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Splenorenal arterial shunt in the treatment of renovascular hypertension. Approach by a lumbar-retroperitoneal incision. In a period of 16 years, 29 consecutive patients were operated on for a splenorenal arterial shunt through a lumbotomy incision and a retroperitoneal approach. There were 18 males and 11 females with a medium age of 42 years. All cases had uncontrollable and severe hypertension for an average medium time of 48 months, 11 patients had variable degrees of renal insufficiency. The diagnosis was made utilizing standard methods including in all cases angiography of the abdominal aorta, celiac axis and renal arteries. One patient died after the operation due to intestinal infarction, the remaining have been followed for a medium time of 50 months. All patients improved or cured their renal insufficiency. The hypertension was cured in 23, improved in 4 and failed in 1, this latter patient was successfully autotransplanted. A precise exposition of the surgical technique is presented with comments about their advantages and indications. A review of the literature in surgical experience with the technique of splenorenal arterial anastomosis has been done.
3
Severe cerebral and systemic necrotizing vasculitis developing during pregnancy in a case of systemic lupus erythematosus. We describe a fatal case of systemic lupus erythematosus (SLE) developing cerebral and systemic necrotizing vasculitis during pregnancy. The patient was discovered to have SLE at 14 weeks' gestation. Although the symptoms disappeared without treatment with corticosteroid in the 2nd trimester, she presented with meningoencephalitis due to vasculitis in the 3rd trimester. Polyarteritis nodosa (PAN)-like necrotizing vasculitis of the small muscular arteries and arterioles, with acute and healing lesions in the leptomeninges, brain parenchyma and visceral organs was observed at postpartum autopsy. PAN-like vasculitis in the central nervous system is quite rare in SLE. This case is also suggestive in terms of the influence of pregnancy on the activity of SLE.
2
Tricuspid valve incompetence caused by nonpenetrating thoracic trauma. Tricuspid valve incompetence from ruptured papillary muscle or chordae as a result of nonpenetrating trauma is uncommon. Blunt trauma causing partial detachment of a leaflet from the annulus is very rare. We report the case of a young adult involved in a car accident who had these findings. Operative repair with resuture of the leaflet to the annulus and annuloplasty using a Carpentier ring resulted in complete recovery.
3
Use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper-reactive malarial splenomegaly In Africa, hyper-reactive malarial splenomegaly (HMS), which is also known as tropical splenomegaly syndrome, can be associated with a prominent lymphocytosis in blood and bone marrow that is difficult to distinguish clinically from chronic lymphocytic leukaemia (CLL). The observation that some patients with HMS become resistant to treatment with anti-malarial drugs has led to the suggestion that HMS may evolve into a malignant lymphoproliferative disorder. To test this hypothesis, 22 Ghanaian patients with HMS and/or lymphocytosis were categorised by degree of response to proguanil according to standard clinical criteria, and DNA was extracted from peripheral blood cells and screened for rearrangements of the Jh region of the immunoglobulin gene with a DNA probe. Clonal rearrangements of the Jh region were found in all 3 patients with no response, in none of 13 patients with sustained response, and in 2 of 6 patients with moderate response or relapse on proguanil therapy. The detection of such rearrangements, and hence clonal lymphoproliferation in individuals with clinical features intermediate between HMS and CLL, supports the hypothesis that HMS may evolve into a malignant lymphoproliferative disorder.
0
Alanine aminotransferase in clinical practice. A review. Alanine aminotransferase is an enzyme produced mainly in the liver. When serum activity is measured, it provides a marker of hepatic disease. This review explores the biochemistry and laboratory analysis of alanine aminotransferase in terms of its significance in human health and disease. Cut-off levels that define abnormality are rather arbitrary and this decreases the specificity of the test in apparently healthy patients. A small, but important, group of patients with alanine aminotransferase abnormality have underlying liver disease that may be treatable. Most can be diagnosed based on history, physical examination, and biochemical-serological profiles. Liver biopsy can complement the diagnostic process in selected circumstances. Literature pertaining to this is critically reviewed.
