- 54 pg/ml on d1-10), while the time of maximal B increased as a function of age.
 Other stressors, such as maternal separation (12 h), cold (4 C; 60 min), or histamine injection (4 mg/kg BW, ip), provoked significant and stressor-specific ACTH and B responses in 10-d old rats.
 Histamine administration increased ACTH secretion above that of vehicle-injected rats, with a peak of secretion 15 min after drug injection (272 +/- 29 vs.
 127 +/- 8 pg/ml; P less than 0.01).
 Histamine-induced B secretion peaked at 60 min (3.7 +/- 0.5 micrograms/dl).
 In contrast to early responses observed after ether, separation, or histamine stress, cold stress in 10-d-old pups caused a large ACTH and B release 4 h after the onset of cold compared to that in maternally deprived pups [ACTH: cold, 457 +/- 61 pg/ml; separated, 150 +/- 14 (P less than 0.01); B: cold, 3.3 +/- 0.4 micrograms/dl; separated, 1.8 +/- 0.2 (P less than 0.05)].
 We did not detect morning-evening (AM-PM) differences in either the pattern or the magnitude of the ACTH or B response to maternal separation or cold stress.
 Suppression of cold-induced ACTH release by B injection (1 mg/kg BW) 2 h before stress was observed until 4 h after stress in the AM and PM, whereas when given after cold, B was less effective in the PM than in the AM at preventing the rise in ACTH levels observed at 4 h.(ABSTRACT TRUNCATED AT 400 WORDS).
",22
4000,"Managing geriatric arrhythmias, I: General considerations.
 Cardiac arrhythmias become increasingly common as people age, but they are not always clinically significant.
 Sinus node dysfunction, AV conduction disturbances, and ventricular and supraventricular arrhythmias will be found but are not always symptomatic.
 Treatment of asymptomatic arrhythmias is controversial and probably not indicated, but in symptomatic elderly, therapy is indicated, since even the very elderly have been found to benefit from it as much as younger patients.
 There are specific guidelines, however, that apply to this age group based on its susceptibility to side effects.
",22
4001,"Risk factors for emphysema. Cigarette smoking is associated with a reduction in the association rate constant of lung alpha 1-antitrypsin for neutrophil elastase.
 The increased risk of developing emphysema among individuals who smoke cigarettes and who have normal levels of alpha 1-antitrypsin (alpha 1AT) is hypothesized to result from a decrease in the antineutrophil elastase capacity of the lower respiratory tract alpha 1AT of smokers compared with nonsmokers.
 To evaluate this hypothesis we compared the time-dependent kinetics of the inhibition of neutrophil elastase by lung alpha 1AT from healthy, young cigarette smokers (n = 8) and nonsmokers (n = 12).
 alpha 1-antitrypsin was purified from lavage fluid using affinity and molecular sieve chromatography, and the association rate constant (k assoc) for neutrophil elastase quantified.
 The k assoc of smoker plasma alpha 1AT (9.5 +/- 0.5 X 10(6) M-1s-1) was similar to that of nonsmoker plasma (9.3 +/- 0.7 X 10(6) M-1s-1, P greater than 0.5).
 In marked contrast, the k assoc of smoker lower respiratory tract alpha 1AT was significantly lower than that of nonsmoker alpha 1AT (6.5 +/- 0.4 X 10(6) M-1s-1 vs.
 8.1 +/- 0.5 X 10(6) M-1s-1, P less than 0.01).
 Furthermore, the smoker lower respiratory tract alpha 1AT k assoc was significantly less than that of autologous plasma (P less than 0.01).
 When considered in the context of the concentration of alpha 1AT in the lower respiratory tract epithelial lining fluid, the inhibition time for neutrophil elastase of smoker lung alpha 1AT was twofold greater than that of nonsmoker lung alpha 1AT (smoker: 0.34 +/- 0.05 s vs.
 nonsmoker: 0.17 +/- 0.05 s, P less than 0.01).
 Consequently, for concentrations of alpha 1AT in the lower respiratory tract it takes twice as long for an equivalent amount of neutrophil elastase to be inhibited in the smoker's lung compared with the nonsmoker's lung.
 These observations support the concept that cigarette smoking is associated with a decrease in the lower respiratory tract neutrophil elastase inhibitory capacity, thus increasing the vulnerability of the lung to elastolytic destruction and thereby increasing the risk for the development of emphysema.
",22
4002,"Hypoxia induces a specific set of stress proteins in cultured endothelial cells.
 Vascular endothelial cells (EC) are the initial cells within the vascular wall exposed to decreases in blood ambient oxygen concentration.
 The mechanisms by which they tolerate low levels of oxygen are unknown, but may parallel the response to other cellular stresses, such as heat shock.
 After 4-8 h of hypoxia, we found a decrease in total protein synthesis in both cultured bovine aortic and pulmonary arterial EC.
 SDS-PAGE and autoradiographic analysis of [35S]methionine-labeled proteins demonstrated the concomitant induction of a specific set of proteins (Mr 34, 36, 47, and 56 kD) in both cell types.
 These hypoxia-associated proteins (HAPs) were cell-associated and up-regulated in a time- and oxygen concentration-dependent manner.
 Comparison of these proteins with heat shock proteins (HSPs) demonstrated that HAPs were distinct from HSPs.
 EC maintained chronically in 3% O2 continued to synthesize elevated levels of HAPs, yet further up-regulated these proteins when exposed to 0% O2.
 The presence of five times the normal media glucose concentration did not alter the appearance of HAPs.
 Hypoxia sensitive renal tubular epithelial cells up-regulated no proteins corresponding to HAPs and were irreversibly damaged within 8 h of exposure to 0% O2.
 In vitro translation experiments demonstrated that the steady-state level of several mRNAs was higher in the anoxic EC than in normoxic EC and encoded for proteins of Mr 32, 35, 37, 40, and 48 kD that were different from proteins encoded by HSP mRNAs.
 The induction of HAPs during acute hypoxia and their continued synthesis in chronic hypoxia suggest that HAPs may be important in the maintenance of endothelial cell integrity under conditions of decreased ambient oxygen.
