,text,label 62,"Enterobacter bacteremia in pediatric patients. Enterobacter has emerged as an important human pathogen, particularly in sick, hospitalized patients. Previous reports of nonepidemic enterobacter bacteremia have focused on adult patients. In this report, the epidemiologic factors, clinical characteristics, treatment, and outcome for 33 patients with enterobacter bacteremia in a large children's hospital during a 5-year period are reviewed. The ratio of males to females was 1.2:1. The patients' ages ranged from 2 days to 24 years, and 18 patients were less than 18 months old. Twenty-two cases were nosocomially acquired; six were polymicrobial in nature. Significantly underlying conditions were present in 32 patients. The biliary tract and central venous catheters were the most common sources of bacteremia. Two-thirds of patients had preceding antibiotic therapy. The overall mortality was 24%; mortality attributable to enterobacter bacteremia was 18%. Statistically significant differences in mortality were associated with an age less than 18 months (P = .031) or thrombocytopenia (P = .017); presence of fever was of borderline significance (P = .098). Enterobacter bacteremia is an important cause of morbidity and mortality in pediatric patients. ",0 1155,"Differential effect of oncotic pressure on cerebral and extracerebral water content during cardiopulmonary bypass in rabbits. To study the effect of oncotic pressure on brain water content during cardiopulmonary bypass (CPB), 14 anesthetized New Zealand White rabbits underwent 60 min of nonpulsatile CPB at normothermia. Animals were grouped according to the composition of the circuit priming fluid. Group 1 animals (n = 7) received a priming fluid (6.5% hydroxyethyl starch in 0.72 N NaCl; 323 +/- 13 mOsm/kg [mean +/- SD]) that maintained normal colloid oncotic pressure (COP) during CPB (19.0 +/- 1.5 mmHg). Group 2 animals (n = 7) received a priming fluid (0.9 N NaCl; 324 +/- 23 mOsm/kg) that led to a hypooncotic state (COP = 6.2 +/- 1.2 mmHg). Blood chemistries and hemodynamics were recorded every 15 min during CPB. Animals were given additional priming fluid and sodium bicarbonate during CPB to maintain a circuit flow of 85 ml.kg-1.min-1 and arterial pH greater than 7.35. There were no significant differences between groups 1 and 2 with respect to temperature, central venous pressure, mean arterial pressure, PaO2, PaCO2, plasma sodium concentration, or osmolality at any time during CPB, although osmolality increased in both groups. After 60 min of bypass, animals were killed and organ water contents were determined by wet/dry weight ratios. A separate group of nine similarly prepared and anesthetized animals that did not undergo cannulation or CPB also underwent measurement of plasma chemistries and tissue water contents and served as nonbypass controls (group 3). Brain and kidney water contents were unaffected by oncotic pressure, whereas duodenum and skeletal muscle had significantly greater water content (P = 0.003 and P = 0.008, respectively) after hypooncotic CPB. ",9 3124,"An interdisciplinary nutrition assessment and intervention protocol for children with disabilities. Because of the multifactorial nature of the nutrition problems associated with developmental disabilities, a well-organized, interdisciplinary effort is necessary to deal with such problems. A team composed of professional and support staff, the client, and the family needs to be involved in an integrated approach to service. The team members share their knowledge and expertise in developing an individual program plan to meet identified needs. This article describes the development and implementation of a prototype for interdisciplinary nutritional evaluation and intervention in an outpatient setting. In 1987, a Regional Nutrition and Feeding Diagnosis and Evaluation Clinic was established through a contractual agreement between the University of Georgia University Affiliated Program and St. Mary's Hospital in Athens, GA. The purposes of the clinic are twofold: to offer direct services to developmentally disabled infants and children who require outpatient services and to provide a unique community-based interdisciplinary training experience for graduate students in nutrition and other health disciplines. The interdisciplinary treatment protocol is based on current knowledge in the treatment of developmental disabilities. ",22 837,"Hemodynamic changes in splenic blood flow during and after distal splenorenal shunt. The purpose of this study was to examine the hemodynamic changes of the spleen and the subsequent influence on the numbers of blood cells both during and 1 month after distal splenorenal shunt (DSRS) with splenopancreatic disconnection in 20 patients with portal hypertension. The intraoperative splenic blood flow, measured with an electromagnetic flowmeter, significantly increased after shunt insertion: the mean percentage increases within the splenic vein and artery were 60% (p less than 0.01) and 37% (p less than 0.05), respectively. The splenic venous blood flow, measured with a pulsed Doppler flowmeter, had not changed significantly 1 month postoperatively (676 +/- 501 to 540 +/- 306 ml/min). The WBC and platelet counts significantly (p less than 0.05 and p less than 0.01, respectively) increased 1 month postoperatively, whereas there was a small, but significant (p less than 0.05), decrease in RBC count. We concluded that splenic blood flow increases immediately after DSRS with splenopancreatic disconnection, but this increase may be only short term. The influence of the postoperative hemodynamic changes on blood cell count is uncertain. ",5 1391,"Influence of high-energy shock waves and cisplatin on antitumor effect in murine bladder cancer. The potential application of high-energy shock waves (HESW) for control of experimental bladder cancer was investigated. Subcutaneous 3-d murine bladder cancer (MBT-2) in C3H mice were exposed to HESW alone (250 to 1,500 shocks) or in combination with cisplatin (5 to 10 mg/kg, i.p.). Although HESW alone showed no influence on tumor growth, HESW/cisplatin combination therapy suppressed tumor growth more than cisplatin alone. Subsequent studies revealed that an air-fluid interface relative to tumor location played a pivotal role for the chemosensitizing effect of HESW. HESW treatment was able to enhance the cisplatin cytotoxicity only when the tumors were placed adjacent to the air-fluid interface. ",11 1616,"Irrigation device for neuroangiographic procedures. A simple irrigation device for use in diagnostic and interventional neuroangiographic procedures is described. The device is used to flush bubbles and blood clots from catheter hubs. The authors also describe a technique in which this device can be used to prevent filling a catheter with air when a guide wire is removed. ",13 1276,"Surgical techniques and reattachment rates in retinal detachment due to macular hole. We evaluated reattachment rates of the transvitreal and transscleral techniques for treating 250 eyes with retinal detachment due to macular hole. The initial success rate of the transvitreal approach was 56% (53/94). There was no difference between the results of gas tamponade alone and vitrectomy and gas tamponade. The initial success rate of the transscleral approach was 83% (130/156). Macular diathermy and macular buckling showed a higher reattachment rate than macular diathermy alone. The final success rates were the same (95%), regardless of which approach was selected as an initial technique. The patients whose initial transvitreal reattachment failed and who underwent additional transvitreal procedures (including macular laser photocoagulation) showed a success rate of 93%. We believe that gas tamponade, which has possibility of better visual prognosis, should be selected as an initial technique because the final success rate was found to be the same regardless of the initial surgical techniques. ",10 3054,"Serum acute phase proteins after orthotopic liver transplantation. Acute phase proteins were measured in six patients before liver transplantation and for 72 h after orthotopic liver transplantation. The ability of the donor liver to mount an acute phase response was demonstrated, although the response was less than that seen in other groups of patients in whom this has been studied. Because of the reduced response to stress, the value of these measurements as indicators of liver function in this group of patients is limited. ",22 2755,"Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans. 4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, may be useful for the treatment of methanol and ethylene glycol intoxications. A placebo-controlled, double blind, multiple dose, sequential, ascending-dose study has been performed to determine the tolerance of 4-MP in healthy volunteers. Oral loading doses of 4-MP were followed by supplemental doses every 12 h through 5 days, producing plasma levels in the therapeutic range. A slight, transient elevation in one or both serum transaminase values was observed in 6 of the 15 subjects treated with 4-MP. This effect was not dose related nor apparently mediated through a hypersensitivity reaction. Serum triglyceride levels were increased in 30% of 4-MP treated subjects, but also in 25% of the placebo subjects. 4-MP treatment did not produce any other significant changes in objective clinical parameters nor in subjective side effects. The results suggest that a mild, transient increase in liver function tests might be observed in some subjects treated with multiple doses of 4-MP. Nevertheless, the slower elimination rate and lesser degree of toxicity of 4-MP would make it preferable to ethanol in therapy of these poisonings. ",20 662,"Histologic, biochemical, and ion analysis of tissue and fluids retrieved during total hip arthroplasty. Large amounts of metal and polyethylene debris and high ion readings are found in capsule and fibrous membranes of both loose titanium and cobalt-chromium stems. Prostaglandin E2, interleukin-1, and collagenase levels are elevated when compared to control values with collagenase having the highest and most consistent elevations. Synovial fluid and blood ion readings were elevated in loose cemented and cementless stems made from both materials. Blood ion readings were not elevated in fixed stems. Fixed stems had much less particulate debris in soft tissues. The data showed that failure of most metal hip stems was initially due to a mechanical cause, with high debris and ion counts occurring secondarily in capsule and fibrous membranes. Particulate debris and high ion readings are primarily a focal problem contained by the periprosthetic fibrous connective-tissue encapsulation within the femoral canal and joint capsules. No systemic problems were manifest in any of the patients examined and followed in this study. ",4 673,"Evaluation of women with possible appendicitis using technetium-99m leukocyte scan. The authors evaluated the use of technetium-99m albumin colloid white blood cell (TAC-WBC) scan in women with possible appendicitis. One hundred and nine women underwent 110 TAC-WBC scans. One woman had a second scan on a separate admission and was considered two individual patients in the analysis. Twenty-six women had appendicitis, 10 of whom had a perforated appendix at surgery. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in 52 women (47%), nine of whom had appendicitis. Fifty-eight scans were read as positive or negative for appendiceal pathology. There were 16 true positives, 5 false positives, 36 true negatives, and 1 false negative. The predictive value of a positive scan was 76%, and the predictive value of a negative scan was 97%. The TAC-WBC scan was positive in 62% of patients with appendicitis and negative in 43% of the patients without appendicitis resulting in an overall accuracy of 47% in the 109 women. The main value of TAC-WBC scan in women with possible appendicitis is its high negative predictive value and the main problem with the TAC-WBC scan is its high indeterminate rate. ",5 996,"Bombesin stimulation of mitogenesis. Specific receptors, signal transduction, and early events. Quiescent cultures of Swiss 3T3 cells can be stimulated to recommence DNA synthesis by polypeptide growth factors, neuropeptides, and various pharmacologic agents that act via multiple signal transduction pathways. Neuropeptides of the bombesin family provide potent mitogens to elucidate these pathways. These peptides bind to specific receptors that have been characterized by radioligand binding and sensitivity to antagonists and identified as glycoproteins with a Mr of 75,000-85,000 by chemical cross-linking. After binding, bombesin elicits a cascade of early molecular events including stimulation of phosphorylation of the acidic Mr 80,000 cellular protein, which is a major substrate of protein kinase C; Ca2+ mobilization mediated by Ins(1,4,5)P3, Na+ and K+ fluxes, transmodulation of EGF receptor, enhancement of cAMP accumulation, and expression of the proto-oncogenes c-fos and c-myc. Studies using membrane preparations and permeabilized 3T3 cells indicate that G proteins play a role in the transduction of the mitogenic signal triggered by the binding of bombesin to its receptor. A pertussis toxin-insensitive G protein couples the bombesin receptor to the generation of a signal that activates protein kinase C, whereas a pertussis toxin-sensitive G protein mediates cross-talk between transmembrane signaling pathways. Bombesin-mediated mitogenesis can be blocked by different antagonists and by interrupting the signal-transduction process at various postreceptor levels. Thus, prolonged treatment with vasopressin causes heterologous desensitization to the mitogenic action of bombesin. This mitogenic block is mediated by uncoupling the receptor from its signaling system. Loss of responsiveness to bombesin-stimulated DNA synthesis is also induced by down-regulation of protein kinase C. ",7 50,"Occurrence of secondary attenuating mutations in avirulent Salmonella typhimurium vaccine strains. The attenuating delta aroA554 mutation in Salmonella typhimurium strain SL3261 was complemented in vitro by selecting for AroA+ recombinant DNA clones. SL3261 containing cloned aroA+ genes did not require exogenous phenylalanine, tryptophan, tryosine, p-aminobenzoic acid, or dihydroxybenzoic acid for growth in defined media. Cloned aroA+ genes did not restore wild-type virulence to SL3261, however, in a murine typhoid model. The delta aroA554 mutation was transduced into S. typhimurium strain SR-11, a mouse-virulent strain recently passaged in mice. The SR-11 delta aroA554 mutant was highly attenuated for mice challenged parenterally. The same cloned aroA+ genes isolated in SL3261 restored the virulence of the SR-11 delta aroA554 mutant to that of wild-type SR-11. These results suggest that while the delta aroA554 allele remains effective in reducing S. typhimurium virulence, laboratory passage of attenuated vaccine strains may lead to the accumulation of additional attenuating defects. ",0 2833,"Liberty and tardive dyskinesia: informed consent to antipsychotic medication in the forensic psychiatric hospital. This paper addresses informed consent to antipsychotic medication of those incarcerated in a forensic psychiatric hospital. The ways in which the unique setting of the forensic psychiatric hospital impinge upon the three components of informed consent--information, voluntariness, and competency--are explored. Special attention is given to the risk-benefit ratio of receiving antipsychotic medication in terms of the liberty interests at stake--freedom of movement, that is, the effects of tardive dyskinesia, and freedom of space, that is, release from the forensic psychiatric facility. ",20 409,"Trabecular or Merkel's cell carcinoma. Two cases of trabecular cell carcinoma of the skin are presented. The clinical presentation and behavior, and the histologic findings, of the tumor are described. Surgical excision of the primary lesion with regional lymph node dissection, if indicated, is the treatment of choice. Distant metastasis is treated by local irradiation. ",3 2842,"The Major Trauma Outcome Study: establishing national norms for trauma care. The Major Trauma Outcome Study (MTOS) is a retrospective descriptive study of injury severity and outcome coordinated through the American College of Surgeons' Committee on Trauma. From 1982 through 1987, 139 North American hospitals submitted demographic, etiologic, injury severity, and outcome data for 80,544 trauma patients. Motor vehicle related injuries were most frequent (34.7%). Twenty-one per cent of patients had penetrating injuries. The overall mortality rate was 9.0%. The mortality rate for direct admissions was strongly related to the presence of serious head injury, 5.0% and 40.0%, when head injuries were less than or equal to AIS (Abbreviated Injury Scale) 3 or greater than or equal to AIS 4, respectively. Survival probability norms use the Revised Trauma Score, Injury Severity Score, patient age, and injury mechanism. Patients with unexpected outcomes were identified and statistical comparisons of actual and expected numbers of survivors made for each institution. Results provide a description of injury and outcome and support evaluation and quality assurance activities. ",20 96,"Syphilis in adults. This article reviews the clinical manifestations of syphilis, diagnostic tests that might help to diagnose accurately the disease, and current recommendations for therapy. The association of syphilis and human immunodeficiency virus infection raises additional questions related to transmission, diagnosis, and therapy of both diseases. ",0 166,"The pharmacokinetics of plasminogen activator inhibitor-1 in the rabbit. The pharmacokinetics of the activated and latent forms of plasminogen activator inhibitor-1 (PAI-1) isolated from HT1080 fibrosarcoma cells (HT1080 PAI-1) and a nonglycosylated form of human PAI-1 isolated from a yeast expression system (rPAI-1) were followed in the rabbit. As assessed by an immunologic assay specific for human PAI-1, guanidine HCI activated HT1080 PAI-1 and rPAI-1 entered the total plasma volume following intravenous bolus administration and exhibited a biphasic clearance pattern. The t1/2s of HT1080 PAI-1 for the initial and beta phases equalled 6.0 and 24.8 minutes, respectively. The t1/2s of rPAI-1 for the initial and beta phases equalled 8.8 and 34.0 minutes, respectively. Similar results were obtained by measuring PAI-1 activity in plasma and with trace amounts of 125I-rPAI-1, suggesting that the above pharmacokinetic behavior could also apply to endogenous PAI-1. The liver was the main site of rPAI-1 clearance. Unactivated, latent PAI-1 exhibited a very different pharmacokinetic profile. Over 80% of latent rPAI-1 cleared from the circulation within 10 minutes (t1/2 = 1.7 minutes). The difference in clearance behavior between activated and latent PAI-1 may be related to the ability of activated PAI-1, but not latent PAI-1, to rapidly form high-molecular-weight complexes with plasma binding factors which were observed in vitro and in vivo. Because PAI-1 could potentially tilt the fibrinolytic balance toward a prothrombotic state, its rapid clearance may represent an important control mechanism governing the circulating levels of this key component of the fibrinolytic pathway. ",3 1397,"Angiotensin and thromboxane in the enhanced renal adrenergic nerve sensitivity of acute renal failure. The roles of intrarenal angiotensin (A) and thromboxane (TX) in the vascular hypersensitivity to renal nerve stimulation (RNS) and paradoxical vasoconstriction to renal perfusion pressure (RPP) reduction in the autoregulatory range in 1 wk norepinephrine (NE)-induced acute renal failure (ARF) in rats were investigated. Renal blood flow (RBF) responses were determined before and during intrarenal infusion of an AII and TXA2 antagonist. Saralasin or SQ29548 alone partially corrected the slopes of RBF to RNS and RPP reduction in NE-ARF rats (P less than 0.02). Saralasin + SQ29548 normalized the RBF response to RNS. While combined saralasin + SQ29548 eliminated the vasoconstriction to RPP reduction, similar to the effect of renal denervation, appropriate vasodilatation was not restored. Renal vein norepinephrine efflux during RNS was disproportionately increased in NE-ARF (P less than 0.001) and was suppressed by saralasin + SQ29548 infusion (P less than 0.005). It is concluded that the enhanced sensitivity to RNS and paradoxical vasoconstriction to RPP reduction in 1 wk NE-ARF kidneys are the result of intrarenal TX and AII acceleration of neurotransmitter release to adrenergic nerve activity. ",11 123,"Effect of vaccination on serotype-specific antibody responses in infants administered WC3 bovine rotavirus before or after a natural rotavirus infection. In an evaluation of WC3 bovine rotavirus (serotype 6) vaccine in infants, some subjects experienced a natural serotype 1 rotavirus infection before vaccination and others after. Therefore, the effects of both WC3 and natural rotavirus strains as either primary or boosting immunogens on serotype-specific neutralizing antibody responses could be determined. After primary natural infection (symptomatic or asymptomatic), neutralizing antibody titers were highest to serotype 1 but were consistently high to serotype 3, and low titers (greater than or equal to 20) to serotypes 2 and 4 were often detected. Previous vaccination with WC3 had little effect on the magnitude of these responses. In contrast, subjects infected with serotype 1 strains before vaccination experienced large (average, 12-fold) rises in neutralizing antibody to human serotypes 1-4 when vaccinated with WC3. Thus, although WC3 and the natural strains are distinct serotypes, their epitopes were sufficiently similar that reinfection with WC3 could boost neutralizing antibody titers to human serotypes in subjects primed by a previous natural infection. ",1 1177,"Neuromuscular diseases: evaluation with high-frequency sonography. Forty-four patients with clinically suspected neuromuscular disease and 12 healthy volunteers underwent high-frequency ultrasound examination of the rectus femoris, vastus medialis, vastus lateralis, and biceps brachii muscles, and the number of perimysial septa was determined. These numbers and muscle/soft-tissue ratios of the lower extremity were compared. Findings were correlated with results of muscle biopsy in all patients with suspected disease. Using the number of perimysial septa in the lower extremity, the authors found significant differences between the muscles of healthy volunteers and those of patients with Duchenne muscular dystrophies, other muscular dystrophies, and spinal muscular atrophies: The receiver operating characteristic curve showed that an average of 12 perimysial septa within 1 cm of muscle is the ideal cutoff value to differentiate subjects without morphologic changes from those with pathologic findings. The authors conclude that this measurement is useful for differentiation of neuromuscular diseases and may be a noninvasive, reproducible means with which to evaluate disease progression. ",9 1906,"Role of magnetic resonance contrast agents in cardiac imaging. Improvements in magnetic resonance imaging (MRI) technology allow adequate spatial and temporal resolution to capture cardiac anatomy and contractile function in exceptional detail and with little risk. However, tissue characterization of the pathophysiologic state of the myocardium may require special indicators or MR contrast agents. These must be tailored for detection by the MRI process, but available agents are effective at low dose and provide a wide range of indicator properties (e.g., myocardial extracellular space, blood pool, capillary permeability and membrane transport). Each agent has a dynamic washin and washout time-intensity curve that may reflect myocardial perfusion or consequences of ischemia. The combined use of MRI and MR contrast agents may provide a single diagnostic examination that fully and quantitatively assesses all indexes of cardiac performance. Such information would be both global and regional, and would be well tolerated by patients. The cost, value and cost-effectiveness of such studies remain speculative. ",13 3336,"Long-term echocardiographic follow-up of patients with a tricuspid bioprosthesis. To clarify the long-term results of bioprosthetic valve function in the tricuspid position, 29 consecutive patients who underwent tricuspid valve replacement (TVR) were evaluated. There were 20 girls/women and 9 boys/men, with ages ranging from 6 to 61 years (mean 41.4 years). The bioprosthetic valves included Hancock in 2, and Carpentier-Edwards in 27. The follow-up period ranged from 32 to 145 months (mean 89 months). Regurgitant flow of the tricuspid bioprosthesis was studied by color Doppler echocardiography. Peak velocity (Vp) and pressure half time (PHT) were measured by continuous wave Doppler echocardiography. Operative mortality was 13.7% (4/29), with the actuarial survival rate, including operative deaths, 75% at 10 years. Valve thrombosis developed in one patient 4 years after TVR. Color Doppler showed regurgitation in 7 of the 20 patients who were completely followed up, but they were all asymptomatic and required no special intervention. Cusp tear or calcification requiring reoperation was not observed in this study, including 8 patients younger than 35 years of age. The Vp was significantly slower, and PHT was significantly prolonged, in the tricuspid rather than the mitral position. These data demonstrate that bioprosthetic valves in the tricuspid position can be used safely. Doppler examination should be performed taking these different flow dynamics into account. ",22 3118,"Hypothalamic-pituitary-adrenal function in patients with the premenstrual syndrome. Patients with primary affective disorders, such as melancholic depression and anorexia nervosa, frequently have a hyperactive hypothalamic-pituitary-adrenal (HPA) axis, characterized by hypersecretion of CRH and a blunted ACTH response to exogenous CRH. Premenstrual syndrome (PMS) is a luteal phase dysphoric disorder characterized by primarily affective and behavioral disturbances. HPA axis function was compared in PMS patients and control women, respectively, diagnosed by DSM3-R criteria or found to have no current psychiatric disorders, determined by the Schedule for Affective Disorders and Schizophrenia-Lifetime Interview. Urinary free cortisol excretion was the same in PMS and normal women, and no differences in urinary free cortisol excretion between the follicular and luteal phases occurred in either group. Two HPA axis abnormalities, however, were noted when PMS patients were compared to normal women. First, basal evening cortisol concentrations in plasma were significantly decreased, while the time-integrated response of plasma cortisol to ovine (o) CRH was significantly increased. Second, the negative correlation between time-integrated plasma ACTH and cortisol responses to oCRH and basal luteal progesterone concentrations present in normal control women was not seen in the PMS patients. These changes in basal and oCRH-stimulated plasma cortisol levels in association with normal urinary free cortisol excretion suggest that women with PMS might have transient or episodic disturbances of their HPA axis, which appear adequately corrected by this system's servomechanisms. This probably explains the maintenance of regular menstrual cycles in PMS patients, which contrasts with the irregular menses observed in patients with depression, anorexia nervosa, or women who participate in chronic strenuous exercise. ",22 1496,"Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study Preeclampsia is a disease unique to pregnancy that contributes substantially to maternal and fetal morbidity and mortality. The condition has been thought to be one of hypoperfusion in which increased vascular resistance characterizes the associated hypertension. This study was designed to test an alternative hypothesis, that preeclampsia is characterized by high cardiac output. In a blinded longitudinal study of nulliparas with uncomplicated pregnancies, cardiac output was measured serially by Doppler technique. Cardiac output was elevated throughout pregnancy in patients who became preeclamptic (P = .006). Six weeks postpartum, the hypertension of the preeclamptic subjects had resolved but cardiac output remained elevated (P = .001) and peripheral resistance remained lower than in the normotensive subjects (P = .001). This study demonstrates that preeclampsia is not a disease of systemic hypoperfusion and challenges most current models of the disease based on that assumption. ",12 485,"Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway. A randomized, multicenter clinical trial was conducted in Western Norway to study the effectiveness of preoperative radiation therapy in operable rectal cancer, given at a dosage of 3150 cGy in 18 fractions, 2 to 3 weeks before radical surgery. Three hundred nine patients were entered into the trial between May 1976 and December 1985. After radiation no tumor was seen in 4.5% of the patients. There was no increased morbidity or mortality at surgery. The 5-year survival for evaluable patients was 57.5% in the control group and 56.7% in the radiotherapy group. For patients operated on for cure the 5-year survival was 60.9% and 64.2% in the control group and radiotherapy group, respectively. Radiation significantly delayed both local and distant recurrences in patients in the radiation group who had curative resection from 13.3 months in controls to 27.1 months. The local recurrence rate in the corresponding groups was 21.1% and 13.7%, respectively. We conclude that higher preoperative radiation doses should be used in new trials as a higher dosage may transform the observed positive effects into a survival benefit. ",3 687,"Bile duct emptying in response to fat: a validation study. Fatty meal sonography has been suggested to assess patients with biliary pain after cholecystectomy, but the effects of gallbladder removal on biliary dynamics has not been studied prospectively. Before elective cholecystectomy, 25 patients had their common hepatic ducts' diameter measured by ultrasonography before and after a fat stimulus. In 23, tests were repeated 1 month, 1 year, and 5 years after surgery. In preoperative studies, 5 patients showed dilatation after fat and 2 of these had stones in the common bile duct. However, another 4 patients with stones or sludge in the duct did not show dilatation, so that the response to fat was a poor indicator of patients requiring common bile duct exploration. No patient had major symptoms after surgery. At 1 month and 12 months, the response to fat was variable with more than half of those tested showing no decrease in duct size. A more consistent pattern emerged at 5 years, when 14 of 18 patients tested showed a decrease in common hepatic duct after fat; 3 were unchanged and 1 increased by 1 mm. The response to fat was less consistent and more difficult to measure in the common bile duct, even 5 years after operation. It was concluded that not all patients with indications for exploration of the common bile duct on operative cholangiography show a dilatation response to fat on preoperative testing. Also, fatty meal sonography should be used with caution because the response to fat in asymptomatic patients soon after operation is unpredictable, with occasional patients showing dilation without apparent obstruction. Measurement of common hepatic duct is preferred to common bile duct and increases in diameter of 1 mm are probably not significant. ",5 1489,"Effect of interleukin-1 on gamete interaction and mouse embryo development. Early stages of endometriosis have been shown to be associated with infertility. The pathophysiology of this relationship is unclear. To determine if interleukin-1 (IL-1), a peritoneal macrophage product, has any effect on gamete interaction and early embryo development, human recombinant IL-1 was added to the coincubation of gametes in the sperm penetration assay (SPA), human zona pellucida assay (ZPPA) and culture medium (Ham's F-10) used for processing semen samples with the layering method, with analysis of velocity and motility after 24 hours. IL-1 was also added to mouse embryos (two cells) cultured for 72 hours. The results showed that IL-1 caused impairment of SPA and ZPPA when compared to control medium, without significant alterations in sperm velocity and motility. Also, IL-1 demonstrated significant inhibition of mouse embryo development. These results help explain subfertility associated with early stages of endometriosis. ",12 1798,"Efficacy of recombinant-derived human superoxide dismutase on porcine left ventricular contractility after normothermic global myocardial ischemia and hypothermic cardioplegic arrest. A porcine model of normothermic global ischemia (40 minutes) followed by systemic cooling to 25 degrees C with 4 degrees C crystalloid cardioplegic arrest (90 minutes) was used to assess the efficacy of recombinant-derived human superoxide dismutase (r-HSOD) on postreperfusion left ventricular function while on cardiopulmonary bypass. Isovolumic hemodynamic function was monitored, and adenine nucleotide pool was measured in myocardial biopsy specimens and coronary sinus effluent. The treatment group of pigs (n = 7) received 15 mg/kg r-HSOD immediately before warm reperfusion, both left ventricular peak systolic pressure and developed pressure were significantly better in the r-HSOD group of pigs (p less than 0.05 vs. placebo). This improvement persisted at 60 minutes of reperfusion (p less than 0.05 vs. placebo). Myocardial ATP and total adenine nucleotides did not differ, nor did adenine nucleotide catabolites in the coronary sinus effluent differ between treatment groups of pigs. The exception to this was the nucleotide catabolite inosine, which was significantly elevated in coronary sinus effluent of pigs treated with r-HSOD at 30 minutes of reperfusion (p less than 0.05 vs. placebo). In this model of global ischemia and reperfusion, a recombinant-derived human free-radical scavenger provides significant protection of systolic but not diastolic function. Values for myocardial ATP and total adenine nucleotide content suggest that the improvement in mechanical function during reperfusion is not due to enhanced preservation of myocardial bioenergetics. ",13 1087,"The epilepsies: clinical implications of the international classification. From the earliest days of neurology, the classification of epileptic seizures into those generalized from the beginning and those with a definable localization in the cortex from the onset has added to knowledge about the function of the nervous system. Further elaboration of the classification of seizures into those localized to the six-layered isocortex and those whose elaboration involves regions of the brain involved with consciousness and memory has provided the basic focus for the burgeoning subspecialty of epilepsy surgery. It is increasingly apparent that the etiology of a seizure disorder is of at least equal or of greater significance than the nature of the seizures it spawns and is the product not only of localization in the nervous system but also of causative factors with implications reaching into areas of genetics, higher cortical function, and intelligence. The prognosis concerning the outcome of the epilepsy under consideration is based on all of these facets. This pathophysiological substratum, of which the seizure is only the presenting symptom, constitutes the epilepsy or epileptic syndrome on which the formulation of a rational treatment plan is based. ",9 1800,"Comparison of medical and surgical therapy for uncomplicated descending aortic dissection. To guide the choice of medical versus surgical therapy for patients with descending (type B) aortic dissection (tear in the descending aorta without involvement of the ascending aorta), multivariate survival analysis was applied to 136 patients admitted to two medical centers between 1975 and 1988 with acute (n = 89) or chronic (n = 47) descending dissection: group 1, all 136 patients; group 2, 106 patients without rupture, pulse loss, or visceral organ compromise; and group 3, 56 patients from group 2 without major cardiac or renal disease (23 surgical and 33 medical). Group 3 medical and surgical subgroups were well matched for baseline characteristics and were potential candidates for either mode of therapy. By Cox model analysis, significant predictors of mortality were pleural rupture, other dissection complications, increasing age, and cardiac disease (all p less than 0.01). Surgical versus medical therapy was not an independent determinant of survival in any of the three groups for acute or chronic dissection. Survival probabilities for all group 3 patients at 1, 5, and 10 years were 0.94, 0.87, and 0.32 (medical) and 0.90, 0.80, and 0.50 (surgical). Despite the limitations of this retrospective study (including the possibility of undefined treatment selection biases), these data suggest that medical or early surgical therapy is associated with equivalent outcome in selected patients with uncomplicated acute or chronic descending aortic dissection. ",13 631,"Quantitative evaluation of digital dental radiograph imaging systems. Two digital imaging systems, a video camera and analog-to-digital converter, and a charge-coupled device linear photodiode array slide scanner, were tested for their suitability in quantitative studies of periodontal disease. The information content in the original films was estimated, and digital systems were assessed according to these requirements. Radiometric and geometric performance criteria for the digital systems were estimated from measurements and observations. The scanner-based image acquisition (digitization) system had no detectable noise and had a modulation transfer function curve superior to that of the video-based system. The scanner-based system was equivalent to the video-based system in recording radiographic film densities and had more geometric distortion than the video-based system. The comparison demonstrated the superiority of the charge-coupled device linear array system for the quantification of periodontal disease extent and activity. ",4 653,"Arthritis: roles of radiography and other imaging techniques in evaluation. Imaging studies are performed on patients with arthritis for a variety of reasons: to determine whether an arthritic condition is present; to establish the specific diagnosis; to determine the extent of disease; to assess the activity of disease; to detect complications of disease; to evaluate progression of disease; to judge the efficacy of drug treatment; to help in selection of surgical candidates; to aid in the choice of surgical procedures; to size, design, or fabricate prostheses; and to identify complications of surgery. Conventional radiography is still the mainstay of all examinations in arthritic patients. Arthrography is best applied to evaluate complications of disease and of surgery, although it may be useful in disease detection and in determining the specific diagnosis. Nuclear medicine studies are best used to identify complications of surgery and may also be useful to assess disease activity or extent. Ultrasound is useful to detect dissecting synovial cysts and deep venous thrombosis. The most valuable role of computed tomography is in the design and fabrication of prostheses and in evaluating complex anatomy of involved joints. Magnetic resonance imaging may be useful in early detection of articular cartilage damage and may assist in determination of the specific diagnosis; enhancement with contrast material may aid in assessment of disease activity. ",4 288,"Hyperthermia alone in the treatment of recurrences of malignant tumors. Experience with 60 lesions. Localized hyperthermia alone has been used for the treatment of cancer recurrences in which previous conventional therapies have failed. Since 1983 and 1988, 57 patients with 60 lesions have been heated by means of a microwave and radiofrequency system. Treatment protocol provided 45 minutes of heating at the intratumor temperature of at least 42 degrees C, twice a week, for a total number of six, eight, or ten heating sessions. Invasive intratumor thermometry was performed for all lesions. Complete response (CR) was obtained in ten cases (16.6%) and partial response (PR) in 14 (23.4%). Higher rates of CR were observed in the chest wall (38.5%) compared with the head and neck area (11.4%), trunk (10%), and limbs (none). Adenocarcinoma was the most responsive histologic type (40%). Squamous cells carcinoma had 7.7% CR. The only case of undifferentiated carcinoma showed CR; there were none on five sarcomas. Long-term local control (24 months) was approximately 7%. The multivariate analysis showed the statistical significance of the histologic variety (adenocarcinoma versus others, P less than 0.0001). Side effects and complications of the treatment were minimal. ",3 2561,"Characteristics and correlates of asthma in a university clinic population. To contribute more comprehensive information about the characteristics of asthma, this article analyzed patients served by the University of Alabama at Birmingham Comprehensive Asthma Program. Their physicians rated one fifth of these patients as having ""severe"" asthma with the remainder about equally divided between ""moderate"" and ""mild"". One in two first received a diagnosis of asthma ten or more years previously. Common comorbidities were hypertension, obesity, rhinitis, bronchitis, sinusitis, and arthritis. One half had visited an emergency room or been hospitalized for asthma in the past year. Inhaled bronchodilators and continuous theophylline were the most commonly prescribed medications. Side effects, especially tachycardia and insomnia, were common and almost exclusively associated with theophylline or corticosteroid therapy. Spirometric assessment showed chronic airflow obstruction in those with more severe asthma. Prevalence of respiratory symptoms, intensity of medication regimen, incidence of side effects, and health care utilization increased as asthma severity increased. ",19 188,"Endosonography of pararectal lymph nodes. In vitro and in vivo evaluation. One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz x cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz x cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent. ",3 2242,"Ischiopagus tetrapus twins: urological aspects of separation and 10-year followup. Conjoined twins occur once in 50,000 births. Only 6% of conjoined twins are of the ischiopagus type in which the twins are joined symmetrically at the pelvis and fusion begins at the level of the common umbilicus. The longitudinal axis extends in a straight line in opposite directions and the genitourinary and gastrointestinal tracts are shared. Tetrapus is a subtype in which all 4 lower extremities are present and oriented at right angles to the axis of the common trunk. Two sets of female ischiopagus tetrapus twins were born in 1977 and successfully separated at the St. Louis Children's Hospital in the following year. We describe the genitourinary and associated anomalies, surgical separation and long-term urological followup of these 2 sets of ischiopagus tetrapus twins. ",15 789,"Esophageal 24-h pH monitoring: is prior manometry necessary for correct positioning of the electrode? In 24-h esophageal pH monitoring, the electrode is usually positioned 5 cm above the manometrically localized esophagogastric junction. In order to replace esophageal manometry for this purpose, we tested whether the esophagogastric junction can be identified correctly by fluoroscopy or the determination of the pH-step between stomach and esophagus, compared with esophageal manometry. The distance from the nares to the esophagogastric junction was determined three times with each of the three methods in 46 patients and 14 volunteers. Fluoroscopy assumed the esophagogastric junction 1.23 +/- 0.23 cm (mean +/- SE) lower than the peak pressure point determined at manometry, pH-step only 0.45 +/- 0.16 cm. With pH-step, only one subject had a difference of more than 3 cm to the manometrically defined esophagogastric junction, whether gastroesophageal reflux disease (as proven by pH monitoring) was present or not. We conclude that the esophagogastric junction can usually be identified with sufficient accuracy by the measurement of the pH-step between stomach and esophagus. Fluoroscopy is far less accurate than pH-step, and should not be used. ",5 3110,"Increased fatigue of isovelocity vs. isometric contractions of canine diaphragm. A comparison of fatigue as a loss of force with repeated contractions over time was performed in canine respiratory muscle by isometric (nonshortening) and isovelocity (shortening) contractions. In situ diaphragm muscle strips were attached to a linear ergometer and electrically stimulated (30 or 40 Hz) via the left phrenic nerve to produce either isometric (n = 12) or isovelocity (n = 12) contractions (1.5 s) from optimal muscle length (Lo = 8.8 cm). Similar velocities of shortening between isovelocity experiments [0.19 +/- 0.02 (SD) Lo/S] were produced by maximizing the mean power output (Wmax = 210 +/- 27 mW/cm2) that could be developed over 1.5 s when displacement was approximately 0.30 Lo. Initial peak isometric tension was 1.98 kg/cm2, whereas initial peak isovelocity tension was 1.84 kg/mc2 (P less than 0.01) or 93% of initial isometric tension. Fatigue trials of 5 min were conducted on muscles contracting at a constant duty cycle (0.43). At the end of the trials, peak isovelocity tension had fallen to 50% of initial isometric tension (P less than 0.01), whereas peak isometric tension had only fallen by 27%. These results indicate that muscle shortening during force production has a significant influence on diaphragm muscle fatigue. We conclude that the effects of shortening on fatigue must be considered in models of respiratory muscle function, because these muscles typically shorten during breathing. ",22 1628,"Left ventricular end-systolic stress-volume index ratio in aortic and mitral regurgitation with normal ejection fraction. To evaluate the left ventricular contractile state in regurgitant valvular disease with normal ejection fraction, we analyzed the end-systolic stress-volume index relationship (ESSVR) by means of cineangiography in 15 normal subjects, 11 patients with aortic regurgitation (AR), and 10 patients with mitral regurgitation (MR) whose ejection fraction (EF) was 60% or more. The end-systolic stress-volume index ratio in normal subjects was 5.57 +/- 0.60 kdyne/cm5/m2 (mean +/- standard deviation), and we defined the range including +/- 2 standard deviations of the ratio as the normal ESSVR range. Six patients with AR and five patients with MR placed inside the normal ESSVR range, termed AR IN and MR IN, but the remaining five patients with AR and MR placed to the right of the normal range, termed AR OUT and MR OUT. EF did not differ between patients with AR IN and AR OUT (69.4 +/- 5.4 verus 70.7 +/- 6.1%) and between MR IN and MR OUT (71.6 +/- 3.6 versus 71.1 +/- 7.9%). The EF of the subdivided groups with AR and MR also did not differ from that of normal subjects (70.7 +/- 7.3%). This finding showed that the left ventricular contractile state was depressed in patients with AR OUT and MR OUT despite a normal EF. In AR and MR the end-systolic stress and end-systolic volume index of OUT did not differ from those of IN, but the end-diastolic volume index of OUT was larger than that of IN (AR OUT 156.8 +/- 27.9 versus AR IN 110.8 +/- 24.1 ml/m2, MR OUT 160.5 +/- 44.7 versus MR IN 101.0 +/ 16.6 ml/m2; both p less than 0.05), and the regurgitant fraction of OUT was higher than that of IN (AR OUT 52.6 +/- 13.6 versus AR IN 29.7 +/- 13.3%, MR OUT 52.9 +/- 10.2 versus MR IN 30.2 +/- 11.4%; both p less than 0.05). In addition, there was a linear inverse correlation between the end-systolic stress-volume index ratio and the end-diastolic volume index in all subjects (r = -0.82, n = 36). In normal subjects there was a linear inverse correlation between end-systolic stress and the EF (r = -0.91, n = 15), but this relationship failed to separate patients with OUT from those with IN. Results of the present study suggest that some patients with AR and MR whose EF was normal had a depressed contractile state, and these patients had a large end-diastolic volume index and a high regurgitant fraction.