1
Caloric expenditure, life status, and disease in former male athletes and non-athletes. This study examined the association between aerobic, caloric exercise expenditure and life status (living vs deceased) as well as the prevalence rates of hypertension (HBP) and cardiovascular disease (CVD) in former male athletes (ATH) and non-athletes (N-ATH). The initial survey for this study was done in 1952. Follow-up surveys of respondents were done in 1960, 1968, 1976, and 1984. The present study used all subjects who responded fully to activity and health questions in 1976 and who were reported as either dead or alive (not lost to follow-up) in 1984. A total of 348 subjects (185 ATH, 163 N-ATH) were assessed and caloric expenditure groups were established by kilocalories (kcal) of aerobic exercise per week; 0 kcal (group 1), 1-399 kcal (group 2), 400-899 kcal (group 3), 900-1499 kcal (group 4), 1500-2499 kcal (group 5), and 2500+ kcal (group 6). Only activity considered to be aerobic was used in the establishment of the aerobic categories. Death rate was highest in groups 1 and 2. Subjects in group 1 tended to be the oldest. Year of birth (age) (P less than 0.001) and CVD (P less than 0.05) as reported in 1976 were significantly related to mortality between 1976 and 1984. College athletic status and 1976 exercise level were not significantly related to mortality. Prevalence of CVD and HBP was highest in groups 1 and 6, suggesting a moderate amount of aerobic activity as optimal.
3
Stenosis of the sphincter of Oddi. "Stenosing papillitis" is a descriptive term for an anatomic deformity of the papilla of Vater that is characterized by narrowing of the lower end of the bile duct and the proximal end of the duct of Wirsung. The defect is secondary to inflammation and fibrosis from the chronic passage of gallstones, episodes of acute pancreatitis, chronic pancreatitis, sclerosing cholangitis, peptic ulcer disease, and cholesterolosis. Patients with papillary stenosis from gallstones may present with episodes of severe upper-abdominal pain several years after cholecystectomy. The pain is often incapacitating, and patients are often addicted to narcotic analgesics. The work-up includes abdominal ultrasonography and CT scanning and endoscopic retrograde cholangiopancreatography even though the findings usually are normal. Liver and pancreatic enzymes are not frequently elevated with the painful episodes. Transendoscopic manometry may reveal elevated pressures within the papillary portion of the distal bile duct. Some patients are relieved of their pain by transduodenal sphincteroplasty and transampullary septectomy, thereby ablating the sphincter of Oddi around the bile and pancreatic ducts and enlarging their openings.
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Central airway obstruction due to cytomegalovirus-induced necrotizing tracheitis in a patient with AIDS. Cytomegalovirus (CMV) infection in patients with the acquired immunodeficiency syndrome (AIDS) can present as either disseminated disease, pneumonitis, retinitis, gastroenteritis, neuropathy, or a subclinical infection. We report a patient whose initial manifestation of CMV infection was severe central airways obstruction due to necrotizing tracheitis. At bronchoscopy, the lesion appeared deeply ulcerated, distinctly different from previously described airway lesions in patients with AIDS. Mucosal biopsies showed characteristic intranuclear and intracytoplasmic inclusions and cultures yielded only CMV. The patient responded partially to ganciclovir, steroids, and antibiotics against suspected anaerobic superinfection but died as a result of central nervous system disease believed due to toxoplasmosis or lymphoma. CMV infection of the upper airway should be considered in the patient with AIDS presenting with atypical cough or stridor and ulcerated endobronchial lesions.
4
Alcohol consumption and blood pressure: a comparison of native Japanese to American men. We compared the cross-sectional association of alcohol consumption with blood pressure in 810 Japanese men (JM) living in Tokyo and 946 white men (WM) living in New York. Mean systolic (JM and WM, p less than 0.001) and diastolic blood pressure (JM, p less than 0.002; WM, p less than 0.001) were associated with alcohol consumption in both groups. Compared to abstainers, the heaviest drinkers had the highest systolic (JM, p = 0.001; WM, p less than 0.01) and diastolic (JM, p less than 0.002; WM, p less than 0.05) blood pressures. The relation of blood pressure to alcohol intake was J-shaped in the Americans, but linear in the Japanese. Exploratory analyses revealed that the J-shape may have been due to under-reporting of heavy alcohol ingestion by American abstainers. When abstainers were excluded, the relationships were similar in both the American and Japanese. The positive association between blood pressure and alcohol consumption persisted after adjustment for age, cigarette smoking, use of antihypertensive medications, body mass index, heart rate, abdominal skinfold thickness, hematocrit, fasting blood glucose, serum uric acid levels and urinary sodium/potassium ratio. Alcohol use was also related to prevalence of hypertension. These findings confirm the presence of an independent association between alcohol intake and blood pressure in both JM and WM and suggest that, despite differences in the metabolism of alcohol, the relation of alcohol consumption to blood pressure is similar in both nationalities.