",22
4003,"Acute biologic response to excimer versus thermal laser angioplasty in experimental atherosclerosis.
 Vascular injury and platelet accumulation after balloon angioplasty are two potentially important triggers of the process of restenosis that may be minimized by the use of laser energy to ablate atherosclerotic plaque.
 The type of laser most suitable to achieve these goals remains unknown.
 Accordingly, angiographic and histologic studies and quantitative platelet deposition analysis were performed on 27 atherosclerotic rabbit iliac arteries randomized to treatment with excimer laser or thermal laser angioplasty.
 Excimer laser angioplasty was achieved with 35 to 40 mJ/mm2 of 308 nm xenon chloride irradiation delivered through a 4.5F catheter made of 13 concentrically arranged 200 microns fiber optics, at a repetition rate of 25 to 30 Hz and a pulse duration of 135 ns; thermal laser angioplasty was achieved with a 1.7 mm metal probe heated with 10 W of continuous wave argon laser energy.
 The baseline and post-laser luminal diameters of excimer laser-treated vessels (0.92 +/- 0.28 and 1.56 +/- 0.48 mm, respectively) were similar to those observed in thermal laser-treated vessels (1.05 +/- 0.44 and 1.61 +/- 0.41 mm, respectively).
 Perforation occurred in 4 (29%) of 14 thermal laser-treated arteries and in 0 of 13 excimer laser-treated arteries (p = 0.04); spasm was observed in only 1 thermal laser-treated vessel.
 On the basis of a quantitative histologic grading scheme (damage scores of 0 to 4), greater degrees of injury were measured in thermal versus excimer laser-treated vessels (2.4 +/- 1.0 versus 1.3 +/- 0.4, p = 0.009).
",22
4004,"Differential impairment of semantic and episodic memory in Alzheimer's and Huntington's diseases: a controlled prospective study.
 A controlled prospective study compared the performance of 14 patients with dementia of Alzheimer type (DAT) and 14 patients with Huntington's Disease (HD), who were matched for overall level of dementia, on a battery of semantic and episodic memory tests.
 The DAT patients were significantly more impaired on measures of delayed verbal and figural episodic memory, and in addition showed a more rapid rate of decline on tests which depend upon the integrity of semantic knowledge (naming, number information, similarities and category fluency).
 In contrast, the HD patients were significantly worse, and showed a more rapid decline on the letter fluency test, a task especially sensitive to deficiencies in retrieval.
 The HD patients were also more impaired than DAT patients on a vocabulary test and on copying geometric figures.
 The observed double dissociations offer compelling evidence that aetiologically distinct forms of dementing illness result in different patterns of cognitive impairment.
",22
4005,"Skin reflectance pulse oximetry: in vivo measurements from the forearm and calf.
 This study describes the results from a series of human experiments demonstrating the ability to measure arterial hemoglobin oxygen saturation (SaO2) from the forearm and calf using a reflectance pulse oximeter sensor.
 A special optical reflectance sensor that includes a heating element was interfaced to a temperature controller and a commercial Data-scope ACCUSAT pulse oximeter that was adapted for this study to perform as a reflectance pulse oximeter.
 The reflectance pulse oximeter sensor was evaluated in a group of 10 healthy adult volunteers during steady-state hypoxia.
 Hypoxia was induced by gradually lowering the inspired fraction of oxygen in the breathing gas mixture from 100 to 12%.
 Simultaneous SaO2 measurements obtained from the forearm and calf with two identical reflectance pulse oximeters were compared with SaO2 values measured by a finger sensor that was interfaced to a standard Datascope ACCUSAT transmittance pulse oximeter.
 The equations for the best-fitted linear regression lines between the percent reflectance, SpO2(r), and transmittance, SpO2(t), values in the range between 73 and 100% were SpO2(r) = -7.06 + 1.09 SpO2(t) for the forearm (n = 91, r = 0.95) and SpO2(r) = 7.78 + 0.93 SpO2(t) for the calf (n = 93, r = 0.88).
 The regression analysis of the forearm data revealed a mean +/- SD error of 2.47 +/- 1.66% (SaO2 = 90-100%), 2.35 +/- 2.45% (SaO2 = 80-89%), and 2.42 +/- 1.20% (SaO2 = 70-79%).
 The corresponding regression analysis of the calf data revealed a mean +/- SD error of 3.36 +/- 3.06% (SaO2 = 90-100%), 3.45 +/- 4.12% (SaO2 = 80-89%), and 2.97 +/- 2.75% (SaO2 = 70-79%).
",22
4006,"Patient-controlled analgesia in children and adolescents: a randomized, prospective comparison with intramuscular administration of morphine for postoperative analgesia.
 A randomized, prospective trial of patient-controlled analgesia (PCA), that is, a method of analgesia administration involving a computer-driven pump activated by patients to receive small doses within defined limits was performed in 82 children and adolescents after major orthopedic surgery to compare (1) intramuscularly administered morphine, (2) PCA morphine and (3) PCA morphine with a low-dose continuous morphine infusion (PCA-plus).
 Patients receiving PCA and PCA-plus had lower pain scores and greater satisfaction than patients receiving intramuscularly administered morphine.
 The three groups used equal amounts of morphine and most measures of recovery were identical in the groups.
 In particular, PCA and PCA-plus did not increase the incidence of opioid-related complications, and patients receiving PCA-plus were less sedated than patients receiving intramuscular therapy.
 We conclude that PCA and PCA-plus are safe and effective methods of pain relief in children and adolescents after orthopedic surgery, are better accepted than intramuscular injections, and do not increase perioperative morbidity.
",22
4007,"Cells derived from omental fat tissue and used for seeding vascular prostheses are not endothelial in origin. A study on the origin of epitheloid cells derived from omentum.
 The use of microvascular endothelial cells derived from omental tissue has been advocated to seed vascular grafts with autologous endothelial cells in high density.
 The purpose of our study was to evaluate the precise origin of these cells.
 Therefore we have compared cellular characteristics of these cells with those of endothelial cells isolated by collagenase treatment of human umbilical veins.
 The omental cells were isolated from from omental tissue from four different patients by incubation in a collagenase-dispase solution.