(ABSTRACT TRUNCATED AT 400 WORDS). ",13 1415,"The effect of post-pubertal varicocele on testicular volume. Paediatric varicocele is a well known entity but its effect on adult infertility has not been adequately clarified. Since measurement of testicular volume is currently the best method of estimating the male reproductive potential, 945 boys aged between 13 and 18 years were examined with regard to testicular volume and the incidence of varicocele. The average volumes for right and left testes were 15.087 +/- 0.237 and 14.514 +/- 0.347 ml respectively, and the incidence of varicocele was 16.7%. The incidence increased from 14.5 to 21.7% as the ages increased from 14 to 18. The differences in volume of the 2 testes in boys with varicocele were statistically significant when compared with the normal group, but this significance failed to become more pronounced when the slight varicocele group (grade I) was included with the normal group and compared with the severe varicocele group (grades II and III). There may be no significant differences between the volumes of the 2 testes in boys with varicocele when careful measurement and strict statistical analyses are applied. However, some boys in the varicocele group were found to have testicular volumes below the confidence interval (mean - SE) or under 1 SD, and the 2 testicular volumes differed in certain age groups. This group requires further follow-up. The results of this study have added further contradictory findings to the issue of paediatric varicocele in terms of testicular atrophy, estimation of potential fertility and the indications for immediate surgery. There is a need for further prospective controlled trials. ",11 1350,"Pooled sequential ejaculates: a way to increase the total number of motile sperm from oligozoospermic men. We investigated the yield of total number of motile spermatozoa from oligozoospermic men by pooling two closely spaced sequential ejaculates. Semen characteristics were compared between sequential ejaculates (within a period of 1 to 4 hours) of 18 oligozoospermic males (sperm concentration less than 20 X 10(6)/mL and total sperm count less than 40 X 10(6) in the ejaculate) and a control group of 16 normozoospermic men. Whereas the median total number of motile sperm of normozoospermic males significantly decreased from 70 X 10(6) in the first ejaculate to 23 X 10(6) in the second sequential ejaculate, such a decrease was not detected in oligozoospermic males, 3.6 X 10(6) and 3.1 X 10(6), respectively. The percent of normozoospermic and oligozoospermic men who demonstrated a decreased (less than 50%), a comparable (50% to 150%), or an increased (greater than 150%) total motile sperm count in the second ejaculate in comparison with the first ejaculate were 69%, 31%, and 0 versus 39%, 28%, and 33%, respectively. Consequently, pooling of two sequential ejaculates significantly increased the median total number of motile sperm from normozoospermic males by 144% and from oligozoospermic males by 329%, (to 10.2 X 10(6]. We suggest that pooling of two sequential ejaculates from oligozoospermic males is a simple and cost effective method to increase significantly the total number of motile sperm for intrauterine insemination, in vitro fertilization, gamete intrafallopian transfer, or semen cryopreservation. ",11 3333,"Endothelialization of vascular prostheses by transplantation of venous tissue fragments. A method to accelerate the endothelialization of vascular prostheses by seeding venous tissue fragments was developed. A piece of peripheral vein was obtained, chopped into small fragments, and stirred into 20 ml of saline, making a tissue suspension. This suspension was sieved through the wall of a highly porous vascular prosthesis (water porosity: 3,600-4,000). The prostheses, (7 mm ID and 5.7 cm in length) seeded with tissue fragments, were implanted into the thoracic descending aortae of 20 dogs, and were removed from 1 to 371 days after implantation. Ten prostheses, preclotted with fresh blood, were used as controls. In the seeded grafts, an infinite number of endothelial cells migrated and proliferated from the fragments. These had produced numerous capillaries by 5 days after implantation that had reached and opened onto the luminal surface of the prosthesis. From these openings, numerous endothelial cells spread out and formed colonies. With the increase in the size of the colonies, the inner surface was completely endothelialized within 5 weeks. This quick neointimal formation by seeding venous tissue fragments might be applicable to several artificial organs. ",22 816,"The clinical importance of drug interactions with antiulcer therapy. The overall safety of a given drug is determined by its toxicity, side effects, and drug-drug interactions. Thus, a clarification of the mechanisms, importance, and clinical implications of any drug-drug interaction with antiulcer therapy is critical to the use of antiulcer medications. Drug-drug interactions may occur as a result of changes in absorption, metabolism, distribution, or excretion. Fortunately, drug distribution or protein binding is unchanged by antiulcer therapy. Antiulcer drugs may affect absorption by several mechanisms. Ionized medications may bind to the divalent cations of antacids and sucralfate to result in poorly absorbed complexes. Reduced gastric acid may decrease the absorption of medications that are weak bases while enhancing the absorption of weak acids. Drug absorption may be impaired by delayed gastric emptying. Several H2-receptor antagonists, including cimetidine and to a lesser extent ranitidine, and the proton pump inhibitor, omeprazole, may reduce the hepatic degradation of drugs metabolized by the cytochrome P450 system. The degree to which such agents alter drug metabolism is determined by the patient's age, genetics, duration of therapy, degree of cytochrome P450 binding, and the regimen. Because the clinical importance of this interaction cannot always be predicted, caution is recommended whenever drugs metabolized by this system are used concurrently. Development of an understanding of the ways in which drug metabolism interactions occur may lead to more effective and safe use of these medications. ",5 1889,"Venous ulcers: pathophysiology and medical therapy. Venous ulcers may occur as a result of lower extremity calf pump failure, with ensuing edema, trapping of white blood cells and deposition of pericapillary fibrin. Acute, smaller lesions are easily treated with adequate compression and occlusive dressings. Larger, more chronic wounds often benefit from some form of external compression. Occlusive dressings and local wound care are most effective when used simultaneously with compression. Sequential compression pumps merit study and may prove to be of therapeutic and prophylactic value. In refractory cases, long-term use of compression devices may be required to prevent ulcer recurrence. ",13 415,"Diet and female sex hormone concentrations: an intervention study for the type of fat consumed. A possible mechanism by which dietary fat may influence the development of breast cancer is by influencing the concentration of female sex hormones. This study investigated the effect of alteration in the type of fat consumed on concentrations of female sex hormones in serum. Female volunteers were randomly assigned to continue on their usual meat-eating diet, change to a vegetarian diet, or change to a diet that was predominantly vegetarian but where fish was consumed at least three times per week. Change to the vegetarian or fish diet had little effect on diet total hormone concentrations; however, the amount of estradiol was significantly decreased in the vegetarian group. When nutrient consumption was correlated with hormone concentrations, prolactin was directly associate with fat consumption, sex-hormone-binding globulin was inversely associated with fat consumption (particularly cholesterol consumption), and the proportion of nonprotein-bound estradiol was directly associated with complex carbohydrate consumption. ",3 810,"Insulin resistance in noncirrhotic idiopathic portal hypertension. To explore further the pathogenesis of glucose intolerance and insulin resistance observed in patients with cirrhosis and portal hypertension, we studied a 35-year-old woman with presinusoidal portal hypertension without cirrhosis due to nodular regenerative hyperplasia of the liver. After oral glucose ingestion, glucose tolerance remained normal; however, this occurred at the expense of a markedly hyperinsulinemic plasma response, suggesting the presence of insulin resistance. To examine this question more directly, we performed a stepwise euglycemic insulin clamp study in combination with an infusion of [6-3H]glucose and [1-14C]palmitate and indirect calorimetry. The ability of insulin to promote total body (primarily muscle) glucose uptake was markedly impaired, whereas its effect to suppress hepatic glucose production was normal compared with results obtained in nine healthy subjects. Moreover, insulin failed to normally suppress plasma free fatty acid turnover and oxidation in this patient. This informative case demonstrates that portal hypertension alone, without hepatic dysfunction from cirrhosis, is associated with impaired insulin-mediated glucose and plasma free fatty acid metabolism and may also play a predominant role in the development of insulin resistance in many cirrhotic patients. ",5 1355,"A comparative study of renal scintigraphy and clearance with technetium-99m-MAG3 and iodine-123-hippurate in patients with renal disorders. The aim of this study was to compare kit prepared technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) with our routine radiopharmaceutical, iodine-123-hippurate our routine radiopharmaceutical, iodine-123-hippurate ([123I]OIH) for renal dynamic scintigraphy. Seventeen patients with different nephrologic disorders or hypertension were first studied with OIH and then reinvestigated with MAG3 2-8 days later. Renal MAG3 gamma camera images were almost identical with those of OIH except for higher (p less than 0.01) liver-to-background ratios at 20 min postinjection, irrespective of kidney function. Urinary peristalsis was visible longer and more clearly in the MAG3 studies. MAG3 and OIH renograms showed identical relative kidney uptake (r = 0.99), but elimination of MAG3 from the kidneys was slower (p less than 0.01). The plasma clearance of MAG3 was lower than that of OIH, but correlated (r = 0.92) significantly. The plasma distribution volume and content in blood cells was lower (p less than 0.01), but the binding of MAG3 to plasma proteins was higher, 90%, as compared with 74% for OIH, p less than 0.01. Urinary excretion expressed as a percent of the given dose 60 min after injection was the same for the two substances. Thus, there are some significant differences in the renal handling, plasma distribution, and cell penetration between MAG3 and [123I]OIH. MAG3, however, seems to have particular qualifications as a radionuclide for dynamic renal scintigraphy, especially in patients who require acute investigations or in those with low renal function. ",11 461,"Combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap for the repair of wide defects of the lower leg. The tensor fasciae latae musculocutaneous flap has great advantages for reconstruction of the abdominal wall, but the medial border of its territory is limited to the thigh. In order to expand the territory, a combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap was devised. This flap was successfully used to resurface a large defect in the lower leg as a distally based musculocutaneous flap. The advantages of this flap are its extremely large territory, the fact that total necrosis of the flap cannot occur, and that as a proximally or distally pedicled flap it is suitable for large defects in the abdominal wall, lower leg, and gluteal region. ",3 427,"Immunocytochemical localization of progesterone receptors in endocrine cells of the human pancreas. Progesterone receptors (PgR) have been immunocytochemically localized in the nuclei of several (40% to 75%) endocrine cells of the human pancreas and in a more variable number of neoplastic cells of 7 of 18 endocrine pancreatic tumors. Conversely the exocrine epithelial cells of the pancreas did not exhibit any PgR immunoreactivity in normal as well as in different pathologic conditions, including pancreatic adenocarcinomas. Estrogen receptors were not detected in any of the pancreatic samples investigated. Double immunocytochemical experiments have documented that PgR immunoreactivity in normal Langerhans islets is a consistent feature of most (75%) glucagon-producing A cells, of approximately 5% to 20% of insulin-producing B cells, and of a variable percentage of pancreatic polypeptide (PP)-producing cells, ranging from 5% to 70%. These figures were not affected by the sex, age, or underlying disease of the patients. The reported findings corroborate previous clinical and experimental evidence indicating that sex steroid hormones may have some regulatory effects on the functional activity of the endocrine pancreas. ",3 911,"Variations in urethral and bladder pressure during stress episodes in healthy women. Pressure variations in the urethra and bladder during stress episodes and their time separations were investigated in 30 healthy female volunteers. The pressure was measured by means of a double microtip transducer catheter with the distal sensor in the bladder and the proximal sensor at the bladder neck, the mid-urethra and the distal urethra. In advance of the pressure spike during cough a pressure rise was demonstrated in the bladder and at all 3 sites of measurement in the urethra. The urethral pressure increments preceding and following the pressure spike were statistically significantly higher in the mid-urethra than the corresponding bladder pressures. This active urethral pressure generation in the mid-urethra and distal urethra was initiated 200 ms before the bladder pressure began to rise. The pressure in the urethral high pressure zone was higher than the bladder pressure in all cases. Passive pressure transmission to the urethral high pressure zone can take place only insignificantly due to a continuous higher pressure inside the urethra than in the bladder and due to the location of the high pressure zone in the demarcation of the abdominal cavity. It was concluded that the urethral pressure rise in the high pressure zone during stress episodes is mainly generated actively by intra- and/or peri-urethral structures. ",7 1154,"Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants. Previous studies have demonstrated that, with the exception of atracurium, resistance to the neuromuscular blocking effects of various muscle relaxants develops in patients receiving anticonvulsant therapy. We studied the effects of 0.5 mg/kg IV atracurium in 53 neurosurgical patients: 21 nonepileptic patients receiving no anticonvulsant therapy (MED = 0); 14 epileptic patients treated with carbamazepine for years (MED = 1); and 18 epileptic patients treated with carbamazepine plus either phenytoin or valproic acid for years (MED = 2). The evoked compound electromyogram of the adductor pollicis brevis was recorded, and results were analyzed using analysis of covariance, with weight and age as covariables. The onset time was not significantly different among the three groups. Times for recovery of baseline and train-of-four responses to stimuli were significantly shorter in the MED = 1 and MED = 2 groups than in control patients (MED = 0). The recovery index (time between 25% and 75% recovery of baseline electromyogram values) was progressively shorter in the three groups (MED = 0: 8.02 min; MED = 1: 5.93 min; MED = 2: 1.96 min; P less than 0.001). This study demonstrates that atracurium, when used on epileptic patients requiring long-term (that is, years of) anticonvulsant therapy, has a shorter duration of action than when used in nonepileptic patients. ",9 2313,"Correcting a stairstep deformity secondary to lower abdominal scars by the use of a decorticated hypogastric flap. The author describes a decorticated hypogastric flap used in the correction and prevention of retracted scars and suprapubic stairsteps. These deformities are common after cesarean sections and in patients who undergo liposuction followed by the retrieval of excess skin. The surgical technique is described. The author also analyzes the advantages and results that occur without an increase in either the time of surgery or complications. ",16 7,"Treatment of fungal skin infections: state of the art. The number of cases of mycotic infections are increasing, presenting physicians today with an unprecedented challenge in handling the treatment and prophylactic control of these disorders. The increase in mycotic disorders is due to many factors, such as longer life span, organ transplantation, and the acquired immunodeficiency syndrome. The pharmaceutical industry is providing physicians with newer, more potent drugs to manage mycoses. An overview of current practice in the use of topical and oral agents, especially ketoconazole, are given in the following specific mycoses: tinea capitis, pityriasis versicolor, seborrheic dermatitis, Trichophyton rubrum infections, vaginal candidiasis, and moist intertriginous tineas. The efficacy of ketoconazole in various vehicles and dosage schedules and of traditional agents such as griseofulvin are discussed with relation to each of the mycoses. ",0 1094,"A study of the seasonal variation of migraine. Available evidence supports the contention that migraine involves a disturbance in serotonin function. Several parameters of serotonin function in humans have been found to vary seasonally and may underlie the seasonal fluctuations observed in many clinical neuropsychiatric phenomena that are thought to involve serotonin dysfunction. We therefore postulated that migraine headaches might also vary seasonally and examined the admissions to our hospital over a 20-year period with a primary diagnosis of migraine. Peak admissions were found to occur most frequently in the spring for females in comparison to males (p less than or equal to 0.04, chi-square). The implications of these findings are discussed. ",9 2539,"Prevalence of previously undiagnosed hypothyroidism in residents of a midwestern nursing home [published erratum appears in South Med J 1991 Jul;84(7):936] Hypothyroidism in the elderly may be associated with nonspecific symptoms. To determine the prevalence of undiagnosed hypothyroidism in residents of a skilled nursing facility, we screened 434 male and 137 female residents, aged 60 years or older, for thyroid dysfunction. Overt hypothyroidism was found in three men and two women. Subclinical hypothyroidism was diagnosed in 42 men (9.7%) and 20 women (14.6%). Tests for thyroid antibodies were positive in all patients with overt hypothyroidism and in 12 (34%) of the 35 men and 12 (67%) of the 18 women with subclinical hypothyroidism who had thyroid antibody testing. All residents with newly diagnosed overt hypothyroidism and 54 (87%) of the 62 with subclinical hypothyroidism had been under medical observation for 1 year or longer. The institutionalized elderly should be screened for hypothyroidism because this abnormality may otherwise remain undiagnosed. The detection of subclinical hypothyroidism is important, as affected individuals are at risk for further decline in thyroid function. ",18 1470,"The relative risks of caesarean section (intrapartum and elective) and vaginal delivery: a detailed analysis to exclude the effects of medical disorders and other acute pre-existing physiological disturbances. OBJECTIVE--To compare maternal mortalities attributable to vaginal delivery, elective caesarean section (CS) and intrapartum CS. DESIGN--The number of deaths associated with each method of delivery was ascertained among unselected and among low-risk women by detailed retrospective review of the case-notes of women who died after delivery. The frequency of each method of delivery throughout the study period was ascertained from the computer database and enhanced by analysis of the case-notes of unselected groups of women. SETTING--The Peninsula Maternity Services (Cape Town) during the years 1975-1986 inclusive. SUBJECTS--A total of 108 maternal deaths arising from 263,075 maternities provided accurate information. The relative frequency of vaginal and abdominal delivery was determined from the computer database. The ratio of elective CS to emergency prepartum CS to intrapartum CS was obtained by review of the first 200 operations in the years 1975, 1977, 1979, 1982 and 1984. MAIN OUTCOME MEASURES--(i) Mortality rates associated with the different methods of delivery in unselected women and in women who were healthy before surgery; (ii) mortality rates apparently attributable to the method of delivery. RESULTS--The overall relative risk of mortality associated with caesarean section compared with vaginal delivery was 7 decreasing to 5 after the exclusion of women with medical or life-threatening antenatal complications (eg, haemorrhage, hypertension). The relative risk associated with intrapartum compared with elective sections was 2.3 decreasing to 1.4 after the exclusion of women with medical disorders or life-threatening complications. The relative risk of maternal mortality which was apparently attributable to intrapartum compared with elective sections was 1.7. However, the 95% confidence intervals of these values, even from this large data-set, are wide. Nevertheless, these rates are in broad agreement with an approximation derived from the British confidential enquiries into maternal deaths. CONCLUSION--The attributable relative mortalities of caesarean section compared with vaginal delivery and intrapartum compared with elective caesarean section are lower than the overall relative mortalities of these modes of delivery and are approximately 5:1 and 1.5:1 respectively. These data are crucially important in the decision to recommend elective caesarean section compared with trial of labour. ",12 2344,"Nutritional assessment and requirements. Nutrition plays an important role in health and disease, both in prevention and treatment. Increasing emphasis is being placed upon nutrition as a therapeutic tool to decrease the morbidity and mortality associated with obesity, hypertension, coronary artery disease, and cancer. Adequate nutrition should be a concern for all health care workers because of its impact on the overall health of patients. Health care professionals should be familiar with the essentials of nutritional assessment and basic nutritional requirements and be able to improve their patients' care in the face of nutritional deficiencies or excesses. ",17 1830,"Alterations in aldosterone secretion and metabolism in low renin hypertension. Low renin essential hypertensives (LRH) have normal plasma aldosterone levels which are inappropriately high in relation to their PRA. Posture is the major determinant for plasma aldosterone and PRA levels, but it is not known whether postural increments (delta) of plasma aldosterone and (delta) PRA are also abnormal in LRH. To evaluate this, LRH (n = 8), normal renin hypertensives (NRH; n = 9), normotensive controls (n = 18), and subjects with idiopathic hyperaldosteronism (IHA; n = 5) were studied in a metabolic unit on a controlled diet over 7 days. Overnight supine and 4-h upright PRA, plasma aldosterone, and 24-h urinary tetrahydroaldosterone (THA) and aldosterone secretion rates (ASR) were measured. The delta in plasma aldosterone after 4 h of upright posture was not different in the four groups. The ratio of delta plasma aldosterone/delta PRA, however, was elevated in both IHA and LRH compared to that in NRH and normals. THA excretion was also elevated in IHA and LRH, but LRH had a normal ASR. This resulted in a higher fractional THA excretion (THA/ASR) in LRH compared to the other three groups. These data further support enhanced adrenal angiotensin-II sensitivity in LRH. Aldosterone was preferentially metabolized to THA in LRH. Since THA has reduced biological activity, this may be a compensatory mechanism to reduce mineralocorticoid activity in LRH. ",13 2276,"Submammary median sternotomy. A vertical skin incision is used as routine approach for sternotomy. The resulting scar is often disappointing and the top is visible and unpleasant, especially for young women. In 35 women ranging from 10 to 48 years (mean 29.2 years), median sternotomy was performed via a submammary skin incision. In all cases an open heart surgical procedure was performed. Adequate exposure of the heart was achieved in every case and there were no technical problems related to this approach, no hospital mortality or major complications. The cosmetic result is excellent and this approach is certainly justified in open heart surgery for young women. ",16 85,"Lung function in children following empyema. Spirometry was performed and response to exercise was measured in 15 children following recovery from empyema to evaluate the impact of pleural infection on subsequent lung function. Seven children underwent chest tube drainage; eight did not. The two groups were similar in age (mean +/- SD, 6 +/- 5 years), sex distribution, bacterial pathogen-producing empyema, and age at follow-up evaluation (12 +/- 5 years). Only one child reported recurrent respiratory symptoms. No child had restrictive spirometric changes (total lung capacity, less than 80%; vital capacity, less than 80% predicted) but seven of 15 had a reduced forced expiratory volume in 1 second (less than 80% predicted) or forced expiratory flow during the middle half of the vital capacity (less than 75% predicted), suggesting mild airway obstruction. No child demonstrated reduced exercise tolerance due to restrictive ventilatory limitations. Mild obstructive abnormalities in lung function were identified with equal frequency in children treated with and without chest tube drainage. ",0 1244,"Effects of physostigmine on spatial attention in patients with progressive supranuclear palsy. We tested patients with progressive supranuclear palsy and control subjects on a task of visuopatial attention. Targets preceded by cues on the same side were termed validly cued; and those on the opposite side, invalidly cued. For all subjects, validly cued targets were responded to faster than those that were invalidly cued. The difference between reaction times for invalidly and validly cued targets, which is hypothesized to measure attentional movement, was significantly increased for the patients. The performance of the controls on certain neuropsychological tests was correlated with their attentional ability. These correlations were altered by progressive supranuclear palsy. Physostigmine treatment of the patients induced a speeding of responses to invalidly cued targets as a function of the duration of the disease. These studies show defects in cognition and attention in patients with progressive supranuclear palsy and demonstrate that physostigmine reduces some of the abnormal visual attentional performance. ",9 1960,"Evaluation of methods for detecting venous reflux. Perspectives in venous insufficiency. Using 793 limbs with nonobstructive venous reflux, we evaluated a number of techniques used for the assessment of venous reflux. The venous Doppler examination was found to be a reliable screening tool with excellent sensitivity and good specificity. Photoplethysmography was 97% sensitive in patients with ambulatory venous hypertension; however, in milder forms of reflux, it was less sensitive. The major drawback of photoplethysmography was the large number of false-positive results obtained. Ambulatory venous pressure measurement and another pressure-based technique, Valsalva-induced foot venous pressure measurement, defined overlapping but different normal and abnormal limbs. Descending venography, when performed as described by Kistner et al, was found to be a reliable tool to assess reflux with more than a 90% sensitivity. The horizontal technique of performing descending venography and nucleotide descending venographies had unacceptably low sensitivity and were abandoned. Features of venous reflux as outlined by these modern technical tools are described. ",13 423,"A chance to cut is a chance to cure? Fifty-seven patients underwent local excision of an invasive distal rectal cancer as an initial operative procedure with curative intent. Five-year survival was 82.5%, and the rectal cancer specific mortality rate was only 10.5%. The level of wall invasion, vascular permeation, tumor ulceration, mobility, and differentiation were the criteria studied for prognosis. Poor prognostic factors included mucinous cell differentiation and full thickness invasion, and in these cases, abdominoperineal resection was recommended. None of the 27 patients without these adverse prognostic factors died from rectal cancer. The other factors did not appear to influence the outcome, and local excision of distal rectal cancer would be the treatment of choice in such selected patients. ",3 1024,"Distortion product otoacoustic emissions in normal and impaired adult ears. Distortion product otoacoustic emissions (DPOEs) were recorded in a group of normally hearing subjects (29 ears) and a group of subjects whose conditions were diagnosed as sensorineural hearing loss (23 ears) to study any correlation that might exist between DPOE characteristics and hearing impairment of different configurations. Three different DPOE paradigms have been used to investigate the influence of different test parameters on the DPOE data for normal and hearing-impaired ears. All normally hearing ears demonstrated detectable DPOEs, provided that the primary tone level was above a certain value. Hearing-impaired ears produced substantially reduced DPOEs compared with normally hearing subjects when the primary frequencies f1 and f2 corresponded to the region of hearing loss. Our data also suggested that, in general, more than one f2/f1 ratio is needed to examine any particular frequency region. The DPOEs provide frequency-specific information about cochlear function, which after further development, may form a basis for a noninvasive, objective method of evaluating cochlear function. ",8 1200,"Electrocorticographic confirmation of focal positron emission tomographic abnormalities in children with intractable epilepsy. The relationship between focal disturbances of glucose utilization demonstrated by positron emission tomography (PET) and electrophysiologic abnormalities defined by intraoperative electrocorticography (ECoG) was studied in eight children (aged 13 months to 12 years) who underwent cortical resection because of intractable seizures. None of the children had pure temporal lobe epilepsy. Computed tomography (CT) and/or magnetic resonance imaging (MRI) were normal in four of the eight children. The scalp electroencephalogram (EEG) showed lateralized interictal epileptiform abnormalities in all eight and lateralized ictal onset in five of eight. In seven children, interictal PET showed focal hypometabolism; the eighth child had focal, ictal hypermetabolism. ECoG at the time of surgery showed epileptiform spiking, slowing, and/or suppression of normal background activity that in every case corresponded to the focus on PET scan. The ECoG findings support the notion that in children with epilepsy focal metabolic abnormalities on PET correspond to electrophysiologically abnormal areas of cortex, which are presumably also the epileptogenic regions. Such areas can appear normal on anatomic imaging studies (CT and MRI). When ictal scalp EEG data are ambiguous or contradictory, PET provides a less invasive means than chronic grid or depth electrode recording for evaluating whether a localized epileptogenic area exists. ",9 3177,"Down-regulation of LFA-1 adhesion receptors by C-myc oncogene in human B lymphoblastoid cells. The function of the c-myc gene and its role in tumorigenesis are poorly understood. In order to elucidate the role of c-myc oncogene activation in B cell malignancy, the phenotypic changes caused by the expression of c-myc oncogenes in human B lymphoblastoid cells immortalized by Epstein-Barr virus were analyzed. C-myc oncogenes caused the down-regulation of lymphocyte function-associated antigen-1 (LFA-1) adhesion molecules (alpha L/beta 2 integrin) and loss of homotypic B cell adhesion in vitro. Down-regulation of LFA-1 occurred by (i) posttranscriptional modulation of LFA-1 alpha L-chain RNA soon after acute c-myc induction, and (ii) transcriptional modulation in cells that chronically express c-myc oncogenes. Analogous reductions in LFA-1 expression were detectable in Burkitt lymphoma cells carrying activated c-myc oncogenes. Since LFA-1 is involved in B cell adhesion to cytotoxic T cells, natural killer cells, and vascular endothelium, these results imply functions for c-myc in normal B cell development and lymphomagenesis. ",22 2000,"Estrogen replacement and coronary artery disease. Effect on survival in postmenopausal women. The relationship among postmenopausal estrogen use, coronary stenosis, and survival was examined retrospectively in 2268 women undergoing coronary angiography. The patients were selected for study if their age was 55 years or older at the time of angiography or if they had previously undergone bilateral oophorectomy. Postmenopausal estrogen use in 1178 patients with coronary artery disease (greater than 70% stenosis) and 644 patients with mild to moderate coronary artery disease (5% to 69% stenosis) was compared with 446 control subjects (0% stenosis) using life-table analysis. Over 10 years of follow-up, there was no significant difference in survival among patients initially free of coronary lesions on arteriography who had either never used (377) or ever used (69) estrogens. Among patients with mild to moderate coronary stenosis, 10-year survival of those who had never used estrogens was 85.0% and it was 95.6% among 99 ""ever users."" Survival was 60.0% among those with more than 70% coronary stenosis who had never used estrogen and it was 97.0% among 70 ever users. The ""never users"" group were older (65 vs 59 years), had a lower proportion of cigarette smokers (40% vs 57.1%), a higher proportion of subjects with diabetes (21.7% vs 12.9%) and hyperlipidemia (58% vs 44%), and approximately equal numbers of hypertensives (56.0% vs 54.3%). Cox's proportional hazards model was used to estimate survival as a function of multiple covariables. Estrogen use was found to have a significant, independent effect on survival in women. We conclude that estrogen replacement after menopause prolongs survival when coronary artery disease is present, but it has less effect in the absence of coronary artery disease. ",13 934,"The relative value of conventional staging procedures for developing prognostic models in extensive-stage small-cell lung cancer. Published prognostic models for small-cell lung cancer (SCLC) have either combined limited- and extensive-stage patients or have not included standard anatomic staging information to assess the relative value of the knowledge of specific sites and number of sites of metastases in predicting survival in extensive-stage disease. We studied 136 extensive-stage patients in whom traditional staging procedures were performed and in whom other previously demonstrated significant pretreatment variables were determined. Using the Cox proportional hazards model, when all data were included, three variables were significant: performance status (PS) (P = .0001), number of sites of metastases (P = .0010), and age (P = .0029). A prognostic algorithm was developed using these variables, which divided the patients into three distinct groups. When the anatomic staging data were omitted, the serum albumin (P = .0313) was the only variable in addition to PS (P = .0001) and age (P = .0064) that was significant. An alternative algorithm using these three variables was nearly as predictive as the original. Therefore, in extensive-stage patients, reasonable pretreatment prognostic information can be obtained without using the number or specific sites of metastases as variables once the presence of distant metastases has been demonstrated. ",7 827,"Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure. OBJECTIVE--To find out whether changes in the daily prothrombin time are of prognostic importance in patients with paracetamol induced fulminant hepatic failure. DESIGN--Retrospective study. SETTING--The Liver Unit, King's College Hospital, London. PATIENTS--150 Consecutive patients with paracetamol induced fulminant hepatic failure admitted between October 1986 and February 1989. MAIN OUTCOME MEASURE--Death. RESULTS--Of the 150 patients, 72 (48%) died. In all, 34 of the 37 (92%) patients with a peak prothrombin time of greater than or equal to 180 seconds died as did 20 of the 41 (49%) with a time of 130-179 seconds, nine of the 25 (36%) with a time of 90-129 seconds, and nine of the 47 (19%) with a time of less than 90 seconds. Of the 42 patients with a continuing rise in prothrombin time between days 3 and 4 after overdose, 39 died (93%) compared with 21 of the 96 (22%) in whom the prothrombin time fell. CONCLUSIONS--These data indicate that a continued increase in prothrombin time on day 4 after overdose and a peak prothrombin time of greater than or equal to 180 seconds identify at an early stage those patients with a less than 8% chance of survival. Liver transplantation should be considered in patients meeting either of these criteria. ",5 2849,"Health locus of control beliefs and alcohol-related factors that may influence treatment outcomes. Treatment programs have based their treatment approach on the premise that alcoholics should exert internal control over situations and events that affect them. Since chronic alcohol use affects the health of an individual, Walston and Walston's Multidimensional Health Locus of Control Scale was administered to 47 alcoholics in a treatment program. The population reflected a higher belief that health status is more under their own control than under the control of chance or powerful others. However, the results indicated that recovering alcoholics with a more powerful other health orientation tended to maintain membership longer with Alcoholics Anonymous, would seek help sooner, would begin heavy drinking at a later age, and would attempt formal treatment more often. ",20 1448,"The effects of basic fibroblast growth factor and suramin on cell motility and growth of rat prostate cancer cells. Suramin, a new type of cancer chemotherapeutic agent with growth factor antagonist properties, has been reported to affect growth of prostate cancer metastatic lesions. Partin et al. have previously reported that prostate cancer cell motility was essential for tumor cell metastasis. We have studied the effects of suramin on cell motility and cell growth in a prostate cancer cell model. We have demonstrated that suramin has differential effects on rat prostate cancer cells in vitro. The effects of suramin on cell growth were biphasic. At low concentrations of 0.01 mM and 0.1 mM, suramin stimulated growth while it was inhibitory at a higher concentration of 1.0 mM, and 10 mM suramin resulted in cell death. Cell motility was inhibited at a suramin concentration above 0.1 mM. The inhibition of cell motility by suramin may be through the blockage of growth factor effects. Reducing serum growth factor concentration reduced cell motility and the motility was restored by the addition of basic fibroblast growth factor (bFGF) to the media. Motility which had been restored by bFGF could then be blocked by the presence of suramin. The inhibition of cell motility by suramin is reversible on washout of the drug. Suramin inhibits cell motility in both the human prostate cancer cells (LNCaP) and the rat (MLL). ",11 155,"Parasite antigenemia in untreated and treated lymphatic filarial infections. To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment. ",2 2964,"The scapular manipulation technique for the reduction of acute anterior shoulder dislocations. Anterior shoulder dislocations are a common occurrence in busy emergency departments. Numerous techniques for treating this problem have been reported. The majority of these techniques use traction and leverage of the humerus, often requiring considerable force and causing significant patient discomfort. We report a simple, relatively painless, and atraumatic method of shoulder reduction involving manipulation of the scapula as well as the humerus. This technique has been used in our emergency department with considerable success and no complications. ",20 2355,"Effects of childbearing on glucose tolerance and NIDDM prevalence [published erratum appears in Diabetes Care 1990 Nov;13(11):1138] The goal of this study was to estimate the effects of childbearing on subsequent glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM) prevalence. A sample of subjects from 64 different locations in the United States were recruited for inclusion in the Second National Health and Nutrition Examination Survey. A complex survey design was used to select a probability sample of subjects from each location. A total of 4577 women were recruited, of whom 3057 underwent clinical and laboratory evaluation for the presence of diabetes mellitus. Women were classified as to their glucose tolerance based on the results of an oral glucose tolerance test or previous physician diagnosis of diabetes mellitus combined with current use of hypoglycemic medication. Childbearing was defined as number of live births experienced by each woman at the time of the interview. Fasting plasma glucose increased linearly with increasing number of live births (coefficient 0.009, 95% confidence interval [CI] 0.006-0.012), as did the 2-h value (coefficient 0.015, 95% CI 0.009-0.021). Adjustment for age, body mass index (BMI), education, and income substantially reduced the magnitude of the association between childbearing and either plasma glucose measurement. When the prevalence of NIDDM in relation to childbearing was examined with logistic regression analysis, a significant linear increase in diabetes prevalence was seen with increasing number of live births (relative prevalence of NIDDM, 1 birth vs. 0 = 1.73, 95% CI 1.39-2.15), but adjustment for age, BMI, education, and income greatly reduced the magnitude of this association (relative prevalence of NIDDM, 1 birth vs. 0 = 1.07, 95% CI 0.98-1.17). ",17 1998,"Doppler diagnostics, indications, and control of surgical treatment in patients with carotid pathology. Major stroke is a relatively common cause of death or disabling invalidism in patients with atherosclerosis. In a large percentage of cases it is caused by stenotic/thrombotic processes in carotid arteries and this emphasizes the importance of the problem of early diagnosis and treatment of carotid pathology. Recently Doppler sonography has become a leading non-invasive method of early screening of stenotic processes in carotid arteries. The aim of the present study was to ascertain the diagnostic abilities of Doppler sonography for screening of carotid pathology, assessment of extra-cranial and intracranial hemodynamics, defining of indications, and control of vascular reconstructions of carotids. ",13 229,"Short-term tamoxifen plus chemotherapy: superior results in node-positive breast cancer. Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival. ",3 3251,"Simplified technique for isolating vascularized rib periosteal grafts. A modified technique for obtaining a vascularized rib periosteal segment utilizing the posterolateral approach is presented. The technique avoids the inclusion of a large muscle cuff or the pleura around the isolated rib segment and therefore minimizes donor-site morbidity and chest complications previously associated with this approach. ",22 1840,"Magnitude and time course of beta-adrenergic antagonism during oral amiodarone therapy. To examine the presence and time course of beta-adrenergic antagonism produced by amiodarone, the heart rate, QT interval and arrhythmia frequency in response to graded doses of isoproterenol were evaluated in eight patients treated with oral amiodarone for sustained ventricular tachycardia. Measurements were made before and every 2 days after beginning oral amiodarone therapy (600 mg twice daily). Isoproterenol was given in doses of 12.5, 25 and 50 ng/kg body weight per min. The mean heart rate at rest decreased from 73.1 +/- 17.8 beats/min on day 0 to 57.8 +/- 15.0 beats/min after 12 days of amiodarone therapy. A significant linear decline in heart rate at rest was observed until day 6 (p less than 0.05 for all comparisons). On all days isoproterenol produced a progressive increase in heart rate that reached 115.5 +/- 20.2 beats/min on day 0 and 94.2 +/- 18.5 beats/min on day 12. Amiodarone blunted the heart rate increase produced by isoproterenol on days 2 to 12 (p less than 0.05 versus day 0). This effect was present by day 2 and did not change significantly thereafter. The mean corrected QT (QTc) interval increased from 430 +/- 30 ms on day 0 to 449 +/- 63 ms on day 12. A significant linear increase in QTc interval was observed until day 6 (p less than 0.05 for all comparisons). There was no systematic effect of isoproterenol on the QTc interval. Five of eight patients had a significant number of isoproterenol-induced premature ventricular complexes. Ventricular ectopic activity in response to isoproterenol was abolished after 4 days of amiodarone therapy. ",13 2915,"Chronic alcohol ingestion increases aortic lipid levels in rats. We evaluated the effects of alcohol ingestion on aortic lipid concentrations in 15 pair-fed Sprague-Dawley rats divided into three groups of five animals each. Control rats were fed a liquid diet, with 36% of their energy provided by maltose-dextrin for 28 days, and the remaining two groups of rats were fed an equivalent proportion of their energy as alcohol for 28 days or 18 months. Alcohol-fed rats exhaled significantly greater quantities of ethane than did controls at 28 days and 18 months. Serum cholesterol levels increased by 40% and triglyceride levels increased by 80%, but phospholipid levels remained unchanged in alcohol-fed rats compared with controls. Aortic concentrations of cholesterol and phospholipids increased twofold and threefold, respectively, in alcohol-fed rats, with a corresponding alteration of the cholesterol-phospholipid ratio at both time intervals. Tissue triglyceride levels were only elevated at 28 days, and no differences in aortic lipid peroxide levels were detected between alcohol-fed rats and controls. The results of the study indicate that alcohol ingestion increases aortic cholesterol, phospholipid, and triglyceride levels at 28 days and cholesterol and phospholipid but not triglyceride levels at 18 months. The mechanisms underlying the accumulation of lipids in aortic tissue need further elucidation. ",20 1027,"Selective management of early glottic cancer. Seventy patients with stage I and II glottic cancer were treated at the University of Utah School of Medicine hospitals from 1980 through 1987. Forty-four patients had stage I cancer and 26 patients had stage II. The overall survival in the stage I group was 82%. Primary site control was 93% with only three deaths due to laryngeal cancer. Local control rates were 93% with CO2 laser excision, 80% with CO2 laser and irradiation, and 67% with radiation alone. Stage II glottic patients had an overall survival of 61.5% with a local control rate of 76%. Twenty-one of 24 patients were treated by full-course irradiation. Of the eight patients who recurred at the primary site, all were irradiation failures who had initial bulky disease and impaired vocal cord mobility. Selective CO2 laser excision was highly effective, whereas radiation therapy results were somewhat disappointing. Open partial laryngectomy should be considered in bulky stage II disease patients. ",8 1934,"Hypertension prevalence and the status of awareness, treatment, and control in the Hispanic Health and Nutrition Examination Survey (HHANES), 1982-84 The prevalence rates of hypertension among adult (ages 18-74) Mexican Americans, Cuban Americans, and Puerto Ricans were estimated using data from the 1982-84 Hispanic Health and Nutrition Examination Survey (HHANES). Hypertension is defined as diastolic greater than or equal to 90 mm Hg, or systolic greater than or equal to 140 mm Hg, or currently taking antihypertensive medication. Among Mexican Americans in the Southwestern United States, 16.8 percent of the males and 14.1 percent of the females were found to be hypertensive. Among Cuban Americans in Dade County, Florida 22.8 percent of the males and 15.5 percent of the females were hypertensive. Among Puerto Ricans in the New York City area 15.6 percent of the males and 11.5 percent of the females were hypertensive. The age-adjusted rates are significantly lower than comparable rates for Whites and Blacks as measured in the second National Health and Nutrition Examination Survey (NHANES II), 1976-80. Control of hypertension in the HHANES populations fall short of the 1990 Objectives for the Nation established by the US Public Health Service 60 percent (34 percent controlled Mexican American hypertensives, 27.8 percent controlled Cuban American hypertensives, and 29 percent controlled Puerto Rican hypertensives. ",13 2420,"Lack of predictive value of islet cell antibodies, insulin antibodies, and HLA-DR phenotype for remission in cyclosporin-treated IDDM patients. The Canadian-European Randomized Control Trial Group. The effect of immunosuppression on the humoral immune response to islet autoantigens and exogenously administered insulin and the predictive value of islet cell cytoplasmic antibodies (ICAs), insulin antibodies (IAs), and HLA-DR phenotype for remission during immunosuppression were studied in a prospective randomized double-blind trial of cyclosporin administration in 98 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients. HLA-DR phenotype and glycosylated hemoglobin were determined at study entry, and insulin requirement, glucagon-stimulated C-peptide, ICAs, and IAs were measured at entry and after 1, 3, 6, 9, and 12 mo of follow-up. Cyclosporin therapy caused significant suppression of the prevalence and serum concentrations of ICAs and IAs. Cyclosporin-treated IDDM patients ICA+ at study entry had higher levels of stimulated C-peptide after 1 mo of study, but the increased beta-cell function was not associated with a higher frequency of insulin-free remission at 1 mo. ICA and IA status at entry did not predict cyclosporin-insulin-free remission as assessed by the prevalence of insulin-free remission or beta-cell function at 3-12 mo of study, and significant decrements in the titers or total disappearance of ICAs were not associated with an increased prevalence or duration of non-insulin-requiring remission or higher stimulated C-peptide values. There was no correlation between the serum levels of ICAs and IAs at entry and beta-cell function at 12 mo of follow-up. ",17 1607,"Neuropsychological outcome of survivors of out-of-hospital cardiac arrest. Thirty patients resuscitated from out-of-hospital cardiac arrest (15 with and 15 without postanoxic coma on admission) underwent a clinical examination and neuropsychological testing. In order to assess quality of life, they were compared to two matched control groups; 15 patients with previous myocardial infarction and 15 healthy subjects. None of the survivors showed severe neurologic impairment, and all had returned to self-sufficient physical activity. However, the behavior rating scale scores were significantly worse in patients with postanoxic coma. The processing ability linked to memory was significantly worse in the postanoxic coma group. Mood disorders were also observed in this group, but they did not have pathological significance. The remarkably low incidence of neurologic and psychological sequelae in these resuscitated patients, particularly in those with early clinical evidence of severe cerebral damage, is an encouraging result that supports the therapeutic systems development and efforts in the management of out-of-hospital cardiac arrest. ",13 27,"Buccal cellulitis. Buccal cellulitis (BC) is an innocuous appearing infection of the cheek that is found in children and has a high incidence of concomitant bacteremia. Typically, the child is younger than 12 months and has a 2 to 8 hour prodrome of coryza and fever before developing the cellulitis on the cheek. A purplish hue on the cellulitic region is highly suggestive of Hemophilus influenzae bacteremia. The differential diagnosis is reviewed. A complete blood count, blood culture, and cellulitis aspirate culture, should be obtained on all patients with BC. Meningitis may be present despite the lack of meningeal signs. A lumbar puncture should be performed on all children at risk for bacteremic BC. The vast majority of these children are bacteremic and require parenteral antibiotics. A typical case of BC is presented and its management is reviewed. ",0 2917,"Cartilage begets bone versus endochondral myelopoiesis. Observations on the cellular events involved in embryonic long-bone formation, ectopic osteogenesis, fracture repair, and the analysis of mesenchymal stem-cell potential provide evidence of the intimate and direct relationship of osteogenesis to angiogenesis and vasculature. The sequence of cellular events is that cartilage is not replaced by bone but, rather, is a target for vascularization and myelopoiesis. With this in mind, it may be necessary to replace the term ""endochondral bone formation"" with ""endochondral myelopoiesis."". ",20 1935,"A note on the measurement of hypertension in HHANES Using data from the HHANES, we found the rates of elevated blood pressure readings on clinical examination to be extremely low for a sample of Mexican American and Puerto Rican women. The prevalence rates were one-fourth to one-fifth the rates found for a comparable sample of White women from NHANESII. These findings are discrepant with the little that is known about hypertension prevalence among Hispanics and with estimates of hypertension prevalence for Mexican Americans and Puerto Ricans drawn from NHANESII. While our HHANES samples women had much lower rates of clinical high blood pressure than Whites, they reported hypertension histories in excess of Whites. Rates of medicine usage among Hispanics were insufficiently large for effective treatment to explain the disparity. The prevalence estimates increased, but the relative discrepancies remained when we altered our sample specifications and clinical high blood pressure measure. A possible explanation for these discrepancies is that few physicians performed the majority of blood pressure readings in our HHANES sample. This may have been statistically inefficient. The discrepancies noted suggest that HHANES may not be a reliable source of information on hypertension among Hispanic women. ",13 2297,"The role of epidermal cytokines in inflammatory skin diseases. Cytokines (hormone-like polypeptide mediators) play a major role in inflammatory and immunoregulatory responses. Skin, and particularly keratinocytes in the skin, represent a potent source for many cytokines, including interleukins 1, 6, 8, and the hemopoietic colony stimulating factors. Cytokines initiate their biologic action by interacting with target cells bearing cytokine receptors and then initiating a cascade of cellular interactions. Certain inflammatory skin diseases have been associated with overproduction of cytokines, alteration in cytokine receptors, or dysregulation of cytokines. While data is still quite preliminary, it is likely that cytokines contribute to the pathogenesis of many inflammatory skin diseases. ",16 1738,"Dietary Ca2+ prevents NaCl-sensitive hypertension in spontaneously hypertensive rats by a sympatholytic mechanism. The current study tested the hypothesis that dietary Ca2+ supplementation reverses the NaCl-sensitive component of hypertension and the associated neurochemical abnormalities in the NaCl-sensitive spontaneously hypertensive rat (SHR-S). Male SHR-S were begun on one of four diets at 8 weeks of age: control (0.75% NaCl/0.68% Ca2+); high NaCl (8.00% NaCl/0.68% Ca2+); high Ca2+ (0.75% NaCl/2.00% Ca2+); and high NaCl/high Ca2+ (8.00% NaCl/2.00% Ca2+). High NaCl SHR-S (X2 weeks) had higher mean arterial pressure (MAP) (161 +/- 4 mm Hg) than controls (149 +/- 3 mm Hg; P less than .05). Supplementation with Ca2+ prevented the rise in MAP in high NaCl rats, but did not alter MAP in controls. The 8% NaCl diet elevated plasma norepinephrine and reduced anterior hypothalamic (AHA) norepinephrine stores and turnover; concomitant Ca2+ supplementation restored both plasma norepinephrine and AHA norepinephrine turnover to normal. Clonidine was microinjected into the AHA of rats maintained on the four diets for 2 weeks to test the hypothesis that dietary Ca2+ supplementation prevents the previously observed NaCl-induced upregulation of alpha 2-adrenoceptors in AHA. Clonidine caused dose-dependent decreases in MAP that were greater in high NaCl rats than in controls. The Ca2+ supplementation prevented the exaggerated depressor response to clonidine in the high NaCl group, but not in the controls. The Ca2+ supplementation had no effect on pretreatment MAP or on MAP responses to clonidine in control NaCl-resistant SHR (SHR-R) or Wistar-Kyoto (WKY) rats. Thus, dietary Ca2+ supplementation prevents the NaCl-induced exacerbation of hypertension and augmented depressor response to clonidine in SHR-S by increasing noradrenergic input to AHA, thereby preventing the upregulation of AHA alpha 2-adrenoceptors. ",13 642,"Effects of rib elongation on the spine. I. Distortion of the vertebral alignment in the rabbit. Elongation of one rib on the right side by 1 cm was achieved in two groups of adult rabbits of different age, by osteotomy and application of a metallic expander. The procedure resulted in immediate deviation of the spine in the frontal and sagittal planes, with moderate scoliosis, convex to the left, and a significant decrease in the normal cervicothoracic lordosis and thoracolumbar kyphosis. Moreover, computed tomography (CT) scanning demonstrated rotation of vertebra about the longitudinal axis relative to the anterior midline of the body, and deviation of the spinous process toward the convex, left side, of the scoliotic deformity. Rib hump developed on the right side--that of the elongated rib. These changes, which occurred simultaneously in the three planes, were less pronounced in the group of older animals. Two weeks after the operation, the distorted configuration of the spine remained unchanged. The observed changes in the alignment of the vertebrae--changes that, except for their direction on the horizontal plane, resembled those associated with idiopathic scoliosis in man--support the earlier proposed link between the early stage of development of this condition and asymmetry of rib growth. ",4 3268,"Reduction in bleeding after heart-lung transplantation. The importance of posterior mediastinal hemostasis. To reduce perioperative hemorrhage following heart-lung transplantation, several technical modifications were introduced in June 1988 to secure better posterior mediastinal hemostasis. The intraoperative and postoperative use of blood and blood products, as well as the chest tube drainage in the first 24 hours postoperatively, were compared in the seven patients operated on since June 1988 with the nine patients operated on before that date. Significant (p less than 0.05) reductions were demonstrated in the intraoperative and postoperative transfusion of packed cells, in the postoperative administration of fresh frozen plasma, and in the chest tube drainage within the first 24 hours postoperatively. The one-month and total hospital mortality rates were 6 percent and 12.5 percent, respectively. It is concluded that newer techniques to obtain optimal posterior mediastinal hemostasis have significantly reduced blood loss following heart-lung transplantation in our experience and have contributed to our excellent early postoperative results. ",22 381,"A downstream initiation element required for efficient TATA box binding and in vitro function of TFIID. The gfa gene encodes glial fibrillary acidic protein, an intermediate filament protein expressed in glial cells. In vitro transcription analysis has shown that the human gfa promoter contains two initiation elements that can independently specify the transcription startpoint. One of the elements is a TATA box 25 base pairs (bp) upstream from the transcription startpoint; the other is located between 10 and 50 bp downstream from the transcription initiation site. We have now shown by transfection that both elements are required for efficient transcription in cultured cells. A partially purified natural human TATA box-binding factor (TFIID) from HeLa cells gave footprints that extended from upstream of the TATA box through the downstream initiator. Deletion of the downstream initiator inhibited both TFIID binding to the TATA box and transcription in vitro. In contrast to natural human TFIID, clone human and yeast TFIIDs expressed in bacteria gave footprints covering only the TATA box region, although hypersensitive sites were observed in the downstream region. The cloned TFIIDs also showed less dependence than natural human TFIID on the downstream initiator for both TATA box binding and in vitro transcription. These results suggest that natural human TFIID contains an additional component(s) that contribute(s) to stable TFIID binding and effective transcription by interacting with the downstream initiator. ",3 2786,"Asbestos content of lung tissue, lymph nodes, and pleural plaques from former shipyard workers. Autopsy samples from eight former shipyard workers were collected from lung parenchyma, tracheal lymph nodes, and pleural plaques. The tissue from each respective area was prepared by a modified bleach digestion technique, and the residue was collected on a 0.2-micron pore polycarbonate or 0.22-micron mixed cellulose ester filter. Quantitation of ferruginous bodies and uncoated fibers was done by light and transmission electron microscopy, respectively. Differences in the asbestos burden were noted for each site. Ferruginous bodies were observed in both parenchyma and nodes but not in plaques. Three subjects were found to have more ferruginous bodies per gram dry weight in their lymph nodes than in their lung parenchyma. Likewise, all subjects were found to have more uncoated fibers per gram in the nodes than in the parenchyma. Amphibole and chrysotile fibers were noted in the lung and extrapulmonary sites, with chrysotile being the predominant asbestiform in plaques. The majority of the uncoated fibers in both the nodes and the plaques were less than or equal to 5 microns in length. However, some fibers with dimensions conforming to the ""Stanton hypothesis"" reached both areas. These residual patterns most likely reflect the impact of clearance on lung burden as opposed to the eventual accumulation and stasis in the extrapulmonary areas. ",20 1192,"Intraoperative dexamethasone irrigation in lumbar microdiskectomy. In 45 lumbar hemilaminectomy/microdiskectomy patients, a control group of 23 patients had the standard operative procedure. The remaining 22 patients were treated with intraoperative irrigation of long-acting dexamethasone before incision closure. Age, weight, gender ratio, mean postoperative hospital stay, mean in-hospital narcotics usage, and incidence of perioperative complications among the two groups were compared. Age and gender ratios were comparable, although the control group was significantly heavier in body weight than the steroid-irrigated group. The steroid-irrigated group had a significant reduction in hospitalization and a marked reduction in narcotics usage compared with the control group. Postoperative fever occurred in one patient in the steroid group. The control group had three postoperative complications. These preliminary observations suggest that dexamethasone irrigation during lumbar diskectomy is a safe and effective adjunct to surgical management. ",9 3224,"Continuous epidural hydromorphone for postthoracotomy pain relief Forty-four patients were treated with a continuous infusion of lumbar epidural hydromorphone (0.05%) after thoracic operations. Postoperatively, visual analog pain scores were obtained. On postoperative day 1 and 2, more than 90% of the patients experienced either no pain (visual analog pain scale = 0) or mild pain (visual analog pain score = 1 to 3) at rest. The incidence of side effects (hypoventilation, pruritis, and nausea) was less than reported with other epidurally administered opioids. Continuous infusion of lumbar epidural hydromorphone produced safe, predictable analgesia after thoracotomy. ",22 580,"Regional chemotherapy for colorectal liver metastases: a phase II evaluation of targeted hepatic arterial 5-fluorouracil for colorectal liver metastases. The results of systemic chemotherapy in patients with liver metastases from colorectal cancer remain dismal. Regional chemotherapy has been advocated as a method of improving the delivery of cytotoxic drugs to tumour, while minimizing systemic toxicity. The use of vasoactive agents to redistribute arterial blood flow towards tumour, and of biodegradable microspheres to slow tumour blood flow, have also been suggested as methods of further improving tumour exposure to drug. We present 21 patients who received intrahepatic arterial chemotherapy for colorectal liver metastases. Combined treatment (angiotensin II, albumin microspheres and 5-fluorouracil) was administered 4-6 weekly, and bolus 5-fluorouracil was given in the intervening weeks. Toxicity was minimal. Responses were seen in seven patients. Fewer than half of the deaths were from liver metastases; a quarter of the patients died from non-cancer-related causes. Survival was prolonged in the treated group compared with historical controls. These results suggest that this regimen has activity in patients with colorectal liver metastases. ",3 3259,"Conduction system injury after aortic valve dilation in the dog single- versus double-balloon catheters. The range of morbidity induced by valvuloplasty is not fully known, but transient conduction disturbances are common. The authors performed aortic valve balloon dilatation on 10 closed-chest dogs with normal aortic valves, using a femoral cutdown approach and fluoroscopic guidance. Four were done with a single 15 mm balloon catheter, and in the other 6 two 12 mm balloon catheters were used. Balloons were inflated to 5 to 12 atms pressure with contrast solution. After several inflations the dogs were sacrificed, the hearts removed and examined. Gross examinations revealed subendocardial hemorrhage in the outflow tract in 5 of the 6 in which double balloons had been used. Microscopically, all aortic valve areas showed hemorrhage, mostly in loose connective tissues of the valve leaflets. The severity of injury appeared greater when two balloons had been used. Histologic examination showed definite injury to the myocytes of the left bundle branch in all 6 of the double-ballooned dogs, but in none of those subjected to the single-balloon procedure. During aortic valve dilation the only manifestation of conduction system injury was prolongation of the QRS complex in 3 of the 6 dogs in which a double-balloon catheter had been used. The results suggest that electrocardiographic conduction disturbances observed in patients undergoing aortic valvuloplasty may be the result of direct injury of conduction tissue and may be more likely to occur when larger balloons are used. ",22 557,"Long survival and prognostic factors in hepatocellular carcinoma. We studied survival and prognostic factors in all cases of hepatocellular carcinoma seen at a Midwestern teaching hospital from 1947 through 1986. Of the 70 cases, 56 were diagnosed during life and 14 at autopsy. There were 47 males and 23 females with age at diagnosis ranging from 14 to 88. Median survival for the 56 patients diagnosed during life was 106 days. Only 11 patients lived longer than one year. Two patients were long survivors and presumed cured, one living 27 years after diagnosis and surgical treatment and the other 19 years. Cox regression model showed young age at diagnosis and low stage of disease at diagnosis to be significant predictors of long survival. White patients survived nearly twice as long as black patients but the difference was not significant. Gender and year of diagnosis did not appear to be important determinants of survival. Pathologic material was still available for one of the two long survivors and the histology was that of fibrolamellar carcinoma of young adults. ",3 1343,"Is preliminary binephrectomy necessary in patients with autosomal dominant polycystic kidney disease undergoing renal transplantation? Patients with end-stage chronic renal failure due to autosomal dominant polycystic kidney disease who underwent renal transplantation with or without preliminary binephrectomy were retrospectively studied to determine the effect of binephrectomy on outcome. Nineteen patients were identified. Thirteen patients had no surgery prior to transplantation and six underwent preliminary binephrectomy. One patient died as a result of the nephrectomy. Twenty-one renal allografts were performed on 18 patients of whom seven have died of sepsis; 10 have functioning grafts and one has returned to dialysis. Patients not undergoing preliminary binephrectomy had a statistically significant (p less than 0.05) increase in mortality and morbidity due to septic complications related to polycystic kidney disease. Indications for bilateral nephrectomy should be reconsidered. ",11 2518,"Interaction between insulin and glucose-delivery route in regulation of net hepatic glucose uptake in conscious dogs. In the presence of fixed basal levels of insulin, the route of intravenous glucose delivery (protal vs. peripheral) determines whether net hepatic glucose uptake (NHGU) occurs. Our aims were to determine if the route of intravenous glucose delivery also plays a role in regulating NHGU in the presence of hyperinsulinemia and to determine if length of fast (18 vs. 36 h) influences regulation of NHGU. Five conscious dogs fasted 18 h were given somatostatin and replacement insulin (245 +/- 34 microU.kg-1.min-1) and glucagon (0.65 ng.kg-1.min-1) infusions intraportally. After a 40-min control period, the insulin infusion rate was increased fourfold, and glucose was infused for 3 h. Glucose was given either through a peripheral vein or the portal vein for 90 min to double the glucose load reaching the liver. The order of infusions was randomized. NHGU was measured with the arterial - venous difference technique. Insulin and glucagon levels were 12 +/- 2, 35 +/- 6, and 36 +/- 5 microU/ml and 55 +/- 12, 61 +/- 13, and 59 +/- 7 pg/ml during the control, peripheral, and portal infusions, respectively. The glucose infusion rate, the load of glucose reaching the liver, and the arterial-portal plasma glucose gradient were 0, 9.58 +/- 2.28, and 10.44 +/- 2.94 mg.kg-1.min-1; 29.4 +/- 3.6, 56.8 +/- 3.4, and 56.8 +/- 2.8 mg.kg-1.min-1; and 2 +/- 1, 5 +/- 1, and -51 +/- 15 mg/dl during the same periods. ",18 2167,"Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro. Parvovirus B19 infection leads to transient aplastic crises in individuals with chronic hemolytic anemias or immunodeficiency states. An additional unexplained sequela of B19 infection is thrombocytopenia. Because B19 is known to have a remarkable tropism for human erythropoietic elements, and is not known to replicate in nonerythroid cells, the etiology of this thrombocytopenia is uncertain. We sought to define the pathobiology of B19-associated thrombocytopenia by examining the role of B19 on in vitro megakaryocytopoiesis. B19 infection of normal human bone marrow cells significantly suppressed megakaryocyte (MK) colony formation compared with mock-infected cells. No such inhibition was observed with a nonpathogenic human parvovirus, the adeno-associated virus 2 (AAV). The B19-MK cell interaction was also studied at the molecular level. Whereas low-density bone marrow cells containing erythroid precursor cells supported B19 DNA replication, no viral DNA replication was observed in B19-infected MK-enriched fractions as determined by the presence of viral DNA replicative intermediates on Southern blots. However, analysis of total cytoplasmic RNA isolated from B19-infected MK fractions showed a low-level expression of the B19 genome as detected by quantitative RNA dot blots as well as by Northern analysis. Furthermore, a frame-shift mutation in a recombinant AAV-B19 hybrid genome segment that encodes the viral nonstructural (NS1) protein significantly reduced the observed inhibition of MK colony formation. These studies indicate tissue-tropism of B19 beyond the erythroid progenitor cell, and lend support to the hypothesis that B19 genome expression may be toxic to cell populations that are nonpermissive for viral DNA replication. ",14 2777,"Late versus early onset problem drinking in older men. Age at onset of problem drinking was studied in 132 older men (age 60 years and older) admitted to a VA geriatric alcoholism outpatient treatment program. Demographics, alcohol history, self reported psychological status, special treatment, and treatment compliance variables were tested for association with onset age. Late onset (defined as onset of the first alcohol problem at or after age 60) was not uncommon, occurring in 15% of the sample (29% of patients age 65 or older). Compared to earlier onset cases, late onset alcohol problems were milder and more circumscribed, and were associated with less family alcoholism and greater psychological stability. Late onset patients were also more compliant with outpatient treatment requirements; however, treatment program variables were better predictors of compliance than onset age. ",20 1771,"Effects of adenosine on human coronary arterial circulation Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 micrograms), intracoronary infusion (10-240 micrograms/min), or intravenous infusion (35-140 micrograms/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5 +/- 0.2.resting CBFV). In normal left coronary arteries (n = 20), 16-micrograms boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6 +/- 0.7.resting CBFV). In the right coronary artery (n = 5), 12-micrograms boluses caused maximal hyperemia (4.4 +/- 1.0.resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 micrograms/min or more into the left coronary artery (n = 6) also caused maximal hyperemia (4.4 +/- 0.1.resting CBFV), and doses up to 240 micrograms/min caused a minimal decrease in arterial pressure (-6 +/- 2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (n = 25) at 140 micrograms/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4 +/- 0.9.resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-micrograms/kg/min infusion, arterial pressure decreased 6 +/- 7 mm Hg, and heart rate increased 24 +/- 14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (delta CBFV, less than 3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients.(ABSTRACT TRUNCATED AT 400 WORDS). ",13 537,"The interplay of local and distant control in the cure of cervical cancer. From 1978 to 1986, 183 women with cervical cancer received definitive radiation therapy after extraperitoneal surgical staging. Relapse-free rates were strong functions of pelvic lymph node metastases and cervical size. The recurrence distribution consisted of 4% isolated local, 13% isolated distant, and 17% combined local and distant failures. With the assumption of independent local and distant failure probabilities, Suit et al.'s method was extended to assess potential improvement in cure attainable with perfect local and distant control, yielding local (LSA) and distant (DSA) survival advantages of 17% and 28%. Various subsets of clinical stage, cervical size, pelvic node metastases, periaortic metastases, and peritoneal metastases had LSA from 12% to 27% and DSA from 12% to 71%. For any prognostic group, LSA never exceeded DSA, showing that effective systemic therapy would have a greater impact on improving survival than would advances in local and regional tumor control. Therapeutic implications and limitations of the extended LSA-DSA model are discussed. This form of analysis can be used to guide the intensity of local and distant treatment to maximize the cure of the patient with cancer. ",3 3219,"Femoral arteriovenous fistula as a complication of percutaneous transluminal coronary angioplasty. A report of five cases. Arteriovenous fistula (AVF) associated with invasive and diagnostic angiographic procedures is rare. The incidence is increased with procedures such as percutaneous transluminal coronary angioplasty (PTCA) but is still quite low. We report five cases of AVF within a 17-month period, representing 0.15 per cent of all cardiac catheterizations and 0.87 per cent of PTCAs. All five patients presented with groin bruits. There were two associated pseudoaneurysms and one patient with deep vein thrombosis. All patients underwent uneventful division of the fistula. A thorough understanding of the anatomy of the femoral triangle is necessary in order to avoid this complication. That all fistulas were in the superficial or profunda femoris arteries emphasizes the importance of avoiding a low groin puncture. Early angiography and surgical intervention are recommended for optimal results. ",22 426,"Expression of aminopeptidase N (CD13) in mesenchymal tumors. For a long time, CD13 molecules have been considered to be restricted to myeloid cells and related neoplasms. Meanwhile, however, expression of CD13 has also been detected in some hepatocellular, gallbladder, renal, and lung carcinomas, and even in some fibrosarcomas and malignant melanomas. In this study, expression of CD13 antigen was immunohistochemically examined in non-neoplastic mesenchymal cells, along with 33 benign and 83 malignant mesenchymal tumors (MET) using CD13 monoclonal antibodies (MAb) My7, U71, WM-15, and MoU48. In non-neoplastic mesenchymal cells, expression of CD13 was restricted to perivascular fibrocytes/blasts, tissue histiocytes, osteoclasts, and to the perineurium of peripheral nerve trunks. Under neoplastic conditions, CD13 was detectable in some tumors of smooth muscle, fibrous, fibrohistiocytic, synovial, osteogenic, and peripheral nerve sheath origin, and even in some tumors of adipose tissue. Tumors of striated muscle origin, of autonomic ganglia, and of cartilage-forming tissues were CD13-negative throughout. Thus in most but not all tumors studied the pattern of expression of CD13 mirrors the situation found in their cells of origin. These findings enrich the data on expression of leukocyte differentiation antigens in extra-hematopoietic tissues. Expression of CD13, which meanwhile is known to be identical to aminopeptidase N, an important peptide-cleaving enzyme, in only some MET might reflect a special functional state of these neoplasms. ",3 474,"Therapeutic dilemmas associated with antenatally detected ovarian cysts. Fifteen instances of ovarian cysts detected antenatally are reported. Seven cysts more than 5 centimeters in diameter were treated surgically because of clinical signs, such as palpable abdominal mass, vomiting and abdominal distension. Seven cysts less than 5 centimeters in diameter, and one cyst more than 5 centimeters in diameter began to regress spontaneously within six months after birth. Because the pathophysiologic nature of neonatal ovarian cysts has not been elucidated and because the borderline between physiologic and pathologic factors is still unclear, we propose a more conservative approach in the management of neonatal ovarian cysts to avoid unnecessary operations. ",3 2927,"Carburetor burns: preventable injuries associated with high morbidity and frequent litigation. We have identified carburetor burns as a significant cause of preventable morbidity, both from long-term functional and cosmetic standpoints. The epidemiology of carburetor burns and our experience are described. All of our patients were male, with a mean age of 35 years. Average burn size was 11.3%. The anatomic distribution of these burns, most often on the dominant hand and on the face, contributes to the morbidity of these burns. This injury has been associated with increasingly frequent litigation. We believe that an active education campaign and the addition of warning labels to car engine compartments would make an impact in decreasing the incidence of carburetor burns. ",20 1746,"Age-related changes in membrane fluidity of erythrocytes in essential hypertension. In the present study, age- and calcium-related changes in the membrane fluidity of erythrocytes were examined in patients with essential hypertension by use of electron spin resonance method (ESR). The erythrocytes were obtained from patients with essential hypertension. We examined the ESR spectra for a fatty acid spin label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes. The values of outer hyperfine splitting and order parameter (S) were significantly higher in subjects with essential hypertension than in the normotensive subjects. This finding indicates that the membrane fluidity of erythrocytes was lower in essential hypertension. Calcium-loading of erythrocytes with the Ca-ionophore A23187 decreased the membrane fluidity (S value was increased) more strongly in essential hypertension than in the normotensive subjects. Furthermore, this Ca-induced change in membrane fluidity was significantly correlated with age in essential hypertension. These results demonstrate that the membrane fluidity of erythrocytes is markedly decreased by calcium, especially in essential hypertension in older patients. This suggests an increased calcium-sensitivity of cell membranes in the aged hypertensive patient. ",13 2279,"A comparative histopathologic study of photodistributed and nonphotodistributed lichenoid drug eruptions. This study compares the histopathologic characteristics of photodistributed and nonphotodistributed lichenoid drug eruptions in 13 patients. Both types have been said to be, in an unknown proportion, different from idiopathic lichen planus in that they can involve the deep as well as the superficial plexus, can contain eosinophils, and have parakeratotic scale. We found that these features were most often present in nonphotodistributed lichenoid drug eruptions and were seldom present in photodistributed eruptions. Thus a biopsy specimen that shows the classic features of lichen planus should not be used as evidence against a drug eruption, especially if the lesions are photodistributed. ",16 2144,"The hematopoietic defect in aplastic anemia assessed by long-term marrow culture. Thirty-two patients with aplastic anemia (AA) have been studied using the long-term bone marrow culture (LTBMC) system. Of these patients, 26 had been treated with immunosuppressive therapy including antilymphocyte globulin (ALG) with or without androgens or high-dose methyl prednisolone. The remaining six patients either required no treatment or were studied before therapy was begun. Thirty-one of 32 patients (96%) had defective hematopoiesis in LTBMC with little or no evidence for the generation of primitive progenitor cells. The only exception was a patient with spontaneous recovery of aplasia in whom the defect was less marked. Crossover LTBMC experiments were performed in 23 cases by inoculating (1) patient marrow hematopoietic cells that had been depleted of adherent cells onto preformed, irradiated, normal stromas to assess the proliferative capacity of the hematopoietic cells, and (2) normal marrow hematopoietic cells that were depleted of adherent cells onto preformed, irradiated stromas from patients with AA to assess stromal function. Results of these experiments demonstrated a hematopoietic defect in all patients that was independent of the degree of hematologic recovery after ALG therapy. Only one patient had a probable stromal defect and this coexisted with a defect in the regenerative capacity of hematopoietic cells. We conclude that LTBMC is a sensitive method for detecting and defining the hematopoietic failure in AA. We suggest that the defective hematopoiesis present in all patients studied may be important in the pathogenesis of clonal evolution in AA. ",14 2708,"Annual summary of vital statistics--1989. US infant mortality continued to decline slowly and the provisional 1989 rate, 9.7 per 1000 live births, was the lowest ever recorded. Final 1988 data showed no change in cause of death distribution or in the wide discrepancy between white and black infant mortality. State rates varied from 6.8 in Vermont to 12.6 in Georgia. Worldwide, the US rate of 10.0 was bettered by 21 other countries, with Japan lowest at 4.8. Births increased in number and rate, because of a higher fertility rate and more women in the childbearing years. The birth rate to mothers 17 years of age and younger increased again. The proportion of women who had no or inadequate prenatal care was essentially unchanged. Deaths, crude death rate, and age-adjusted death rate decreased. The excess of births over deaths added almost 1.9 million persons to the US population, the highest rate of natural increase since 1971. The marriage rate was essentially unchanged, whereas the divorce rate decreased slightly, to the lowest level since 1973. With the exception of human immunodeficiency virus infection, homicide, and pulmonary malignancies, rates for most causes of death declined from 1988 to 1989. In comparison with 1940, most declines were substantial, led by pneumonia, down about 80%, and perinatal conditions, down about 75%. The only large-scale increases among major causes in the half century were in two diseases related to cigarette smoking: chronic obstructive pulmonary disease, up eightfold, and respiratory cancer, up almost sixfold. Death rates from all other cancers, as a group, decreased by some 20% and from cardiovascular diseases by some 60%. ",19 2374,"Fasting and postprandial concentrations of somatostatin-28 and somatostatin-14 in type II diabetes in men. Recent evidence suggests that somatostatin-28 (SRIF-28), cleaved from prosomatostatin by cells of the upper intestine, acts as a nutrient-stimulated inhibitor of insulin secretion in healthy men. A role for SRIF-28 in the pathophysiology of diabetes has not been previously explored, although several groups have measured circulating somatostatinlike immunoreactivity (SLI) in diabetic subjects. To investigate the possible mediation of abnormal insulin secretion in diabetes by SRIF-28, plasma levels were measured in 10 non-insulin-dependent diabetic men and 9 age- and weight-matched control subjects. Concentrations of SRIF-14 and SLI were also obtained. Subjects were admitted for study after an overnight fast, blood was collected before and at 30-min intervals for 4 h after a fat meal, and plasma samples were analyzed for SRIF-28 and SRIF-14 by specific methods. Basal glucose levels in the diabetic men were significantly higher than in control subjects (10.2 +/- 1 vs. 5.8 +/- 0.2 mM), but insulin levels were similar (79 +/- 14.2 vs. 93.3 +/- 14.2 pM). The diabetic men had significantly lower basal SRIF-28 levels than the control subjects (11.4 +/- 0.6 vs. 14.6 +/- 1.0 pM, P = 0.017). After fat intake, SRIF-28 levels throughout the 4 h of study were indistinguishable in the two groups (270 vs. 292% of basal). Basal SRIF-14 and SLI levels were not significantly different in the two groups, and SRIF-14 and SLI concentrations rose similarly after the meal. There were no correlations between basal SRIF-28 and glucose or insulin levels. ",17 944,"Cytomegalovirus infections after allogeneic bone marrow transplantation. Cytomegalovirus (CMV) infection occurs in approximately 50% of all recipients of allogeneic bone marrow transplants and is seen more frequently in CMV-seropositive patients than in CMV-seronegative patients. Sources of infection include reactivation of latent endogenous virus, blood products from CMV-seropositive blood donors, and the use of marrow from a CMV-seropositive donor for a CMV-seronegative recipient. The most common and severe clinical syndrome associated with CMV infection in allogeneic transplant recipients is interstitial pneumonia, which occurs in approximately 15% of patients. Risk factors for CMV pneumonia include old age, conditioning with total-body irradiation, and severe graft-vs.-host disease. The rapid diagnosis of CMV pneumonia has been facilitated by immunochemical staining of bronchoalveolar lavage fluid or by centrifugation of cell cultures with CMV monoclonal antibodies. The treatment of CMV pneumonia remains problematic, but therapy with a combination of intravenous immune globulin (IVIG) plus ganciclovir has resulted in survival rates substantially better than those achieved in previous trials of antiviral therapy. In CMV-seronegative patients, CMV infection and pneumonia can be prevented or modified by the use of CMV-seronegative blood products and IVIG. IVIG may also have the additional benefits of preventing other infectious complications and graft-vs.-host disease in patients receiving CMV-seronegative blood products. For CMV-seropositive patients, effective prophylaxis for CMV reactivation and pneumonia has not yet been established, but a clinical trial of prophylactic ganciclovir is now under way. ",7 187,"Multicentric endobronchial granular cell myoblastoma. Granular cell myoblastoma (GCM) is a rare benign neoplasm involving the tracheobronchial tree. It is believed to arise from the Schwann cell. Four cases of tracheobronchial GCM, all of which were multicentric, are presented and a conservative therapeutic approach is suggested. ",3 778,"Advanced assessment of the abdomen and gastrointestinal problems. There are many unique physical assessment findings that are associated with specific gastrointestinal disorders. The detection of these findings enables the nurse to manage gastrointestinal emergencies on the patient unit in a timely fashion, preventing deterioration and maintaining the safety of the patient. These skills build well on the traditional, detailed, and comprehensive assessments the nurse makes when using the nursing process. Specific abdominal assessments include detection of signs associated with appendicitis such as rebound tenderness and McBurney's, Rosvig's, and Aaron's signs. The nurse must always be alert to the possibility of peritonitis and the urgency of early detection and treatment. The patient with cirrhosis of the liver presents a distinct clinical picture. There is a need for subtle evaluation of mental status to detect early signs of hepatic coma. Another extra-abdominal assessment of this complication is asterixis. Finally, the assessment of the patient is enhanced when the nurse is able to help identify the location of bleeding. Improving abdominal and gastrointestinal system assessment leads to early detection of nursing problems and appropriate interventions. ",5 3180,"Stapling or suturing for anastomoses of the left side of the large intestine. Two hundred and fifty patients undergoing elective surgical treatment involving anastomoses of the left side of the colon or colon and rectum have been studied in a randomized trial in which the EEA (U. S. Surgical Corp.) circular stapler has been compared with single layer sutured anastomoses. Only patients in whom either technique was feasible were included in the analysis. The operative techniques were largely standardized. Patients were studied by means of a limited barium enema on the ninth or tenth postoperative day. The data have been analyzed for leakage rate (clinical and roentgenologic), other complications and degree of experience of the surgeon. Eleven patients were excluded from the analysis because the selected technique could not be carried out; of these, eight were in the stapled group in which it was possible to perform a sutured anastomosis. There were no instances in which it was possible to staple but not possible to suture. The remaining three exclusions were patients in whom either a coloanal anastomosis or a Hartmann procedure was performed. There was no over-all difference in the leakage rate--roentgenologic, clinical or total--between the two groups. However, when analyzed by the surgeon, the clinical leakage rate for surgeons in training was greater for sutured anastomoses than for stapled anastomoses (p = 0.053). Thus, it appears that the benefits of experience are more pronounced for sutured anastomoses but that, in experienced hands, neither technique is superior. ",22 373,"Neoadjuvant Cis-DDP in esophageal cancers: an experience at a regional cancer centre, India. We are analysing the results of 80 patients who underwent surgery during 1983-84 for esophageal cancer. Forty patients who received pre-operative single agent Cis-DDP were grouped under ""A"" and 40 patients who went for surgery directly were grouped under ""B"". Twenty-two patients (55%) of Group A showed tumor necrosis. Both groups underwent resection and hand-sewn anastamosis of the esophagus. There were 10 post-operative deaths among 80 resected cases, 9 of them being from anastomatic leak. Cis-DDP has induced negligible side effects. A comparatively high survival rate during early years in patients who responded to Cis-DDP suggests that neoadjuvant chemotherapy might be of value. ",3 1449,"Endourological experience with cystine calculi and a treatment algorithm. Between May 1984 and January 1988, 18 patients (31 pyeloureteral units) with documented symptomatic cystine stones were treated. Stone size ranged from 5 to 56 mm. in largest diameter, with an average of 21 mm. All pyeloureteral units were treated initially by endourological methods, including ureteroscopy in 10, percutaneous ultrasonic lithotripsy in 9, extracorporeal shock wave lithotripsy (ESWL) in 10 and chemolysis in 2. Of the patients 10 required a combination of these technologies and 2 required an open operation. Of the 31 units 23 were free of stones when the patient was discharged from the hospital. Of 8 patients with retained stones only 3 had fragments greater than 3 mm. in diameter. Based on this experience an algorithm was developed for the urological management of cystine stones. Ureteral calculi may be removed by ureteroscopic techniques or manipulated into the renal pelvis and managed as renal stones. Cystine renal calculi of less than 1.5 cm. may be treated with ESWL monotherapy. Stones of 1.5 to 3 cm. may be treated with ESWL and dissolution, or percutaneous ultrasonic lithotripsy plus dissolution. Staghorn calculi may be treated by percutaneous ultrasonic lithotripsy plus ESWL and/or dissolution for retained fragments. ",11 2117,"Contrast echocardiographic mapping of collateralized myocardium in humans before and after coronary angioplasty Conventional coronary arteriography is able to demonstrate the presence of coronary collateral vessels but cannot delineate the specific region of myocardium to which they supply blood. To test the hypothesis that contrast echocardiography can specifically identify collateralized myocardium, contrast echocardiographic perfusion ""maps"" were compared in patients with (n = 12) and without (n = 12) angiographic evidence of coronary collateral flow, both before and after coronary angioplasty. Contrast echocardiographic images of the mid-left ventricle in the short-axis view at end-diastole were obtained after separate injections of a sonicated contrast agent into both the right and the left coronary arteries. A computer-based contouring system was used to determine the individual areas of myocardium perfused by each of the two coronary arteries and then to superimpose the images of the two perfusion beds. The resulting area of overlapping perfusion represented myocardium receiving blood flow from both coronary systems and was defined as collateralized myocardium. To normalize for heart size, overlap area was expressed as a percent of total myocardial area, which was the area between endocardium and epicardium in the short-axis view. To adjust for differences in vascular distribution, overlap area was expressed as a percent of the perfusion area of the recipient vessel. In patients with angiographic collateral flow, the recipient vessel was that vessel receiving the collateral flow. In patients without angiographic collateral flow, the right coronary artery was considered the recipient vessel. Overlap area was 1.3 +/- 0.4% of total myocardial area and 6.6 +/- 1.7% of recipient vessel area in patients without angiographic evidence of collateral flow compared with 30.6 +/- 2.5% and 89.2 +/- 6.4%, respectively, in patients with angiographic collateral flow (p less than 0.001 for both). In four patients in whom angiographic collateral flow was abolished by angioplasty, overlap area decreased from 30.3 +/- 5.3% to 6.8 +/- 2.7% of total myocardial area and from 100% to 18.5 +/- 5.4% of recipient vessel area (p less than 0.05 for both). Thus, contrast echocardiography is able to map the specific myocardial territory perfused by coronary collateral flow and document an immediate reduction in perfusion in this territory when collateral flow is abolished by angioplasty. ",13 1412,"Double-blind, placebo-controlled, cross-over study of flavoxate in the treatment of idiopathic detrusor instability. Detrusor instability occurs in approximately 10% of the adult population, producing troublesome symptoms. The pharmacotherapy currently available is usually only partially effective and cannot be adequately evaluated except under ""blind"" conditions because of the significant component attributable to placebo effects. The results of the present study revealed no advantage resulting from treatment with flavoxate, as assessed both subjectively and objectively. We suggest that this therapy does not appear to be beneficial in the medical management of detrusor instability. ",11 572,"Tyrosine kinase and control of cell proliferation. The usefulness of phosphotyrosine antibodies for the detection of physiologically regulated or deregulated tyrosine kinases is discussed in this report. This rather rare enzymatic activity is shared by receptors for some polypeptide growth factors and by the products of Class 1 oncogenes. The antibodies are able to detect proteins phosphorylated on tyrosine in fibroblasts stimulated with growth factors such as EGF and PDGF. The major phosphorylated protein species are the receptors themselves, which undergo phosphorylation only after the addition of the exogenous factor and only transiently. Phosphotyrosine antibodies were able to detect the products of the retroviral Class 1 oncogenes, which are endowed with deregulated tyrosine kinase activity. In fact, in these cases a constitutive phosphorylation of the relevant proteins was observed, which occurred continuously and independently of the presence or lack of exogenous ligands. A tyrosine kinase constitutively activated in human gastric carcinoma cells was detected by P-Tyr antibodies. This molecule has been characterized at the molecular level, and the mechanisms responsible for its enzymatic activation have been investigated. The question of whether the tyrosine kinase identified is responsible for the induction and the maintenance of the transformed phenotype in gastric carcinomas remains to be answered. It is reasonable to suggest that this might be the case by analogy with other situations such as Class 1 oncogenes activated by transduction by retroviruses, abnormal expression of EGF receptors, or deregulated activity of c-abl-encoded proteins in chronic myelogenous leukemia and acute lymphoblastic leukemia. Thus, the search for deregulated kinases by means of phosphotyrosine antibodies seems to be useful for identifying