3
An overview of intimal hyperplasia. Many hypotheses have been postulated for the development of intimal hyperplasia in vein and prosthetic grafts. In these hypotheses, the central theme seems to be endothelial injury, but not always denuding injury. As we progress into the biologic era with more sophisticated research tools, the study of the endothelial cell may give us the answers to the problem of intimal hyperplasia. In addition, the leukocyte is still a relatively unknown entity and further modification of their function may hold promise.
4
Induction of transforming growth factor beta 1 resistance by the E1A oncogene requires binding to a specific set of cellular proteins. Transforming growth factors beta (TGF-beta s) are potent inhibitors of epithelial cell growth in culture and might play a similar role in vivo. Several studies have suggested that acquisition of TGF-beta resistance is an important step in epithelial tumor development. Here, we show that resistance to TGF-beta 1 growth inhibition can be induced by transformation of keratinocytes with the E1A, but not the ras, oncogene. Mutational analysis revealed that these effects closely correlate with the ability of E1A proteins to bind to the retinoblastoma gene product (p105) as well as to three other cellular proteins (p60, p107, and p300). Only partial resistance to TGF-beta 1 growth inhibition was elicited by E1A mutants that bind to a subset of proteins, whereas complete resistance was induced by E1A mutants that bind to all four proteins together. Total protection against TGF-beta growth inhibition was also induced by concomitant introduction into cells of an E1A mutant binding to the p60/p105/p107 proteins and one binding to p300. In parallel with these effects, epidermal transglutaminase, a marker of keratinocyte differentiation, was induced by TGF-beta in control but not in E1A-transformed cells. TGF-beta 1 receptor levels were only partially down-modulated by an intact E1A gene and not significantly affected by the various truncated mutants. Thus, the ability of E1A to induce TGF-beta resistance depends on its ability to bind, and presumably inactivate, several cellular proteins that may be involved in transmission of the TGF-beta signal and seem to act downstream from its receptor(s).
4
Adenomyomatosis of the gallbladder. A premalignant lesion? Gallbladder cancer is the most common malignant tumor of the biliary tract, but its early diagnosis is uncommon. The use of ultrasonography has increased the detection of benign gallbladder tumors, and the premalignant potential of gallbladder adenomas is now undisputed. Adenomyomatosis of the gallbladder has recently been suggested to have malignant potential, and we report a case of adenocarcinoma of the gallbladder occurring in localized adenomyomatosis that was successfully treated by radical curative surgery. The more rigorous use of ultrasonography and a more aggressive approach to "benign" polypoid lesions of the gallbladder may represent the best way of achieving early diagnosis and cure in gallbladder cancer.
1
Treatment of Fournier's gangrene with adjunctive hyperbaric oxygen therapy. Fournier's gangrene is a devastating infection and often is associated with a high morbidity and mortality. Surgical debridement and antibiotics are the cornerstones of therapy. This case describes the use of hyperbaric oxygen as an adjunct in the treatment of Fournier's gangrene.
4
Retrobulbar alcohol injection in blind painful eyes. We studied 39 blind painful eyes in 39 patients who were treated with retrobulbar injection of absolute (96%) alcohol for their severe ocular pain at the King Khaled Eye Specialist Hospital from January 1984 to January 1987. There were 21 (54%) male and 18 (46%) female patients; all were followed for at least three months. The protracted ocular pain was mainly due to: end-stage (absolute) glaucoma in 31 (80%) eyes, uveitis or endophthalmitis in four (10%) eyes, or corneal ulcer in two (5%) eyes. One eye had painful phthisis bulbi, and one eye had infraorbital neuralgia. The complications encountered were transient and included blepharoptosis in eight (21%) eyes, external ophthalmoplegia, and corneal epithelial defect. The effective time of the injection to relieve pain ranged from two weeks to two years (mean, 29 weeks). The authors believe that there is still a place for retrobulbar alcohol injection for blind painful eyes when enucleation or evisceration is not possible.