 Part of the material was processed by Percoll density gradient centrifugation in an attempt to purify the isolates.
 Cellular characteristics of both types of cells were determined by studying the morphologic features of the cells and by determining the presence of von Willebrand factor, antigens EN-4 and PAL-E specific for endothelial cells, cytokeratins 8 and 18, vimentin and desmin, and uptake of diI-acetylated low-density lipoprotein.
 Epitheloid cells from omental tissue, isolated after collagenase treatment and either purified or nonpurified by Percoll density gradient centrifugation, differed from human umbilical vein endothelial cells with respect to the presence of surface microvilli, the expression of von Willebrand factor, EN-4 and PAL-E, and the presence of cytokeratins 8 and 18 and desmin.
 von Willebrand factor (in a granular staining pattern) and the presence of EN-4 and PAL-E were only detected in human umbilical vein endothelial cells.
 Vimentin was present in both cell types, whereas cytokeratins 8 and 18 and desmin were only present in cells derived from omentum.
 From these data we conclude that the so called microvascular endothelial cells from omentum are not endothelial but mesothelial in nature.
",22
4008,"Subclavian artery to innominate vein fistula after insertion of a hemodialysis catheter.
 Insertion of hemodialysis catheters for temporary use is now preferentially performed by percutaneous infraclavicular subclavian vein catheterization.
 This method involves passage of a stiff dilator and a peel-away sheath over a guide wire, and is usually carried out without fluoroscopy.
 For the most part this has proved to be a valuable and safe approach.
 However, a small incidence of major complications occurs, which needs to be emphasized.
 Sixteen cases of arteriovenous fistulas between the subclavian artery or its branches and the subclavian vein have been reported so far in the literature.
 To date only one case of subclavian artery to innominate vein fistula has been reported.
 We report the second case with this complication and suggest possible preventive measures.
",22
4009,"Diagnosis of popliteal artery entrapment syndrome: the role of duplex scanning.
 The authors present a new diagnostic procedure to quickly and noninvasively diagnose the popliteal artery entrapment syndrome.
 A large personal experience on the surgical treatment of such a disease (29 cases in 22 patients) allowed us to focus on the optimal diagnostic procedure useful to detect this problem at an early stage.
 The technique is based on continuous-wave Doppler and duplex scanning studies done both in the resting state and during active contraction of the calf muscles.
 If compression of the popliteal artery occurs with contraction of the calf muscles, it will be detected by a decrease in flow.
 This finding will also direct the radiologist to obtain films when the maneuver is repeated.
 This makes it unlikely that the diagnosis will be missed.
 Since July 1988 a total of 1212 patients were evaluated with continuous-wave Doppler for suspected chronic ischemia.
 From this group 41 patients were selected to be studied again with the combined continuous-wave Doppler and duplex scanning method for possible popliteal artery entrapment syndrome.
 Two cases were discovered and verified by dynamic angiography guided by continuous-wave Doppler and treated surgically.
",22
4010,"Follow-up status of patients with angiographically normal coronary arteries and panic disorder.
 Cardiology patients with normal coronary angiography demonstrate continuing and substantial social, health, and work disability.
 We hypothesized that the diagnosis of panic disorder would mark those for whom continuing disability is most likely.
 We interviewed 72 such patients at the time of their normal angiogram, and then again an average of 38 months later.
 Those with panic disorder (n = 36) demonstrated significantly more disability at follow-up than did the other study patients.
 We conclude that those patients with normal angiograms who have panic disorder are more disabled than those who do not have panic disorder.
 Panic disorder in psychiatric samples has been shown to be highly treatable.
 Therefore, early identification and treatment of panic disorder in this group is likely to minimize the suffering associated with this condition.
",22
4011,"The effect of muscle-sparing versus standard posterolateral thoracotomy on pulmonary function, muscle strength, and postoperative pain.
 Increased interest in alternative approaches to thoracotomy has developed because of the considerable morbidity associated with the standard posterolateral technique.
 We conducted a prospective, randomized, blinded study of 50 consecutive patients to compare postoperative pain, pulmonary function, shoulder strength, and range of shoulder motion between the standard posterolateral and the muscle sparing thoracotomy techniques.
 Pulmonary function (forced expiratory volume in 1 second and forced vital capacity), shoulder strength, and range of motion were measured preoperatively and at 1 week and 1 month postoperatively.
 Pain was quantitated by postoperative narcotic requirements, the visual analogue scale, and the McGill pain questionnaire.
 Morbidity, mortality, and hospital stay were compared between the standard posterolateral and muscle-sparing techniques.
 There were no differences in postoperative pulmonary function, shoulder range of motion, extent of lung resection, surgical approach time, mortality, or hospital stay.
 There was significantly less postoperative pain in the muscle-sparing group.
 The narcotic requirement was less in the first 24 hours (p = 0.0169), and visual analogue scale scores were significantly lower (p less than 0.05) throughout the first postoperative week.
 Shoulder girdle strength was decreased at 1 week in the standard incision group whereas the strength was preserved with the muscle-sparing approach.
 Muscle strength had returned to preoperative levels by 1 month in both groups.
 Morbidity was identical in the two groups with the exception of postoperative seromas.
 The prevalence of seroma was 23% in the muscle-sparing group and 0% in the standard incision group (p = 0.0125).
 We have demonstrated that the muscle-sparing incision may be a reasonable alternative to the standard posterolateral approach.
",22
4012,"Hospital management of voluntary total fasting among political prisoners 
 In 1989 20 political detainees, held without trial for up to 32 months, were admitted, on hunger strike, to the Johannesburg Hospital, South Africa.
 Most were held under the regulations of the State of Emergency (since revoked) and 5 were held incommunicado under section 29 of the Internal Security Act (still in force).
 Guidelines for ethical management were based on the Declaration of Tokyo, which included the understanding that such detentions constituted mental torture.
 Conditions of detention in hospital were complicated by police interference in medical and nursing care, and by the chaining of some prisoners to their beds.
 Doctors are in a unique position to protest against inhuman treatment of prisoners, and should use this authority.