new activated oncogenes in clinical oncology. ",3 13,"Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis. The direct involvement of Clostridium difficile in the lesional tissue of pseudomembranous colitis has not been demonstrated; the organism's effects have been assumed to be strictly toxin mediated. Because C. difficile cytotoxin may be found incidentally in the intestinal lumina of asymptomatic infants, the role of the organism in a variety of pediatric intestinal diseases is uncertain. The authors studied seven cases of fatal pediatric pseudomembranous colitis in which the presence of C. difficile was uniformly demonstrable in lesional tissues with the use of both an intestinal spore stain and a specific immunostain. The patients had either underlying Hirschsprung's disease or hematologic malignancy; the striking pathologic features peculiar to these patients were altered mucosal mucin and immunologic barriers in the former group and neutropenia in the latter. Two patients had demonstrable circulating cytotoxin in serum or ascitic fluid, and C. difficile was identified invading colonic mucosa or submucosa. Such phenomena did not occur in control pediatric patients with multiple other intestinal lesions. Altered host factors may be responsible for the intestinal invasion of C. difficile and its systemic toxin circulation in cases of fatal pediatric pseudomembranous colitis. ",0 215,"Adjuvant chemotherapy of breast cancer. Many women will not be cured of breast cancer by even the best early detection and surgical techniques because of micrometastases present at diagnosis. Adjuvant therapy has extended the disease-free interval for most patients and lengthens overall survival for many. Combination chemotherapy has become the standard form of adjuvant treatment for premenopausal women with breast cancer and positive lymph nodes after primary therapy. With minimal toxicity, disease-free and overall survival are improved. Results are less impressive or less clear-cut for postmenopausal women or any woman with negative lymph nodes. Long-term toxicities of adjuvant chemotherapy may include second malignancies and cardiac dysfunction. Although these complications probably are rare, they must be considered seriously when weighing chemotherapy for patients in whom its benefits may be slight. Innovations likely to become standard in adjuvant therapy decision making include risk assessment with new prognostic indicators (growth fraction, oncogene expression) and investigation of dose intensification using bone marrow growth factors and autologous stem-cell support. ",3 1159,"Auras and subclinical seizures: characteristics and prognostic significance. The characteristics and prognostic significance of subclinical seizures and independent auras were studied in 40 patients with partial epilepsy who had long-term electroencephalographic (EEG) monitoring with intracranial electrodes. Focal, restricted subclinical seizures were noted in 23 patients, and 11 patients experienced auras that were accompanied by ictal EEG discharges. Auras and subclinical seizures usually were identical in EEG appearance, but were distributed differently among patients. The subclinical seizures and auras usually had the same origin as complex partial seizures, but did not always reliably indicate complex partial seizure origin. Subclinical seizures and auras were of favorable prognostic significance for patients undergoing temporal lobectomy. A majority (greater than 80%) of individuals with subclinical seizures and auras were free of complex partial seizures after surgery, whereas a minority (29%) of patients without subclinical seizures and auras became free of complex partial seizures. ",9 2506,"Familial hypercatabolic hypoproteinemia. A disorder of endogenous catabolism of albumin and immunoglobulin. The metabolism of albumin and IgG was investigated in two siblings, products of a first-cousin marriage, a female aged 34 yr and a male aged 17, who had a marked reduction in their respective serum concentrations of IgG (1.3 and 3.1 mg/ml) and albumin (19 and 21 mg/ml). The metabolism of radioiodinated IgG and albumin was studied in the two patients. The total circulating and body pools of IgG were less than 28% of normal. The IgG synthetic rates were within the normal range. However, the IgG survival was short, with their respective fractional catabolic rates increased fivefold to 31% and 36% of the intravenous pool per day (normal, 6.7 +/- 2%/d). Furthermore, the patients had reduced total body pools, normal synthetic rates, and increased fractional catabolic rates for albumin. There was no proteinuria or abnormality of renal or liver function. In addition, the patients did not have circulating antibodies directed toward IgG, IgA, or albumin. Furthermore, both patients had normal fecal 51Cr-labeled albumin tests, thus excluding excessive gastrointestinal protein loss. We propose that these siblings have a previously unrecognized familial disorder characterized by reduced serum concentrations of IgG and albumin caused by a defect in endogenous catabolism, leading to a short survival of these proteins that is associated in this family with chemical diabetes and a skeletal deformity. ",17 1381,"Toxicity comparison of neoadjuvant versus adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in radical cystectomy patients. A reduction in the toxicity of M-VAC chemotherapy has been postulated for patients who receive these drugs prior to radical cystectomy for muscle invasive bladder carcinoma. A review of the toxicity and patient dropout rates from a group of 9 patients who received neoadjuvant M-VAC was little different from 9 patients who were treated with M-VAC after radical cystectomy. This similarity suggests that preoperative M-VAC should not be favored on the basis of reduced patient morbidity. ",11 1267,"The use of conchal cartilage graft in involutional entropion. A simple and stable technique for repairing involutional entropion is described. Through a transconjunctival incision between the lower border of tarsus and the lower lid retractor, the eyelid is divided between the tarsus and the orbicularis oculi muscle into external and internal layers. The internal layer is moved upward until the eyelashes turn outward, and then through-and-through sutures are placed to fix it in this corrected state. The resultant defect between the lower end of the tarsus and the retractor is filled with a conchal cartilage graft. The raw surface of the cartilage is epithelialized from the surrounding mucosa within 1 to 2 weeks without shrinkage. This technique is more stable than any other technique that we have performed. ",10 1821,"Effects of anxiety on family members of patients with cardiac disease learning cardiopulmonary resuscitation. The effects of anxiety on learning cardiopulmonary resuscitation (CPR) by family members of patients with cardiac disease was examined. Family members of hospitalized patients (n = 17), family members of nonhospitalized patients (n = 12), and a control group (n = 21) all took one of nine Heart Saver programs in which CPR was taught and performance evaluated. Subjects took the State Anxiety Inventory three times: immediately before the program, immediately after the performance test, and 2 months after completion of the program. Family members of hospitalized patients had significantly higher before-program anxiety scores than the other groups. This difference was not present immediately after the program or 2 months later. Family members of hospitalized patients showed a significant decline in anxiety over the three testing times. These outcomes support the benefit of teaching CPR to this group. ",13 1440,"Minimizing urinary incontinence in the nursing home. In the nursing home, urinary incontinence is a common problem that all too often is treated as an irremediable ""problem of aging"" by physicians, nurses, and patients. Its etiologies are numerous, as are approaches to treatment in this setting. However, with a thoughtful approach to diagnosis and care, the primary care physician may be able to determine which patients, with which forms of urinary incontinence, will benefit from specific therapies. ",11 859,"Whole organ sectioning of mixed parotid tumors. A pathologic study involving 15 standard formal parotidectomy specimens was carried out using the whole organ sectioning technique. Histopathologic characteristics noted included the presence of exposed capsule, breaks of the capsule, capsular incompleteness, tumor ingrowth and thickness, cellularity, and lymphocytic infiltration. Tracings of histopathology slides were used to reconstruct the three-dimensional configuration of each tumor as viewed from different angles. No tumor had a smooth surface. At the extreme, two tumor lumps were connected by just a narrow waist. Separated tumors were not seen. In only one specimen did a lymph node contain an additional tumor in the form of an adenolymphoma. All tumors showed some exposed capsule or ""bare area"" to a degree affected mainly by the position of the tumor. Capsular damage was occasionally seen and was usually minor. Capsular incompleteness and tumor ingrowth make global capsular dissection unsafe. It is concluded that formal parotidectomy remains the operation of choice for pleomorphic adenoma of the parotid gland, although capsular dissection (otherwise termed enucleation) cannot be entirely avoided during the procedure. ",6 483,"Oral contraceptives and breast cancer. Review and meta-analysis. To evaluate the relation between use of oral contraceptives and the incidence of breast cancer, the authors reviewed the epidemiologic literature and used quantitative methods to summarize the data. Study results for any use of oral contraceptives were pooled using a model that accounted for both interstudy and intrastudy variability. The authors also explored interstudy variability and modeled a duration-effect relation between oral contraceptive use and breast cancer. Case-control and follow-up studies were considered separately. Overall, the authors observed no increase in the risk of breast cancer for women who had ever used oral contraceptives, even after a long duration of use. These results were consistent across study design. However, data combined from case-control studies revealed a statistically significant positive trend (P = 0.001) in the risk of premenopausal breast cancer for women exposed to oral contraceptives for longer duration. This risk was predominant among women who used oral contraceptives for at least 4 years before their first term pregnancy (relative risk = 1.72; 95% confidence interval = 1.36 to 2.19). Additional study is required to determine whether this finding in a subgroup of exposed women is confirmed and whether the risk remains increased with advancing age. ",3 333,"Cytomegalovirus in the brain: in vitro infection of human brain-derived cells. Models for human cytomegalovirus (HCMV) brain infection have been developed in a variety of brain-derived cells in which the factors governing virus infectivity might be studied in vitro. Studies were initiated with brain endothelial cells, the likely portal of entry for virus into the central nervous system. Primary explant cultures of brain endothelial cells, derived from homogenates of healthy human brain, supported complete viral gene expression and cytopathic effect (CPE). Endothelial cells do not appear to be a barrier for HCMV passage into the central nervous system. Astroglial lines (primary explant or tumor-derived) varied in their ability to support HCMV replication. Some (T98G) supported incomplete (immediate-early) gene expression while others (A-172) did not support any detectable gene expression. Some astroglial lines (HS-683) supported extensive virus replication with minimal viral CPE. Neuronal cell lines (SK-N-MC) were fully permissive. The more differentiated glial lines (astrocytoma) were fully permissive to HCMV infection; however, the less differentiated glial lines (glioblastoma) were partly or nonpermissive. ",3 447,"Clinical management of port-wine stain in infants and young children using the flashlamp-pulsed dye laser. The flashlamp-pulsed dye laser (FLPDL) at 585 nm, a wavelength well absorbed by oxyhemoglobin, causes highly selective vascular injury. In addition, the 450 microsecond pulse duration produced by this laser approximates the thermal relaxation time for dermal blood vessels thereby confining the energy to the target. This new laser effects excellent lightening of port-wine stain (PWS) in infants and young children without the adverse complications of hypertrophic scarring, permanent pigmentation abnormality, or textural changes, complications often seen with conventional laser systems. The FLPDL now permits treatment of this patient population expected to gain the most benefit from early laser therapy in a much safer manner, before the psychological complications of being a ""marked"" person develop. The purpose of this report is to: (1) describe the theoretical considerations behind achieving selective removal of PWS that can be understood and used by a nonsurgically-oriented practitioner; and (2) describe the practical application of the device used in the clinical management of infants and young children. ",3 1084,"Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures. A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire-electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow-up period make this a pilot study, but the results are promising. ",9 2672,"Relapse from safer sex: the next challenge for AIDS prevention efforts. Prevention campaigns to reduce sexual transmission of human immunodeficiency virus (HIV) typically emphasize the initial adoption of safer sex techniques. We present data from a 5-year prospective study to show that the vast majority of resident gay men in San Francisco have made these initial risk reductions. Rather, relapse from safer sex techniques is now the predominant predominant kind of high-risk sex, accounting for approximately two thirds of all prevalent high-risk sex in the 1988 wave of data collection. Predictors of relapse from safer sex are identified, and these are discussed in terms of their implications for preventing relapse from the exclusive practice of safe sex. In communities that have already manifested widespread behavioral risk reductions and in which HIV infection is highly prevalent, finding ways to prevent relapse of behavioral risk reductions will be the next important challenge in the fight against acquired immune deficiency syndrome. ",19 1149,"Physical features of Prader-Willi syndrome in neonates. A retrospective study of 16 patients was undertaken to identify physical features that may typify neonates with Prader-Willi syndrome. Several features known to be typical of Prader-Willi syndrome in early infancy were confirmed, including hypotonia and genital hypoplasia. A number of features that have not previously been emphasized as characterizing Prader-Willi syndrome were also identified, most notably abnormal cry and, in males, signs of genital hypoplasia but with an apparently normal phallus. Other features included disproportionately large head circumference, disproportionately large anterior fontanelle, mild micrognathia, mild anomalies of the gingivae or alveolar ridges, and changes in the appearance of the skin. Appreciation of these features may assist the pediatrician in recognizing the child with Prader-Willi syndrome during the neonatal period, before the appearance of better-known findings of later onset, such as obesity and acromicria. ",9 1605,"Echocardiographic definition of the left ventricular centroid. II. Determination of the optimal centroid during systole in normal and infarcted hearts. Although two-dimensional echocardiography is widely used in both clinical and experimental evaluations of regional cardiac wall motion, there is no established clinical method for quantitative analysis of the wall motion, not even for the normal radial motion observed in short-axis images. Measurement of radial wall motion requires determination of a centroid from which the radii emanate. Depending on its definition, the centroid is variously affected throughout systole by cardiac translation, regional wall motion and any shift of the subject position or transducer. A floating centroid is defined relative to the ventricular walls frame by frame, whereas a fixed centroid never moves with respect to the transducer. Evaluation of the best approach to definition of a centroid was previously presented (part I, this issue). The next question is how to use the centroid. This study examines which of four centroid applications provides the best reference for quantifying regional wall motion during systole. Method 1 is a floating centroid (defined separately for every image frame), method 2 uses the end-diastolic centroid as a fixed reference for all image frames, method 3 uses the end-systolic centroid as a fixed reference and method 4 uses the average as a fixed reference. Wall motion was measured with respect to each of these centroids by determining radial wall motion from end-diastole to end-systole and correlating radial motion throughout the cardiac cycle with that in normal control hearts. ",13 2977,"Comparison of phenytoin with noncompetitive N-methyl-D-aspartate antagonists in a model of focal brain ischemia in rat. Recent in vitro and in vivo experiments have suggested that excitatory amino acid antagonists, particularly those active at the N-methyl-D-aspartate receptor subtype, are effective in ameliorating ischemic injury due to their antiexcitotoxic activity. However, these drugs are also potent and effective in vivo anticonvulsants. The present experiments compared the noncompetitive N-methyl-D-aspartate antagonists phencyclidine and MK-801 with the anticonvulsant phenytoin in a model of focal brain ischemia. Fisher F-344 rats were subjected to tandem occlusion of the middle cerebral and ipsilateral common carotid arteries under halothane anesthesia. Compounds were administered intravenously 30 minutes and 24 hours after arterial occlusion; infarct size was assessed at 48 hours after occlusion. Phencyclidine had no effect on infarct volume at 1 mg/kg, significantly reduced (by 36%) infarct volume at 3 mg/kg, and produced a nonsignificant 26% decrease at 10 mg/kg. The more potent and selective noncompetitive antagonist MK-801 reduced (by 32%) infarct volume significantly at 0.1 mg/kg, produced a nonsignificant 23% decrease at 0.3 mg/kg, and had no effect at 0.5 mg/kg. Phenytoin, which is not a glutamate antagonist, reduced the infarct volume by 45% at 28 mg/kg. A single dose of phenytoin (28 mg/kg) administered 30 minutes after occlusion was neuroprotective, but delaying drug administration for more than 2 hours was ineffective. These data suggest that blockade of the N-methyl-D-aspartate receptor is effective in reducing the infarct size after focal cerebral ischemia. The neuroprotective activity of phenytoin suggests that this may be related to the common anticonvulsant action. ",21 2396,"Long-term maternal-fetal exposure to high-low insulin concentrations alter liver but not brain insulin receptors. We investigated the effects of long-term (5 to 6 days) in vivo exposure to hyperinsulinemia and hypoinsulinemia on maternal and fetal rat (18 to 20 days' gestation; term approximately 21 days) brain and liver insulin receptors. Further we studied the in vitro effects of long-term insulin exposure on cultured rabbit neuronal cell insulin receptors. Long-term glucose infusions to maternal rats resulted in maternal and fetal hyperglycemia and mild hyperinsulinemia, which decreases the liver insulin receptor abundance of the mother but increased that of the fetus. Streptozotocin-induced maternal diabetes resulted in maternal and fetal hyperglycemia with hypoinsulinemia (or near-normal insulin levels) and increased maternal and fetal liver insulin receptors. The maternal and fetal brain insulin receptor abundance failed to change at high or low insulin concentrations. Similarly long-term insulin (5 micrograms/ml) exposure failed to alter cultured neuronal cell insulin receptors as well. We conclude that perturbations in maternal and fetal circulating insulin concentrations fail to affect the brain insulin receptors. This protective phenomenon may be critical in maintaining the normal neuronal energy balance and functioning during certain disease states such as diabetes mellitus and hyperinsulinism. ",17 2335,"Anti-(U1) small nuclear RNA antibodies in anti-small nuclear ribonucleoprotein sera from patients with connective tissue diseases. Small nuclear ribonucleoprotein (snRNP) particles are a class of RNA-containing particles in the nucleus of eukaryotic cells. Sera from patients with connective tissue diseases often contain antibodies against the proteins present in these snRNPs. Antibodies against the RNA components of snRNPs, the U snRNAs, are thought to be rare. We tested 118 anti-snRNP sera for the presence of anti-snRNA antibodies and found them in 45 sera (38%). In all sera the antibodies (IgG and F(ab)2 fragments thereof) were exclusively directed against U1 snRNA. The anti-(U1) RNA antibodies were always accompanied by anti-(U1)RNP antibodies but were not found in sera which contain antibodies of the Sm serotype directed against all nucleoplasmic U snRNP particles. Like anti-RNP antibodies, anti-U1 RNA activity is confined to sera from patients with SLE or SLE overlap syndromes and is rarely found in patients with other connective tissue diseases. By analyzing binding to subfragments of U1 snRNA made in vitro, it was demonstrated that anti-(U1)RNA antibodies recognize epitopes distributed throughout the U1 RNA molecule. In most sera, however, either the second or the fourth hairpin loop is the main target of the antibody. The possible mechanisms that could lead to the production of this new type of autoantibody are discussed. ",16 2994,"Laryngomalacia in children. Two hundred three (68 percent) of 297 children with laryngomalacia had associated respiratory disorders by flexible fiberoptic bronchoscopy (FFB). Associated disorders included congenital respiratory anomalies, a variety of anatomic obstructions of the upper and lower airways, and aspiration disorders. Mean age for isolated laryngomalacia (type 1) was 11.5 weeks (range, 5 weeks to 4 months) while children with laryngomalacia and associated respiratory disorders (type 2) had a mean age of 9.06 years (range, 6 weeks to 18 years). We conclude the following: (1) complete evaluation of the pediatric airways (bronchoscopy) is recommended in every symptomatic child with diagnosis of laryngomalacia confirmed by laryngoscopy; (2) type 1 laryngomalacia was more common in early infancy while type 2 laryngomalacia was associated with older age; (3) although type 2 laryngomalacia is the most common endoscopic diagnosis in our experience, the majority of cases were associated with lower airway dysfunction. ",22 2681,"Anaphylaxis to grand keyhole limpet (abalone-like shellfish) and abalone. We report five patients who developed moderate to severe anaphylactic reactions induced by the ingestion of grand keyhole limpet (GKL) and abalone. Specific IgE-mediated hypersensitivity to these shellfish was demonstrated by history, prick skin test, and RAST. RAST inhibition technique revealed the cross-antigenicity between GKL, abalone, and keyhole limpet hemocyanin. ",19 2083,"Aspirin in the primary prevention of angina pectoris in a randomized trial of United States physicians. PURPOSE: The objective of this study was to examine the effect of low-dose aspirin (325 mg on alternate days) on the primary prevention of angina pectoris in the United States Physicians' Health Study. Despite a postulated role of platelets in atherogenesis and myocardial ischemia, the effect of chronic platelet inhibition on the development of clinical angina pectoris is unknown. SUBJECTS AND METHODS: The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial among 22,071 male physicians aged 40 to 84 years, free from previous myocardial infarction, stroke, and transient cerebral ischemia at entry, and followed for an average of 60.2 months. The 21,738 physicians who were also free from angina pectoris at baseline constituted the study population for the present analyses. RESULTS: During 106,652 person-years of follow-up, 331 patients with confirmed angina pectoris were diagnosed, 194 of whom underwent a coronary revascularization procedure (coronary artery bypass graft surgery or coronary angioplasty). As compared to participants assigned placebo, the relative risk of confirmed angina pectoris in the aspirin group was 1.10 (95% confidence interval [CI], 0.88 to 1.38). For coronary revascularization, the relative risk was 1.19 (95% CI, 0.88 to 1.59). After simultaneous control for other coronary risk factors in a proportional-hazards model, these relative risks remained near unity at 1.07 (95% CI, 0.84 to 1.36) and 1.11 (95% CI, 0.81 to 1.52), respectively. When the risks of angina pectoris were examined according to year of randomization in the trial, there was no pattern of increasing benefit with longer duration of treatment. CONCLUSION: These randomized trial data indicate that chronic platelet inhibition with low-dose aspirin for an average duration of 60.2 months does not reduce the incidence of angina pectoris. ",13 1649,"Anatomic correlations of the long-axis views in biplane transesophageal echocardiography. The number of views obtainable during transesophageal echocardiography (TE) has been limited by the fixed position of the transducer at the end of the probe. This has confined standard TE studies to short-axis tomography of the heart and aorta. Recently, a biplane TE probe has become available that is capable of both long- and short-axis imaging. This study prospectively assessed the application of the long-axis plane of the biplane probe in providing complementary long-axis views in ambulatory patients. Six standard long-axis views could be obtained and were compared with corresponding anatomic sections to illustrate anatomic relations and facilitate structure identification. The long-axis views provide a better appreciation of the 3-dimensional nature of cardiac anatomy and function, especially in demonstrating the relation of vertically aligned structures. ",13 1408,"Continence level following radical prostatectomy. The relationship of the urethral anastomosis and postoperative continence following radical prostatectomy is uncertain. The objective of this study was to determine radiographically the functional level of continence following radical prostatectomy relative to the site of the intraoperative urethral anastomosis. In 8 patients having a radical prostatectomy, an intraoperative hemoclip was placed at the site of the urethral anastomosis and the postoperative functional level of continence was determined using a standing lateral cystogram. The functional level of continence was 9 mm (SD = 3.0) distal to the site of the urethral anastomosis. The level in the urethra that continence occurs may be a function of the intrinsic continence parameters of each individual patient. ",11 1844,"Prostaglandin modulation of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium chloride combined with efferent cardiac sympathetic stimulation in dogs. Prostaglandins inhibit efferent cardiac sympathetic nerve effects by acting at presynaptic sites and may act to suppress some arrhythmias. In the present study, the effects of intravenous administration of prostacyclin (PGI2) and prostaglandin E2 (PGE2) on early afterdepolarizations and ventricular tachycardia induced by cesium chloride (0.5 mmol/liter per kg body weight intravenously) combined with stimulation of bilateral ansae subclaviae in anesthetized dogs were examined. The right atrium was paced at a constant cycle length of 600 ms. A left ventricular endocardial monophasic action potential catheter was used to detect early afterdepolarizations. Prostacyclin (0.2 microgram/kg per min) reduced the amplitude of the early afterdepolarizations (39.2 +/- 8.4% of the monophasic action potential amplitude during control study to 28.7 +/- 5.5%, n = 10; p less than 0.001) as well as the prevalence of ventricular tachycardia (11 of 14 dogs during control study to 5 of 14 dogs; p = 0.031). Prostaglandin E2 (0.2 to 0.6 microgram/kg per min) did not significantly reduce the early afterdepolarization amplitude (34.7 +/- 8.9% to 25.1 +/- 10.7%, n = 8; p = 0.085) or the prevalence of ventricular tachycardia (8 of 10 versus 6 of 10 dogs; p = 0.50). Alpha- and beta-adrenoceptor blockade with combined intravenous administration of propranolol (0.5 mg/kg) and phentolamine (0.3 mg/kg) decreased the amplitude of the early afterdepolarizations induced by cesium chloride and bilateral ansae subclaviae stimulation from 38.6 +/- 11.2% to 18.8 +/- 3.3% (n = 6; p = 0.005). Additional administration of PGI2 further reduced the early afterdepolarization amplitude from 18.8 +/- 3.3% to 9.8 +/- 4.8% (n = 6; p = 0.001). ",13 1111,"Parathyroid hormone-related peptide in lactation and in umbilical cord blood. Parathyroid hormone-related peptide (PTHrP) is expressed in lactating rat mammary glands after suckling, as a result of increases in prolactin rather than suckling per se. In addition, PTHrP produced in the fetal parathyroid glands and placenta may be responsible for stimulation of placental calcium transport. In the current study, we used a radioimmunoassay for human PTHrP to measure levels of the peptide in (1) human breast milk, cow's milk, and two infant formulas; (2) sequential plasma samples in prepartum and postpartum lactating women; (3) women with pathologic hyperprolactinemia; and (4) human umbilical cord blood. In normal subjects, plasma PTHrP levels ranged from less than 2 to 5 pmol/liter. In contrast, human breast milk contained substantially increased levels of immunoreactive PTHrP. Similar elevations were found in cow's milk and in one infant formula. Column chromatography of breast milk demonstrated that PTHrP immunoreactivity included a region of adenylate cyclase stimulating activity, consistent with the presence of biologically active PTHrP. Plasma prepartum PTHrP values did not differ from corresponding postpartum values in lactating women. Women with hyperprolactinemia had a mean plasma PTHrP value in the high-normal range. Umbilical cord blood had considerably suppressed parathyroid hormone values but PTHrP levels that were indistinguishable from those in normal human plasma. Thus, PTHrP is present in high concentrations in breast milk but apparently does not gain access to the maternal circulation in significant amounts. In addition, women with pathologic hyperprolactinemia seem not to have increased levels of circulating PTHrP. ",9 210,"Malignant melanoma and pigmented lesions: a diagnostic and management dilemma. We document two cases of malignancy occurring at the site of partially removed benign nevi. Because of the difficulty in clinical diagnosis and the uncertainty in its behavior, we propose that any recurring melanocytic nevus expanding beyond the original surgical scar be re-excised and the specimen carefully analyzed to ensure complete removal. ",3 3020,"Lesions in side branches of arteries having undergone percutaneous transluminal coronary angioplasty: a histopathologic study. Percutaneous transluminal coronary angioplasty (PTCA) may cause occlusion in side branches. No histologic studies, however, have been made on side branches of the arteries in which PTCA has been performed. A histologic study was therefore made to explain the effect of PTCA on side branches. Histologic specimens were prepared by serial step sectioning from 15 side branches of 10 autopsied cases that had undergone PTCA. The results of examination by light microscope were as follows: (1) Stenoses due to PTCA were seen in seven branches (46.7%). (2) The stenoses were classified into three types: (a) stenosis due to blocking of the orifice of a side branch by the disrupted portion of the intima of the main artery (one branch); (b) stenosis due to medial dissection of the main artery or further dissection occurring even in the side branches (three branches); and (c) stenosis due to fragmentation of the internal elastic lamina of the main artery accompanied by proliferation of smooth muscle cells even in the side branch (three branches). It is now clear that stenosis is caused in side branches long after PTCA. Extra care is required when major side branches exist in the portion where this procedure is to be performed. ",22 2688,"Late pulmonary allergic responses in actively but not passively IgE-sensitized rats. Previous studies suggested that although rats that were passively sensitized [monoclonal murine immunoglobulin E (IgE)] would respond to pulmonary antigen challenge with an immediate increase in resistance, they exhibited no late increases in resistance, unlike late changes in rats actively sensitized to preferentially produce IgE antibody. We hypothesized that passively sensitized rats also would not develop antigen-induced pulmonary inflammation. In a blinded protocol we compared immediate responses and pulmonary resistance and inflammation at 8, 19 and 24 h after challenge with placebo antigen, with dinitrophenol-bovine serum albumin (DNP-BSA) to elicit a passively sensitized response, or with ovalbumin (OA) to elicit an actively sensitized response. Despite similar immediate responses to OA and DNP-BSA, only the rats challenged with OA had marked inflammatory changes and a significant incidence of late elevations in resistance. Inflammation scores and lung resistance were significantly correlated only in the OA group. We also observed that anesthesia with fentanyl/droperidol significantly attenuated the immediate but not the late responses to antigen challenge, compared with rats anesthetized with ketamine. We conclude that IgE-mediated immediate responses to pulmonary antigen challenge are insufficient, and may be unnecessary, to initiate antigen-induced late inflammatory changes. ",19 1863,"Renal autotransplantation in children: a successful treatment for renovascular hypertension. Renovascular hypertension in children is not a common disease. With improved surgical technique the incidence of nephrectomy has decreased and renovascular reconstruction is currently the preferred method to manage this entity. Between 1977 and 1988, 21 patients with renovascular hypertension were treated at our hospital: 7 patients 6 to 16 years old underwent renal autotransplantation. Of the children 4 had unilateral and 3 had bilateral disease requiring bilateral autotransplantation. Autotransplantation was performed by anastomosis of each renal artery end-to-side to the common iliac artery. The renal veins were anastomosed end-to-side to the common iliac veins. The ureters were left intact in all but 1 patient who required a bench operation. Of the 4 patients who had a unilateral procedure 3 are cured and 1 is improved with a normal blood pressure on a small dose of antihypertensive medication. The 3 patients with bilateral autotransplants are cured. These results, with normalization of the blood pressure in 86% of the patients and improvement in blood pressure in 14% with a patency rate of 87%, are similar to other reported reconstructive modalities in children. ",13 2807,"The physician's role. Physicians can play an important role in society's response to alcohol problems. In diagnosis, alcohol problems among patients are frequently overlooked. Physicians should routinely ask patients about alcohol intake. In light of evidence on the effectiveness of brief interventions, especially with heavy-drinking but nondependent patients, physicians' treatment efforts should be focused in this direction. Patients who are alcohol dependent might best be treated by nonphysicians. Research contributions of physicians should be concentrated on topics for which physician input is needed: longitudinal studies of health consequences, factors contributing to mortality and health service costs, biochemical markers of alcohol use and basic pharmacology. Strong evidence links population alcohol consumption levels to overall harm. Therefore, prevention efforts should be aimed at the population as well as at people who may be at risk. Physicians can contribute to these efforts by influencing public policy and by setting healthy examples in their own alcohol use. ",20 2614,"Immunoblot analysis of sera from patients with allergic bronchopulmonary aspergillosis: correlation with disease activity. Immunoblot analysis was used to evaluate the IgG, IgE, and IgA responses to Aspergillus fumigatus antigen with the sera of five patients with allergic bronchopulmonary aspergillosis (ABPA) before, during, and after suspected exacerbation of their disease. The results revealed a heterogenous antibody response, unique for each patient, to specific Aspergillus fumigatus antigens that correlated with the molecular weights of previously well-characterized antigens of importance in the immunopathogenesis of ABPA. A rating scale was devised for measuring band intensity that allowed the patient's antibody responses to be reproducibly semiquantitated. Immunoblot analysis demonstrated qualitative and semiquantitative information that is not available with other in vitro assays used in the study of patients with ABPA, such as ELISA. These initial results emphasize the need for additional evaluation of this technique to assess its potential clinical application in this disease. ",19 2016,"Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster. The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology. ",13 3240,"Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias. Although work on class III antiarrhythmics remains at an early stage, these agents still appear to possess greater efficacy and less proarrhythmia than conventional class I agents in those experimental arrhythmia models considered to be most representative of the clinical situation. Although prolongation of repolarization carries with its own tendency for pause-dependent arrhythmogenesis (i.e., torsade de pointes), available data suggest that this may be a function of nonspecificity in potassium channel block rather than a general characteristic of class III activity. The availability of new and more selective blockers of specific cardiac potassium channels under development as class III agents have already helped to clarify basic questions about the ionic mechanism of repolarization in the heart, and one hopes that a growing clinical data base will eventually determine the relative safety and efficacy of these agents in preventing symptomatic and life-threatening arrhythmias. ",22 1535,"Expression of rat prolactin-like protein B in deciduoma of pseudopregnant rat and in decidua during early pregnancy. The rat PRL-like protein-B (rPLP-B) complementary DNA (cDNA), originally cloned from a late term placental library, hybridizes to transcripts in the deciduoma tissue artificially produced in pseudopregnant rats. The expression of rPLP-B in deciduoma is first observed 48 h (pseudopregnancy day 7) after the deciduogenic stimulus and increases to a maximum by 96-120 h (pseudopregnancy day 9-10). In situ hybridization studies show that rPLP-B hybridizes specifically to the antimesometrial cells of deciduoma tissue in day 9 pseudopregnant rats and to the homologous cells of the decidua that surround the embryo-trophoblastic structure at day 9 of pregnancy. A temporal study on the expression of rPLP-B during pregnancy shows that rPLP-B is concomitantly expressed by the decidual cells of maternal origin and the cytotrophoblast of fetal origin around day 13 of pregnancy. ",12 1887,"Protein phosphorylation during ischemia. Many investigations have shown that calcium and adenosine triphosphate are crucial to central nervous system functions. It is probable that alterations of these substances during central nervous system ischemia are involved in the processes that cause irreversible neural damage. Calcium regulates several protein kinases that are responsible for phosphorylation of proteins vital for many central nervous system functions. Using a rabbit spinal cord ischemia model, we found protein kinase C and calcium/calmodulin-dependent kinase were severely affected during the first hour of ischemia. Protein kinase A was not significantly affected. The time course of lost protein kinase C enzyme activity closely corresponded to irreversible loss of neurologic function, and there is evidence that protein kinase C inhibitor activity is generated. Also, drugs that inhibit protein kinase C increased neurologic damage when administered during the early phases of ischemia. These results suggest that protein phosphorylation, particularly by protein kinase C, is critical to maintenance of neurologic function. ",13 250,"An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. Glutathione S-transferases (GSTs), a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents, can be separated by biochemical and immunologic characteristics into three distinct classes named alpha, mu, and pi. Previous studies have indicated that there is marked heterogeneity in the expression of different GST isoenzymes in different normal and malignant tissues. To better understand the regulation of the human pi class glutathione S-transferase isoenzyme (GST-pi), the tissue distribution of this protein wa studied by an immunohistochemical technique using an anti-GST-pi polyclonal antibody in normal paraffin-embedded human tissues. These studies indicate that there is a broad distribution of GST-pi in normal human tissues and establish a precise localization within the different organs studied. GST-pi was expressed predominantly in normal epithelial cells of the urinary, digestive, and respiratory tracts, suggesting a possible role for GST-pi in detoxication and elimination of toxic substances. Previous studies have indicated that GST-pi and the putative drug efflux pump P-glycoprotein are both overexpressed in multidrug-resistant human breast cancer cells and in xenobiotic resistant preneoplastic rat hyperplastic liver nodules. Results from this study indicate that there are also similarities between the normal tissue distribution GST-pi and that previously reported for mammalian P-glycoprotein, particularly in secretory epithelia. This finding suggests that these two gene products, which have been implicated in the development of resistance to cytotoxic drugs, may be coregulated in normal and malignant cells. ",3 1928,"Developing improved observational methods for evaluating therapeutic effectiveness. Therapeutic efficacy is often studied with observational surveys of patients whose treatments were selected nonexperimentally. The results of these surveys are distrusted because of the fear that biased results occur in the absence of experimental principles, particularly randomization. The purpose of the current study was to develop and validate improved observational study designs by incorporating many of the design principles and patient assembly procedures of the randomized trial. The specific topic investigated was the prophylactic effectiveness of beta-blocker therapy after an acute myocardial infarction. To accomplish the research objective, three sets of data were compared. First, we developed a restricted cohort based on the eligibility criteria of the randomized clinical trial; second, we assembled an expanded cohort using the same design principles except for not restricting patient eligibility; and third, we used the data from the Beta Blocker Heart Attack Trial (BHAT), whose results served as the gold standard for comparison. In this research, the treatment difference in death rates for the restricted cohort and the BHAT trial was nearly identical. In contrast, the expanded cohort had a larger treatment difference than was observed in the BHAT trial. We also noted the important and largely neglected role that eligibility criteria may play in ensuring the validity of treatment comparisons and study outcomes. The new methodologic strategies we developed may improve the quality of observational studies and may be useful in assessing the efficacy of the many medical/surgical therapies that cannot be tested with randomized clinical trials. ",13 566,"Pedunculated giant lipoma of the esophagus. A patient with a giant lipoma of the esophagus presented with progressive dysphagia and odynophagia, fever, and recurrent melena. Two years previously, when the symptoms were less pronounced, it had been misdiagnosed as achalasia. After surgical removal of the lipoma, the patient became symptom free. ",3 1467,"The effect of maternal ethanol infusion on placental blood flow and fetal glucose metabolism in sheep. Intravenous infusion of 1 g ethanol/min over 1 hr to seven catheterised pregnant ewes decreased blood flow on both sides of the placenta. The reductions in blood flow were maintained for at least 2 hr after the infusion of ethanol had ceased. Although blood flow was reduced, fetal blood gases were unchanged. Plasma glucose concentrations were unchanged by ethanol, but fetal glucose supply and consumption were both decreased following maternal ethanol infusions. If maintained by chronic alcohol consumption these changes could contribute to the growth retardation seen in the Fetal Alcohol Syndrome. ",12 3039,"Percutaneous pedestal in cochlear implantation. Direct electrical connection between an external sound-processing device and intracochlear electrodes is accomplished via a percutaneous pedestal. Patient pedestal complaints and experience have been recorded. Pedestal problems have been classified into six classes, with class 0 indicating no problems and the severity of problem increasing in classes 1 through 4. Class 5 indicates pedestal trauma. No class 5 problems were encountered. At 48 months of experience, 53% of patients were class 0 and 26% were class 1. The pedestal experience is detailed in the paper. The percutaneous pedestal has been found to be a well-tolerated, efficient system for information transfer in cochlear implant patients. ",22 932,"Effect of fasting on the lung glutathione redox cycle in air- and oxygen-exposed mice: beneficial effects of sugar. Fasting increases susceptibility to hyperoxic lung damage in mice, at least in part, by decreasing lung glutathione level. To determine whether fasting alters other components of the glutathione redox cycle, and whether a diet of sugar alone reverses fasting's effects, normally fed, sugar-fed, and fasted mice were exposed to room air or 100% oxygen for up to 4 days. In air-exposed mice, fasting decreased glutathione peroxidase (GP) and glutathione reductase (GR) activities 15% to 20% on days 3 and 4 (p less than 0.01) and glutathione level 25% to 30% on days 2 to 4 (p less than 0.05). When corrected for protein concentration, GP and GR values were similar to those in the fed mice, but glutathione levels remained lower on days 2 and 3 (p less than 0.05). Oxidized glutathione (GSSG) was unchanged, but the ratio of GSSG to total glutathione (reduced glutathione plus GSSG) increased on day 2 (p less than 0.05). In oxygen-exposed fed mice, GP increased 62% and GR increased 39% on day 4 (p less than 0.05), the time when the lung injury was most severe; glutathione increased 30% on days 3 and 4 (p less than 0.05); and GSSG increased threefold and eightfold on days 3 and 4 (p less than 0.01). Oxygen-exposed fasted mice were all dead by day 3 (versus no deaths in the fed mice), failed to increase GR and total glutathione in response to the oxidant stress, and increased GP and GSSG on day 3 to the same extent as the fed mice did on day 4. ",7 2697,"The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air BACKGROUND. The enzyme 5-lipoxygenase catalyzes the metabolism of arachidonic acid to form products that have been implicated in the airway obstruction of asthma. We hypothesized that if products of the 5-lipoxygenase pathway are important in mediating this obstruction, then prevention of their formation should decrease the severity of an induced asthmatic response. METHODS. In a randomized, double-blind, placebo-controlled, crossover study, we examined the effect of A-64077, a 5-lipoxygenase inhibitor, on the bronchoconstriction induced by hyperventilation of cold, dry air in 13 patients with asthma. The completeness of 5-lipoxygenase inhibition was confirmed by examining the profile of eicosanoids produced in whole blood ex vivo after activation with the calcium ionophore A-23187. RESULTS. A-64077 decreased the mean (+/- SEM) ionophore-induced synthesis of leukotriene B4, a 5-lipoxygenase product, by 74 percent (from 265.3 +/- 30.3 to 69.5 +/- 21.5 ng per milliliter, P less than 0.001), but it did not affect the ionophore-induced synthesis of thromboxane B2, a cyclooxygenase metabolite of arachidonic acid (80.0 +/- 17.1 ng per milliliter before A-64077 vs. 75.8 +/- 14.3 ng per milliliter after A-64077). In concert with the selective inhibition of 5-lipoxygenase by A-64077, the amount of cold, dry air (expressed as respiratory heat exchange) required to reduce the forced expiratory volume in one second by 10 percent was increased by 47 percent after A-64077 (3.0 kJ per minute for placebo vs. 4.4 kJ per minute for A-64077, P less than 0.002). Similar results were obtained when minute ventilation was used as an indicator of outcome (27.5 liters per minute for placebo vs. 39.8 liters per minute for A-64077, P less than 0.005). CONCLUSIONS. Selective inhibition of 5-lipoxygenase by A-64077 is associated with a significant amelioration of the asthmatic response to cold, dry air, suggesting that 5-lipoxygenase products are involved in this response. This approach may be useful in the treatment of asthma. ",19 1050,"More than one mutant allele causes infantile Tay-Sachs disease in French-Canadians. Two Tay-Sachs disease (TSD) patients of French-Canadian origin were shown by Myerowitz and Hogikyan to be homozygous for a 7.6-kb deletion mutation at the 5' end of the hexosaminidase A alpha-subunit gene. In order to determine whether all French-Canadian TSD patients were homozygotes for the deletion allele and to assess the geographic origins of TSD in this population, we ascertained 12 TSD families of French-Canadian origin and screened for occurrence of mutations associated with infantile TSD. DNA samples were obtained from 12 French-Canadian TSD families. Samples were analyzed using polymerase-chain-reaction (PCR) amplification followed by hybridization to allele-specific oligonucleotides (ASO) or by restriction analysis of PCR products. In some cases Southern analysis of genomic DNA was performed. Eighteen of the 22 independently segregating mutant chromosomes in this sample carried the 7.6-kb deletion mutation at the 5' end of the gene. One chromosome carried the 4-nucleotide insertion in exon 11 (a ""Jewish"" mutation). In this population no individuals were detected who had the substitution at the splice junction of exon 12 previously identified in Ashkenazi Jews. One chromosome carried an undescribed B1 mutation; this allele came from a parent of non-French-Canadian origin. Patients in three families carried TSD alleles different from any of the above mutations. The 5' deletion mutation clusters in persons originating in southeastern Quebec (Gaspe) and adjacent counties of northern New Brunswick. ",9 1665,"Technetium-99m sestamibi in chronic coronary artery disease: the European experience. Since the introduction of technetium-99m methoxy-isobutyl isonitrile (Tc-99m sestamibi) in Europe, there has been a growing interest in its use. Several European multicenter trials have been conducted to evaluate this new agent in relation to the traditional perfusion marker thallium-201, and other studies are in progress to understand the use of this perfusion marker for the diagnosis of coronary disease, for use in conjunction with pharmacologic vasodilation, for use in the assessment of ventricular function and wall motion and for the assessment of interventions. ",13 435,"Successful Fontan-type operation for a nonresectable right ventricular tumor. A large intracavitary right ventricular tumor in a 24-year-old patient was considered nonresectable because it involved the interventricular septum, the free ventricular walls, and the tricuspid valve. Surgical palliation consisted of closure of the tricuspid and pulmonary valves, and the right atrium was anastomosed to the pulmonary artery bifurcation. The patient is asymptomatic 7 years after operation, and the neoplasm (a rhabdomyoma) has not increased in size. ",3 1918,"Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease. Fish oil has consistently been shown to lower triglyceride levels, but its effects on low-density lipoprotein (LDL) cholesterol remain controversial. The current study compares the long-term effects of 2 different fish oil preparations (ethyl ester and triglyceride) versus olive oil in patients with coronary artery disease. Eighty-nine subjects were randomly assigned to receive capsules containing 6 g/day (triglyceride group) or 7 g/day (ethyl ester group) of n-3 fatty acids, or capsules containing 12 g/day of olive oil for 6 months. Mean triglyceride levels decreased by 28% in the ester and 32% in the triglyceride fish oil groups (p less than 0.05 for both). LDL cholesterol levels increased by 3% (difference not significant) in the ester and 12% (p less than 0.05) in the triglyceride fish oil groups; in hypertriglyceridemic subjects the increase was 23% (p less than 0.01) and 14% (difference not significant), respectively. Plasma phospholipid fatty acid analysis showed a fivefold increase in eicosapentaenoic acid levels in both fish oil groups (p less than 0.001), and a long-term decrease in arachidonic acid levels (p less than 0.001). Achieved eicosapentaenoic acid level correlated with the degree of increase in LDL cholesterol (r = 0.38, p less than 0.05). These data suggest that fish oil administration is associated with an increase in LDL cholesterol levels in a diverse group of patients with coronary artery disease; this change appears to be correlated with n-3 fatty acid absorption. The impact of this increase in LDL is unknown, but should be considered as potentially adverse. ",13 1052,"A discriminant validity study of negative symptoms with a special focus on depression and antipsychotic medication. If the construct validity of the negative symptom syndrome is to be established, the conceptual and operational overlap between negative symptoms and other syndromes such as depression and the effects of medication must be explained. The author assessed 26 patients with schizophrenia and 21 patients without schizophrenia, most of whom had depression, at the end of an average 2-week drug washout period and after approximately 2 months of psychotropic medication administration. Negative symptoms were remarkably consistent in patients with schizophrenia despite pharmacological intervention. In contrast, the patients without schizophrenia manifested significant decreases in negative symptoms. ",9 628,"The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador. BACKGROUND AND METHODS. Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism. RESULTS. Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients' heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 micrograms per liter) and normal to moderately elevated in the adults. The serum level of growth hormone-binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low--less than or equal to 7 micrograms per liter in the children and less than or equal to 66 micrograms per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone-dependent IGF-binding protein-3 were also low. CONCLUSIONS. We describe an inbred population with a high incidence of growth hormone-receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males. ",4 1621,"Two cases of spontaneous internal carotid artery occlusion due to giant intracranial carotid artery aneurysm. Although spontaneous thrombosis of a giant intracranial aneurysm is relatively common, occlusion of its parent artery is rare. We describe two recent patients in whom the parent artery spontaneously occluded. One patient had severe stenosis of the left internal carotid artery, with delayed appearance of a faint shadow of vascular widening near the posterior clinoid process. One month later, complete occlusion of the left internal carotid artery was shown angiographically. The second patient had dysarthria and left hemiparesis, resulting in the diagnosis of a left internal carotid artery giant aneurysm. He had suffered an episode of visual disturbance of the right eye 5 years before. Angiography showed the right cervical internal carotid artery to be occluded. We believe the mechanism of parent artery occlusion in our two patients to be due first to stretching of the internal carotid artery by the enlarged aneurysm, followed by compression of the internal carotid artery by the aneurysm itself. Next, the anterior clinoid process and the optic nerve are involved, and, finally, thrombosis of the aneurysmal cavity extends into the internal carotid artery itself. ",13 445,"Reliability of colposcopy and directed punch biopsy A group of 118 women underwent laser cone biopsy. Data were collected routinely on proforma case notes and entered into a computerized database. The histology of the cone biopsies was compared with that of previous, colposcopically directed punch biopsies, with the cytology of smears taken in the clinic and with the colposcopic diagnosis. The punch biopsy had a 54% false negative rate and neither of the two microinvasive carcinomas biopsied in this way were detected by the biopsy. Ten of 24 women with negative punch biopsies had CIN III in the cone. When the punch biopsy showed CIN II or worse, the cone biopsy confirmed the presence of CIN in 86%. There was some evidence of false negative cone biopsies. The data suggest that management should not be based solely upon the punch biopsy result but should include consideration of the cytology and colposcopy findings. Excisional methods of treatment are more likely to reveal early invasion and adenocarcinoma-in-situ. ",3 2318,"Functional studies of soluble low-affinity interleukin-2 receptors in rheumatoid synovial fluid. Since abnormal regulation of interleukin-2 (IL-2) has been demonstrated in rheumatoid arthritis (RA), the functional role of low-affinity soluble IL-2 receptors (sIL-2R) purified from RA synovial fluids (SF) was studied. Picomolar levels of sIL-2R were detected in RA SF using an enzyme-linked immunosorbent assay. Levels were higher in serum and SF from RA patients than in controls (P less than 0.001) and higher in RA SF than in paired RA serum (P less than 0.01). Soluble IL-2R from RA SF had estimated molecular weights of 40-50 kd and 80-100 kd by gel filtration analysis. The 80-100-kd peak is likely to be a dimer of the 40-50-kd peak, since a single 45-kd peak was found after elution from sodium dodecyl sulfate-polyacrylamide gels. Since inhibitory activity for lymphocyte proliferation was found in the 80-100-kd range, the sIL-2R were purified with an anti-CD25 affinity column and further analyzed. The purified fractions did not interfere with the proliferation of mitogen-stimulated lymphocytes or with the binding of radiolabeled IL-2 to CTLL-2 cells, although direct binding of IL-2 was demonstrated. The affinity of sIL-2R from RA SF for binding IL-2 was in the range of 25 nM, which is similar to the affinity of sIL-2R purified from a human T cell clone, indicating that both sIL-2R are low-affinity receptors for IL-2. We conclude that the concentration and binding affinity of low-affinity sIL-2R purified from RA SF render them unable to interfere with IL-2-related activities. ",16 2730,"Defective expression of p70/75 interleukin 2 receptor in T cells from patients with systemic lupus erythematosus: a possible defect in the process of increased intracellular calcium leading to p70/75 expression. Phytohemagglutinin (PHA) stimulated T cells from patients with systemic lupus erythematosus (SLE) showed hyporesponsiveness to interleukin 2 (IL-2) and expressed less p70/75 IL-2R than healthy controls. Ionomycine (IM, calcium ionophore) which selectively upregulated p70/75 expression, induced less p70/75 in patients with SLE than in healthy controls. However, intracellular calcium levels of T cells from patients with SLE increased as much as those from healthy controls, when T cells were stimulated by IM or PHA. Our results suggest that an impaired expression of p70/75 IL-2R in T cells from patients with SLE is not due to a defective calcium influx but to the events after the rise of calcium levels. ",19 1614,"Percutaneous transluminal angioplasty of crural arteries. The authors dilated 103 stenosed crural arteries in 71 patients. Primary success was defined as traversing and reducing the lesion to a residual stenosis of less than 30%. This was achieved in 96% of cases. Complications included one vessel rupture and one occluding intimal flap, which were treated by the vascular surgeon with bypass and venous patch, respectively. One hematoma at the puncture site was treated surgically because of its size. With modern materials such as steerable guide wires and low-profile balloon catheters, dilation of crural arteries has become safe. Until now, the indications for percutaneous transluminal angioplasty (PTA) of crural arteries have been limited to Fontaine stages III and IV disease. The authors believe that the indications for PTA in Fontaine stage IIb disease are justified, especially if intervention improves outflow after a more proximal recanalizing procedure is performed. ",13 3018,"Use of somatostatin for complications occurring after liver transplantation. Somatostatin can be helpful after liver transplantation in some well-defined indications. In uncontrolled digestive haemorrhage, a short course of somatostatin therapy can be of great help in controlling the acute bleeding and to avoid emergency laparotomy. Somatostatin could also be helpful in bilio-pancreato-intestinal fistula, but in this case its advantage over elective surgical treatment remains to be confirmed. ",22 940,"Viral pneumonias. A diagnostic and therapeutic challenge. Viral pneumonias are both a diagnostic and a therapeutic challenge for primary care physicians. The illness should be suspected when an upper respiratory tract infection progresses to include dyspnea and cyanosis. Rapid diagnostic tests are now available to detect most of the viruses that cause pneumonias. Fortunately, viral pneumonias usually resolve without specific antiviral therapy; however, ribavirin is indicated for respiratory syncytial virus pneumonia in children and ganciclovir sodium (Cytovene) for cytomegalovirus pneumonia in immunocompromised patients. Acyclovir (Zovirax) is indicated for pneumonias due to herpes simplex virus and varicella-zoster virus infections. A high index of suspicion for bacterial superinfections is essential to reduce the risk of death from this complication. ",7 2753,"Pneumatic firearm injuries: trivial trauma or perilous pitfalls? This report describes an injury due to a pneumatic firearm. Though powder firearm injuries are generally considered serious, pneumatic weapon injuries are often viewed as minor or insignificant trauma. Children and adolescents primarily wield these weapons contributing to their ""harmless"" aura. However, dramatic increases in muzzle and impact velocities have transformed the newer generation of pneumatic firearms into formidable weapons. Consequently, the literature is replete with increasing incidences of serious injury due to pneumatic weapons. ",20 2291,"Epidermal growth factor/transforming growth factor alpha receptors and psoriasis. The abnormal growth and differentiation in psoriasis is reflected in the abnormal regulation of Epidermal Growth Factor/Transforming Growth Factor Alpha (EGF/TGF alpha) receptor metabolism. In psoriasis and other hyperproliferative skin conditions these receptors are persistently expressed throughout the interfollicular epidermis as long as the growth stimulatory signal persists. One of the first biochemical signs of effective therapy of psoriasis is the return of the EGF/TGF alpha receptor pattern toward the primarily basilar distribution seen in normal human adult skin. Whether the abnormal expression of TGF alpha in the involved skin induces the persistent expression of EGF receptors is not known nor is the signal that causes the increased production of TGF alpha. Studies to determine what factors regulate EGF receptor expression and TGF alpha induction may yield important new insights into the pathogenesis and therapy of psoriasis. ",16 3101,"Antibodies to nuclear lamin C in chronic hepatitis delta virus infection. Sera of patients with chronic hepatitis delta virus infection stained the nuclear periphery in indirect immunofluorescence. Using proteins of isolated nuclei, isolated nuclear matrices, the nuclear pore complex-lamina fraction and purified lamins A and C as antigen source in immunoblotting experiments, nuclear lamin C was identified as the reactive antigen. Most sera tested (8 of 10) recognized nuclear lamin C exclusively, but not the nuclear lamins A and B. Antibodies reacting with both nuclear lamins A and C, which share extensive sequence homologies, have been reported to occur in autoimmune hepatitis and primary biliary cirrhosis. The present findings suggest that the novel autoantibody associated with chronic hepatitis delta virus infection recognizes an epitope localized in the short carboxyterminal region of nuclear lamin C. ",22 2041,"Clinical and electrophysiological characteristics of ventricular tachycardia in children with normal hearts. Characteristics of 18 patients with clinical ventricular tachycardia (VT) and normal hearts documented by physical examination, echocardiography, and angiocardiography were analyzed. There were 13 males and 5 females, aged 1 to 16 years (mean +/- SD, 9.7 +/- 4.8 years). Six patients had hemodynamic instability during VT and the other 12 patients were hemodynamically stable. Two patients (11%) presented with sustained VT and 16 (89%) with episodes of nonsustained VT at varying intervals (3 of 16 with repetitive monomorphic VT). Among 14 patients on whom exercise tests were performed, seven had exercise-induced VT. During electrophysiologic studies, VT was induced in 16 of 18 (89%) (in 13 patients with morphology identical to clinical VT). VT was induced by programmed stimulation (single, double, and burst stimulation of the right atrium or right ventricular apex during sinus rhythm or during pacind for eight beats) in 5 of 18 (28%) patients; with isoproterenol, VT was aggravated spontaneously in 6 of 15 (40%) patients; and during stimulation VT was induced in 8 of 15 (53%) patients. Among patients whose VT was not induced during programmed stimulation, VT was induced with the addition of isoproterenol in 11 of 12 (92%). All 14 patients in follow-up are in stable condition, seven patients with medication and seven without medication. Pediatric patients with normal hearts and clinically detected VT usually have VT induced by programmed stimulation, either with or without isoproterenol stimulation. ",13 2863,"Public support for policy initiatives regulating alcohol use in Minnesota: a multi-community survey. Public support for policies to control alcohol sales and consumption was surveyed in seven Minnesota communities. A total of 438 women and 383 men were asked to indicate their level of support of or opposition to nine different proposals designed to regulate alcohol. There was general support for all policies, which was strongly related to characteristics of respondents and type of policy proposed. Women were significantly more supportive of all items than were men. Marriage, older age and low alcohol consumption were also associated with support. Education and voter status generally were not. Policies and activities that serve primarily to protect youth received the strongest support. Restrictions and prohibitions such as limiting advertisements were less popular. The least support was expressed for increases in taxes on alcohol and for measures that would eliminate an existing practice such as prohibiting wine-cooler sales at convenience stores. The majority of respondents also indicated that they felt the individual, as opposed to the manufacturer or retailer, was responsible for problems associated with alcohol and should be the focus of intervention. Strategies for shifting the focus from the individual to environmental and regulatory control are discussed. ",20 2529,"Short term treatment of acromegaly with the somatostatin analog octreotide: the first double-blind randomized placebo-controlled study on its effects. Several studies suggest that the somatostatin analog octreotide, or SMS 201-995, may effectively reduce GH hypersecretion. However, no double blind, placebo-controlled study has substantiated these findings. We present the results of a randomized double blind 14-day clinical trial with octreotide in 20 patients with acromegaly. The drug was given sc every 8 h and to the initial dose (50 micrograms) was added another 50 micrograms every other day up to 200 micrograms. GH levels, calculated as the mean values of 12 observations at hourly intervals during 0700-1800 h, and insulin-like growth factor-I (IGF-I) levels were significantly reduced during octreotide treatment. Responses varied from a reduction of 97% of the basal mean GH level to no significant reduction in 2 of 10 patients. There was a good correlation between the reduction of GH and IGF-I levels. The main side-effects were gastrointestinal and well tolerated. We found a spontaneous variation of daily mean GH and IGF-I levels (at 0700 h) in the placebo group, ranging from approximately 150% to 50% of the GH and 120% to 80% of the IGF-I levels noted on day 0. In patients treated with octreotide, the occurrence of GH rises between administration times suggests that it may be desirable to give octreotide every 6 h in some patients. ",18 676,"Absorption and motility of the bypassed human ileum. The authors assessed absorption and motility of the human ileum after a prolonged period of disuse. In eight patients with ulcerative colitis, a manometric-catheter assembly was placed via the ileostomy into the unused portion of distal ileum two months after ileal pouch-anal anastomosis and temporary diverting loop ileostomy. The distal ileum was perfused at 5 ml/min with an isosmotic solution of either sodium chloride or ileal chyme diluted with sodium chloride for three hours before and three hours after a meal on two consecutive days. Absorption was measured, single and clustered pressure waves were identified and quantitated with the aid of a computer program, and a motility index was calculated. Mean absorption +/- S.E.M. of both perfusates was poor on day 1 (-10 +/- 2 ml/25 cm x 30 min), and the meal induced no ileal motor response. By day 2, however, absorption of both perfusates was much improved (-1 +/- 2 ml/25 cm x 30 min; P less than 0.05), and the number of discrete clustered contractions and the motility index now clearly increased after the meal (2.6 +/- 0.6 vs. 7.2 +/- 1.0 clustered waves/hr; 7.5 +/- 0.5 vs. 9.7 +/- 0.2 motility units/30 min; P less than 0.05). The conclusion was that absorption and motility of the human ileum were impaired after two months of disuse, but that ileal absorption and motility improved one day after the introduction of isosmotic ileal perfusates. ",5 1333,"Pharmacokinetics of enoxacin and its oxometabolite following intravenous administration to patients with different degrees of renal impairment. Enoxacin is a fluorinated quinolone with potential clinical use in the treatment of serious infections. Twenty-three patients (age, 19 to 87 years) with different degrees of renal function, including a group undergoing chronic hemodialysis, received enoxacin (400 mg) by intravenous infusion (1 h). Blood samples were collected before infusion; at the end of infusion; and at 5, 10, 20, 30, 45, 60, 90, and 120 min and 3, 4, 6, 12, 18, 24, 48, and 72 h after infusion. Enoxacin and oxoenoxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters (mean +/- standard deviation) were calculated by using a noncompartmental PK model according to creatinine clearances (in milliliters per minute). Total clearance of enoxacin decreased from 4.95 +/- 1.16 ml/min per kg in the group with normal creatinine clearance to 0.76 +/- 0.21 ml/min per kg in the patients with severe renal failure (creatinine clearance, less than 15 ml/min), whereas the elimination half-life increased from 4.5 +/- 1.0 to 20 +/- 5 h, respectively. The elimination of oxoenoxacin (the main metabolite of enoxacin) in urine was markedly decreased when creatinine clearance was less than 15 ml/min. Hemodialysis removed an insignificant amount of enoxacin and oxoenoxacin. These data indicate that as creatinine clearance falls below 30 ml/min, the daily enoxacin dose should be reduced by half. During prolonged administration of enoxacin to patients with creatinine clearances of less than 30 ml/min, the accumulation of oxoenoxacin might lead to unexpected side effects. ",11 1941,"Pulmonary hypertension after heparin-protamine: roles of left-sided infusion, histamine, and platelet-activating factor. Severe pulmonary hypertension after protamine neutralization of heparin is an infrequent but life-threatening event following cardiopulmonary bypass. The effect of left ventricular infusion of protamine on pulmonary hypertension as well as a possible role of platelet-activating factor (PAF) or histamine in the heparin-protamine reaction was investigated in 30 pigs in four different groups during general anesthesia. Group 1 animals received 250 IU/kg heparin, followed by 100 mg protamine intravenously after 15 min. In group 2 protamine was infused into the left ventricle. Group 3 animals received the histamine H1- and H2-antagonists clemastine and ranitidine 5 min before protamine infusion. In group 4 the PAF receptor blocker WEB 2086 was given 5 min before protamine. Platelet-activating factor was measured by a bioassay in serum samples of group 1 and group 4 animals. In all four groups protamine caused severe pulmonary hypertension, thromboxane A2 release, and a transient decrease in leukocyte counts. No PAF release was detected after protamine infusion. Neither left ventricular infusion of protamine nor histamine or PAF antagonists prevented or attenuated the reactions after protamine infusion. The authors conclude that left ventricular infusion of protamine provides no protection from pulmonary hypertension, and that histamine and PAF are not involved in the acute pulmonary vasoconstriction after protamine neutralization of heparin. ",13 88,"Dependence of oxygen consumption on oxygen delivery in children with hyperdynamic septic shock and low oxygen extraction. We studied the effect of increasing systemic oxygen delivery (DO2) by packed RBC (PRBC) transfusion on oxygen consumption (VO2) in children with hyperdynamic septic shock. After routine resuscitation with volume loading and pharmacologic support, patients were studied if they had significant derangements of oxygen transport variables defined as: baseline VO2 less than 180 ml/min.m2 and oxygen extraction (O2 extr) less than 24%. Eight studies were performed. PRBC transfusion increased DO2 from 636 +/- 167 to 828 +/- 266 ml/min.m2 (p less than .01) without increasing cardiac index (5.2 +/- 1.3 vs. 5.0 +/- 1.4 L/min.m2). VO2 increased from 112 +/- 36 to 157 +/- 60 ml/min.m2 (p less than .01) while O2 extr was unchanged (18 +/- 3% vs. 19 +/- 6%). Despite initial low O2 extr, VO2 can be increased in pediatric septic shock by a further increase in DO2. Since VO2 correlates with survival, one should consider enhancing DO2 further despite initial low O2 extr and high DO2. Effects on morbidity and mortality require further study. ",0 857,"An esthetic approach to vertical root extrusion in a patient with an anterior open bite: report of case. A previous attempt to locate the root canal system in the maxillary left central incisor with a bur created a perforating root defect at the level of the alveolar crest. The patient received root canal therapy. Next, vertical root extrusion was chosen to expose sound tooth structure apical to the defect so that a crown could be constructed. With an anterior open bite, the natural crown was left intact and it was possible to position the anchor bar in an incisal and lingual position, maintaining esthetics for the patient during both the extrusive and stabilization phases of treatment. ",6 1368,"Effects of intracavernosal trazodone hydrochloride: animal and human studies. Trazodone hydrochloride is an oral antidepressant agent which has been associated with the improvement of erections in impotent men and the development of prolonged erections or priapism in potent men. An in vivo study in animal and human subjects was performed to gain experience with the effect of intracavernosal trazodone. In the anesthetized New Zealand White rabbit, intracavernosal trazodone or its major metabolite m-chlorophenylpiperazine (m-CPP) produced full penile erection in 76% and 84% of animals studied respectively with doses ranging from one to 15 mg. On the other hand, intracavernosal administration of five mg. papaverine resulted in a prolonged erection in 90% of animals studied. In 13 selected volunteer patients, intracavernosal trazodone caused tumescence but not full penile erection with corporal body pressures of 28.2 +/- 5.8 mm. Hg. Intracavernosal papaverine or papaverine and phentolamine in these subjects resulted in significantly higher corporal body pressures of 58 +/- 18 mm. Hg (p less than .05). Intracavernosal administration of alpha adrenoceptor agonists but not normal saline resulted in complete detumescence of trazodone- or m-CPP-induced prolonged erection in the animal studies. Intracavernosal trazodone results in erectile activity that appears in part based on its local alpha blocking activity but like other intracavernosal alpha-blocking agents is not as effective in initiating penile erections as are intracavernosal agents that directly induce smooth muscle relaxation. ",11 1172,"Rett syndrome: findings suggesting axonopathy and mitochondrial abnormalities. We report the histopathologic findings of 3 sural nerve biopsies and 1 muscle biopsy from 3 patients with Rett syndrome. The 3 sural nerve biopsies demonstrated a few ultrastructural abnormalities, including the presence of many Pi-granules and mitochondrial changes in the cytoplasm of Schwann cells, occasional bands of Bungner and onion-bulb formations, and mitochondrial alterations in myelinated axons. Morphometric analysis disclosed reduction in the number of large myelinated fibers with normal densities in comparison to those of an age-matched normal control. Light microscopic examination of the biopsied muscle from a 6-year-old patient with Rett syndrome revealed the existence of many small, dark, angulated fibers with NADH-TR staining. Ultrastructural investigation of the muscle confirmed the presence of the dumbbell-shaped mitochondria. Peripheral nerve involvement and the possibility of mitochondrial abnormalities in Rett syndrome were suggested by the results. ",9 160,"Cisplatin-fluorouracil interaction in a squamous cell carcinoma xenograft. Patients with squamous cell carcinoma of the head and neck are treated with cisplatin and fluorouracil according to a schedule based on the findings of clinical studies. A similar schedule showed a supra-additive effect in the treatment of xenografted human squamous cell carcinoma of the head and neck. We sought to ascertain whether this schedule was optimal. A single intraperitoneal injection of cisplatin (7.5 mg/kg) was combined with three injections of fluorouracil given during a 24-hour period (total dose, 150 or 80 mg/kg) before, during, or after cisplatin administration. The combined effect of cisplatin and fluorouracil on tumor growth and toxic effects was schedule dependent. Consideration of both toxic effects and tumor growth inhibition, as assessed by reduction of the area under the growth curve, the optimal administration interval was found to be fluorouracil given 3 days after cisplatin administration. ",3 2731,"Subtrochanteric fractures. A retrospective analysis. In a retrospective review of 107 patients treated during an eight-year period for subtrochanteric fractures, the average follow-up period was 25.5 months (range, six to 96 months). Comparisons of fracture patterns, fixation devices, and complications of osteosynthesis were made in an attempt to identify fixation devices that are best suited for the treatment of this difficult orthopedic problem. The Seinsheimer system of classification was used, and the fracture at risk was identified. Long spiral fractures with associated butterfly fragments in the osteopenic bone of elderly patients occurred most frequently, with complications of osteosynthesis and inherent instability. Despite the theoretic biomechanical advantages offered by the intramedullary systems, follow-up observations showed better results in patients with treatment by extramedullary devices. ",20 3200,"Surgical staples in cesarean section: a randomized controlled trial. This randomized controlled trial compares the use of the Auto Suture Poly CS 57 disposable surgical stapler (n = 98) with standard hysterectomy (n = 102) in low transverse cesarean sections. Subjective assessment of blood loss by the surgeon resulted in lower mean (+/- SEM) total blood loss estimates in the stapled group (492 +/- 24 ml) than in the nonstapled group (579 +/- 38 ml) (p = 0.05). However, surgeon's estimation of blood loss as a result of the hysterotomy and blood loss estimated by the hemoglobin deficit measured on the second postoperative day did not significantly differ between the two groups. The use of the stapling device tended to lengthen the total operating time, which averaged 42.5 minutes in the group with the staples and 39.2 minutes in the group with the standard hysterotomy (p = 0.05). The risk of febrile morbidity, the frequency of endometritis, and the length of hospitalization were similar in the two groups. Our results do not support the routine use of the Auto Suture Poly CS 57 disposable surgical stapler in low transverse cesarean sections. ",22 598,"Radiographic appearances in lumbar disc prolapse. The pre-operative lumbar spine radiographs of 200 consecutive patients who had undergone discectomy for prolapsed intervertebral disc were reviewed. Prolapse was recognized as bulging or sequestration of the disc with consequent root compromise. Measurement of the lumbar level of the interiliac line was shown to correlate with the level of disc prolapse and the incidence of transitional vertebrae at the lumbosacral junction was significantly higher than normal. A pathological value for the lumbosacral angle could not be identified. ",4 1141,"Pharmacology of recovery after stroke. Laboratory research during the past decade has begun to provide insights into the neurobiologic basis of functional recovery after brain injury. It is clear that drugs influencing specific neurotransmitters also can influence the recovery process. Some of these drugs may be beneficial, but others may be detrimental. Some of the difficulties in interpreting the results of these behavioral studies are reviewed, and potential mechanisms of drug effects are discussed. These types of studies are leading to an increased awareness of the potentially harmful effects of some drugs often given to stroke patients. Pharmacotherapy designed to enhance functional recovery after stroke may be possible in the future. ",9 512,"The cytobrush for evaluating routine cervicovaginal-endocervical smears. While the conventional wooden spatula/cotton-tipped applicator has remained the method of obtaining Papanicolaou smears for most clinicians at the University of California at Los Angeles, the Student Health Service (SHS) adopted the Zelsmyr cytobrush as its sole method of obtaining cervical samples in late 1986. A study was done to define changes in both the adequacy of sampling and the detection rate for both squamous and glandular epithelial abnormalities with the cytobrush. To accomplish this goal, 1,000 cytobrush and 244 conventionally obtained smears were analyzed prospectively, and 3,864 SHS samples obtained in 1986 prior to the change in method were reviewed retrospectively. As compared to cervical samples obtained by conventional methods, the cytobrush smears contained significantly more endocervical cells and had fewer drying artifacts. Both methods obtained equivalent squamous samples and had similar final class distributions. No case of endocervical adenocarcinoma carcinoma in situ or invasive adenocarcinoma was detected. SHS patients who had initial ""no endocervical cells"" samples but whose repeat sample did contain endocervical cells retained the same class in more than 75% of cases. This study confirmed that the cytobrush technique produces Papanicolaou smears with improved sampling of the squamocolumnar junction but questioned whether that results in an increased detection rate for cervical pathology. ",3 4,"Denatured muscle grafts for nerve repair. An experimental model of nerve damage in leprosy About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy. ",0 2009,"Relation between intraventricular pressure and volume in diastole. The pressure-volume curves for 10 patients with various types of heart disease were studied throughout mid to late diastole when both pressure and volume were increasing. The results were used to test a currently held theory that the form of this relation is exponential. It was found that for the patients examined this hypothesis was not valid. ",13 532,"The Patterns of Care Outcome Study for cancer of the uterine cervix. Results of the Second National Practice Survey. This report summarizes the outcome results of the Patterns of Care Study (PCS) of cancer of the uterine cervix from 565 patients treated in 1978. The 5-year survival with no evidence of disease was: Stage I, 74%; Stage II, 56%; and Stage III, 33%. The 5-year local in-field failure rate was: Stage I, 12%, Stage II, 27%; and Stage III, 51%. Extent of parametrial involvement, unilateral versus bilateral, may be important in determining survival and local failure. The four-year actuarial survival was 58% for unilateral involvement versus 47% for bilateral (P = 0.06), and the local failure rate was 32% for unilateral versus 45% for bilateral (P less than 0.05). When analyzed by stage, patients with Stage IIb disease with unilateral parametrial involvement showed a trend toward improved survival and decreased local failure compared with those with bilateral Stage IIb cancers (P = 0.1). The use of intracavitary irradiation significantly improved survival and reduced local failures. Furthermore, the number of intracavitary applications was important. When two or more intracavitary applications were used compared with one application, local in-field failure was significantly reduced, 29% versus 17% at 4 years (P less than 0.001), and four-year survival was improved, 60% versus 73% (P = 0.01). The four-year actuarial rate of major complications depended on the stage: Stage I, 8%; Stage II, 15%; and Stage III, 13%. There was a statistically significant increase in major complications in patients undergoing laparotomy for staging versus no laparotomy 23% versus 11% at 4 years (P less than or equal to 0.01) and a trend toward increased major complications in patients who were thin or had prior abdominal surgery. This study confirmed the stage-dependent outcome of treatment of cancer of the uterine cervix with radiation and indicated that further division of Stage IIb to indicate prognostic significance of unilateral or bilateral parametrial involvement may be warranted. This study also confirmed the importance of intracavitary radiation in optimizing control established by the 1973 PCS. It further suggests that where possible, two intracavitary insertions may yield better results than one insertion. ",3 2966,"Effect of early feeding on the postburn hypermetabolic response in rats. The effect of early enteral feeding on the hypermetabolic response following burn injury in a rat burn model has been investigated. The rates of heat production and partitioned heat loss were determined on the fourteenth postburn day for five treatment groups: I) burn, fed rat chow ad libitum starting 2 hours postburn; II) burn, fed by gastrostomy beginning 2 hours postburn; III) burn, fed by gastrostomy, delayed until 72 hours postburn; IV) controls, fed by gastrostomy 2 hours post anesthesia; and V) controls, fed rat chow ad libitum 2 hours post anesthesia. Gastrostomy feedings delivered 175 kcal/kg.day. The mean rates of heat production and heat loss for the three burn groups did not differ significantly whether rats were fed chow ad libitum, or by gastrostomy early or late. Contrary to previous studies using a guinea pig model, method and timing of feeding in this burned rat model had no significant effect on the postburn increment in the rate of heat loss and the corresponding increment in the rate of heat production. ",20 2218,"Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin The effects on gut blood flow velocities of parenteral indomethacin (0.2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent--or in some cases even retrograde--diastolic flow. In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fall in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7.4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantially less (22% compared with 47%) and later (median time to maximum fall 37.3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus. These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. ",15 48,"Prevalence and diagnosis of Legionella pneumonia: a 3-year prospective study with emphasis on application of urinary antigen detection. During a 3-year period the frequency of legionellosis in hospitalized patients with community-acquired and nosocomial pneumonias was 3.4% (23/684 cases) and 5.9% (33/559), respectively. Of the diagnostic tests evaluated, detection of Legionella pneumophila serogroup 1 antigen in urine had the highest sensitivity, with 86% of culture-proven cases being positive. Sensitivities of serologic tests and examination of respiratory secretions (culture and direct immunofluorescence) were 36% and 26%, respectively. The diagnostic value of serology and of examination of respiratory secretions can be low when specimens are obtained and processed under the typical conditions of hospitalization. Urinary antigen detection represents an important diagnostic addition, and examination of postmortem lung tissue from fatal cases with pneumonia is an important adjunct for estimating the prevalence of legionellosis and for assessing the effectiveness of premortem diagnostic tests. ",0 2655,"The buddy volunteer commitment in AIDS care. Buddy volunteers provide crucial assistance to people with HIV-related illnesses. Based on volunteers' self-administered questionnaires, our study describes the nature of buddy work. Volunteers indicated their satisfaction with both personal performance and buddy program administration. Several factors were associated with volunteer satisfaction. This report is a first attempt to describe this special relationship created in response to the human immunodeficiency virus (HIV) epidemic. ",19 2808,"The role of medical schools in the prevention of alcohol-related problems. There is agreement that physicians can play a major role in the prevention of alcohol problems among their patients and that medical schools should prepare physicians for this role by teaching three major subject areas: knowledge, attitudes and clinical skills. Despite this agreement and the acknowledged high prevalence of alcohol problems in clinical populations, medical school coverage of these problems is not proportional to their importance. Barriers to adequate coverage of alcohol problems are traditional attitudes, confusion as to whether such problems are ""medical"" and lack of adequate faculty role models. These problems could be remedied by encouragement and training of interested faculty members, establishment of substance abuse centres in university medical schools, integration of alcohol-related material with relevant topics in all departments and inclusion of alcohol-related questions on medical qualifying exams. ",20 1944,"Prehospital cardiac arrest: the impact of witnessed collapse and bystander CPR in a metropolitan EMS system with short response times. OBJECTIVE: Numerous studies have shown initiation of bystander CPR to significantly improve survival from prehospital cardiac arrest. However, in emergency medical services (EMS) systems with very short response times, bystander CPR has not been shown to impact outcome. The purpose of this study was to determine the effect of bystander CPR on survival from out-of-hospital cardiac arrest in such a system. DESIGN: Prehospital, hospital, and death certificate data from a medium-sized metropolitan area were retrospectively analyzed for adult, nontraumatic cardiac arrest during a 16-month period. RESULTS: A total of 298 patients met study criteria. One hundred ninety-five arrests (65.4%) were witnessed, and 103 (34.6%) were unwitnessed. Twenty-five witnessed victims (12.8%) were discharged alive, whereas no unwitnessed victims survived (P less than .001). Patients suffering a witnessed episode of ventricular fibrillation/tachycardia (VF/VT) were more likely to survive (21.9%) than were other patients (2.0%, P less than .0001). Among witnessed patients, initiation of bystander CPR was associated with a significant improvement in survival (20.0%) compared with the no-bystander CPR group (9.2%, P less than .05). Bystander CPR was also associated with improved outcome when witnessed patients with successful prehospital resuscitation were evaluated as a group; 18 had bystander CPR, of whom 13 (72.2%) survived compared with only 12 of 38 patients with no bystander CPR (31.6%, P less than .01). CONCLUSION: Our data revealed improved survival rates when bystander CPR was initiated on victims of witnessed cardiac arrest in an EMS system with short response times. ",13 2640,"Cytomegalovirus. An update for primary care physicians. Cytomegalovirus infection is spread in various ways--from mother to fetus or baby, from small children in day-care centers to caregivers and parents, by blood transfusions, by sexual contact. Although the illness is usually inconsequential, congenital infection can have severe consequences, including mental retardation and hearing loss. Dr Bean describes the different aspects of this virus and discusses a promising vaccine that may prevent congenital disease. ",19 137,"An HIV-1 and HIV-2 cross-reactive cytotoxic T-cell epitope. The HLA-B27-restricted HIV gag cytotoxic T-lymphocyte (CTL) epitope, 265-279, is highly conserved amongst HIV-1 isolates, only one, HIV-1ELI, having a single amino acid substitution. Over the same region HIV-2 differs by five amino acids. As a broadly cross-protective AIDS vaccine should protect against infection from all isolates of HIV-1 and HIV-2, we tested CTL specific for the HIV-1 265-279 epitope with peptide analogues from HIV-1ELI, HIV-2 and two simian immunodeficiency virus (SIV) isolates, and with recombinant vaccinia viruses expressing the respective gag genes, to determine whether there was any cross-reactivity for this CTL epitope. CTL from the HIV-1-infected donor could recognize the HIV-1ELI peptide, the HIV-2 peptide and recombinant vaccinia virus-infected target and one of the two SIV peptide-treated targets. Epitopes that exhibit such cross-reactivity may be valuable in vaccine design. ",1 2405,"Effects of lovastatin in diabetic patients treated with chlorpropamide. Patients with non-insulin dependent diabetes mellitus (NIDDM) have a higher risk of atherosclerotic cardiovascular disease than nondiabetic subjects. In seven patients with both hypercholesterolemia and NIDDM controlled by chlorpropamide, lovastatin (20 mg b.i.d. for 6 weeks) lowered low-density lipoprotein cholesterol by 28%, total cholesterol by 24%, and apolipoprotein B by 24%. Lovastatin levels for a 4-hour period (measured as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitory activity) were similar to those measured previously in nondiabetic patients. Lovastatin did not alter chlorpropamide kinetics or glycemic profiles. No patient had an elevation in serum transaminases or creatinine phosphokinase, and no patient had any other laboratory or clinical drug-related adverse experience during the study. Lovastatin was as effective in reducing low-density lipoprotein cholesterol in patients with NIDDM as in nondiabetic subjects. Diabetic control was unaltered, and no evidence of alteration in lovastatin or chlorpropamide blood levels was noted. ",17 3061,"Percutaneous puncture of a nondeflatable coronary artery angioplasty balloon. We report a case in which a balloon catheter became permanently inflated in a coronary artery saphenous vein bypass graft. While still inflated, the balloon was forcibly withdrawn from the graft into the external iliac artery and successfully deflated via percutaneous puncture using a CHIBA needle. ",22 931,"A randomized controlled trial of glucocorticoid prophylaxis against experimental rhinovirus infection. The effects of combined intranasal and systemic glucocorticoid steroids on the local inflammatory response, and symptoms due to experimental rhinovirus infection were studied in 45 adults randomized to prophylaxis with either placebo or steroids. Intranasal beclomethasone (168 micrograms twice a day) was begun 4 days before viral challenge and continued 5 days after challenge. Oral prednisone (30 mg twice daily) was given for 3 days beginning 1 day before challenge. During the first 48 h after viral inoculation, nasal obstruction, nasal mucus weights, and kinin concentrations in nasal lavages were lower in steroid recipients, but subsequent increases in these variables in the steroid group resulted in no significant cumulative differences between treatment groups. These data suggest that steroid prophylaxis may suppress nasal inflammation and cold symptoms during the first 2 days in experimental rhinovirus colds. ",7 1167,"Screening for early dementia using memory complaints from patients and relatives. This study examined whether the subjective impression of memory function might differentiate healthy elderly subjects from patients with memory complaints, and whether memory complaints differed between patients with and without a dementing illness. Both self-assessment and relatives' responses on a new memory questionnaire differentiated patient groups from control subjects. The relatives' form measuring deterioration in memory function over time identified dementing individuals from those with non-dementing causes for their memory complaints. Factor analysis indicated that patients' memory