2
The impact of quitting smoking on symptoms of chronic bronchitis: results of the Scottish Heart Health Study. Scotland has high rates of death from diseases of the respiratory system and high rates of smoking, especially among women. Data on self reported smoking and prevalence of chronic cough and chronic phlegm among 10,359 men and women aged 40-59 years were obtained from the Scottish Heart Health Study. Overall, current cigarette smokers had rates of chronic cough and chronic phlegm four to five times those of never smokers after standardisation for age (32.3% v 6.5% for men and 24% v 5.5% for women for chronic cough; 31% v 8.3% for men and 21% v 5.5% for women for chronic phlegm). Ex-smokers' symptom rates were a little above those of never smokers and were significant for chronic cough among women and chronic phlegm among men. Men had higher symptom rates than women and this was true for smokers, ex-smokers, and never smokers. The higher rates among men could not be explained by higher cotinine concentrations. Tests to detect "deceivers" among ex-smokers and never smokers using biochemical validation suggested that 87 (1.5%) respondents were in fact smoking; they were excluded from analyses. There were substantially lower rates of chronic cough and chronic phlegm within a year of stopping smoking, and two to four years after stopping 89-99% of the difference between current smokers and never smokers was accounted for (99% and 93% for men and women with chronic cough, 96% and 89% for men and women with chronic phlegm). Even 10 years after stopping, rates of symptoms among ex-smokers remained a little above those of never smokers (except for women with chronic phlegm), though these differences were not statistically significant. Former heavy smokers continued to have rates of chronic cough and chronic phlegm that were higher than those of former light and moderate smokers (though not significantly so). These are cross sectional data, but they emphasise the importance for chronic bronchitis symptoms of giving up cigarette smoking, though the amount previously smoked continues to exert a small influence.
4
Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study. The cosegregation of the O-demethylation of codeine to morphine with the sparteine oxidation polymorphism was confirmed. Hence morphine could not be detected in the plasma of any of the poor metabolizers, whereas detectable morphine plasma levels were found in 10 of 12 extensive metabolizers. Pain thresholds to laser stimuli were determined before drug intake and 90, 150, and 210 minutes after drug intake. Codeine significantly increased the pricking pain thresholds in the extensive metabolizers (p less than 0.05), whereas there were no significant changes in the poor metabolizers. No change in pain thresholds occurred with placebo in any of the two phenotypes. In the extensive metabolizers there was a significant positive correlation between the increase in pain threshold and plasma concentration of codeine. The study supports the hypothesis that morphine formation is essential for achievement of analgesia during codeine treatment.
2
Detection, prevalence, and prognosis of asymptomatic carcinoma of the cervix. Between 1979-1986, 82 of 407 patients (20%) treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis. Sixteen (20%) of these 82 patients had stage IA, 60 (73%) had stage IB, and six (7%) had stage IIA disease. Asymptomatic patients represented 16 of 23 (70%) of stage IA, 60 of 196 (31%) of stage IB, and six of 77 (8%) of stage IIA. In the Netherlands, population screening for cervical carcinoma is conducted on women aged 35-55 years. To examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups, we studied the patients referred to our department. Among the patients younger than 35 years with cervical carcinoma, 20 of 70 (29%) were asymptomatic with disease detected by incidental screening, whereas eight of 177 (5%) in the group 55 years or older had been detected by incidental screening. In the age category 35-55 years, 54 of 160 (34%) were asymptomatic. Patients aged 35-55 years had undergone population screening or incidental screening. In the patients 55 years or older, asymptomatic disease was significantly less prevalent than in younger patients. Only one of the 66 asymptomatic patients in stage IB or higher suffered tumor recurrence. Among symptomatic patients, 25 of 136 (18%) with stage IB and 17 of 71 (24%) with stage IIA had tumor recurrence. Despite the favorable prognosis of patients with asymptomatic carcinoma, asymptomatic presentation could not be shown to be a significant prognostic factor, as were tumor diameter and lymph node status.