",22
4013,"Cerebrospinal fluid fistula and endoscopic sinus surgery.
 Seven cases of cerebrospinal fluid fistulae occurring as a result of endoscopic sinus surgery in a total of 800 ethmoidectomies are discussed, along with 1 case referred for consultation.
 One cerebrospinal fluid fistula was intrasphenoid, 4 were posterior ethmoid/base of skull, 2 were anterior ethmoid, and 1 was ethmoid cribriform.
 Six of 8 fistulae were closed endoscopically.
 The sphenoid sinus cerebrospinal fluid fistula was closed successfully with fibrin glue and Gelfoam.
 Five cerebrospinal fluid fistulae were closed successfully using fascia, muscle, and Gel-foam.
 Two cerebrospinal fluid fistulae were treated conservatively, and only 1 stopped.
 Anatomic and technical aspects related to the occurrence of cerebrospinal fluid fistulae are discussed.
 Management and treatment of cerebrospinal fluid fistulae occurring during and after endoscopic sinus surgery is emphasized.
 When identified intraoperatively or delayed, cerebrospinal fluid fistulae can be managed successfully by endoscopic technique.
",22
4014,"Synchronous positive and negative myoclonus due to pontine hemorrhage.
 We report a case of synchronous positive and negative myoclonus following pontine hemorrhage.
 Constant synchronous jerking of the eyes, tongue, face, mandible, larynx, pharynx, and diaphragms persisted during sleep.
 Jerking of limb muscles occurred during volitional activities, but not at rest.
 Inability to sustain glottic adduction during phonation contributed to severe dysarthria.
 Electromyography (EMG) revealed positive myoclonus of the branchial musculature with synchronous negative myoclonus in a generalized distribution.
 Treatment with trazodone reduced the ocular myoclonus but worsened the dysphagia.
 We suggest that a single neural rhythm generator may produce both positive and negative myoclonus.
",22
4015,"The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration 
 Three dominant mutations of mec-4, a gene needed for mechanosensation, cause the touch-receptor neurons of Caenorhabditis elegans to degenerate.
 With deg-1, another C.
 elegans gene that can mutate to induce neuronal degeneration and that is similar in sequence, mec-4 defines a new gene family.
 Cross-hybridizing sequences are detectable in other species, raising the possibility that degenerative conditions in other organisms may be caused by mutations in similar genes.
 All three dominant mec-4 mutations affect the same amino acid.
 Effects of amino-acid substitutions at this position suggest that steric hindrance may induce the degenerative state.
",22
4016,"Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport.
 The p53 protein is rendered temperature-sensitive by a point mutation.
 Rat cells transformed by this mutant p53 and an activated ras oncogene grow well at 37 degrees C but cease DNA synthesis and cell division when shifted to 32 degrees C.
 Immunostaining demonstrates that the mutant p53 protein is in the nucleus of the arrested cells at 32 degrees C but in the cytoplasm of the growing cells at 37 degrees C.
 This is the first example of a protein which is temperature-sensitive for nuclear transport.
 The translocation from cytoplasm to nucleus and vice versa occurs 6 h after temperature shift and is coincident with the inhibition of DNA synthesis; transport from cytoplasm to nucleus does not require protein synthesis.
 Remarkably, inhibition of protein synthesis at 37 degrees C also results in the rapid appearance of mutant p53 in the cell nucleus.
 These results suggest the presence of a short-lived protein responsible for holding p53 in the cytoplasm at 37 degrees C but not at 32 degrees C.
 Analysis of a non-temperature-sensitive mutant p53 protein shows that its cytoplasmic location is sensitive to protein synthesis inhibitors but not to temperature.
",22
4017,"Hypoxanthine levels in vitreous humor: evidence of hypoxia in most infants who died of sudden infant death syndrome.
 Postmortem changes of the hypoxanthine in vitreous humor in humans were investigated.
 Hypoxanthine is formed from hypoxic degradation of adenosine monophosphate.
 Repeated sampling was performed in 13 deceased adults.
 Keeping the bodies at +6 degrees C, the increase of the hypoxanthine levels was estimated to 3.5 mumol/L per hour when sampling was started more than 12 hours after death (range 2.8 to 5.6 mumol/L per hour).
 Results of hypoxanthine measurements from vitreous humor in 73 infants with sudden infant death syndrome, 17 infants and children who died sudden violent deaths, and 6 neonates who died suddenly without hypoxemia prior to death were corrected according to the expected postmortem hypoxanthine increase.
 The time between death and autopsy was similar in the three groups studied.
 The corrected median hypoxanthine level in the group with sudden infant death syndrome was 227 mumol/L, which is significantly higher than in the other groups; 22 mumol/L in the group who had violent deaths (P less than .01), and 0 mumol/L in the neonate group (P less than .01).
 The findings seem to confirm that sudden infant death is preceded by a relatively long period of tissue hypoxia in most cases.
",22
4018,"Esophageal and gastric endoscopy in critically ill patients. How can it help you?
 Bleeding from the upper gastrointestinal tract in a critically ill patient is a tough diagnostic situation.
 Endoscopy can help physicians determine the cause of bleeding and can also provide several therapeutic options.
 The authors discuss these applications of the current technology.
",22
4019,"Emergency resuscitation in children. The role of intraosseous infusion.
 Intraosseous infusion is a temporary procedure for use in pediatric emergencies when intravenous access is difficult.
 Multiple drugs and fluids can be safely administered through the intraosseous route.
 Dosage and rate of infusion are essentially the same as with intravenous infusion.
",22
4020,"Do you have patients with anorexia or bulimia? Understanding is the first step in helping.
 Anorexia nervosa and bulimia nervosa have, in recent years, become disorders of major concern.
 Young women are particularly prone to such eating disorders, and substantial numbers have involved themselves in the practices that identify these problems.
 Understanding the thinking behind these disorders is helpful in recognizing them and developing a treatment approach.
 The most effective medication for bulimia reported to date is fluoxetine hydrochloride (Prozac).
 The concurrent participation of a physician, nutritionist, and family therapist in the care of these patients is ideal.
",22
4021,"Interaction of the v-rel protein with an NF-kappa B DNA binding site.