complaints correlated with depression rather than objective memory performance, while relatives' ratings correlated with objective memory scores, not depression. Stepwise discriminant function analyses showed that objective memory testing greatly improved specificity but not sensitivity of the subjective memory questionnaire alone. ",9 714,"Relative frequencies of portosystemic pathways and renal shunt formation through the ""posterior"" gastric vein: portographic study in 460 patients. Percutaneous transhepatic portography was carried out in 460 patients with portal hypertension to study various collateral routes. Besides the left gastric vein, which was the most frequent collateral route and feeder of esophageal varices, a distinct vein located between the left gastric vein and the short gastric vein constituted a major collateral route in 191 patients (42%). In terms of frequency, this vein was more significant than the short gastric (34%) and the paraumbilical vein (24%) as a collateral route. We propose that this previously anonymous vein be called the ""posterior gastric"" vein because it runs posterior to the stomach. This vein also formed a renal shunt, a common cause of encephalopathy, in 43 (23%) of the 191 patients; the relative frequency of renal shunt formation by this vein was significantly greater than that by the left gastric vein (12%) and the short gastric vein (18%). ",5 954,"The penetration of aminoglycosides into the alveolar lining fluid of rats. The effect of airway inflammation. The concentration-time profile of gentamicin and tobramycin in the alveolar lining fluid (ALF) of rats was determined after intravenous bolus injection using bronchoalveolar lavage (BAL). BAL can be used for evaluating the penetration of both aminoglycosides into the ALF if highly sensitive detection methods are used, and an endogenous marker (urea) can be applied to avoid the unpredictable dilutional effect of the lavage procedure. The concentration of gentamicin and tobramycin in ALF reached a peak after 5 and 10 min, respectively, and remained high when plasma concentrations were declining, suggesting an accumulation reservoir in the lung acini. The ratio of the AUC of the concentration-time profile in ALF and plasma was 0.67 and 0.45 for gentamicin and tobramycin, respectively. The penetration of both aminoglycosides into the ALF was significantly higher after induction of airway inflammation by inhalation of endotoxin. The ratio of the AUC in ALF and plasma in the endotoxin-exposed animals was 0.76 and 0.55 for gentamicin and tobramycin, respectively. The ratio of the AUC of the concentration-time profile of gentamicin in ALF to that of tobramycin was 1.27 without inflammation and 1.44 after endotoxin exposure. Thus, both with and without inflammation, gentamicin penetrates better into the ALF than does tobramycin. ",7 1472,"Alterations in phospholipase A2 activity during luteal regression in pseudopregnant and pregnant rats. The activity of phospholipase A2 was measured in microsomes prepared from ovaries of superovulated pseudopregnant rats during spontaneous and prostaglandin F2 alpha-induced regression and during regression in pregnant rats. Microsome samples were incubated at 40 C for 90 min in Tris buffer (pH 8.3) with 1.0 mM CaCl2 added. The substrate, radiolabeled phosphatidylcholine, was incorporated into liposomes. During spontaneous regression, there was a significant 2- to 4-fold increase in phospholipase A2 activity, when compared with levels at mid-pseudopregnancy (days 8-9). This elevation was correlated with a significant decrease in plasma progesterone concentration. On day 6 or 7 of pseudopregnancy, treatment of rats with luteolytic doses of prostaglandin F2 alpha also caused a significant increase in phospholipase A2 activity, which remained elevated throughout the 72-h sampling period. In pregnant rats there was a small but significant rise in phospholipase A2 activity after parturition. These results indicate that the activity of phospholipase A2 increases during luteal regression in pregnant and pseudopregnant rats and that it could be involved in the mechanism that causes the loss in progesterone secretion. ",12 196,"Left ventricular fibroma: echocardiographic diagnosis and successful surgical excision in three cases. The management of three patients with left ventricular fibromas is outlined. All were asymptomatic children. Routine chest radiography suggested cardiac masses. M-mode and two-dimensional echocardiography were valuable adjuncts to conventional angiography in assessing these children. Electrocardiographic changes, present in all cases, were shown to regress postoperatively. We stress the importance of these noninvasive aids in the initial investigation and outline our operative methods of reconstruction. ",3 3070,"Vagal modulation of the rate-dependent properties of the atrioventricular node. Vagal effects on atrioventricular (AV) nodal conduction are accentuated by increases in heart rate. To establish the mechanism of these rate-dependent negative dromotropic actions, we studied the properties governing AV nodal adaptation to changes in heart rate in chloralose-anesthetized dogs in the absence and presence of bilateral cervical vagal nerve stimulation (20 Hz, 0.2 msec). Stimulation protocols were applied to evaluate the contributions of changes in AV nodal recovery, facilitation, and fatigue independently of each other. Vagal stimulation slowed AV nodal recovery in a voltage-dependent way, increasing the time constant of recovery (tau r) from 80 +/- 7 to 194 +/- 16 msec (mean +/- SEM, p less than 0.01) at the highest voltage studied. The facilitating effect of a premature (A2) beat was manifested by a leftward shift of the recovery curve (A3H3 versus H2A3) of a subsequent A3 beat. The magnitude of shift depended on the A1A2 coupling interval and was reduced by vagal stimulation at all A1A2 intervals (maximum shift: control, 63 +/- 12 msec; vagus, 24 +/- 11 msec; p less than 0.01). When recovery and facilitation were kept constant, abrupt increases in AV nodal activation rate caused a slow (tau = 75 beats) increase in AH interval (fatigue). Vagal stimulation increased the magnitude of this process (maximum: control, 11 +/- 2 msec; vagus, 27 +/- 3 msec; p less than 0.001), without altering its time course. At activation rates comparable to sinus rhythm in humans, vagal stimulation at an intermediate voltage increased the AH interval by 25 msec. As heart rate increased, vagally induced changes in dynamic processes amplified AH prolongation up to fivefold at maximum rate. The role of vagal changes in individual functional properties depended on heart rate, but slowing of recovery was the single most important factor, constituting over 50% of overall vagal action at rapid rates. We conclude that vagal stimulation alters the ways in which the AV node responds to changes in activation rate and that at rapid rates most of the negative dromotropic action of the vagus is due to changes in the AV nodal response to tachycardia. Alterations in rate-dependent AV nodal properties are a novel and potentially important mechanism through which interventions may affect AV nodal conduction. ",22 2595,"Effects of GLQ223 on HIV replication in human monocyte/macrophages chronically infected in vitro with HIV. GLQ223 is a formulated version of tricosanthin, a single-chain ribosome-inactivating protein that was shown in earlier studies to inhibit human immunodeficiency virus (HIV) replication in T-lymphoblastoid cells and to decrease HIV p24 levels in HIV-infected monocyte-derived macrophages as measured by flow cytometry. The current studies were performed to test the selectivity of the observed inhibitory effects on HIV replication in chronically infected macrophages infected in vitro. Peripheral blood-derived monocyte/macrophages were infected in vitro and cultivated in suspension for at least two weeks prior to GLQ223 treatment. Anti-HIV effects were quantitated by measurement of cytoplasmic HIV p24, by both enzyme-linked immunosorbent assay (ELISA) and flow cytometry and HIV RNA levels were measured by slot blot analysis. Incorporation of [3H]leucine into trichloroacetic acid- (TCA) precipitable protein was also evaluated as an index of nonspecific inhibitory effects mediated by the compound in infected and uninfected cultures. Five days after a single 3-h treatment with GLQ223 there was a concentration-dependent decrease in all measurable HIV parameters within infected cultures. The anti-HIV effects persisted at least 28 days without evidence for increasing HIV expression. GLQ223 treatment of parallel uninfected macrophage cultures showed no significant inhibition of tritiated leucine uptake. These experiments demonstrate that a single pulsed exposure with GLQ223 of macrophages infected with HIV in vitro caused a sustained, concentration-dependent decrease in both HIV p24 antigen levels as well as HIV RNA without causing measurable toxicity in uninfected cultures. ",19 595,"Mechanism of the pivot shift. The mechanism of the pivot shift was investigated by analysing movements under valgus torque in 29 fresh cadaveric knees. The movements were measured in three dimensions, using biplanar photography, when all the ligaments were intact, and then after the ligaments were sequentially divided. When only the anterior cruciate ligament was sectioned, the pivot shift occurred in seven out of 20 knees examined. In the other 13, though the pivot shift was not observed, an abnormal internal rotation occurred at between 10 degrees and 50 degrees of flexion. Division of the iliotibial tract in addition to division of the anterior cruciate ligament stopped the pivot shift, as the tibia remained internally rotated throughout the range of flexion. The axis of rotation of the pivot shift was located at the medial collateral ligament, which was kept tight by the applied valgus torque. The sudden movement in the pivot shift was caused by a complex interaction between the geometry of the knee and the valgus torque applied. ",4 2398,"Assessment of vitamin A status by a disk applicator for conjunctival impression cytology. Conjunctival impression cytology was performed on 236 Indonesian preschool children, half of whom had mild xerophthalmia and half of whom were age-matched controls. We devised an applicator that applies a paper disk of fixed area to the conjunctiva with even pressure. The disk applicator was used to collect impression cytology specimens from the temporal bulbar conjunctiva of one eye while the original strip technique was used on the other eye. Mean (+/- SD) serum retinol values for children with normal and abnormal discs were 22.0 +/- 8.6 micrograms/dL and 18.0 +/- 7.2 micrograms/dL P less than .0001). Mean serum values for normal and abnormal strips were 21.7 +/- 8.6 micrograms/dL and 19.0 +/- 7.7 micrograms/dL (P less than .03). Specimens obtained with the new disk applicator corresponded more closely with serum vitamin A levels and therefore vitamin A status than those obtained with the traditional strip technique. ",17 405,"Dacron fabric-enveloped hydroxyapatite prosthesis for sternal tumor defect: an autopsy report. A 38-year-old housewife with solitary plasmacytoma of the manubrium who underwent a subtotal sternectomy treated by resection of the lesion is reported. This was followed by replacement with a Dacron fabric-enveloped hydroxyapatite prosthesis. The Dacron fabric was sutured to the surrounding tissues, and then the clavicle was passed through the cylindrical-shaped Dacron fabric to form a sternoclavicular joint capsule. The patient returned to her daily life 3 months after the operation. She had no trouble in her daily living, without any dislocation of the sternoclavicular joints or any displacement of the artificial sternum. The autopsy examination about 1 year after the operation showed that the Dacron fabric enveloping the artificial sternum became stronger with time. The sternoclavicular joint also was stably fixed, and the Dacron fabric fulfilled its function as an artificial articular capsule and biologic fixation of the surrounding supporting tissues. ",3 3321,"Effect of electrocautery on wound healing in midline laparotomy incisions. The effect of electrocautery on midline fascial wound healing was studied in 108 Sprague-Dawley rats. Midline wound tensile strength was significantly reduced in fascia incised with the coagulation current compared with the cutting current or scalpel. In addition, tissue necrosis and inflammation as well as adhesion formation between the incision and abdominal viscera were more extensive in animals with incisions made using coagulation current. The results of the study indicate that the use of electrocautery coagulation current is associated with increased tissue damage and a significant reduction in the tensile strength of healing wounds. The contribution of electrocautery to wound complications in patients needs further evaluation. ",22 2311,"Cutaneous phototoxic occurrences in patients receiving Photofrin. Incidence of cutaneous phototoxic reactions induced by intravenous injection of Photofrin polyporphyrin was assessed in a series of 180 patients (266 injections) undergoing photodynamic therapy (PDT) at Roswell Park Cancer Institute during the period 1986-1989. In addition to the usual verbal questions regarding phototoxic reactions solicited at follow-up, forty-two patients in this group also responded to a written questionnaire designed to solicit answers to specific questions. Photofrin doses ranged from 0.5 to 2.0 mg/kg. Overall, 20-40% of patients reported some type of phototoxic response. ",16 1882,"Deleterious effects of testicular venous occlusion in young rats. To determine the differences between testicular arterial and venous obstruction, the spermatic artery or vein, or both, were occluded for varying periods of time in young rats. Two months later, at the conclusion of the study, the testes were examined. Histologic degeneration after vascular obstruction was graded by a modified Johnsen's tubular biopsy score (TBS). The testicular concentrations of enzymes (lactic dehydrogenase and sorbitol dehydrogenase), known to decrease with testicular injury, were measured. TBS and seminiferous tubule diameter (STD) were found to decrease significantly after two hours of vascular occlusion and were similar regardless of whether the obstruction was produced by occlusion of arterial inflow or venous drainage, or both. Testicular concentration of enzymes decreased significantly after permanent ligation of the spermatic artery and vein, but decreased minimally when the vascular obstruction lasted less than 120 minutes. Testicular injury produced by venous occlusion was equally severe and occurred as rapidly as injury produced by arterial or combined arteriovenous occlusion. No significant injury was noted in the contralateral testes in any group. ",13 975,"Selection and evaluation of recipients for heart-lung and lung transplantation. Heart-lung and lung transplantation is being successfully performed with increasing frequency in patients with end-stage cardiopulmonary and pulmonary disease. Transplantation must now be considered as a therapeutic option in selected patients, and physicians are required to understand the principles involved for determining suitable candidates and operative procedures of choice. Indications, contraindications, and choice of operation with respect to underlying disease are discussed herein, as are methods of evaluation and appropriate timing for transplantation. Special considerations regarding specific patient populations are also addressed. In properly selected patients, heart-lung and lung transplantation provide a viable therapeutic option in those with end-stage disease who are unresponsive to conventional management. ",7 2948,"The asymptomatic patient with suspected myocardial contusion. Diagnostic criteria and guidelines for hospital admission for suspected myocardial contusion (MCC) remain unclear. This study defines and examines the clinical sequelae of patients admitted with a suspicion of MCC. Criteria for observation following isolated, minor blunt chest trauma are suggested. Hospital and trauma registry records of patients admitted over a 33-month period with suspected MCC were reviewed. Conventional evaluation criteria, cardiac-related complications, and associated injuries were analyzed for 524 patients. Twenty-eight cardiac-related complications occurred in 27 of 524 patients (5%). These complications included 23 dysrhythmias, 3 infarctions, and 2 pericardial effusions. There were 23 patients with abnormal admission electrocardiograms and 4 with normal ones. Of the latter, one patient developed dysrhythmia 4 hours after admission, and three had other major multi-system injuries requiring admission to the intensive care unit. The overall incidence of cardiac-related complications in minimally injured patients was 0.1%. There were no complications in patients with isolated chest wall contusions, a normal admission electrocardiogram, and a normal rhythm at 4 hours. There was no significant association between creatine phosphokinase isoenzymes or echocardiogram and cardiac-related complications. The complete absence of significant cardiac sequelae in patients with isolated chest wall contusion, normal admission and 4-hour electrocardiograms, and no other associated major injuries suggests that these patients need not be admitted. ",20 3176,"Percutaneous biliary drainage for high obstruction. PBD is the preferred route of palliative drainage for patients with high biliary obstruction. The frequency of bifurcational obstruction in this setting requires familiarity with drainages from both the right and the left transhepatic approach. The preferred right transhepatic approach is fluoroscopically guided; on the left, ultrasonography is the guidance of choice. Large caliber drainage catheters are required, and dilatation of the necessary transhepatic tracts is extremely painful unless adequate inhalation anesthesia or, preferably, epidural anesthesia, is provided. Long-term biliary drainage requires a choice between internal-external external drainage catheters and endoprostheses that is made by considering the patient's life expectancy and his or her adjustment to a stent extending to the outside. The feasibility of corrective procedures if an internal-external drainage catheter or an endoprosthesis becomes blocked needs to be considered before definitive placement. The interventional radiologist becomes intimately involved in the follow-up care of patients and frequently has to direct appropriate patient evaluation. Familiarity with antibiotic regimens is important. ",22 794,"Sexual and physical abuse in women with functional or organic gastrointestinal disorders. STUDY OBJECTIVES: To determine the prevalence of a history of sexual and physical abuse in women seen in a referral-based gastroenterology practice, to determine whether patients with functional gastrointestinal disorders report greater frequencies of abuse than do patients with organic gastrointestinal diseases, and to determine whether a history of abuse is associated with more symptom reporting and health care utilization. DESIGN: A consecutive sample of women seen in a university-based gastroenterology practice over a 2-month period was asked to complete a brief questionnaire. MEASUREMENTS: The self-administered questionnaire requested information about demographics, symptoms, health care utilization, and history of abuse. Physicians indicated the primary diagnosis for each patient and whether she had ever discussed having been sexually or physically abused. RESULTS: Of 206 patients, 89 (44%) reported a history of sexual or physical abuse in childhood or later in life; all but 1 of the physically abused patients had been sexually abused. Almost one third of the abused patients had never discussed their experiences with anyone; only 17% had informed their doctors. Patients with functional disorders were more likely than those with organic disease diagnoses to report a history of forced intercourse (odds ratio, 2.08; 95% CI, 1.03 to 4.21) and frequent physical abuse (odds ratio, 11.39; CI, 2.22 to 58.48), chronic or recurrent abdominal pain (odds ratio, 2.06; CI, 1.03 to 4.12), and more lifetime surgeries (2.7 compared with 2.0 surgeries; P less than 0.03). Abused patients were more likely than nonabused patients to report pelvic pain (odds ratio, 4.05; CI, 1.41 to 11.69), multiple somatic symptoms (7.1 compared with 5.8 symptoms; P less than 0.001), and more lifetime surgeries (2.8 compared with 2.0 surgeries; P less than 0.01). CONCLUSIONS: We found that a history of sexual and physical abuse is a frequent, yet hidden, experience in women seen in referral-based gastroenterology practice and is particularly common in those with functional gastrointestinal disorders. A history of abuse, regardless of diagnosis, is associated with greater risk for symptom reporting and lifetime surgeries. ",5 1688,"Hypertension: racial differences. Racial differences in the prevalence, course, and pathophysiologic characteristics of hypertension in black and white populations are reviewed. Accumulated epidemiologic data indicate that the prevalence of hypertension among blacks is greater than that among whites in almost all age- and sex-matched groups. Hypertensive blacks have a higher incidence of left ventricular dysfunction, stroke, and renal damage, but a lower incidence of ischemic heart disease, than do hypertensive whites. A significant pathophysiologic difference between blacks and whites is salt sensitivity; normotensive, as well as hypertensive, blacks tend to be salt sensitive. Blacks also tend to have lower renin levels than do whites, while dopamine response to a salt load is diminished among blacks as compared with whites. These differences and others lead to the recommendation that hypertension among blacks should be managed initially with salt restriction; if dietary control is insufficient, administration of an antihypertensive agent with 24-hour efficacy, which lowers vascular peripheral resistance, promotes sodium excretion, and potentially improves renal hemodynamics, is recommended. A calcium channel blocker may satisfy these requirements. ",13 1260,"Glaucoma screening: too little, too late? Screening for glaucoma, usually by measuring intraocular pressure, has been popular, but repeated analysis indicates poor sensitivity and specificity. More extensive testing is required. Such testing should be focused on high-risk groups, including blacks and the elderly. Regular comprehensive eye examinations, on a schedule adjusted for these and other risk factors, are probably the most cost-efficient means of identifying patients with glaucoma. The primary care provider has a pivotal role: to encourage patients to undergo such examinations when warranted; and to encourage those on intraocular-pressure-lowering medications to comply with their medication use. ",10 1689,"Diet, smoking, and alcohol: influence on coronary heart disease risk. The Framingham study on coronary heart disease (CHD) has shown that life-style, particularly diet, smoking, and alcohol consumption, has a great impact on the incidence of CHD. Blood lipoproteins, rather than total blood cholesterol, have been found to be more accurate predictors of CHD risk. Blood triglyceride, previously considered to have little bearing on CHD risk, was found to have a negative impact in many cases. A population subgroup with high triglyceride greater than or equal to 1.7 mmol/L (greater than or equal to 150 mg/dL), low high-density lipoprotein less than or equal to 1.04 mmol/L (less than or equal to 40 mg/dL), increased insulin resistance, and a higher incidence of diabetes mellitus has been found to be at increased risk for CHD. Diet intervention trials have shown that a reduction in total cholesterol and saturated fat consumption produced reduction in CHD incidence proportionate to the fall in cholesterol. Cigarette smoking increased CHD risk moderately; those who smoked one pack per day had twice the risk of nonsmokers. Alcohol consumption actually lowered CHD incidence in the Framingham study; however, when alcohol consumption was greater than two drinks per day, a rise in mortality from cancer and stroke was observed. ",13 144,"Diffuse cutaneous leishmaniasis acquired in Peru. A case of diffuse cutaneous leishmaniasis (DCL) acquired in Peru is described. The causative agent was Leishmania mexicana amazonensis as determined by isoenzyme analysis and species-specific monoclonal antibody binding characteristics. Histological examination of biopsy material showed a large number of intracellular and extracellular amastigotes and few lymphocytes. Treatment with meglumine antimoniate (Glucantime) administered iv at a dosage of 20 mg antimony/kg body weight/day for 60 days resulted in visible improvement of the lesions, but not in clinical or parasitological cure. ",2 3113,"The effect of adjunctive arteriovenous fistula on prosthetic graft patency: a controlled study in a canine model. Bilateral 6 mm PTFE grafts were placed from the external iliac artery to the femoral artery with ligation of the intervening segment of the iliofemoral artery in 14 dogs. An arteriovenous fistula was constructed at the distal anastomosis on one randomly selected side in each animal while the contralateral graft served as a control. Graft follow-up ranged between 8 and 12 months in all animals. Serial arteriography was performed to confirm graft and fistula patency and demonstrated persistence of antegrade flow into the arterial tree distal to all patent bypasses. Femoral intraarterial pressures distal to patent grafts were identical on both sides in each animal throughout the study. Cumulative life-table patency rates showed higher patency for the arteriovenous fistula bypasses than the control grafts at all time intervals: 71% vs. 57% at 3 months, 48% vs. 25% at 6 months, and 40% vs. 22% at 12 months, respectively. This is the first controlled study that provides experimental evidence suggesting that these bypasses may produce increased patency of prosthetic arterial grafts and lends support to their use in a clinical, prospective, randomized study. ",22 1828,"Assessment of major venous anomalies by computerized tomography. Congenital anomalies of major venous structures are not common but their identification and relative position, particularly in relation to an abdominal aortic aneurysm, are of significant value in planning and conducting aortic operations. Computed tomography (CT) has become a common method of preoperative evaluation of aortic disease. Its reliability in providing accurate information regarding aneurysmal size, configuration, and extension, as well as the presence of intraluminal thrombus and involvement of the renal and iliac arteries, has been demonstrated. Simultaneous visualization of the major adjacent venous structures with the use of contrast enhancement is obtained, but anatomic variants can be overlooked because they are commonly subtle and considered incidental. The preoperative diagnosis of these venous abnormalities is significant to the vascular surgeon. Such information can be accurately and reliably acquired with the present CT techniques without the need for further diagnostic studies. ",13 1583,"Torsade de pointes: a critical care nurse's dilemma. Torsade de pointes is a polymorphous ventricular tachycardia characterized by a gradual change in the direction of the QRS complex. Because critical care nurses are the first to recognize arrhythmias, they require the knowledge and skill to intervene appropriately. This case report focuses on identification of the characteristics, contributing factors, therapeutic modalities, and relevant nursing diagnoses for the patient with torsade de pointes. ",13 2392,"Haplotype analysis of the human apolipoprotein B mutation associated with familial defective apolipoprotein B100. Haplotype analysis was conducted on the mutant allele of 14 unrelated subjects heterozygous for a mutation in the codon for amino acid 3500 of human apolipoprotein B100. This mutation is associated with defective binding of low-density lipoprotein to the low-density lipoprotein receptor and with moderate hypercholesterolemia. Ten markers were used for haplotyping: eight diallelic markers within the structural gene and two hypervariable loci flanking the gene. Seven of eight unequivocally deduced haplotypes were identical, and one revealed only a minor difference at one of the hypervariable loci. The genotypes of the six other affected subjects were consistent with this same assigned haplotype. These data are consistent with a common ancestral chromosome and provide no evidence for a recurrent mutation at this potentially hypermutable CG dinucleotide, despite the fact that this mutation is not rare. ",17 1832,"Coronary Artery Surgery Study (CASS): comparability of 10 year survival in randomized and randomizable patients. The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial. ",13 1675,"Comparison of intravenous amrinone and dobutamine in congestive heart failure due to idiopathic dilated cardiomyopathy. A prospective randomized study was performed in 46 consecutive patients with refractory congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy to compare the hemodynamic responses to 48-hour infusions of amrinone and dobutamine. Both drugs substantially reduced pulmonary arterial wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index. Amrinone caused a greater decrease in right atrial pressure than dobutamine (p less than 0.02) and had a positive chronotropic effect not observed with dobutamine (p less than 0.01). The increase in heart rate produced by amrinone correlated inversely with the changes in right atrial and pulmonary arterial wedge pressures, suggesting a baroreceptor response to reduced preload. Dobutamine produced a larger increase in stroke volume index than amrinone (p less than 0.01). Ninety-one percent of patients receiving amrinone and only 65% receiving dobutamine had reduction of greater than or equal to 30% in pulmonary arterial wedge pressure (p less than 0.05). Cardiac index increased greater than or equal to 30% in similar numbers of patients given amrinone (74%) and dobutamine (65%). Negative fluid balance was recorded in all patients receiving amrinone and in 78% of patients receiving dobutamine (p less than 0.05). Target hemodynamic criteria were achieved in 83% of patients receiving 10 micrograms/kg/min of amrinone. The effective maintenance dose of dobutamine was extremely variable. No clinically important adverse effects were observed with either drug regimen. Both amrinone and dobutamine are effective and safe agents for short-term parenteral therapy of patients with dilated cardiomyopathy in severe CHF that is unresponsive to oral medication. ",13 1140,"Molecular biology of atherothrombotic brain infarction. Because reduced high density lipoproteins may contribute to atherothrombotic brain infarction, we performed molecular biologic and metabolic studies to characterize high density lipoprotein metabolism with respect to its role in reverse cholesterol transport, to clone the high density lipoprotein receptor, and to determine gene polymorphism for apolipoprotein A-I, the major protein of high density lipoprotein, because altered structure may impair reverse cholesterol transport. For high density lipoprotein metabolism measurements, high density lipoprotein 3 was isolated, purified, and labeled with iodine-125. The radiolabeled high density lipoprotein 3 was reinjected, and daily blood samples were taken for 10 days. Synthesis rates and fractional catabolic rates were determined from the specific activities and daily decrements. Preliminary data indicate that stroke-prone individuals' fractional catabolic rates for high density lipoprotein 3 are twice those of normal individuals. Also, the conversion of high density lipoprotein 3 to high density lipoprotein 2 is reduced in these individuals, suggesting that high density lipoprotein may be abnormally processed in individuals prone to atherothrombic brain infarctions. We surveyed more than 100 patients with carotid stenosis using a 2.2-kb probe for the apolipoprotein A-I gene. A subset of these patients displays polymorphism with restriction enzymes SacI or PstI. These preliminary findings suggest that gene polymorphism for apolipoprotein A-I may provide a molecular clue of atherothrombic brain infarction. ",9 2292,"Immunologic mechanisms in psoriasis. The demonstration of activated T lymphocytes, HLA-DR+, I-CAM1+, gamma IP-10+ keratinocytes, and increased levels of lymphokines in active plaques suggests that immunologic mechanisms may play a role in the pathogenesis of psoriasis. Epidermal hyperplasia and inflammation in psoriasis may be linked by those cytokines many of which are produced by both keratinocytes and leukocytes. Epidermal acanthosis and keratinocyte mitoses have been observed in delayed-type hypersensitivity reactions and after the intradermal injection of gamma interferon. Gamma interferon and its induced proteins have been demonstrated in active psoriatic plaques. Increased levels of the keratinocyte autocrine cytokines, transforming growth factor (TGF)-alpha and interleukin (IL)-6, have been detected in active plaques. The apparent overexpression of IL-6 in hyperplastic psoriatic tissue may explain features of psoriasis that link keratinocyte proliferation with immune activation and tissue inflammation. Both IL-6 and gamma interferon increased TGF-alpha expression in normal cultured keratinocytes. Cytokines produced during immune activation and other inflammatory processes may lead to epidermal hyperplasia. ",16 1001,"Comparison of propofol and thiopental/halothane for short-duration ENT surgical procedures in children. Experiences with propofol in pediatric anesthesia are limited. We undertook a study to evaluate the quality of induction and recovery from anesthesia with propofol compared to thiopental/halothane. Twenty children received 3 mg.kg-1.min-1 of propofol as a loading dose followed by a maintenance dose of 0.1 mg.kg-1.min-1 (+/- 10%). Twenty children received 5-7 mg/kg of thiopental, and maintenance was provided with halothane (0.5%-1.5%). The interval between the end of the administration of propofol or thiopental/halothane and extubation, as well to discharge to the ward, was significantly shorter with propofol (4.4 versus 13.5 min and 7.22 versus 30.4 min, respectively). Spontaneous movements and pain on injection were seen significantly more frequently with propofol, whereas laryngospasm and hiccup were only observed with thiopental. During the first 6 h after the surgical procedure, analgesics were needed significantly more often in the thiopental group. Nausea and vomiting also were observed more frequently in the thiopental group. In conclusion, propofol used as a single anesthetic is a satisfactory technique for ENT surgery of short duration in children. ",8 2347,"Is menarche associated with diabetic retinopathy? The goal of this study was to evaluate the association between menarchal status and diabetic retinopathy. Diabetic retinopathy was present in 51 of 129 females; 7 were premenarchal, and 44 were postmenarchal. The range of severity of retinopathy was greater in the postmenarchal group. In multivariate analyses, duration of diabetes, menarchal status, and diastolic blood pressure were associated with the prevalence of diabetic retinopathy. After partitioning the duration of diabetes into years before and years after menarche, both were significant, but the number of years of diabetes after menarche was more strongly associated. At a 4-yr follow-up examination, more postmenarchal than premenarchal females had progression of their retinopathy (P = 0.06). These data suggest that stage of sexual development, as reflected by menarchal status, is associated with the presence and possibly the risk of progression of diabetic retinopathy. ",17 1762,"Severe mitral insufficiency post-balloon valvuloplasty: the late changes found in a disrupted mitral valve. The case of a 45-yr-old woman who had balloon valvuloplasty for rheumatic mitral stenosis is presented. An anterior mitral leaflet tear occurred as a complication of the procedure. Both partial healing of the anterior mitral leaflet and gradual dilatation of the left atrium occurred which allowed the damaged valve to remain in situ for several months. Some of the late changes which occur after such a complicated valvuloplasty are illustrated here, as this patient eventually required surgery and valve excision for definitive repair. ",13 3296,"Comparison of i.m. ketorolac trometamol and morphine sulphate for pain relief after cholecystectomy. I.m. ketorolac trometamol 30 mg was compared with morphine sulphate 10 mg after cholecystectomy in a double-blind, multiple dose, randomized study of 100 patients. Assessments of pain were made immediately after operation (day 1), and the next morning (day 2). Pain intensity (verbal response score and visual analogue scale) was recorded before injection and then over a 6-h period. Pain relief was assessed also. The effect of ketorolac on operative blood loss and platelet function was examined. Time to commencing oral intake and the duration of administration of i.v. fluids were recorded. Adverse events were noted. Ketorolac produced significantly less analgesia than morphine on day 1, but on day 2 the two drugs produced a similar effect. Blood loss was not increased by ketorolac, although platelet function was impaired. Repeated i.m. administration of ketorolac did not produce any serious adverse effects. ",22 1384,"Tissue, developmental, and tumor-specific expression of divergent transcripts in Wilms tumor. The Wilms tumor locus on chromosome 11p13 has been mapped to a region defined by overlapping, tumor-specific deletions. Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb (WIT-2) mapping to this region were isolated from a kidney complementary DNA library. Expression of WIT-1 and WIT-2 was restricted to kidney and spleen. RNase protection revealed divergent transcription of WIT-1 and WIT-2, originating from a DNA region of less than 600 bp. Both transcripts were present at high concentrations in fetal kidney and at much reduced amounts in 5-year-old and adult kidneys. Eleven of 12 Wilms tumors classified as histopathologically heterogeneous exhibited absent or reduced expression of WIT-2, whereas only 4 of 14 histopathologically homogeneous tumors showed reduced expression. These data demonstrate a molecular basis for the pathogenetic heterogeneity in Wilms tumorigenesis. ",11 2509,"Continuous subcutaneous insulin infusion (CSII), multiple injections (MI) and conventional insulin therapy (CT) in self-selecting insulin-dependent diabetic patients. A comparison of metabolic control, acute complications and patient preferences. Continuous subcutaneous insulin infusion (CSII) and multiple injections (MI) have been shown to have metabolic advantages in highly-selected insulin-dependent diabetics (IDDs), but there have been few comparative studies in self-selected IDDs. With MI, the optimal insulin preparation for overnight insulin delivery has not been defined. We compared conventional 2-3 injection therapy (CT), CSII and MI with human isophane insulin (MI/human isophane) and human ultralente insulin (MI/human ultralente), respectively, at bedtime in self-selected IDDs. Of 275 IDDs who were invited to participate, 52 individuals (18.9%) entered the study. Most indices of glycaemic control showed better values on CSII and also on MI compared to CT, but the differences were small. Fasting blood glucose was higher on MI/human ultralente than on MI/human isophane. Only one subcutaneous abscess and one case of ketoacidosis requiring hospitalization occurred on CSII. Serious hypoglycaemic episodes were non-significantly increased on intensified therapy. Most patients clearly preferred intensified insulin therapy; approximately one half CSII. ",17 1781,"Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs. The effect of myocardial ischemia, induced by long-term exercise, on regional myocardial function and coronary collateral development was examined in pigs after gradual occlusion of the left circumflex coronary artery (LCx) with an ameroid occluder. Thirty days after surgery, regional myocardial function and blood flow were assessed during exercise in 22 pigs separated into exercise (n = 12) and sedentary groups (n = 10). The exercise group trained on a treadmill for 25 +/- 1 days, 30-50 min/day, at heart rates of 210-220 beats/min. After 5 weeks, another exercise test was performed. In the exercise group, after training, we observed an improvement in systolic wall thickening, expressed as a percentage of rest, in the collateral-dependent LCx region from 64 +/- 8% to 87 +/- 6% (p less than 0.01) at moderate exercise levels (220 beats/min) and from 45 +/- 7% to 73 +/- 7% (p less than 0.01) at severe exercise levels (265 beats/min). Transmural myocardial blood flow in the LCx region expressed as a ratio of flow in the nonoccluded region of the left ventricle also increased significantly (p less than 0.01) during severe exercise after 5 weeks. The sedentary group showed an improvement in systolic wall thickening in the LCx region during moderate exercise compared with the initial exercise test (p less than 0.05) but no significant change in systolic wall thickening or myocardial blood flow ratios during severe exercise after 5 weeks. We conclude that long-term exercise after gradual LCx coronary artery occlusion in pigs improves myocardial function and coronary collateral reserve in collateral-dependent myocardium during exercise. ",13 2648,"Cytomegalovirus in the setting of infection with human immunodeficiency virus Human cytomegalovirus (CMV) has several possible roles in the pathogenesis of AIDS. CMV causes a number of clinical syndromes, including retinitis, pneumonitis, and gastroenteritis in patients infected with human immunodeficiency virus type 1 (HIV-1). In addition, CMV may potentiate the cellular immunodeficiency observed in patients with HIV infection either directly or through enhancement of HIV replication. Finally, CMV may predispose the host to bacterial or fungal infection by compromising the integrity of mucosal barriers to infection. Therapy with ganciclovir for CMV infection may result in a decrease in morbidity related to the virus, but problems with drug toxicity and resistance to the agent mandate the development of additional therapeutic approaches. ",19 1144,"Ionic channels, cholinergic mechanisms, and recovery of sensorimotor function after neocortical infarcts in rats. Unilateral photochemical infarcts were produced in the hind limb sensorimotor neocortex of 243 rats by intravenous injection of the fluorescein derivative Rose Bengal and focal illumination of the intact skull surface. Facial contact stimuli governed the degree and recovery rate of contralateral tactile/proprioceptive forelimb placing reactions. Contralateral forelimb placing recovered, whereas hind limb placing was resistant to recovery. Infarcted rats displayed marked recovery of spontaneous limb usage (beam traversing). However, deficits in isolated tactile/proprioceptive hind limb placing reactions endured. Posttreatment with the class IV calcium antagonist flunarizine after neocortical infarction protected sensorimotor function in a dose-dependent manner. This protective effect may be due to the peculiar ionic channel blocking profile of flunarizine. Scopolamine hydrobromide reinstated contralateral placing errors in infarcted rats at a dosage that did not affect neurologically intact rats. The cognitive enhancer sabeluzole, a novel benzothiazol derivative, dose-dependently blocked the anticholinergic-induced deterioration of a sensorimotor deficit in rats. ",9 1101,"Compliance, reliability, and validity of self-monitoring for physical disturbances of Parkinson's disease. The Parkinson's Symptom Diary. Previous clinical research in Parkinson's disease has recognized the value of self-monitoring procedures in which patients observe and record the frequency and severity of their own symptoms as these occur within the patient's social and work environment. We discuss issues of methodology and report a study of compliance, test-retest reliability, and validity with a new self-monitoring instrument, the Parkinson's Symptom Diary. Two recordings of frequency (loss of balance, hesitation-freezing) and two ratings of severity (tremor, difficulty walking) were made four times daily for one week by patients (N = 73) who were without apparent loss of cognitive or memory functions. A total of 91% of the diaries received (97% of requested) met strict compliance criteria so that independent sampling over days could be assumed. Test-retest stability over one month was demonstrated for each score (all Spearman rho greater than .85) in a representative subsample of 28 patients. Criterion validity was demonstrated for each score by an expected pattern of correlations with independently obtained observer ratings of the same or related indices of disease, and by comparison with Hoehn and Yahr disability stages. By its simplicity, this self-assessment device can be an invaluable complement to traditional methods of clinical and laboratory assessment in the care and evaluation of Parkinson patients. ",9 564,"Head and neck paragangliomas: a clinicopathologic study with DNA flow cytometric analysis. A total of 11 head and neck paragangliomas were the subject of pathologic study, including histologic, immunohistochemical, and DNA flow cytometric analyses. We cannot absolutely predict aggressive clinical behavior using histologic parameters alone, but we can use such parameters to segregate patients into low-risk and high-risk groups. Several trends were observed in the current study. Tumors with higher S-phase fractions, G2/M fractions, or aneuploid cell populations tended to behave ""aggressively."" The presence of sustentacular cells in the primary tumors cannot be used as an absolute indicator of tumor metastatic potential, as two metastatic paragangliomas in this study contained sustentacular cells in both the primary and metastatic lesions. DNA ploidy status cannot be used as an absolute prognostic parameter as the two metastatic tumors were composed of diploid primary and metastatic lesions. The three tumors with aneuploid cell populations showed ""aggressive"" histologic and clinical features, but the length of the follow-up period for these cases is too limited to draw any conclusions. Although no absolute criteria can be used at present to gauge aggressiveness, close follow-up of these patients is essential, especially if pathologic findings suggest an ""aggressive"" course (ie, ""malignant"" histology, higher S-phase fractions, G2/M fractions, aneuploid cell populations, or decreased sustentacular cell density). ",3 2201,"Aberrant morphogenesis of the central nervous system. This overview of congenital defects of the CNS has emphasized pathogenesis. As developmental pathways continue to be elucidated, this approach remains to an extent hypothetical. When, however, an understanding of the features of morphogenesis and dysmorphogenesis helps to indicate time of onset or to elucidate causal factors, important steps toward the prevention of birth defects are taken. ",15 707,"Bile sampling, processing and analysis in clinical studies. Obtaining a proper bile sample for investigative purposes is of utmost importance to obtain valid results. Bile can be collected by direct aspiration of the gallbladder, by duodenal intubation or by T-tube drainage. The optimal method of collection depends on the investigative question, as well as on the resources available to the investigator. The procedures for obtaining, processing and analyzing human bile (gallbladder and hepatic) are summarized, pointing out the disadvantages and pitfalls that may occur. ",5 1711,"Improved survival and reduced myocardial necrosis with cardiopulmonary bypass reperfusion in a canine model of coronary occlusion and cardiac arrest. STUDY QUESTION: Does cardiopulmonary bypass (CPB) improve resuscitation rates and limit infarct size after cardiac arrest and acute myocardial infarction? DESIGN: Controlled randomized trial with all animals undergoing left anterior descending coronary artery occlusion and subsequent ventricular fibrillation and resuscitation. All animals were supported for four hours after resuscitation in an intensive care setting. INTERVENTION: Group 1 (eight) was resuscitated with standard external CPR and advanced life support. Group 2 (eight) was resuscitated with CPB. MEASUREMENTS AND MAIN RESULTS: Group hemodynamic, resuscitation variables, number resuscitated, and number of four-hour survivors were compared. Ischemic and necrotic myocardial weights were determined with histochemical staining techniques in four-hour survivors. Infarct size was measured as the ratio of necrotic weight to ischemic weight. Significantly fewer dogs were resuscitated in group 1 (four of eight) than in group 2 (eight of eight) (P less than .05). Group 2 survivors required significantly less epinephrine and lidocaine than group 1 survivors (P less than .05) and higher aortic diastolic and coronary perfusion pressures after CPB (P less than .001). The ratio of myocardial necrotic weight to ischemic weight at four hours was 0.82 +/- 0.25 in group 1 and 0.22 +/- 0.25 in group 2 (P less than .05). However, collateral blood flow was not measured in