0
Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia. The prognostic implications of t(9;22)(q34;q11) were assessed at a median follow-up of 3.5 years in 434 children receiving intensive treatment for acute lymphoblastic leukemia (ALL). Four-year event-free and overall survivals were 81% and 88%, respectively, in 419 children lacking t(9;22), but were 0% and 20%, respectively, in 15 children with t(9;22) (P less than .001). Poor outcome for children with t(9;22)-positive ALL was particularly notable because we have reported improved survival in other historically poor prognosis ALL cytogenetic categories when treated with similarly intensive therapy. We recommend that very intensive treatment approaches, including bone marrow transplantation in first remission, be considered for all children with t(9;22)-positive ALL.
4
Threshold perimetry in tilted disc syndrome. Twelve consecutive patients (17 eyes) with tilted disc syndrome underwent quantified visual field examination with the G1 Octopus program (Interzeag AG, Schlieren, Switzerland). Visual fields were abnormal in all cases. Although field loss was more pronounced in the superotemporal quadrant (P less than .001), it also involved the other three quadrants, thus demonstrating that optic nerve hypoplasia in tilted disc syndrome is apparently not entirely sectorial. Linear regression analysis showed that an increase in mean defect correlated with increase in myopic refractive error (P less than .05). However, the increase in myopic refractive error was found to be related to a decrease in corrected loss variance (P less than .05), indicating that in tilted discs with higher myopia, field loss is more homogeneous. With this series of patients, short-term fluctuation was within normal ranges in all visual fields, showing that this may be an additional clue for differential diagnosis from acquired disorders.
2
Otitis media in day-care children. A report from the International Primary Care Network. The relationship between day care and acute otitis media and its adverse consequences was analyzed as part of a collaborative multinational study. Data from primary care research networks in eight countries were collected on 1335 children, aged 0 to 60 months, at the time of initial visits to their primary care physicians for acute otitis media. A history of recurrent acute otitis media, poor hearing, and tonsillectomy or adenoidectomy were all more frequent in day-care children aged 25 to 60 months, compared with those cared for at home. Day-care children were brought to their physicians more promptly after the onset of symptoms and received more referrals to otolaryngologists at the time of the index visit for acute otitis media. Day care may pose a significant risk for otitis media and its adverse consequences.
4
Burden: a review of measures used among caregivers of individuals with dementia This paper critiques and discusses 10 measures of burden that have been used with caregivers of individuals with dementia. Current measures target diverse caregiver and care recipient populations, and vary in conceptualization and measurement of burden. Although many measures contain reliability data, relatively few report content validity, convergent/divergent validity, criterion validity, or sensitivity to change. Implications of these limitations for research and clinical practice are discussed.
2
Survival rates from out-of-hospital cardiac arrest: recommendations for uniform definitions and data to report. Survival rates for out-of-hospital cardiac arrest vary widely among locations. We surveyed the definitions used in published studies of out-of-hospital cardiac arrest. Data from 74 studies involving 36 communities showed survival rates ranging from 2% to 44%. There were five different case definitions and 11 different definitions of survivors. The absence of uniform definitions prevents meaningful intersystem comparisons, prohibits explorations of hypotheses about effective interventions, and interferes with the efforts of quality assurance. The most satisfactory numerator for a survival rate appears to be survival to hospital discharge; the most appropriate denominator appears to be witnessed adult cardiac arrest of presumed heart disease etiology, with ventricular fibrillation as the initial identified rhythm. Proposed definitions for the data emergency medical services systems should report as they examine their cardiac arrest survival rates are presented.