 The avian reticuloendotheliosis virus T contains within its genome the oncogene rel.
 The expression of this gene is responsible for the induction of lymphoid tumors in birds.
 Recently, the rel gene was shown to be related to the p50 DNA binding subunit of the transcription factor complex NF-kappa B.
 Binding sites for the NF-kappa B complex are found in the enhancer regions of a number of genes, including the immunoglobulin kappa gene and the human immunodeficiency virus long terminal repeat.
 In this communication we identify an activity from avian reticuloendotheliosis virus T-transformed avian lymphoid cells that binds in an electrophoretic-mobility-shift assay to an NF-kappa B binding site from the kappa enhancer.
 This activity contains proteins immunologically related to rel, as detected by polyclonal and monoclonal antibodies directed against v-rel.
 In a DNA affinity precipitation assay using the NF-kappa B site from the human immunodeficiency virus long terminal repeat, v-rel and several other proteins were identified.
 These data suggest that oncogenic transformation by v-rel is the result of an altered pattern of gene expression.
",22
4022,"Nerve growth factor corrects developmental impairments of basal forebrain cholinergic neurons in the trisomy 16 mouse.
 The trisomy 16 (Ts16) mouse, which shares genetic and phenotypic homologies with Down syndrome, exhibits impaired development of the basal forebrain cholinergic system.
 Basal forebrains obtained from Ts16 and euploid littermate fetuses at 15 days of gestation were dissociated and cultured in completely defined medium, with cholinergic neurons identified by choline acetyltransferase (ChAT) immunoreactivity.
 The Ts16 cultures exhibited fewer ChAT-immunoreactive neurons, which were smaller and emitted shorter, smoother, and more simplified neurites than those from euploid littermates.
 Whereas the addition of beta-nerve growth factor (100 ng/ml) augmented the specific activity of ChAT and neuritic extension for both Ts16 and euploid cholinergic neurons, only Ts16 cultures exhibited an increase in the number and size of ChAT-immunoreactive neurons.
 Furthermore, Ts16 ChAT-immunoreactive neurites formed varicosities only in the presence of beta-nerve growth factor.
",22
4023,"Stage transitions in B-lymphocyte differentiation correlate with limited variations in nuclear proteins.
 Total nuclear proteins extracted from cell lines representing various stages of differentiation of mouse B lymphocytes were studied by computer analysis of two-dimensional gels.
 Of the 1438 spots present on the gels, 55 varied significantly in intensity during differentiation.
 The variations occurred most often in steps correlating with those classically defined for B-cell differentiation.
 Seventeen spots were not detectable in at least one of the stages (qualitative variations) and could represent switching on or off of genes coding for nuclear proteins.
 Detailed analysis of the 55 variable spots showed that they fall into small sets characterized by similar expression profiles, which argues for a combinatorial, multistep control mechanism of gene expression.
 In addition, analysis of the expression of all the nuclear proteins resolved on the gels clearly differentiated B-lineage cells from myeloid cells and suggested that the most important transition in B-cell differentiation occurs between the resting B cell and plasmocyte stages.
",22
4024,"Expressional potency of mRNAs encoding receptors and voltage-activated channels in the postmortem rat brain.
 The stability and integrity of mRNAs encoding neurotransmitter receptors and voltage-activated channels in the postmortem rat brain was investigated by isolating poly(A)+ mRNA, injecting it into Xenopus oocytes, and then examining the expression of functional neurotransmitter receptors and voltage-activated channels in the oocyte membrane by electrophysiological recording.
 This approach was also used to assess the stability of mRNAs in brains that were incubated in oxygenated mammalian Ringer's solution for various lengths of time and from brains that were freshly frozen and then thawed at room temperature.
 Oocytes injected with mRNA from up to 21-hr postmortem brains gave large agonist- and voltage-activated responses, indicating that mRNAs encoding neurotransmitter receptors and voltage-activated channels are relatively stable in postmortem brain tissue.
 In contrast, oocytes injected with mRNA from brains incubated in Ringer's solution exhibited smaller responses, and oocytes injected with mRNA from tissue that was frozen and then thawed displayed very small or undetectable responses.
 Northern blot analysis using a nucleic acid probe for rat brain Na(+)-channel mRNA indicated that the size of the Na+ currents in injected oocytes reflected the levels of mRNA for Na+ channels in the different mRNA preparations.
 Thus, the expressional potency of mRNAs encoding neurotransmitter receptors and voltage-activated channels is quite stable in postmortem brains in situ, but it is reduced if the brains are kept in oxygenated saline, and freezing and thawing of tissue results in rapid degeneration of mRNA.
",22
4025,"Long-chain (sphingoid) bases inhibit multistage carcinogenesis in mouse C3H/10T1/2 cells treated with radiation and phorbol 12-myristate 13-acetate.
 Sphingosine and other long-chain (sphingoid) bases inhibit protein kinase C, the putative cellular receptor for the tumor promoter phorbol 12-myristate 13-acetate (PMA), and exert potent effects on diverse cell functions.
 We tested the ability of long-chain bases to modulate multistage carcinogenesis in mouse C3H/10T1/2 cells exposed to gamma-rays and PMA.
 Sphingosine and sphinganine completely blocked the enhancement of radiation-induced transformation by PMA (promotion) and partially suppressed transformation by radiation alone.
 N-Acetylsphingosine, a ceramide analog, did not inhibit transformation.
 Sphingosine was rapidly taken up by the cells and metabolized; hence, the long-chain bases were added daily to achieve prolonged inhibition.
 Long-chain bases inhibited protein kinase C activity in C3H/10T1/2 cells and suppressed the down-regulation of this enzyme by PMA.
 Our results establish that long-chain bases are highly effective inhibitors of carcinogenesis in this model.
 Our results also indicate that the suppressive effects may be mediated, in part, by inhibition of protein kinase C.
 The data suggest that sphingosine and other long-chain bases derived from complex sphingolipids may act as cancer-preventative agents.
",22
4026,"Open-heart surgery in Jehovah's Witnesses.