this study. CONCLUSION: This pilot study further substantiates the improvement in resuscitation rates obtainable with CPB. CPB may also limit infarct size during the postresuscitation period and requires further study. ",13 2171,"Iron: nutrition monitoring and nutrition status assessment. The majority of anemias in the United States are characterized by low mean corpuscular volume and thus are classified as microcytic. Iron deficiency, chronic disease and thalassemia traits are the three leading causes of microcytic anemia. The true cause of anemia must always be sought so that the prevalence estimates of iron deficiency are accurate and so that appropriate treatment can be initiated for the anemic individual. In both the clinical setting and in surveys, the most frequent differential diagnosis of microcytic anemia will involve distinguishing between iron deficiency and chronic disease. Erythrocyte sedimentation rate (ESR), zeta-sedimentation rate (ZSR), and C-reactive protein (CRP) are elevated in a variety of diseases. These indicators may help differentiate the anemia of chronic disease from iron deficiency, so that iron deficiency is not overestimated in hospitalized and aged populations. The red cell distribution width (RDW) appears to be elevated to a greater extent in iron deficiency than in chronic disease or thalassemia traits. RDW and CRP are two of several indicators of iron status in the third National Health and Examination Survey (NHANES III). ",14 1870,"The effects of dopamine on myocardial functional recovery after reversible ischemic injury. Dopamine frequently is used to improve cardiac performance after acute myocardial ischemia. Inotropic agents, however, increase myocardial oxygen demand and could potentially delay recovery from ischemic injury. To evaluate this problem, we studied eight chronically instrumented dogs in the conscious state and performed two 15-minute coronary occlusions 48 hours apart. After one of the occlusions, either dopamine (15 micrograms/kg/min) or saline placebo was administered intravenously from 1.0 to 1.5 hours of reperfusion. The alternative infusion was given during the second study. Preload recruitable work area, the area beneath the stroke work versus end-diastolic length relationship, was used to assess intrinsic myocardial performance. Ischemia decreased preload recruitable work area to 13% of control after both occlusions. After reperfusion, a 30-minute dopamine infusion acutely increased myocardial function nearly threefold as compared with placebo. Myocardial performance after dopamine administration, however, was significantly depressed compared with placebo throughout the remaining 24 hours of reperfusion (p less than 0.01). These data indicate that dopamine may impair functional recovery after ischemic myocardial injury and suggest that inotropic interventions should be used in this setting only when absolutely indicated. ",13 792,"Rectal prolapse in infants and children. Rectal prolapse that is intractable to the usual medical therapy was successfully managed without significant complications in 10 patients by simple subcutaneous encirclement of the anus with a heavy nonabsorbable suture, which was in place until the suture was removed or broke after 4 to 6 months. Four patients required two sutures and one needed a third insertion. Since this procedure is simple, has no serious complications, and controls rectal prolapse, it is recommended as the preferred initial surgical treatment of this condition. ",5 2459,"Evidence for a secular change in obesity, height, and weight among Navajo Indian schoolchildren. A survey measuring heights and weights of 1969 schoolchildren residing on the Navajo Indian Reservation was conducted in 1989. The findings were compared with National Center for Health Statistics (NCHS) reference data and with surveys of Navajo children from 1955, 1968, and 1981. Approximately twice as many children exceeded the 95th percentile of weight-for-age (11.2% of girls, 12.5% of boys) than would be expected for the NCHS reference population. The mean weight-for-height z scores exceeded those for the NCHS reference population for all ages in both sexes. Compared with data from 1955, mean heights increased 6.1% among boys and 4.4% among girls whereas mean weights increased 28.8% among boys and 18.7% among girls across all age groups. The data suggest that there has been a secular change in height, weight, and obesity in Navajo Indian children over the past 35 y. ",17 796,"Collis gastroplasty: origin and evolution. In 1957 J. Leigh Collis published his innovative operation for treating the difficult problem of the irreducible hiatal hernia, esophagitis, and stricture. The design of the operation was based on the relatively primitive understanding of hiatal hernia and the newly emerging concept of reflux esophagitis. A variety of antireflux operations by different surgeons emerged over the years to follow. The original Collis gastroplasty has been subsequently modified with the addition of both partial and complete fundoplication procedures. The place of the modified Collis gastroplasty-fundoplication operations in today's approach to the problems of hiatal hernia and gastroesophageal reflux disease remains unsettled. ",5 2178,"Rheologic properties of mixed hemoglobin gels: deoxyhemoglobins S and A. To obtain new information concerning the behaviors, and in turn the structures, of gels formed from mixtures of S and A hemoglobins, their physical properties have been characterized by stress relaxation with a rotational rheometer. The variables manipulated were (1) initial total hemoglobin concentration, (2) mole fraction of hemoglobin S present in the mixture, (3) hemoglobin A as intact tetramer only or as both tetramer and hybridized hemoglobin AS, (4) annealing time, (5) shear history, (6) temperature, and (7) temperature and time of annealing. Characteristics monitored to gain information about the effect of these variables on gel properties were (1) lag time, (2) polymer mass, (3) polymer fraction, (4) polymer composition, (5) equilibrium total hemoglobin activity, and (6) solidity/total or hemoglobin S polymer mass (or total or hemoglobin S fraction). As expected, mixed hemoglobin SA gels were less solid than those of pure S of similar initial hemoglobin concentrations because of lower polymer mass, and gel properties were influenced by shear history, annealing time, temperature, and temperature and time of annealing. However, when solidities were compared on the basis of similar quantities of gel present, mixed hemoglobin SA gels were found to be more solid than those of pure S as the mole fraction of hemoglobin S decreased in the initial mixture. This is explained by the predominant influence on gel properties of high hemoglobin activity incurred by the volume exclusion effect of the total hemoglobin concentration. The presence of hemoglobin A with hemoglobin S results in polymers and gels that differ from those found in pure hemoglobin S. Pathophysiologic implications of these findings for sickle cell disorders are proposed. ",14 840,"Gallstone clearance: a randomized study of extracorporeal shock wave lithotripsy and chemical dissolution Following extracorporeal shock wave lithotripsy it is not known whether gallstone fragments are cleared from the gallbladder without the use of oral dissolution therapy. To assess the efficacy of lithotripsy and dissolution therapy, alone or in combination, 35 patients were randomized to one of three treatment groups: lithotripsy alone, dissolution therapy alone or combined lithotripsy and dissolution therapy. All patients had symptomatic gallstones, functioning gallbladders and comparable stone profiles. Lithotripsy was administered using a piezoelectric lithotripter. Dissolution therapy consisted of combined bile acid and terpene. Clearance was assessed at 6 months using ultrasound and oral cholecystography. Patients with less than 50 per cent stone clearance at the end of 6 months were considered failures. The number of patients with total or partial clearance in the combined group (7/10) was significantly greater than those in the lithotripsy alone group (0/10, P less than 0.002). Gallstone clearance following lithotripsy appears to be dependent upon dissolution therapy. ",5 795,"Preoperative stabilisation in congenital diaphragmatic hernia. Between January 1983 and November 1986, 26 newborn infants with congenital diaphragmatic hernia were treated by early operation at a mean of 7 hours of age. A further 23 infants admitted between December 1986 and December 1989 were stabilised for a mean period of 40 hours before operation. There was no significant difference in survival between the two groups. Delayed operation is not detrimental to infants with congenital diaphragmatic hernia. ",5 3128,"Tympanosclerosis of the middle ear: late results of surgical treatment. The late results of one stage operation for middle ear tymanosclerosis in 73 patients during the period January 1965 to December 1980 are presented. Mean observation time was 11.2 years (range 3-20.2 years), with a follow-up rate 86 per cent. Among 64 patients with stapes fixation, 59 had removal of tympanosclerotic masses and stapes mobilization, and five cases underwent stapedectomy. The series was divided into six groups and the results analyzed. The best and most stable results occurred in the group with stapes mobilization and an intact ossicular chain followed by the group with stapes mobilization and Type II tympanoplasty with incus interposition. The poorest late results were obtained in ears with lacking stapes crura and stapes mobilization, and in ears subjected to stapedectomy. No case of post-operative sensorineural hearing loss occurred. We recommend that care is taken to preserve an intact ossicular chain at stapes mobilization performed at the same stage as myringoplasty. Also in ears with a defective ossicular chain but intact stapes with tympanosclerotic fixation we recommend stapes mobilization in one stage. In ears with fixation of the stapes footplate and defective crura, we recommend stapedectomy or stapedotomy in two stages. ",22 2793,"Analysis of potential risks associated with 7.5% sodium chloride resuscitation of traumatic shock [published erratum appears in Arch Surg 1991 Jan;126(1):43] We evaluated the potential side effects of rapidly infusing 250 mL of either 7.5% sodium chloride or 7.5% sodium chloride per 6% dextran 70, using lactated Ringer's as the control, to 106 critically injured patients in two prospective double-blinded emergency department trials. Eight patients had a significant hyperchloremic acidemia in association with infusion of the hypertonic solutions, but all eight were moribund before infusion and many factors other than hyperchloremia could have contributed to their acidemia. Other blood chemistry changes that might have been associated with the hypertonic solutions, such as hyperosmolality or hypernatremia, were made insignificant by other factors, such as high blood alcohol levels or concomitant administration of sodium bicarbonate. There were no cases of central pontine myelinolysis; bleeding was not potentiated. There was no difficulty with crossmatching of blood. No anaphylactoid reactions occurred. In a setting of limited volume resuscitation, the solutions are likely to have a favorable risk-to-benefit ratio. ",20 2495,"Hypoglycemia alters striatal amino acid efflux in perinatal rats: an in vivo microdialysis study. In adult brain, during insulin-induced hypoglycemia, striatal extracellular fluid concentrations of the excitatory amino acids glutamate and aspartate rise markedly (fourfold to tenfold). In this study, we used in vivo microdialysis to determine if insulin-induced hypoglycemia altered striatal amino acid efflux in similar fashion in the immature brain. Microdialysis probes were inserted into the right striatum of rats on postnatal day 7. After a 2-hour recovery period, in each animal a 30-minute baseline sample was obtained. Then insulin (0.6 mu/kg, intraperitoneal injection) was administered (n = 6) and dialysate sampling was continued over the next 210 minutes (terminal blood glucose level less than 5 mg/dl). Untreated control rats (n = 6) were sampled over the same time interval. After pre-column derivatization with o-phthaldialdehyde, dialysate samples were assayed by high-pressure liquid chromatography with electrochemical detection to measure their amino acid content; eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected. In controls, amino acid efflux did not change over 4 hours. In hypoglycemic animals, glutamate efflux increased (peak: 238 +/- 85% of baseline, p = 0.02, repeated measures analysis of variance [ANOVA]), glutamine efflux declined (to 44 +/- 5% of baseline, p = 0.002, ANOVA), and taurine efflux increased (up to 310 +/- 120% of baseline; p less than 0.06, ANOVA). In contrast with 9- to 12-fold increases in aspartate efflux reported in adult striatum, aspartate efflux increased only slightly (to 174 +/- 69% of baseline; not significant). ",17 2037,"Efficacy and safety of low- and high-dose sotalol versus propranolol in the prevention of supraventricular tachyarrhythmias early after coronary artery bypass operations. Supraventricular tachyarrhythmias are reported in up to 40% of patients early after coronary artery bypass graft operations. In a randomized study, we compared the efficacy and safety of the class III antiarrhythmic beta-blocking drug sotalol versus propranolol at low and high doses in the prevention of supraventricular tachyarrhythmias in 429 consecutive patients after coronary artery bypass graft operations. Patients with severely depressed left ventricular function and other contraindications for beta-blockers were excluded. From the fourth hour up to the sixth day after coronary artery bypass, 74 patients received low-dose sotalol (40 mg every 8 hours), 66 patients low-dose propranolol (10 mg every 6 hours), 133 patients high-dose sotalol (80 mg every 8 hours), and 156 patients high-dose propranolol (20 mg every 6 hours). Baseline characteristics were comparable in all groups. Supraventricular tachyarrhythmia was observed in 10 of 72 (13.9%) who received low-dose sotalol, 12 of 64 (18.8%) who received low-dose propranolol, 13 of 119 (10.9%) who received high-dose sotalol, and 19 of 139 (13.7%) who received high-dose propranolol (not significant). Drug-related adverse effects necessitating discontinuation of the drug occurred in four receiving low doses (2.9%) and in 31 receiving high doses (10.7%) (p less than 0.02). In conclusion, no medication was found to be superior, although supraventricular tachyarrhythmias tended to be less prevalent in patients treated with sotalol than in those treated with propranolol. Moreover, significantly fewer adverse effects were noted in both low-dose groups. Therefore, low-dose beta-blocking treatment, especially low-dose sotalol, seems preferable. ",13 2805,"Ureteric substitution with Boari bladder flap. Between 1986 and 1989, 12 patients underwent ureteric substitution with a Boari bladder flap at this Institute. The indications were ureteric injury following hysterectomy, difficult forceps delivery, difficult ureterolithotomy, ureteric strictures caused by a Dormia basket and previous ureteric surgery, tuberculosis, retroperitoneal fibrosis and a post-ureteric reimplantation fistula. There were 2 patients with a solitary kidney and 2 in acute renal failure. Double J stenting was carried out in 11 patients and the stent was removed 3 to 6 weeks post-operatively. Good results, with no morbidity or mortality, were achieved in all but 1 patient where a simple Silastic stent had migrated to the pelvis and required open surgery to remove it. We attribute our success to the tension-free anastomosis, a wide based posterior flap with preservation of its vascular supply, the use of a double J stent and vicryl suture material. ",20 2733,"The outcome of nonoperatively treated complete tears of the anterior cruciate ligament in active young adults. The results of nonoperative treatment of 72 patients with complete anterior cruciate ligament (ACL) tears, documented by examination under anesthesia and arthroscopy, were evaluated. All patients had an acute injury with hemarthrosis in a previously normal knee. Patients having meniscal repair were excluded as were those with collateral or posterior cruciate ligament tears or associated fractures. Treatment in all cases consisted of a standard protocol of early rehabilitation and bracing. A detailed rating of symptoms and function was performed at an average of 38 months postinjury (range, eight to 84 months). Overall results were 11% excellent, 20% good, 15% fair, and 54% poor. Thirty-five percent had ACL reconstruction during the follow-up period. Results indicate that young adults who return to a vocation requiring strenuous physical activity frequently can expect unsatisfactory results after nonoperative treatment of an acute complete tear of the ACL. ",20 1420,"Kt/V and hemodialysis morbidity revisited. Analysis of the National Cooperative Dialysis Study (NCDS) showed that dialysis morbidity was related to Kt/V. Recently, various formulae have been shown to be accurate for easier calculation of Kt/V. We calculated Kt/V in an outpatient unit utilizing Kt/V = -In (R - 0.03 - UF/W) in 51 patients. Kt/V was less than 0.8 in 16 patients (Group A), 0.8-1.0 in 20 (Group B), and greater than 1.0 in 15 (Group C). There was no difference in hematocrit (Hct), BUN, creatinine, serum phosphorus, and albumin. Ratio of men to women was 11/5, 15/5, and 4/11; mean age was 54, 63, and 58 years; mean body weight 177, 144, and 122 lb in Groups A, B, and C, respectively. Dialysis-related hospital admissions were similar (p greater than 0.05). These data suggest patients with higher body weights, and men, frequently had a Kt/V less than 0.8. Kt/V that did not influence biochemical parameters or hospitalizations in this population. This indicates that Kt/V may not be a good predictor of morbidity, and/or some heavier patients may do fairly well even with a Kt/V less than 0.8. The search for a better index of dialysis adequacy should be continued. ",11 2624,"Activation of the complement system in human immunodeficiency virus infection: relevance of the classical pathway to pathogenesis and disease severity. In vitro studies implicate classical and alternative complement pathway activation in the pathogenesis of human immunodeficiency virus (HIV) infection. To ascertain their importance in vivo, activation fragments of the classical (C4d), alternative (Ba), and common (C3d) pathways were measured and fragment to parent molecule ratios derived in 74 HIV-infected individuals and related to circulating immune complex (CIC) levels, Centers for Disease Control (CDC) stage, and beta 2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels. All fragments and ratios were significantly higher in patients (P less than .01) than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with increasing CDC stage (P less than .001), while CD4+ lymphocytes decreased linearly (P less than .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with increasing CIC and beta 2-microglobulin, and C4d and C4d to C4 correlated with decreasing CD4+ lymphocytes (P less than .05). The relationship of classical complement pathway activation to disease progression and CD4+ lymphocytes suggests its involvement in the pathogenesis of HIV infection. ",19 2386,"Promoting adherence to low-fat, low-cholesterol diets: review and recommendations. Evidence that lowering blood cholesterol levels reduces risk of coronary heart disease has prompted widespread recommendations that hyperlipidemic individuals undergo dietary therapy. However, the extent to which people can adopt and maintain diets to lower lipids is unclear. In our article, we review what is currently known regarding adherence to low-fat diets and present an approach to dietary counseling for lowering cholesterol that incorporates elements of behavioral self-management and social learning theory. We discuss specific recommendations for counseling hyperlipidemic patients based on the Dietary Alternatives Study. Recommendations include providing patients with an adequate knowledge base to make dietary changes, using goal setting and self-monitoring to help patients initiate dietary changes, enlisting support from the patient's family, and enhancing self-efficacy to promote long-term dietary maintenance. ",17 2693,"Value of a multiantigen radioallergosorbent test in diagnosing atopic disease in young children. The purpose of this study was to investigate the value of a new multiantigen radioallergosorbent test, Phadiatop Paediatric, in the diagnosis of atopy in children less than 7 years of age. The diagnosis of atopic disease was established by history, physical examination, total serum IgE concentration, and the results of prick skin tests or radioallergosorbent tests or both, and then compared with the result of the Phadiatop Paediatric test for each patient. One hundred two patients (62 boys) between the ages of 4 months and 7.3 years were enrolled (median age 3.2 years). After the history and physical examination, 42% of the patients were believed to be atopic and 32% to be nonatopic; the diagnosis was uncertain in 26%. Skin prick test reactions to a variety of foods and inhalants were positive in 41 of 63 children tested; results of radioallergosorbent tests were positive in 35 of 61 children. Overall, atopy was diagnosed in 53 children and 49 were found to be nonatopic. When the clinical diagnosis was used as the gold standard, the Phadiatop test resulted in a correct diagnosis of atopy in 49 of 53 cases and of no atopy in 43 of 49 cases: sensitivity = 92%, specificity = 88%, and efficiency = 90%. Although the Phadiatop Paediatric test does not indicate specific sensitivities, it provides the clinician with a useful screening test for atopic disease in children 7 years of age or less, and the researcher with a means of validating atopic populations. ",19 2017,"Enhanced chemiluminescence as a measure of oxygen-derived free radical generation during ischemia and reperfusion. It has been suggested that oxygen-derived free radicals may contribute to the myocardial injury associated with ischemia and reperfusion. As the presence of enhanced free radical generation is a prerequisite for such damage, several techniques have been used to provide evidence of increased oxygen free radical production during reperfusion; however, all such techniques have substantial limitations. In this study, we used enhanced chemiluminescence to evaluate oxygen free radical generation during ischemia and reperfusion in the isolated Langendorff-perfused rat heart. The chemiluminescent technique, which has high sensitivity and can monitor radical generation continuously, avoids some of the limitations of earlier methods. Chemiluminescence (expressed as counts per second) decreased from 219 +/- 11 at baseline to 142 +/- 9 during ischemia and markedly increased to a peak of 476 +/- 36 during the first 3-5 minutes of reperfusion. This was followed by a slow decline over 11-16 minutes to a steady-state level of 253 +/- 14 (each sequential change in chemiluminescence was highly significant; p less than 0.001). Superoxide dismutase (2,000 units/min) significantly decreased peak reperfusion chemiluminescence to 316 +/- 17 (p less than 0.01). Hearts subjected to a second period of ischemia and reperfusion had a higher peak chemiluminescence (626 +/- 62), which also was significantly attenuated by 1,000 units/min superoxide dismutase (398 +/- 16; p less than 0.01). ",13 311,"Primary non-Hodgkin's T-cell lymphoma of the esophagus. A case with peculiar endoscopic ultrasonographic pattern. We report a case of primary esophageal non-Hodgkin's T-cell lymphoma in a young white female. At admission, endoscopy revealed large, irregularly shaped, esophageal ulcerations with super imposed candidiasis. Endoscopic ultrasonography to assess submucosal alterations and periesophageal involvement revealed a diffuse hypoechogenic thickening (up to 5 mm) of the esophageal wall, a pattern consistent with lymphomatous infiltration. Definitive diagnosis was made with the aid of histology and immunohistochemistry. ",3 560,"Embryonic stem cell virus, a recombinant murine retrovirus with expression in embryonic stem cells. The expression of Moloney murine leukemia virus and vectors derived from it is restricted in undifferentiated mouse embryonal carcinoma and embryonal stem (ES) cells. We have developed a retroviral vector, the murine embryonic stem cell virus (MESV), that is active in embryonal carcinoma and ES cells. MESV was derived from a retroviral mutant [PCC4-cell-passaged myeloproliferative sarcoma virus (PCMV)] expressed in embryonal carcinoma cells but not in ES cells. The enhancer region of PCMV was shown to be functional in both cell types, but sequences within the 5' untranslated region of PCMV were found to restrict viral expression in ES cells. Replacement of this region by related sequences obtained from the dl-587rev retrovirus results in MESV, a modified PCMV virus that confers G418 resistance to fibroblasts and ES cells with similar efficiencies. Expression of MESV in ES cells is mediated by transcriptional regulatory elements within the 5' long terminal repeat of the viral genome. ",3 3338,"Comparison of Delphin and BioMedicus pumps. There is an increasing use of centrifugal pump systems for cardiopulmonary bypass (CPB) and circulatory assistance. The BioMedicus and Delphin centrifugal pump systems were tested in two side-by-side, identical in vitro flow loops for blood trauma and flow probe accuracy. Blood parameters tested were hemoglobin, hematocrit, lactate dehydrogenase, free plasma hemoglobin, and platelet counts. The Delphin pump demonstrated significant increases in plasma hemoglobin levels at the three flow rates tested: 2 L/min (p less than 0.05), 4 L/min (p less than 0.005), and 6 L/min (p less than 0.05). After 4 hr of pumping, the drop in platelet counts was significantly greater in the BioMedicus loop as compared with the Delphin loop (p less than 0.05) at the 2 L/min and 4 L/min flow rates; however, platelet levels remained within normal ranges in both systems. At 6 L/min, no statistical difference in platelet counts was noted. The flow probe readings were found to deviate by as much as 58% of stopwatch timed flow rate comparisons at low flow rates, but improved to within 10% or better at 6 L/min. ",22 2205,"Prenatal screening: when and for whom? This report discusses the role of prenatal screening in preventing congenital abnormalities or, when prevention is not possible, in avoiding the conception or the birth of those who would have untreatable abnormalities. Women who are found by screening not to be immune to rubella can be safely vaccinated prior to pregnancy; those found to be at risk of having children with genetic disorders such as Tay-Sachs disease or thalassemia have the option of avoiding the conception of affected offspring. Screening during pregnancy permits the primary prevention of Rh disease and its sequelae when it results in the prophylactic administration of Rh-immune globulin to unsensitized Rh-negative women. Maternal serum alpha-fetoprotein screening identifies pregnant women who are at increased risk of carrying fetuses with neural tube defects or Down's syndrome, giving them the option of avoiding the birth of affected fetuses through abortion. Recombinant DNA technology will permit screening for many more genetic disorders as the disease-related genes and mutations are identified. For many of these disorders, the ability to predict the risk of disease will antedate preventive and therapeutic interventions by many years. During this lag phase, issues concerning the validity of the tests, the severity of the conditions for which screening is offered, the safety of the interventions, and the autonomy of the pregnant women in deciding to be screened are important. ",15 750,"Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution Gallbladder motility was evaluated by ultrasonography in 75 cholesterol gallstone patients and in 77 matched control subjects. All 75 gallstone patients were candidates for oral bile acid therapy (radiolucent gallstones, less than 2 cm in diameter, in well-opacified gallbladder), and 38 of them were also studied during ursodeoxycholic acid administration. An additional 20 gallstone patients were studied 1 year after confirmed gallstone dissolution with oral bile acids. Gallstone patients showed significantly greater fasting and residual volumes, a decreased percent of gallbladder emptying, but a similar absolute emptying and emptying rate compared with the control subjects. Greater fasting volumes and reduced percents of gallbladder emptying were also found in gallstone-free patients who achieved complete dissolution with oral bile acids. After ursodeoxycholic acid administration, fasting gallbladder volumes were greater, and percents of gallbladder emptying were further decreased than in untreated gallstone patients. In conclusion, greater fasting volumes, and not reduced gallbladder contractility, account for the defective gallbladder function in radiolucent (cholesterol-rich) gallstone patients. This condition is likely to precede, and possibly to promote, gallstone formation because it persists after gallstone dissolution. Ursodeoxycholic acid administration worsens the defect observed in gallstone patients. This finding also suggests, although indirectly, that the expected normalization of cholesterol saturation during oral bile acid administration is not paralleled by an improvement in gallbladder function. ",5 2729,"Epidemiology of acquired immune deficiency syndrome in persons aged 50 years or older. Acquired immune deficiency syndrome (AIDS) has afflicted persons of all ages, yet only recently has attention been devoted to AIDS in older persons. To examine the epidemiology of AIDS in persons greater than or equal to 50 years old in the United States, we analyzed cases reported to the Centers for Disease Control. The number reported annually in persons greater than or equal to 50 years old increased from 13 in 1981 to 3,562 in 1989. Through December 1989, 11,984 had been reported, representing 10% of all cases. Although male homosexual contact accounted for most cases in persons aged 50-69, blood transfusion became a more common means of exposure with increasing age, accounting for 28% of cases in persons aged 60-69 and 64% of cases in individuals aged greater than or equal to 70. The proportion of women increased from 6.1% in persons with AIDS aged 50-59 to 28.7% of those aged greater than or equal to 70. The proportion of AIDS diagnoses made in the same month as death increased from 16% in persons aged 50-59 to 37% in those aged greater than or equal to 80, suggesting either more rapid progression of disease or increasing delay in diagnosis. As the incidence in older persons continues to increase, clinicians caring for older patients must become more familiar with AIDS. ",19 1924,"Effectiveness of the once-daily calcium antagonist, lacidipine, in controlling 24-hour ambulatory blood pressure. The efficacy of the new once-daily dihydropyridine calcium antagonist, lacidipine, in reducing ambulatory intraarterial blood pressure (BP) was examined in 12 untreated hypertensive patients. The intraarterial recording was commenced 24 hours before the first 4-mg dose and was continued for a further 24 hours thereafter. After dose titration and chronic therapy, a second 24-hour ambulatory BP recording was made. There was a steady onset of drug action, maximal at 2 hours, but with reflex tachycardia after the first dose. Chronic administration reduced BP throughout the 24-hour period, without tachycardia. Mean daytime reduction in BP was 20 mm Hg systolic (p less than 0.005) and 12 mm Hg diastolic (p less than 0.02). Mean nighttime reduction was 8-mm Hg systolic (p less than 0.05) and 6-mm Hg diastolic (difference not significant). There was no postural decrease in BP on 60 degrees head-up tilting and hypotensive action was maintained during isometric exercise (reduction at peak of 32/18 mm Hg, p less than 0.05) and throughout dynamic exercise (reduction at peak of 23/14 mm Hg, p less than 0.05). Lacidipine is an effective once-daily antihypertensive agent, with good control of stress response. ",13 2182,"Normal reticulin level in iliac bone marrow. While the level of marrow reticulin may be a factor that is used when the presence of a hematologic disorder is being considered, to our knowledge no study has graded the amount of reticulin present in normal iliac bone marrow. Grading reticulin stains of bone biopsy specimens from 100 hematologically normal patients documented that the normal amount of reticulin in the marrow is low. Twenty-seven percent of the patients had marrow reticulin grade 0 using the Bauermeister scale, 42% had grade N, 27% had grade 1, and 4% had grade 2; no patient had a Bauermeister grade 3 or 4 reticulin level. Knowledge of the normal range of reticulin is essential when the reticulin level is used as a factor in evaluating the possibility of a hematologic disorder. ",14 451,"Elevated insulin receptor content in human breast cancer. The growth of breast cancer cells is under the regulation of hormones, growth factors, and their receptors. In the present study, we have employed a new, sensitive, and specific radioimmunoassay for the direct measurement of insulin receptors in surgical specimens of breast cancers. In 159 specimens the insulin receptor content was 6.15 +/- 3.69 ng/0.1 mg protein. This value was more than sixfold higher than the mean value found in both 27 normal breast tissues obtained at total mastectomy (0.95 + 0.68, P less than 0.001) and in six normal specimens obtained from reduction mammoplasty (0.84 +/- 0.78, P less than 0.001). The insulin receptor content in breast cancer tissues was also higher than in any normal tissue investigated including liver (Pezzino, V., V. Papa, V. Trischitta, A. Brunetti, P.A. Goodman, M.K. Treutelaar, J.A. Williams, B.A. Maddux, R. Vigneri, and I.D. Goldfine, 1989. Am. J. Physiol. 257:E451-457). The insulin receptor in breast cancer retained its ability to both bind insulin and undergo insulin-induced tyrosine kinase activation. Immunostaining of the specimens revealed that the insulin receptor was present in malignant epithelial cells, but was not detected in stromal and inflammatory cells. Univariant analysis revealed that the insulin receptor content of the tumors correlated positively with tumor size (P = 0.014), histological grading (P = 0.030), and the estrogen receptor content (P = 0.035). There were no significant correlations between insulin receptor content and the age, body weight, menopausal status, and nodal involvement of the patients. These studies indicate, therefore, that the insulin receptor content is increased in breast cancers and raise the possibility that the insulin receptor may have a role in the biology of these tumors. ",3 697,"Use of the pudendo-anal reflex in the treatment of neurogenic faecal incontinence. An electrical stimulator has been devised to treat neurogenic faecal incontinence caused by pudendal nerve neuropathy and works on the basis of repeated stimulation of the pudendo-anal reflex arc. Although conduction in the pudendo-anal reflex arc may be prolonged, and is so in neurogenic faecal incontinence, it must be shown to be present before the method can be used. This stimulation results in an immediate rise in the pressure in the anal canal and a significant increase in the electromyographic activity of the external anal sphincter. Maintenance of the stimulus over a two month period raised the mean resting pressure significantly in the anal canal and increased the reflex and voluntary responses of the external anal sphincter to coughing and squeezing actions respectively. The length of the sphincter was not affected. There was widening of the mean motor unit potential duration, though this was not significant. The resting electromyogram was enhanced after the course of treatment, indicating greater spontaneous activity in the external sphincter. The changes led to seven of the eight patients studied becoming continent at the end of the treatment. ",5 567,"Primary leiomyoma of the liver. A 30-yr-old woman with right upper quadrant abdominal pain was found to have a hepatic leiomyoma. This is the youngest patient in whom this rare tumor has been found. The diagnostic approach toward gastrointestinal leiomyomata is emphasized, including the role of immunohistochemistry. ",3 990,"Hospitalization decision in patients with community-acquired pneumonia: a prospective cohort study. PURPOSE: To identify a low-risk subset of patients with community-acquired pneumonia that could safely be treated in the ambulatory setting; and to assess how clinicians make the hospitalization decision. PATIENTS AND METHODS: We performed a prospective, observational study of 280 ambulatory and hospitalized adults with clinical and radiographic evidence of pneumonia. Patients were followed to assess all potential morbid complications and 6-week mortality. Physicians responsible for managing these patients were surveyed to assess the reasons for treating in a hospital or ambulatory setting and the therapies that dictate hospitalization. RESULTS: Sixty-one percent (170 of 280) of patients did not have an indication for admission at presentation using modified Appropriateness Evaluation Protocol criteria (a severe vital sign abnormality, alteration in mental status, suppurative complication, arterial hypoxemia, severe laboratory abnormality, or an acute coexistent medical problem requiring admission independent of the pneumonia). Among these 170 patients, 38% had a complicated course defined as death within 6 weeks, development of a new suppurative or medical complication due to pneumonia, intensive care unit admission, persistent fever or use of intravenous fluids or oxygen beyond 3 days, hospitalization lasting more than 3 days, or subsequent hospitalization in patients initially treated in the ambulatory setting. Five predisposing factors for a complicated course were identified in logistic regression models. The odds ratio for age more than 65 years was 2.7; for comorbid illness, 3.2; for temperature more than 38.3 degrees C (101 degrees F), 4.1; for immunosuppression, 12.0; and for a high-risk etiology, 23.3. The risk of a complicated course increased linearly with the number of risk factors, from 12% with none to 100% with four or more factors (p less than 0.001). Physicians most often relied on the general clinical appearance of the patient when making the triage decision, and most commonly cited intravenous antibiotics and chest physical therapy as treatments requiring hospitalization. CONCLUSIONS: If validated, our findings could improve physicians' assessment of prognosis, and may identify a low-risk subset of patients with community-acquired pneumonia who could safely be managed in the ambulatory setting. ",7 1079,"Cemented and ingrowth fixation of the Miller-Galante prosthesis. Clinical and roentgenographic comparison after three- to six-year follow-up studies. One hundred thirty-nine cemented and 132 cementless Miller-Galante total knee prostheses were followed between three and six years (average, 43-44 months). The fixation technique was based on patient age, bone quality, and ability to delay full-weight bearing. Clinical follow-up studies were possible on 116 cemented knees. Fifteen knees were lost because of death before the three-year follow-up study, and eight knees required component removal. One hundred twenty-three cementless knees were available for clinical follow-up studies; there were three deaths, and six failures required component removal. No cemented failure was due to fixation, and three cementless failures were due to lack of tibial ingrowth in two and pain of undetermined etiology in one. Preoperative knee scores were slightly significant with cemented knees averaging 48 points and cementless knees averaging 52 points. A similar significant difference was maintained at the final follow-up study. No significant differences were noted for pain, limp, or support scores. Average range of motion was similar in the two groups. Radiolucent lines about the femoral component were rare. Cementless tibial radiolucencies were partial in up to 20% of examined zones, and complete tibial tray radiolucency was seen in only three patients. No correlation between radiolucency and knee scores was seen. ",9 1552,"The evaluation of the abdominal aorta: a ""how-to"" for cardiac sonographers. A thorough evaluation of the abdominal aorta can be readily achieved by use of the standard views of the echocardiographic examination. The ultrasound evaluation of the abdominal aorta represents a logical extension of the standard echocardiographic examination of the adult patient. This article provides the information needed to carry out a complete ultrasound examination of the abdominal aorta including the anatomy, the vascular disease, and the steps involved in accomplishing the ultrasound examination of the abdominal aorta. ",13 1281,"Experimental endoretinal biopsy. We performed transvitreal endoretinal biopsy in rabbit eyes to develop a reliable and safe technique to obtain retinal specimens from attached retina. Pars plana vitrectomy without lensectomy was followed by injection of Ringer's solution into the subretinal space to produce a focal retinal detachment. The apex of the focal detachment was excised by intraocular scissors and removed from the eye by pneumohydraulic expulsion. A fluid-air exchange reattached the retina. The biopsy sites were evaluated clinically and by light and electron microscopy at regular intervals up to 20 weeks postoperatively. The initial five procedures were performed without heparin in the infusion fluid, and they were complicated by severe fibrin reaction and early retinal detachment. Of the remaining 17 eyes, 15 were without intraoperative complication and maintained attached retinas. The biopsy site developed an early ring of hyperpigmentation along the border, and the biopsy bed became increasingly hyperpigmented because of cytoplasmic hyperplasia and hypertrophy of the pigment epithelium. Epiretinal membranes and subretinal neovascularization were observed histologically. Retinal biopsy specimens were reproducible and suitable for diagnostic studies. ",10 2249,"Olive oil as a cause of contact allergy in patients with venous eczema, and occupationally. From 1985 to 1989, 13 cases of contact allergy to olive oil have been identified in the Departments of Dermatology of Kristianstad and Ostersund Hospitals. Known components of olive oil could not be proved to be the cause of the allergy. This high number of patients with contact allergy to olive oil and possible explanations are discussed. ",16 3284,"Psychosocial correlates of temporomandibular joint pain and dysfunction. This study examines psychological differences between temporomandibular joint pain and dysfunction (TMJPD) patients, pain controls, and healthy controls. Two hundred and two patients were classified, according to the diagnostic criteria of Eversole and Machado, as either myogenic facial pain (n = 42), internal derangement type I (n = 69), internal derangement type II (n = 85), or internal derangement type III (n = 6). Patients completed the Basic Personality Inventory, the Illness Behavior Questionnaire, the Multidimensional Health Locus of Control, the Perceived Stress Scale, and the Ways of Coping Checklist. Subjects also answered question pertaining to TMJPD symptomatology, including chronicity and severity. After conservative treatment with simple jaw exercise and ultrasound, patients were contacted again at 5 months to complete follow-up questionnaires similar to those previously completed. Comparison groups were comprised of 79 patients attending outpatient physiotherapy clinics for pain-related injuries not involving the temporomandibular joint and 71 pain-free, healthy students. Data were analyzed using multivariate statistics. The results indicate a significant relationship between pain intensity (and to some extent chronicity) and diverse measures of personality among the pain controls but not among the TMJPD patients. This calls into question the validity of assuming individual pain disorders are subsets of a larger, homogenous pain disorder population. TMJPD patients and pain controls score higher on hypochondriasis and anxiety than the pain-free controls but these elevations are not clinically significant. The elevations decrease to normal levels in response to a positive treatment outcome. There were no differences between the TMJPD patients and the pain controls on any of the measures. These results suggests that TMJPD patients do not appear to be significantly different from other pain patients or healthy controls in personality type, response to illness, attitudes towards health care, or ways of coping with stress. ",22 867,"Primary repair of the bilateral cleft lip nose: a 15-year review and a new treatment plan. For 15 years a forked flap has been used for columella reconstruction in primary repair of the bilateral cleft lip nose. With the adolescent growth spurt, three unfavorable features have become apparent: (1) the columella may grow too long and the nostrils too large, (2) often the nasal tip remains broad, and (3) there is a drift of the columellar base and the lip-columellar angle is transgressed by scar. This procedure has therefore been discontinued. A new treatment plan is presented in which the columella is reconstructed from tissues in the splayed-out nasal tip. ",6 3024,"Ethical principles in geriatric nephrology. Seven principles are suggested to resolve ethical issues raised by medical developments affecting an aging society. First, there must be clear identification of the goals of medical treatment. Second, treatments must consider the whole person. Third, physiological concerns are more important than chronological age. Fourth, a patient's choice must be respected when choice is the result of an informed decision-making process. Fifth, access has to be equitable while respecting the sixth principle which requires allocation of resources. Finally, society must more clearly identify the appropriate principles to guide the care of the dying person. ",22 993,"Inspiratory flow dynamics during mechanical ventilation in patients with respiratory failure. We studied the effect of inspiratory flow rate on respiratory resistance during mechanical ventilation in 15 patients with acute respiratory failure (ARF). Resistance was measured by both constant flow inflation and occlusion methods as inspiratory flow rates were increased from 0.66 to 2.0 L/s. Endotracheal tube resistance was subtracted from total resistance to obtain respiratory resistance. In contrast to the flow-dependent increase in endotracheal tube resistance, respiratory resistance decreased continuously as flow rate and airway pressure increased, except in four of six patients with asthma in whom respiratory resistance increased as flow increased. Mechanical airway dilatation, tissue resistance, stress relaxation, and time-constant inequalities may contribute to the decrease in respiratory resistance. In status asthmaticus, however, the effects of turbulence, noncompliant airways, and/or ""reflex"" bronchoconstriction may be sufficient to cause a flow-dependent increase in resistance. ",7 3253,"Simplified technique for control of femoral arterial bleeding after coronary angioplasty. A method of achieving arterial control by inserting an embolectomy catheter through the femoral introducer sheath in the patient with femoral arterial bleeding after PTCA is described herein. This approach allows quick control with less dissection and negligible blood loss. ",22 2003,"Transesophageal echocardiography in the diagnosis of ostial left coronary artery stenosis. The diagnosis of ostial stenosis of the left main coronary artery is usually made by use of coronary angiography. However, positioning of the catheter across the obstruction may obscure this diagnosis during contrast injection. Although a damping of arterial pressure when the catheter enters the left coronary artery may suggest ostial stenosis, it may not be possible to make this diagnosis with certainty during cardiac catheterization. We report a series of four patients in whom the left coronary ostium and proximal left coronary arteries were visualized by means of transesophageal echocardiography. Both ostial narrowing by plaque and abnormally fast flow velocities were seen. In each case the echocardiographic findings contributed to the subsequent management of the patients. ",13 374,"In vivo selection and characterization of a murine mammary tumor subline with high potential for spontaneous lymph node metastasis. A transplantable mammary adenocarcinoma, grown in Balb/c mice, with a marked enhancement in its draining lymph node metastatic ability (MM3LN), was obtained through an in vivo procedure from a variant tumor moderately metastatic to lymph nodes (MM3). Both MM3 and MM3LN presented a similar latency and tumor growth rate and reached the same tumor mean diameter at death. MM3LN tumor-bearing mice exhibited a larger mean survival time. The new variant showed a 2.5-fold higher incidence of tumor-draining lymph node metastases than MM3 line, with no differences in the incidence of lung metastases. Morphology as well as cytogenetic and in vitro