4
Protein turnover in uraemia in the rat. 1. The effect of uraemia on the rates of protein synthesis and protein degradation in liver, heart and vastus lateralis muscle were examined in the rat. Uraemia was induced by a five-sixths nephrectomy and the rates of protein turnover were compared with pair-fed sham-operated littermate controls. 2. The procedure produced plasma concentrations (means +/- SEM) of urea of 7.3 +/- 0.4 mmol/l in control and 39 +/- 2 mmol/l in uraemic rats, and of creatinine of 41 +/- 1 mumol/l in control and 133 +/- 7 mumol/l in uraemic rats. 3. Uraemia reduced the rates of protein synthesis in liver, heart and muscle by 35 +/- 5, 4.0 +/- 1.2 and 4.0 +/- 0.6%/day, respectively, compared with control rats (P less than 0.01). Since the reductions in tissue growth rate were too small to be accounted for by the reduction seen in protein synthesis alone, this implied that protein degradation was also reduced. Uraemia also caused an 18% reduction in the rate of growth as measured by the increase in tail length (P less than 0.01). 4. Uraemia reduced both protein synthesis and protein degradation. Protein synthesis exceeded protein degradation in all tissues. This would cause a reduced rate of protein accumulation in the uraemic compared with the control rats, and hence a reduced rate of growth.
4
Melioidosis. Forgotten, but not gone! Melioidosis, infection by the soil bacterium Pseudomonas pseudomallei, has the potential for prolonged latency with recrudescence into an acute, often fulminating, and fatal infection. Although the organism is never found in North America, infection is endemic in areas of southeast Asia, and populations of service personnel exposed during the Vietnam war and southeast Asian immigrants are at risk of severe recrudescent disease. Diagnosis, however, has been missed or delayed because of lack of familiarity with this disease. We present a case of recrudescent melioidosis that illustrates the difficulties encountered in diagnosis and treatment. This case involves a 76-year-old Vietnam veteran who presented with melioidosis of the bone 18 years after exposure to the organism and 10 years after a missed diagnosis of latent pulmonary disease. This case illustrates the protean nature of latent infection and the difficulty of selecting successful antibiotic therapy.
4
In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
1
Neuromuscular function in polio survivors at one-year follow-up [published erratum appears in Arch Phys Med Rehabil 1991 Mar;72(3):213] Many polio survivors complain of progressive loss of strength, work capacity, endurance, and ability to recover from fatiguing activity. These variables were measured initially and one year later in the quadriceps muscles of 28 symptomatic and 16 asymptomatic persons who had polio and 38 control individuals. Peak knee extension torque was measured isokinetically and isometrically. Endurance, or the amount of time the subject could maintain isometric torque at 40% of maximal torque, was measured. Work capacity was determined as the product of isometric torque and endurance time. Recovery of strength was measured at regular intervals for ten minutes after the endurance test. Statistical analysis was done by repeated measures ANOVA. Although the initial measures showed significant deficits in mean peak torque, work capacity, and recovery of strength in symptomatic postpolio subjects, no significant changes were found one year later in any of the variables. We conclude that symptomatic postpolio subjects do not lose significant neuromuscular function in one year.
2
Interventional radiology of the biliary tract. Intraductal radiation. One palliative method of treating patients with a high duct cholangiocarcinoma is the use of 192Ir wire. This is placed through the tumor, which has been previously intubated, and delivers a high local dose of radiation. The mean survival time in 30 patients treated with intraductal radiation was 16.8 months, an improvement compared to surgical bypass or endoscopic and radiologic drainage procedures.
0
Strongyloides stercoralis associated with a bleeding gastric ulcer. Infection with the helminthic parasite, Strongyloides stercoralis, is usually acquired by skin invasion (or occasionally via ingestion of larvae). After transformation to the adult form, the parasite preferentially localises in the small intestine, especially in the duodenal and jejunal part. A remarkable feature of Strongyloides is its property of endogenous reinfection. In the case of an immunocompromised host a massive infection, called hyperinfections Strongyloides, may occur. Numerous gastrointestinal complications of strongyloides infections, sometimes with a lethal outcome, have been reported. The intestinal manifestations are usually limited to the small bowel, and rarely involve the stomach. We report a patient with complicated strongyloides infection of the stomach.
1
Incisional hernioplasty with Mersilene. Thirty large incisional abdominal hernias (myoaponeurotic defects greater than 10 centimeters) were successfully repaired by a technique of incisional hernioplasty which implants a large Mersilene (polyester fiber) prosthesis in the space between the abdominal muscles and the peritoneum. The prosthesis extends far beyond the borders of the myoaponeurotic defect, and is solidly held in place by intra-abdominal pressure and later by fibrous ingrowth. The prosthesis protects against recurrence in two ways. First, it prevents peritoneal eventration by adhering to the visceral sac and rendering it indistensible. Second, the prosthesis unites and consolidates the abdominal wall. Consequently, the procedure uniquely exploits the very force which caused the hernia to prevent a recurrence. A prosthesis of Mersilene is essential for success because it is supple and elastic enough to conform freely to the curvatures of the visceral sac, has the necessary grainy texture to grip the peritoneum and prevent slippage and is reactive enough to induce a rapid fibroblastic response to ensure fixation.