 During a 7-year period, 11 adult members of the religious sect Jehovah's Witnesses underwent cardiac surgery with extracorporeal circulation.
 No homologous blood transfusions were given.
 Blood-conserving procedures were employed, viz.
 initial collection of autologous blood, haemofiltration or processing (Cell Saver) of blood collected during extracorporeal circulation and reinfusion of shed mediastinal blood.
 The total perioperative blood loss averaged 1080 ml (15 ml/kg body weight), equalling 19% of total body blood volume.
 The mean haemoglobin on discharge from hospital was 11.0 g/100 ml.
 There was no perioperative mortality.
 Postoperative pulmonary function was good and there was no serious morbidity.
 Jehovah's witnesses with serious, surgery-necessitating heart disease can be offered operation comprising recognized blood-conserving procedures.
",22
4027,"Effect of dipyridamole (Persantin) on blood flow and patency of aortocoronary vein bypass grafts.
 The effect of dipyridamole was investigated in 360 patients undergoing coronary bypass surgery.
 They were randomly allocated to receive dipyridamole (100 mg orally q.i.d.
 for 2 days preoperatively, 5 mg/kg body weight/24 h i.v.
 peroperatively and 100 mg orally q.i.d.
 for 1 year postoperatively) or placebo.
 Withdrawn from the study were 48 patients on dipyridamole and 57 on placebo.
 Cardiovascular and/or cerebrovascular events or need for anticoagulant treatment were the reasons for withdrawal in 22 (13%) of the dipyridamole, and 34 (18%) of the placebo group.
 Logistic regression analysis of risk factors influencing graft patency showed significant relation to peroperatively measured coronary blood flow.
 A positive trend of treatment was observed (p = 0.08).
 Vein graft blood flow measured during bypass surgery (245 patients) was significantly greater in the dipyridamole group (p less than 0.01).
 The occlusion rate was lower in vessels with peroperative blood flow greater than 30 ml/min (vein-marginal p less than 0.01, vein-dexter p less than 0.05, vein-diagonal 0.05 less than p less than 0.1).
 Dipyridamole increases coronary blood flow and graft patency following coronary bypass surgery.
",22
4028,"Factitious cyclic hypersomnia: a new variant of factitious disorder.
 The central goal of patients with factitious disorders is to receive medical care.
 Unnecessary diagnostic procedures and recurrent hospitalizations often ensue.
 We saw a 39-year-old man with a novel variation of this disorder: factitious cyclic hypersomnia, or the simulation of recurrent episodes of excessive sleep.
 This case highlights the observations that patients whose illnesses are simulated may have diverse symptoms, that no syndrome is immune to factitious imitation, and that attempts at treatment, though exceedingly challenging, are always contingent upon appropriate recognition.
",22
4029,"The value of routine preoperative laboratory testing in predicting postoperative complications: a multivariate analysis.
 The purpose of this study was to evaluate the ability of preoperative laboratory testing to predict postoperative complications.
 Five hundred twenty patients undergoing elective surgery had their American Society of Anesthesiologists' classification, ponderal index, electrolyte values, glucose levels, blood urea nitrogen/creatinine values, complete blood counts, coagulation studies, total protein/albumin/lymphocyte count, electrocardiogram, chest radiograph, urinalysis, pulmonary function tests, type of anesthesia, and type of operation recorded preoperatively.
 Patients were followed prospectively after surgery for the development of complications.
 The data were analyzed by univariate and multivariate methods.
 Postoperative complications were strongly associated with American Society of Anesthesiologists' classification, type of anesthesia, and type of operation.
 However, only a few laboratory tests, such as electrocardiogram, chest radiograph, and nutritional status, were associated with postoperative complications.
 Therefore, in general, preoperative laboratory testing should only be undertaken for specific indications.
 Recommendations for routine tests are made depending on the age of the patient.
",22
4030,"Bacteriologic quality of intraoperative autotransfusion.
 Controversies remain about the bacteriologic aspects of intraoperative blood salvage despite the widespread use of this technique.
 In this prospective study, intraoperative salvaged blood was cultured in 401 patients, according to a direct plating technique.
 Bacterial growth was detected in 12.7% of cases.
 These results were compared with those obtained in control studies with sterile water and blood bank units under the same culture conditions.
 Most microorganisms were coagulase-negative staphylococci, followed by other skin and environmental contaminants.
 Quantitative estimates of contaminations showed low counts of colony-forming units (CFU/ml): 82% of positive cultures yielded 1 or 2 CFU/ml and 6% had 5 to 20 CFU/ml.
 Patients were followed up for a minimum of 3 months to detect septic complications.
 No statistically significant correlation could be found between bacteriologic results of autotransfused blood and infectious complications.
 This study suggests that bacteriologic monitoring of patients who have undergone autotransfusion may help in detecting surgical field contamination.
 It also confirms that intraoperative autotransfusion adds little septic risk to cardiac surgery.
",22
4031,"Predisposing factors in bladder calculi. Review of 100 cases.
 One hundred patients, aged twenty to ninety-two years, underwent 111 procedures for removal of bladder calculi.
 Most patients (88) had some type of bladder outlet obstruction.
 Two types of stones were identified: those that had apparently formed in the upper tract and been trapped in the bladder (17 cases) and those that appeared to have formed in the bladder in the presence of various types of outlet obstruction.
 Stone analysis revealed uric acid stones in 50 percent, calcium oxalate stones in 19 percent, and stones of mixed composition in 31 percent.
 Five patients had metabolic abnormalities predisposing to stone formation; in 2 cases, these abnormalities were discovered during the evaluation for stone disease.
 Treatment depended on stone characteristics, associated pathology, and the general health of the patient.
 A review of the literature with regard to the morbidity and mortality of combining treatment of vesical calculi and bladder outlet obstruction secondary to prostatic obstruction is included.
",22
4032,"Application of microwave tissue coagulation in partial nephrectomy.
 Microwave tissue coagulation was used during partial nephrectomy in 10 mongrel dogs, without clamping the renal artery.
 There were no major complications, such as retroperitoneal hematoma, abscess formation, or macroscopic infarction of the kidney tissue related to this new procedure.