adhesion properties were studied in order to characterize the new subline. This murine tumor model has potential application in the study of the metastatic process in lymphoid tissue. ",3 1284,"Extraorbital use of a disinserted superior oblique as a sling in third nerve palsy: a new single-stage surgical technique. The management of third cranial nerve palsy is surgical. The usual technique is to correct alignment of the eyes in the first stage, followed by ptosis correction by a sling operation in the second stage. A new single-stage surgical technique involved the disinsertion of superior oblique muscle to bring the eye in a midline position. Simultaneously it is used extraorbitally as a sling to raise the ptotic upper eyelid. Postoperatively a fairly good cosmetic effect was achieved, but the upper eyelid showed a paradoxic aberrant elevation on eso-depression. ",10 2951,"The use of diazepam in chloroquine poisoning. A 39-year-old patient was found to be unconscious after having taken 2.5 g of chloroquine. Treatment consisted mainly of gastric lavage and diazepam. Experimental and clinical evidence is presented to show that diazepam in varying doses significantly decreases the mortality rate. ",20 555,"Extended neck dissection. From the time Crile described radical neck dissection in 1906, this surgical procedure became popular in the management of metastatic cancer in the neck. Over the past two decades, the modified neck dissection has been effectively utilized for conservation of function and cosmesis while achieving the same oncologic goals. However, there are several instances where the above standard procedures are not adequate for resection of malignant tumors. Although there is a definite trend toward conservation procedures, extended neck dissection is often necessary especially in patients with N2 and N3 disease. Apart from the standard structures removed in radical neck dissection, the other structures removed in extended neck dissection include skin, the digastric muscle, hypoglossal nerve, vagus nerve, sympathetic chain, ramus mandibularis, carotid artery, tracheo-esophageal nodes, etc. Over the past seven years, we have performed 40 extended neck dissections. All the patients had N2 or N3 disease in the neck. Nine patients had unknown primaries. Thirteen patients had their primary tumors in the oral cavity and 11 in the laryngopharynx. Five patients had primary tumor in the salivary glands and two patients had metastatic melanoma. Patients who underwent extensive skin excision had pectoralis myocutaneous flap reconstruction. All patients received postoperative radiation therapy. One patient died of cardiac problems 4 weeks after operation. Local control was achieved in 70%. The most difficult region for local control was the disease behind the mastoid process, and the most difficult problems were patients with involvement of the subdermal lymphatics. Our data suggests that there are definite situations where extended neck dissection is indicated with satisfactory local control of the nodal disease. ",3 2435,"Folate status of adolescents: effects of folic acid supplementation. This study was designed to determine the folate status of an adolescent population and to demonstrate the effect of folic acid supplementation on subjects with low folate status. In phase one, folate status was evaluated in a biracial sample of 164 adolescents 12 to 15 years old. Socioeconomic, demographic, anthropometric, and 7-day food record data were collected, and serum and erythrocyte folate levels were determined. Thirty-five adolescents considered to have had low folate status 6 months earlier participated in phase two, a 2-month supplementation period and reevaluation. No racial differences were observed in folate status, as indicated by amount of folate in the blood and diet. Boys had significantly (p less than .05) higher folate levels in serum and erythrocytes than did girls. Thirteen percent of the boys and 40% of the girls were folate deficient as judged by amount of erythrocyte folate less than 317 nmol/L (140 ng/mL). The folate-deficient subjects had significantly (p less than .05) lower values of hemoglobin than did the normal subjects. Seventeen percent of the boys and 42% of the girls had folate intakes below the recommended dietary allowance for folate. Supplementation of 400 micrograms folic acid daily for 2 months resulted in significant (P less than .05) increases in serum folate, erythrocyte folate, and hemoglobin values and a decrease in mean corpuscular volume. Evidence of high prevalence of low folate status, positive relationship between erythrocyte folate and hemoglobin, and responses of hemoglobin and mean corpuscular volume to the supplement indicated that folate consumption may not be optimal in some groups of adolescents, especially in girls. ",17 3208,"Effect on outcome of prolonged exposure of patients to nitrous oxide. Prolonged (several days or repeated) exposure to nitrous oxide (N2O) can cause injury or death. To assess whether relatively prolonged anesthesia with N2O in normal patients might similarly cause untoward effects, we investigated whether the addition of N2O to isoflurane anesthesia caused injury to patients having surgical resection of acoustic neuroma lasting approximately 10 h. Twenty-six patients undergoing surgical resection of acoustic neuroma were randomly assigned to a regimen that included or excluded N2O (50%-60%) during isoflurane anesthesia plus intravenous adjuvants. On average, slightly less isoflurane (0.24%) was used during anesthesia with N2O. We measured standard clinical variables (blood pressure, heart rate), oxygen saturation, neurologic status, pain, and the incidence and type of morbid outcomes. Exposure to N2O did not increase the incidence of morbid outcomes (including hepatic injury, infection, or hypoxemia), prolong hospitalization, or increase common postoperative complaints such as nausea, vomiting, coughing, or headache. Patients anesthetized with either regimen were equally satisfied with their anesthetic. ",22 2214,"Maternal serum alpha-fetoprotein screening activities of state health agencies: a survey Maternal serum alpha-fetoprotein (MSAFP) screening has been demonstrated to be cost-effective on a population basis and is becoming standard practice. The American Society of Human Genetics has twice published policy statements to define the essential elements of a quality screening program. The present study reviewed the impact of these policy statements on state public-health agencies with respect to regulation or provision of MSAFP screening in their jurisdictions. With a few exceptions, states have not elected to play a major role in provision or regulation of this test. There is need to address issues of funding, standards, and data collection in a collaborative effort, if policy statements on genetic services are to be translated into effective state population screening. ",15 3319,"Prevalence and prognostic significance of exercise-induced ventricular arrhythmias after coronary artery bypass grafting. Exercise-induced ventricular arrhythmias occur often after coronary artery bypass grafting (CABG), but their prognostic significance is unknown. Two hundred patients examined by exercise electrocardiography and cardiac catheterization (including left ventriculography, bypass graft and native coronary artery angiography) before and 3 months after CABG were prospectively followed up. Exercise-induced ventricular arrhythmias occurred more often after (49 of 200 patients, 24.5%) than before (32 of 200 patients, 16.0%) CABG (p less than 0.05). There were no differences between the patients with and without ventricular arrhythmias in the prevalence of graft patency (79 vs 80%) or the postoperative ejection fraction (57 +/- 9 vs 57 +/- 12%). Ten cardiac deaths occurred during the mean follow-up time of 61 +/- 19 months, 8 of which were witnessed sudden cardiac deaths. All cardiac deaths occurred in patients who did not have exercise-induced ventricular arrhythmias after CABG. The postoperative ejection fraction was lower in the cardiac death patients (42 +/- 16%) than in the survivors (58 +/- 10%) (p less than 0.01). No other clinical or angiographic variable predicted the occurrence of cardiac death. Thus, the prevalence of exercise-induced ventricular arrhythmias increases after CABG, but the occurrence of ventricular arrhythmias does not indicate an increased risk of cardiac death. ",22 1778,"Prognostic value of electrophysiology testing in asymptomatic patients with Wolff-Parkinson-White pattern [published erratum appears in Circulation 1991 Mar;83(3):1124] The prognostic value of electrophysiology testing was studied in 75 asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. All patients underwent electrophysiology testing at entry to the study and were followed up annually for a total of 348 patient-years (median, 4.3 years). There were 44 male and 31 female patients, and age at enrollment ranged from 7 to 77 years (mean, 34 +/- 14 years). The median effective refractory period of the accessory pathway was 293 msec (interquartile range, 280-310 msec), and the median shortest RR interval between preexcited beats during atrial fibrillation (SRR) [corrected] was 274 msec (240-320 msec). Twenty-three patients had an SRR of 250 msec or less and eight patients had a median shortest SRR interval of 200 msec or less. Twelve patients had inducible sustained reciprocating tachycardia, 10 patients had inducible nonsustained reciprocating tachycardia, and 23 patients had inducible sustained atrial fibrillation. Twenty patients (27%) lacked retrograde conduction over the accessory pathway. No patient died suddenly during a median follow-up of 4.3 years. Six patients (8%) became symptomatic with documented supraventricular tachycardia, of whom two underwent operative ablation of their accessory pathways. No patient with absent retrograde accessory pathway conduction during the electrophysiology study became symptomatic. Inducible sustained or nonsustained reciprocating tachycardia at electrophysiology study did not predict the development of subsequent symptomatic supraventricular tachycardia. Nine patients lost preexcitation during follow-up. Age at enrollment (relative risk/decade, 1.4; 95% confidence interval, 1.0-1.8) and anterograde accessory pathway refractory period (relative risk, 1.06/10 msec; 95% confidence interval, 1.0-1.12) were independent predictors of loss of preexcitation. ",13 3150,"The anatomy and physiology of nerve injury. Nerves have a structure of considerable complexity with features of special relevance to nerve injury and nerve regeneration. These include variations in the cross-sectional areas devoted to fascicular and epineurial tissue, the fascicular redistribution and mixing of different branch fibers brought about by fascicular plexuses, and the numbers of nerve fibers representing individual branches. The elasticity and tensile strength of nerve trunks and their capacity to resist traction deformation reside in the fascicular tissue, while the epineurium provides a protective cushion against compression. The microstructure of nerve trunks provides the basis for a classification of nerve injuries into five degrees of severity with partial and mixed types--each with a clearly defined pathology and distinguishing clinical features. Following a transection injury, changes occur in the severed axons, endoneurial tubes, fasciculi, and nerve trunk. The type of injury and the nature of these changes determine the outcome of axon regeneration. ",22 3029,"Facial nerve injury and hemifacial spasm. We studied evidence of facial nerve damage in patients with hemifacial spasm. Three types of evidence of nerve damage were analyzed: objectively measured weakness in eyelid protractor strength, clinically evident weakness of muscles innervated by the seventh nerve, and clinically evident aberrant seventh nerve regeneration. Of the 60 patients in the study, 54 (90%) had at least one of these features of seventh nerve damage. Objectively measured eyelid protractor weakness was noted in 27 of 58 patients (47%) who were tested. Clinically apparent weakness of at least one of four facial muscle groups was noted in 42 of 60 patients (70%). Aberrant seventh nerve regeneration was documented in 25 of 60 patients (42%). These findings indicate that facial nerve damage is common in patients with hemifacial spasm. ",22 3198,"A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy. PURPOSE: To construct and test prospectively a bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy. PATIENTS AND METHODS: In an inception cohort of 617 patients starting long-term anticoagulant therapy in one hospital, data were gathered retrospectively and bleeding was classified using reliable explicit criteria. We constructed a bleeding risk index by identifying and weighting independent predictors of major bleeding using a multivariate proportional-hazards model. The bleeding risk index was tested in 394 other patients prospectively identified in a second hospital. The index was compared to physicians' predictions. RESULTS: Major bleeding developed before discharge in 61 of all 1,011 patients (6%). The bleeding risk index included four independent risk factors for major in-hospital bleeding: the number of specific comorbid conditions; heparin use in patients aged 60 years or older; maximal prothrombin or partial thromboplastin time 2.0 or more times control; liver dysfunction worsening during therapy. In the testing group, the index predicted major bleeding, which occurred in 3% of 235 low-risk patients, 16% of 96 middle-risk patients, and 19% of 63 high-risk patients (p less than 0.001). The bleeding risk index performed as well as physicians' predictions, and integration of the bleeding risk index with physicians' predictions led to a classification system that was more sensitive (p = 0.03) than physicians' predictions alone. In 86% of patients with a high risk of major bleeding, we identified specific ways of improving therapy, e.g., avoiding overanticoagulation and nonsteroidal anti-inflammatory agents. CONCLUSION: The bleeding risk index provides valid estimates of the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy and complements physicians' predictions. The possibility that bleeding can be prevented in high-risk patients warrants prospective evaluation. ",22 1499,"Effect of angiotensin II infusion during normal pregnancy on flow velocity waveforms in the uteroplacental and umbilical circulations Women destined to develop preeclampsia show an increased systemic pressor response to infused angiotensin II, and the angiotensin sensitivity test has been accepted as an appropriate means of identifying these women. However, the effect of angiotensin II infusion on uteroplacental blood flow is unknown and may be deleterious. Patients undergoing angiotensin sensitivity tests as part of a protocol examining the effect of aspirin on the incidence of preeclampsia were studied with Doppler velocimetry performed before and during the angiotensin II infusion. Fetal well-being was documented with biophysical profiles performed before and after the infusions. Neither the systolic-diastolic ratios in the uterine and umbilical arteries nor the biophysical profile scores were altered significantly (P = .43, P = .23, Wilcoxon signed-rank median test, and P = .35, Fisher exact test, respectively). These findings suggest that the angiotensin sensitivity test does not increase resistance to flow in the uterine or umbilical circulation, and therefore may be used safely in screening for preeclampsia. ",12 1904,"Clinical nuclear magnetic resonance spectroscopy: insight into metabolism. Nuclear magnetic resonance (NMR) spectroscopy can nondestructively evaluate changes in metabolites with different disease states, as well as with therapeutic interventions. Animal studies have provided the basis for understanding changes in high-energy phosphates with myocardial ischemia. Studies of graded ischemia due to partial coronary stenosis have shown the sensitivity of the ratio of phosphocreatinine to inorganic phosphate to small reductions in myocardial blood flow and its relation to myocardial function. The application of NMR spectroscopy to humans requires precise localization techniques to avoid acquiring contaminating information from structures around the heart, such as the chest wall and diaphragm. With these localization techniques, metabolic evidence of ischemia has been demonstrated in patients with myocardial infarction and patients with known coronary disease, although the sensitivity of this technique for the diagnosis of inducible ischemia is unknown. At rest, patients with dilated and hypertrophic cardiomyopathies often have an elevated phosphodiester resonance, possibly signifying abnormal breakdown of membrane phospholipids. Increasing oxygen demand in these patients does not usually alter high-energy phosphates, suggesting that oxidative energy metabolism is preserved under these conditions. NMR spectroscopy is a powerful tool to increase understanding of metabolic changes in a variety of pathologic conditions. ",13 2704,"Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids? When used in high doses, inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal axis. The influence of the mode of drug inhalation on the degree of this suppression is not clear. Hypothalamo-pituitary-adrenal function was assessed by measurement of 0900 h serum cortisol concentrations, a short tetracosactrin test, and 24 hour urine free cortisol excretion in 48 adults with asthma taking 1500-2500 micrograms beclomethasone dipropionate daily via a metered dose aerosol. Twelve patients had hypothalamo-pituitary-adrenal suppression, as judged by subnormal results from at least two of the three tests or (in one patient) by an abnormal insulin stress test response. These patients then changed to inhaling the same dose of beclomethasone dipropionate through a 750 ml spacer device (Volumatic). The endocrine tests were repeated from nine days to eight weeks later in 10 patients. Comparison with initial values showed that adding the spacing device caused an increase in the median 0900 h cortisol concentration from 126 nmol/l to 398 nmol/l, in the post-tetracosactrin cortisol concentration from 402 nmol/l to 613 nmol/l and in 24 hour urine free cortisol excretion from 54 nmol to 84 nmol. The rise in serum cortisol concentration in response to tetracosactrin did not change. Evidence of persisting hypothalamo-pituitary-adrenal axis suppression was present in only four of the 10 patients; the most pronounced improvements in function tended to occur in those who had never required long term oral corticosteroids. The results from this uncontrolled study suggest that asthmatic patients taking high dose beclomethasone dipropionate may minimise adverse effects by using a large volume spacer device. ",19 1767,"Biphasic effects of doxorubicin on the calcium release channel from sarcoplasmic reticulum of cardiac muscle. To define the mechanism of doxorubicin cardiotoxicity, the effects of doxorubicin and caffeine were examined on calcium release channels from cardiac sarcoplasmic reticulum. We found that calcium release from cardiac sarcoplasmic reticulum vesicles was induced by both compounds. When sarcoplasmic reticulum vesicles were incorporated into planar lipid bilayers, calcium-permeable channels were observed. Addition of caffeine (2.5-10 mM) increased channel open probability from less than 0.1% to 40%, and this effect persisted for a mean of 44 minutes. In contrast, doxorubicin (2.5-10 microM) had a biphasic effect; initially, doxorubicin activated the channel, whereas after a mean of 8 minutes, the channel became irreversibly inhibited. Although the degree of channel activation by doxorubicin was concentration dependent, the time needed to inactivate the channel was concentration independent. Pretreatment with dithiothreitol (0.2 mM) prevented doxorubicin-induced channel inactivation, and channel activity persisted for an average of 58 minutes. Dithiothreitol alone did not alter channel open probability. Our results support the hypotheses that 1) the integrity of sulfhydryl groups is important for some aspects of calcium release channel function and 2) activation and inactivation of the channel are separable processes. The biphasic effect of doxorubicin on channel function may also correspond to the clinically observed adverse effects of doxorubicin, a widely used chemotherapeutic agent that, after prolonged usage, causes a dilated cardiomyopathy. ",13 1813,"Arterial blood oxygen desaturation in infants and children during upper gastrointestinal endoscopy. Arterial blood oxygen desaturation and abnormal electrocardiographic changes have been reported in adults undergoing upper gastrointestinal endoscopy. We studied 32 infants and children less than 12 years of age using pulse oximetry and continuous electrocardiography before, during, and after upper gastrointestinal endoscopy performed under intravenous sedation. Sinus tachycardia was the most common electrocardiographic change, and no clinically significant electrocardiographic abnormalities were induced by the procedure. Desaturation to less than or equal to 90% was found in 37.5% of the patients and was most commonly noted during the endoscopy procedure and in patients with cardiopulmonary disease. The desaturation was unpredictable because there was no correlation between desaturation and medication, tolerance to the procedure, weight, or age of the child. Some patients who subjectively appeared to tolerate the procedure well had significant desaturation. The use of pulse oximetry should be considered for all children undergoing upper gastrointestinal endoscopy. ",13 2563,"Reactive airway dysfunction syndrome in three police officers following a roadside chemical spill. The reactive airway dysfunction syndrome (RADS) is a recently described syndrome in which bronchial hyperreactivity and asthmatic symptoms develop in previously healthy individuals after a single large exposure to an irritating gas, fume, or vapor. We report a cluster of three Philadelphia police officers who developed RADS after a common exposure to toxic fumes from a roadside truck accident. Results of initial pulmonary function testing were normal in all three, and methacholine challenge was required for diagnosis in two out of the three. This syndrome needs to be recognized by physicians dealing with environmental or industrial medicine as a potential cause of loss of work or inability to perform on the job. Also, there is a potential for multiple individuals to develop this syndrome from a single incident. ",19 2551,"Rebound increase in serum thyrotropin, anti-'microsomal' antibodies and thyroglobulin after discontinuation of L-thyroxine. We assayed serum thyrotropin (TSH), antimicrosomal antibodies (MSA), antithyroglobulin antibodies and thyroglobulin in seven individuals with subclinical autoimmune hypothyroidism during two 6-month periods with L-thyroxine substitution and placebo, respectively. Serum TSH decreased during L-thyroxine administration, with a rebound increase in serum TSH of about 6 months duration during placebo treatment, and a parallel increase in serum thyroglobulin. In agreement with previous observations by other groups, we found decreased serum concentrations of MSA during L-thyroxine treatment in three individuals. In addition, a slow but significant transient increase in serum MSA was recorded during placebo administration in the four individuals who showed the most pronounced increase in serum TSH (greater than 20 mU l-1). This association between serum levels of MSA and TSH is most probably related to antigen presentation at the surface of the thyrocyte. We conclude that changes in serum TSH concentration should be taken into account in the interpretation of MSA in patients with thyroid disease, whether untreated or treated with L-thyroxine. ",18 3075,"Iron chelation by deferoxamine inhibits lipid peroxidation during cardiopulmonary bypass in humans. Iron catalysis is involved in oxygen-derived free radical generation and subsequent lipid peroxidation, which have been reported to occur during cardiopulmonary bypass in humans. We assessed the effects of the iron chelator deferoxamine on the susceptibility of circulating low density lipoproteins (LDLs) to induced peroxidation in 20 adult patients (10 controls and 10 treated) undergoing cardiopulmonary bypass for coronary or valve procedures. Deferoxamine was given both intravenously (30 mg/kg body wt, starting 30 minutes before bypass and extending for the next 4 hours) and as an additive to the cardioplegic solution (250 mg/l). Blood samples were taken from both atria before and immediately after the end of cardiopulmonary bypass. Plasma lipid peroxidation was assessed by measuring spectrophotometrically the thiobarbituric acid reactive substances (TBARS) content of selectively isolated LDLs after their exposure to a peroxidizing agent. Before cardiopulmonary bypass, the right and left atrial blood values of LDL-TBARS were not significantly different between the two groups. Cardiopulmonary bypass resulted in a lipid peroxidation of significantly greater magnitude in control than in treated patients. Postbypass right atrial values for LDL-TBARS (expressed in mumol/mmol LDL-phospholipids) were 45.7 +/- 17.2 (mean +/- SEM) in control patients and 6.9 +/- 2.9 in treated patients (p less than 0.02), whereas in the left atrial blood, LDL-TBARS yielded values of 62.7 +/- 20.5 and 10.3 +/- 3.9, respectively (p less than 0.01). ",22 19,"Effects of method of hemostasis on wound-infection rate. Adequate hemostasis is important in preventing postoperative wound infection. This study compared four methods of hemostasis: specific pinpoint vessel electrocautery (SPC), specific vessel ligation with 4-0 vicryl (SVL), nonspecific electrocautery of vessel plus excessive surrounding tissue (NSC), and nonspecific ligation of vessel and excessive surrounding tissue with 4-0 vicryl (NSL), on the rate of wound infection in rabbits that were contaminated with 10(6) Staphylococcus aureus. There was no statistical significant increase in the rate of wound sepsis when electrocautery was used in a fashion producing minimal nonviable tissue compared to specific vessel ligation. Electrocautery use for specific vessel hemostasis does not result in a higher wound infection rate in contaminated wounds. ",0 2744,"Locked intramedullary nailing for displaced tibial shaft fractures [published erratum appears in J Bone Joint Surg [Br] 1991 Jan;73(1):181] We analysed the results of 93 tibial shaft fractures treated with the Grosse-Kempf locked nail. Twenty-six fractures were comminuted, 19 were open grade I to II, and 54 were located outside the middle third of the tibia. The deep infection rate was 3.2%. There were only two poor results. The use of this method is recommended and discussed. ",20 2873,"Children riding in the back of pickup trucks: a neglected safety issue. Motor vehicle-related trauma is the leading cause of death in children in the United States. All states have pediatric restraint requirements for passenger vehicles to help prevent these deaths and injuries. Only a few states, however, possess safety laws or restrictions for passengers who ride in the back of pickup trucks. A retrospective review of medical records for a 40-month period revealed 40 patients whose injuries were a direct result of being a passenger in the cargo area (bed) of a pickup truck. Their injuries and other pertinent data are discussed. Representatives from the Highway Safety Commission of each state were surveyed about their specific highway safety laws. The responses revealed that all states and the District of Columbia have child restraint requirements for passenger automobiles, 34 states have adult restraint laws, but only 17 states have any type of restriction for passengers riding in the back of pickup trucks. Seventy-one percent of the states with pickup truck regulations include only the preschool-age child. Data from the National Highway Traffic Safety Administration concerning pickup trucks and passenger fatality are presented and discussed. ",20 2364,"Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM? The chronic hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) evolves gradually and is usually preceded by more transient hyperglycemia, classified as impaired glucose tolerance (IGT). Already in this phase, there is an increased risk of cardiovascular complications, and many IGT subjects, like NIDDM patients, often display several of the metabolic and circulatory disturbances that are associated with hyperglycemia, e.g., insulin resistance, hyperinsulinemia and/or hyperproinsulinemia, delayed insulin release, dyslipidemia, and hypertension. Therefore, and because untreated hyperglycemia is a self-perpetuating condition, early detection and early intervention may be necessary to prevent the progression and complications of NIDDM. This in turn would necessitate screening procedures, and the therapeutic goal should include both euglycemia and normalization of plasma insulin, plasma lipids, and blood pressure. A study in the German Democratic Republic indicated that the mortality in screening-detected NIDDM patients did not differ from that in patients detected in routine care. In a Swedish study on screening-detected NIDDM subjects, only those who had IGT rather than manifest NIDDM could maintain fasting blood glucose less than or equal to 6 mM for 5 yr by hypocaloric dietary regulation alone. In those with screening-detected NIDDM, the delayed acute insulin release and net postprandial hyperglycemia were improved by addition of glipizide, and most managed to attain and maintain fasting blood glucose less than or equal to 6 mM for approximately 2 yr after such addition. However, after 4 yr, there was an increase in blood glucose, suggesting that preventive intervention either may not be possible or may have to start in the IGT phase. ",17 500,"Modified Van Nes rotationplasty for osteosarcoma of the proximal tibia in children Above-knee amputation has been the traditional treatment for osteosarcoma of the proximal tibia. Recent advances in chemotherapy have encouraged the development of limb-salvage techniques. Van Nes rotationplasty for malignant lesions of the distal femur has increased in popularity as a reconstructive technique, but no similar procedure has been described for lesions of the proximal tibia. We have developed a modified rotationplasty for this lesion and have performed it in four children. The surgical technique, postoperative management and results of the procedure are described. Two patients had delayed wound healing. No other complications have developed and our patients were disease-free at follow-up, while the appearance of the leg was well accepted by the patients and their parents. This procedure is a useful addition to the armamentarium of the tumour surgeon for the treatment of malignant lesions of the proximal tibia. ",3 604,"High lumbar disc degeneration. Incidence and etiology. Three hundred seventy-nine consecutive magnetic resonance images (MRIs) with dual-echo images of the entire lumbar spine were reviewed by the authors. All 379 patients presented with back pain and/or leg pain; they were interviewed and examined. Pain drawings were completed by all. There were 42 patients (11.1%) with disc pathologies involving T12-L1, L1-2, and/or L2-3 levels. Six patients (1.6%) had isolated disc degeneration and/or herniations limited only to these high lumbar segments. The remaining 36 patients had degenerative changes of the higher discs with variable involvement of the lower lumbar discs. Out of 12 spondylolistheses of L5 on S1, 7 had high disc pathologies at one or more levels presenting as skipped lesions; more severe high disc lesions were noted in Grade II slips. Isolated high disc degeneration is often associated with pre-existing abnormalities such as end-plate defects, Scheuermann's disease, limbus vertebra, and so forth, and stressful cumulative work activities such as in construction workers, airplane mechanics, and so forth. High disc degeneration was noted above or below previous fractures. High disc involvement with diffuse changes in lower lumbar spine was more commonly found in ascending fashion in older age groups, and in patients who have had previous lower lumbar spine surgeries, prior fusions in particular. Our findings suggest that altered mechanics are associated with the high lumbar disc pathologies. ",4 3205,"Intravenous fluid load and recovery. A double-blind comparison in gynaecological patients who had day-case laparoscopy. The effect of intra-operative fluid and dextrose administration upon recovery was tested in a randomised, double-blind trial. Three groups of 25 patients, each undergoing laparoscopic examination as day cases, were studied. The two groups who received fluid (20 ml/kg compound sodium lactate solution) showed significant improvement (p less than 0.05) in the variables that reflected hydration. The fluid group who also received dextrose (1 g/kg) exhibited further significant improvement. Intra-operative fluid and dextrose administration appears to confer some benefit upon recovery in patients who have minor surgery. ",22 1519,"Comparison of endometrial biopsy and urinary pregnanediol glucuronide concentration in the diagnosis of luteal phase defect. To determine if pregnanediol glucuronide (PG) excretion is useful in luteal phase assessment, we compared daily first morning urinary PG concentrations during the luteal phase in nine normal and nine deficient cycles. Total luteal pregnanediol excretion (44.1 +/- 11.3 versus 64.0 +/- 11.6 area units +/- SEM) was not different. However, significantly less pregnanediol was excreted by the abnormal group during the 1st 5 days of the luteal phase (12.7 +/- 1.2 versus 18.0 +/- 1.7 area units +/- SEM, respectively). Thus, delayed PG excretion may be characteristic of luteal phase defect and measurement of urinary PG may be useful only if daily samples during the early luteal phase are obtained. ",12 1512,"Prior cesarean delivery in women with secondary tubal infertility. The history of cesarean delivery was evaluated in a population-based case-control study of secondary infertility in King County, Washington. Sixty-one married women diagnosed with secondary infertility due to tubal problems who had a previous viable pregnancy were compared to 343 married women who had a previous viable pregnancy and then had a live birth that was conceived at the same time the infertile women began trying to conceive. The risk of tubal infertility was not substantially elevated in women who had a previous cesarean delivery in the most recent viable pregnancy compared to women with vaginal delivery (odds ratio = 1.2; 95% confidence interval = 0.4, 3.7). ",12 2350,"Incidence of IDDM during 1984-1986 in population aged less than 30 yr. Residents of Turin, Italy. The goal of this study was to measure the incidence of insulin-dependent diabetes mellitus (IDDM) during 1984-1986 in residents of Turin, Italy, aged less than 30 yr. The primary data source was the list of all subjects diagnosed with IDDM who attended diabetes clinics in Turin. Other data sources were the general register of death certificates, the list of hospital discharges, and the computerized data base of insulin prescriptions. Eighty incident cases of IDDM were identified during the study in 1,130,284 person-yr for those less than 30 yr of age. Age-adjusted (world standard) incidence rates were 8.05, 8.10, and 6.96/100,000 in the age-groups 0-14, 0-19, and 0-29 yr, respectively. Estimated completeness of the primary data source compared with all other data sources was 91%, whereas the estimated completeness of ascertainment of the registry was 99%. Incidence rates of IDDM in northern Italy compare with those of European countries with low-medium incidence. A population-based register is being established for the province of Turin (951,445 inhabitants aged 0-29 yr) for the collection of incident cases since 1984. ",17 1070,"Adjuvant chemotherapy for primary lymphoma of the central nervous system. Ten immunocompetent patients with primary non-Hodgkin's lymphoma of the central nervous system were treated by the neuro-oncology service at the University of California at San Francisco (UCSF). After undergoing surgery for biopsy or removal of their tumors, these patients (group 1) received irradiation with hydroxyurea followed by adjuvant chemotherapy with the combination of procarbazine, lomustine (CCNU), and vincristine. The outcome of treatment in this group was compared with that in three other groups of patients with primary CNS lymphoma: patients treated at the UCSF Cancer Research Institute who underwent surgery and radiation therapy (RT) (group 2); patients described in the literature who had surgery and RT (group 3); or patients described in the literature who had surgery, RT, and chemotherapy (group 4). Median and quartile survival times were greater in patients who received adjuvant chemotherapy (group 1, 30 and 50 months; group 4, 20 and 25 months) than in patients who did not receive chemotherapy after RT (group 2, 13 and 20 months; group 3, 15 and 24 months). These results suggest that adjuvant chemotherapy is useful in the treatment of primary CNS lymphoma. ",9 1643,"Mechanisms in heart failure and the role of angiotensin-converting enzyme inhibition. The four major diagnostic criteria for the syndrome of congestive heart failure are left ventricular dysfunction, exercise intolerance, pulmonary congestion or edema and ventricular arrhythmias. Activation of norepinephrine, angiotensin II, vasopressin and atrial natriuretic peptide may be a key factor in the vasoconstriction and increased impedance to left ventricular ejection in heart failure. Interventions that interfere with these vasoconstrictor mechanisms should have a salutary effect on left ventricular performance. Treatment with angiotensin-converting enzyme (ACE) inhibitors, alpha-adrenoceptor blockers and vasopressin antagonists has resulted in hemodynamic benefits, but it has been more difficult to demonstrate long-term clinical effectiveness. Reductions in mortality have been demonstrated in patients with heart failure treated with vasodilators and ACE inhibitors. Improvement in the quality of life and prolongation of life are the only two appropriate goals in the management of heart failure. Further understanding of the role of angiotensin II and its interference by ACE inhibition in the tissue processes of heart failure is needed. ",13 2920,"Extending intramedullary rods in congenital pseudarthrosis of the tibia. Five patients with Boyd type II congenital pseudarthrosis of the tibia underwent excision of the pseudarthrosis and double onlay bone grafting. Stability was maintained by extending intramedullary rods. Clinical union was achieved in all cases at a mean of 8.6 months (range six to 11). The rods extended by 15.7% (range 2% to 31.4%) as growth occurred. One rod was removed because of infection and a vascularised free fibular graft was subsequently performed. The extending rods provided stability while union occurred and did not require revision as the legs grew. The rods can be removed easily and have not jeopardized further surgical options. ",20 452,"Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. Cisplatin (DDP) is the most effective drug for the treatment of human ovarian cancer, but the mechanisms that determine sensitivity to the cytotoxic action of DDP are not well understood. Treatment of two human ovarian carcinoma cell lines with epidermal growth factor (EGF) simultaneously increased sensitivity to DDP and caused a persistent change in morphology in the absence of any mitogenic effect. Sensitization to DDP was shown to be dependent on both EGF concentration and EGF receptor number in C127 mouse fibroblasts expressing the human EGF receptor after transfection with a pBPV plasmid construct containing the human EGF receptor gene under control of the transferrin receptor 3'-inducible regulator. Sensitization of human ovarian carcinoma cells to DDP was not blocked by inhibition of protein synthesis. EGF did not enhance sensitivity to DDP or alter morphology in DDP-resistant human ovarian carcinoma cells despite the presence of functional EGF receptors on these cells. These results showed that elements of the signal transduction pathway activated by EGF determined cellular sensitivity to DDP, and that a DDP-resistant phenotype is associated with a defect in this signal transduction pathway. ",3 978,"Pulmonary blood volume and edema in postpneumonectomy lung growth in rats. After pneumonectomy in young animals, the contralateral lung undergoes compensatory growth and generally attains the same weight and air space volume as both lungs in age-matched controls. In this study, we determined the contribution of lung edema and increased blood volume to the weight gain in rats. Three weeks after pneumonectomy (n = 18) or sham pneumonectomy (n = 17), the pulmonary blood volume and the extravascular water and albumin were evaluated by use of 51Cr-labeled erythrocytes and 125I-labeled albumin. The air space volume, blood-free lung weights, and DNA and protein content were also compared. The data show that the total pulmonary blood volumes and the blood volume per gram of blood-free dry lung were similar in pneumonectomized and age-matched sham controls. The total extravascular albumin and the extravascular albumin per gram of blood-free dry lung were also similar as well as the extravascular lung water, wet-to-dry weight ratios, DNA and protein content, and air space volumes. These data indicate that the increased weight of the postpneumonectomy lung was due to cellular and stromal proliferation. The blood volume and interstitial fluid increased in proportion to the increase in lung parenchyma. Neither vascular congestion nor increased extravascular protein and water contributed to the observed weight gain. ",7 2053,"The placebo effect in heart failure. Many patients who are enrolled in controlled clinical trials of new drugs for the treatment of heart failure show favorable hemodynamic and clinical responses to placebo therapy. This ""placebo effect"" results from both the creation of a supportive therapeutic environment and the spontaneous improvement that is commonly seen when measurements of symptoms and cardiac function are repeated frequently over long intervals of time. Three months of treatment with a placebo produces a reduction in symptoms in 25% to 35% of patients, an increase in cardiac output and a decrease in pulmonary wedge pressure, and an increase in exercise tolerance of up to 90 to 120 seconds. Physicians commonly seek to maximize the ""placebo effect,"" since the goal of treatment in the clinical setting is to improve the quality of the patient's life. On the other hand, clinical investigators seek to minimize the ""placebo effect,"" since the goal of a research study is to test the hypothesis that the new drug is superior to a placebo. ",13 1672,"Response of angiographically normal and atherosclerotic left anterior descending coronary arteries to acetylcholine. Acetylcholine-induced constriction of human coronary arteries in vivo is commonly attributed to endothelial dysfunction. To examine the effects of 2 other important determinants of vascular responses--namely, agonist concentration and the segment of circulation under study--the diameters of proximal, middle and distal segments of the left anterior descending artery (LAD) and coronary sinus oxygen saturation were measured in 10 patients with angiographically normal coronary arteries (group 1) and in 7 patients with coronary atherosclerosis (group 2) after intracoronary acetylcholine was infused at concentrations from 10(-7)M to between 10(-4)M and 10(-2)M. In group 1, acetylcholine caused minor (less than or equal to 6%) but progressive dilatation of the LAD up to 10(-4)M, but constriction, particularly of the distal segments and tertiary branches, occurred at higher concentrations. Over the same concentration range, coronary sinus oxygen saturation rose progressively from a basal level of 36 +/- 3% to a maximum of 72 +/- 3% in the absence of changes in heart rate and blood pressure, suggesting marked progressive dilatation of resistance vessels. Concentrations greater than or equal to 10(-3)M caused intense constriction of distal epicardial vessels and, in some cases, anginal pain and objective signs of ischemia. Conversely, in group 2, acetylcholine (infused only up to 10(-4)M for ethical reasons) failed to cause significant changes in LAD diameter. These data suggest that the local acetylcholine concentration and coronary vascular segment under study may determine the observed response to at least an equivalent extent as does the presence or absence of coronary atherosclerosis, raising the question of whether a constrictor response to intracoronary acetylcholine reliably indicates the presence of coronary atherosclerosis. ",13 2229,"Respiratory muscle function in cystic fibrosis. Maximal static expiratory and inspiratory mouth pressures (PEmax and PImax) and quadriceps femoris muscle strength were measured in 25 patients aged 16-28 years with cystic fibrosis (mean FEV1 46% predicted). Mean (SD) PEmax was 64% (18%) predicted (below 75% predicted in 16 of the 25 patients), and PImax was 64% (24%) predicted (below 75% predicted in 14 patients). Quadriceps muscle strength was 68% (20%) predicted (below 75% predicted in 17 patients). The relatively small reduction in respiratory muscle strength in these patients was unlikely to have contributed appreciably to their respiratory problems. ",15 2022,"Should family doctors screen asymptomatic children for high blood pressure? Whereas the United States Task Forces on Blood Pressure Control in Children have recommended annual blood pressure screening in all children, a working party of the British Hypertension Society has formed the opposite opinion. Relevant literature is reviewed here, and the conclusion reached that on epidemiological and ethical grounds, screening children for hypertension cannot at present be justified. ",13 527,"Parental age in sporadic hereditary retinoblastoma. Of 104 children with sporadic hereditary retinoblastoma born between 1945 and 1970, we studied the age of their parents at the birth and compared this age with the mean age of parents at the birth of their children during the same period in The Netherlands. The mean age of fathers at the birth of their children with sporadic hereditary retinoblastoma (33.7 years) was significantly higher than the mean age of fathers at the birth of their children in the general population (32.5 years) (P less than .05, one sided). Similarly, the mean age of mothers at the birth of their children with sporadic hereditary retinoblastoma (31.2 years) was significantly higher than the mean age of mothers at the birth of their children in the general population (29.5 years) (P less than .05, one sided). We further analyzed this parental age factor by measuring the relative risk of age groups and comparing the incidence of sporadic hereditary retinoblastoma in the various parental age groups with the incidence of sporadic hereditary retinoblastoma in the total population. Mothers 35 years of age or older had a relative risk of 1.7 to have a child with sporadic hereditary retinoblastoma compared with mothers in the population in general (P = .006, one sided). Similarly, fathers 50 years of age or older had a relative risk of 5.0 to have a child with sporadic hereditary retinoblastoma compared with fathers in the population in general (P = .04, one sided). No parental age effect was found in children with nonhereditary retinoblastoma. We conclude that a high paternal and a high maternal age are significant risk factors for sporadic hereditary retinoblastoma. ",3 2727,"A method of pharmacoepidemiologic analysis that uses computerized Medicaid. A method of pharmacoepidemiologic data analysis that utilizes computerized Medicaid data is presented. A cohort design in which Medicaid enrollees receiving drugs that are normally used to treat similar underlying conditions is described. A period of time in which Medicaid service transactions are evident is required before an individual is eligible for selection into a cohort. Selection of study subjects and descriptions of cohorts are based on Medicaid service histories occurring during the preliminary, prerequisite period. Time at risk is considered to begin after a prescription for a study drug is dispensed and continues until either a refill is dispensed, a prescription for an alternative drug within the same therapeutic class is dispensed, or a predetermined number of days has passed. Subjects are followed forward in time and relevant health care transactions that are suggestive of suspected adverse drug reactions are noted. Incidence densities associated with sequentially ranked prescriptions within sequential courses of therapy are compared. Methods to increase the accuracy of case ascertainment are briefly discussed. Separate validation studies may be used to evaluate the validity of computerized case ascertainment methods and to compensate for misclassification of outcome. The proposed method is intended to provide timely estimates of risk for selected outcomes. For outcomes that cannot be accurately ascertained from computerized data, this method may be useful in determining the feasibility of more customized studies. ",19