 The advantages of microwave coagulation are reduced blood loss, shorter operative time, and minimal risk of vascular injury.
",22
4033,"Effect of nisoldipine on hemodynamic responses to defibrillation.
 Sequences of ventricular fibrillation-defibrillation cause transient hypertension; we hypothesized that this ""adrenergic overshoot"" might be blunted by the functional antiadrenergic effect of the calcium channel blocking drug nisoldipine, with a potentially beneficial reduction in myocardial oxygen requirements.
 However, other calcium channel blocking drugs have been shown to reduce shock success for defibrillation, a deleterious effect.
 Thus the purposes of this study were to assess the effect of nisoldipine on the hemodynamic responses to the sequences of ventricular fibrillation-defibrillation, and its effect on the energy requirements for defibrillation.
 In 16 dogs we administered intravenous nisoldipine (1 microgram/kg bolus followed by an infusion of 0.075 to 0.50 microgram/kg/min) to lower mean blood pressure 10% and 20% below baseline.
 Ventricular fibrillation was induced electrically, and shocks of varying energy levels (30, 50, and 100 joules) were administered to determine defibrillation energy requirements.
 Heart rates and blood pressures were recorded up to 3 minutes after each shock to determine hemodynamic responses.
 Measurements were made before nisoldipine administration and again at the two levels of drug-induced blood pressure decline.
 We found that the usual systolic blood pressure ""overshoot"" after defibrillation (typically maximum at 15 to 30 seconds after shocks) was significantly blunted after nisoldipine administration (p less than 0.05).
 Heart rate slowing after defibrillation (a cholinergic response) was not affected.
 Nisoldipine did not alter shock success rates, which varied from 12 +/- 7%SE at 30 joules to 68 +/- 12% at 100 joules.
 Thus nisoldipine blunted the ""adrenergic overshoot"" of systolic blood pressure following defibrillation, a potentially beneficial effect, without altering the energy requirements for transthoracic defibrillation.
",22
4034,"Isotonic high-sodium oral rehydration solution for increasing sodium absorption in patients with short-bowel syndrome.
 We compared the effect of a standard oral rehydration solution and a high-sodium polymeric-glucose solution on sodium absorption in short-bowel syndrome.
 Six patients with high jejunostomy were tested in a random order with the standard solution or a solution containing maltodextrins (18 g Glucidex 12/L) enriched with 2.5 g NaCl/L.
 Solutions were administered via a nasogastric tube at a rate of 2 mL/min.
 Jejunal effluent was collected during an 8-h period.
 The net 8-h fluid absorption was not significantly different in the two periods.
 Glucose absorption was greater than 90% of the administered amount for both solutions.
 Net sodium absorption was greater for the maltodextrin solution than for the standard solution (56 +/- 12 vs 24 +/- 20 mmol, P less than 0.05).
 We conclude that replacement of glucose with maltodextrins and addition of sodium in the standard oral rehydration solution results in improved sodium absorption in short-bowel syndrome.
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4035,"Hairless micropig skin. A novel model for studies of cutaneous biology.
 Reported here is the structural and immunohistochemical similarities between the Yucatan hairless micropig (HMP) skin and that of humans.
 Hairless micropig skin surface was composed of complex intersecting furrows that created geometric patterns remarkably similar to human skin surface glyphics.
 The dermal--epidermal interface consisted of undulant downgrowths that interdigitated with dermal papillae.
 Hairless micropig epidermis contained two morphologically distinct populations of basal keratinocytes (serrated and nonserrated).
 Similar heterogeneity has been seen only in human epidermis and primate palmar epidermis.
 Immunohistochemistry revealed that the HMP epidermis is reactive with monoclonal and polyclonal antisera to keratin proteins.
 Melanocytes reactive with antisera to S-100 protein, as in human skin, also were observed in HMP epidermis.
 Organization of dermal extracellular matrix, including collagen and elastic fibers, and the organization and reactivity of the microvasculature with antisera to factor VIII, were consistent with human skin.
 The costicosteroid-induced atrophy and subsequent rebound phenomenon after withdrawal of steroid observed in HMP skin was similar with that observed in humans.
 It is concluded that HMP skin approximates human skin significantly more precisely than most existing species and is an excellent model for studies of cutaneous physiology and pharmacology.
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4036,"Induction of inflammatory cell infiltration and necrosis in normal mouse skin by the combined treatment of tumor necrosis factor and lithium chloride.
 Previously we reported that lithium chloride (LiCl) potentiates tumor necrosis factor (TNF)-mediated cytotoxicity in vitro and in vivo.
 Here, using a murine normal skin model, it is shown that a subcutaneous injection of TNF plus LiCl induces acute dermal and subcutaneous inflammation and necrosis.
 Histology showed a marked initial dermal and subcutaneous neutrophil infiltrate by approximately 2 hours, followed by a predominantly mononuclear infiltrate by 24 hours, which remained present for several days.
 Tumor necrosis factor or LiCl alone induced negligible inflammation, disappearing after 6 hours; furthermore there was never necrosis or ulceration of the overlying skin in case of single-agent application.
 In vitro studies showed that the combination of TNF and LiCl, but not either agent alone, was directly cytotoxic to fibroblastic cells of murine skin.
 No inflammatory infiltration was visible in tumors treated intratumorally or perilesionally with TNF plus LiCl, although the latter treatment resulted in a perilesional leukocyte infiltration.
 Furthermore the combination of TNF and LiCl had no effect on macrophage cytotoxicity to L929 tumors.
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4037,"Cultured human atherosclerotic plaque smooth muscle cells retain transforming potential and display enhanced expression of the myc protooncogene.
 The proliferation of vascular smooth muscle cells (SMC) is critical to atherosclerotic plaque formation.
 The monoclonal hypothesis proposes that the stimulus for this SMC proliferation is a mutational event.
 Here we describe a procedure for growing human plaque smooth muscle cells (p-SMC) in culture.
 We show that p-SMCs derived from two patients differ from SMC cultured from normal vascular tissue in expression of the protooncogene myc.
 One p-SMC strain was extensively characterized; these diploid, karyotypically normal cells have a finite life span in culture.
 Ultrastructural examination revealed two populations, one with classic contractile SMC appearance, the other, modulated to a synthetic state.
 Northern blotting showed a 2- to 6-fold and a 6- to 11-fold enhanced expression of myc by p-SMC, compared to SMC derived from healthy human aorta (HA-SMC) and saphenous vein (HV-SMC), respectively.
 In contrast, the p-SMC and HV-SMC expressed similar levels of message for the genes N-myc, L-myc, Ha-ras, fos, sis, myb, LDL receptor, EGF receptor, IGF I receptor, IGF II, and HMG CoA reductase.
 Finally, although p-SMCs are not tumorigenic, DNA isolated from these cells is positive in the transfection-nude mouse tumor assay.
 Myc, however, does not appear to be the transforming gene because no newly introduced human myc gene was detected in the p-SMC-associated nude mouse tumor.
 Thus human atherosclerotic p-SMCs possess both an activated myc gene and a transforming gene that is retained throughout many cell passages.
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4038,"Traditional versus laparoscopic cholecystectomy.
 Laparoscopic cholecystectomy is a minimally invasive procedure whereby the gallbladder is removed using laparoscopic techniques.
 The indications are similar to those for elective traditional cholecystectomy, but selection of patients is important for success.
 Contraindications are currently evolving.
 Patients with advanced cholecystitis, abdominal sepsis, ileus, bleeding disorders, pregnancy, and morbid obesity should not undergo this procedure.
 The procedure requires good traditional surgical skills, as well as additional laparoscopic (and laser) skills.
 Operative time is slightly longer than for traditional cholecystectomy, but decreases with experience.
 Morbidity is low, but there is a concern about bile duct injuries.
 Mortality is very low (0%) and is comparable to traditional cholecystectomy (0.4%).
 The major advantages of laparoscopic cholecystectomy are the short hospital stay (average: 2 days) and early return to normal activity (7 days).
 This results in a reduction in hospital costs.
 Adequate training and credentialing are important processes to foster good patient outcomes.
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4039,"The European experience with laparoscopic cholecystectomy.
 A retrospective survey of 7 European centers involving 20 surgeons who undertook 1,236 laparoscopic cholecystectomies was performed.
 The procedure was completed in 1,191 patients.
 Conversion to open cholecystectomy was necessary in 45 patients (3.6%) either because of technical difficulty (n = 33), the onset of complications (n = 11), or instrument failure (n = 1).
 There were no deaths reported, and the total postoperative complication rate was 20 of 1,203 (1.6%), with 9 being serious complications requiring laparotomy.
 The total incidence of bile duct damage was 4 of 1,203.
 The median hospital stay was 3 days (range: 1 to 27 days) and the median time to return to full activity after discharge was 11 days (range: 7 to 42 days).
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4040,"Complications of laparoscopic cholecystectomy.
 The emergence of laparoscopic cholecystectomy as a viable alternative to traditional cholecystectomy has been greeted with enthusiasm by the surgical community.
 This new technique is not without complications, both potential and real.
 The complications associated with diagnostic laparoscopy are well documented, as are those associated with traditional cholecystectomy.
 All of these may also be seen with laparoscopic cholecystectomy.
 The incidence of their occurrence, however, may vary.
 It remains too early to evaluate the complication rates from this new procedure, as reports of large series are just beginning to emerge.
 Early reports are encouraging but caution that bile duct injury, hemorrhage, and even death may occur.
 Early enthusiasm for this new method must be tempered with care in its practice if complication rates are to be maintained at an acceptable level and the procedure is to earn a permanent place in the armamentarium of the surgeon.
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4041,"Interruption of professional and home activity after laparoscopic cholecystectomy among French and American patients.
 With a laparoscopic approach, patients can undergo cholecystectomy with a shorter hospitalization, minimal pain, and quicker recovery.
 It has not been demonstrated, however, that patients actually return to work after laparoscopic cholecystectomy faster than the traditional 4- to 6-week absence from work after a standard open procedure.
 A survey of 104 French and 84 American patients undergoing laparoscopic cholecystectomy revealed that postoperative discomfort was completely resolved in 2 weeks in 73% of French and 93% of American patients.
 All but 11 French and 5 American patients were back to normal home activities by 2 weeks after the operation.
 Of the 35 American and 40 French patients who had professional activity outside the home, 63% and 25%, respectively, returned to work within 14 days.
 Five (14%) of the American patients and 12 (30%) of the French patients returned to work 4 weeks or more after the operation.
 The amount of physical activity on the job correlated with the period off work, but, interestingly, at least six patients with very hard physical activity at work (including construction workers) were able to return to full work activity within 1 week.
 These data suggest that early return to work is possible and that pain resolves quickly after laparoscopic cholecystectomy.
 The economic benefit of having patients back on the job quickly, however, may be less than expected until cultural norms change with regard to leave of absence after major surgery.
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4042,"Enhanced mobilization of intracellular Ca2+ induced by halothane in hepatocytes isolated from swine susceptible to malignant hyperthermia.
 Halothane, in a dose-dependent manner, induced the release of intracellular Ca2+ in hepatocytes prepared from swine.
 The magnitude of the release induced by halothane was greater for hepatocytes prepared from animals susceptible to malignant hyperthermia (MH) than for those from normal swine.
 Two different methods were used to ascertain the release of Ca2+ induced by halothane: 1) the release of 45Ca2+ from nonmitochondrial stores of saponin-permeabilized hepatocytes was measured; and 2) changes in luminescence from intact hepatocytes loaded with the Ca2(+)-sensitive photoprotein aequorin were recorded.
 It was also observed that, although 1,4,5-inositol trisphosphate (IP3), guanosine-5-triphosphate, and arachidonic acid all induced a significant release of 45Ca2+ from permeabilized swine hepatocytes, only the quantities of 45Ca2+ released by IP3 were significantly greater for the hepatocytes prepared from the animals susceptible to MH.
 These data indicate an abnormal Ca2+ homeostasis in hepatocytes isolated from swine susceptible to MH, which supports the hypothesis that membrane systems from multiple organs may be affected in this genetic disorder.
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