1
Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain. To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.
2
Xenon-enhanced computed tomographic measurement of cerebral blood flow in patients with chronic subdural hematomas. We compared clinical symptoms with extent of brain shift on computed tomographic (CT) scans and quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced CT scans in 10 patients with chronic subdural hematomas. Five patients had only headache and minimal or no brain shift on a CT scan. The other five had hemiparesis and/or mental disturbance in addition to headache and moderate or severe brain shift on a CT scan. The mean hemispheric CBF decreased about 7% in patients with headache and about 35% in patients with hemiparesis and/or mental disturbance. It decreased also on the side without the hematoma. The CBF reduction was always more pronounced in the putamen and thalamus than in the cortex. On the contrary, the cortex CBF was mostly preserved or even elevated in both groups of patients. We speculate that CBF reduction in patients with a chronic subdural hematoma occurs initially in central cerebral areas like the basal ganglia and thalamus, and then extends to the entire hemisphere including the cortex as brain compression and displacement progress. Central cerebral area involvement might be more responsible for clinical symptoms than the cortex.
2
Rotator cuff lesions: signal patterns at MR imaging. The signal intensity patterns of rotator cuff lesions at magnetic resonance (MR) imaging were evaluated in 80 patients who had surgical correlation and in 13 asymptomatic individuals (14 shoulders). Six cadaver shoulders were examined with MR, and histologic correlation was obtained in four. All studies were performed at 1.5 T with a flexible circular surface coil. The accuracy of MR imaging in detection of full-thickness cuff tears (31 patients) was 0.95 and of partial thickness tears (16 patients), 0.84. The most common and accurate pattern for full-thickness cuff tears (22 of 31 tears) was a region of intense signal seen on T2-weighted images. Less often the torn region consisted of an extremely degenerated and attenuated tendon with moderate signal intensity or was obscured by low-signal-intensity scar. The intense signal pattern on T2-weighted images was also accurate, although a less common finding (seven of 16 cases), in the diagnosis of partial tears. Tendinitis was recognized as focal or diffuse regions of increased signal intensity or a nonhomogeneous pattern of increased signal often associated with tendinous enlargement. In some patients, manifestations of subacromial-subdeltoid bursitis was present. Tendon degeneration was also manifested as regions of increased signal intensity. Some similarity and overlap of signal patterns of partial interstitial tears, tendinitis, and tendon degeneration are observed.
4
Surgical resection of a solitary liver metastasis in a 46-year-old patient with a malignant thymoma. Clinical history, surgical treatment, and pathologic findings of a solitary liver metastasis of a malignant thymoma in a 46-year-old female are reported. An extensive literature review has revealed no record of surgical resection of liver metastasis in a patient with invasive thymoma.
0
Liver abscess complicating intratumoral ethanol injection therapy for HCC. We report a patient who developed multiple liver abscesses and sepsis caused by lactobacilli after the percutaneous intratumoral injection of ethanol for hepatocellular carcinoma. We diagnosed the liver abscess at an early stage because of a the finding of gas on ultrasound and computed tomography. Blood cultures grew Gram-positive rods, which were of the Lactobacillus species. The patient responded to the administration of antibiotics, and his hepatic tumors have not recurred in the 7 months since treatment. This is the first report of liver abscess following percutaneous ethanol injection therapy.
0
Clinical evaluation of an algorithm for the interpretation of hyperamylasemia. Total amylase concentration in serum continues to be widely determined in the diagnosis of acute pancreatic disease. Accumulated experience has made clear, however, that this determination has distinct limitations. Consequently, the knowledge of the origin of hyperamylasemia may have an important influence on treatment, hospitalization, and extent of clinical investigations. We undertook a logical and systematic approach to the interpretation of hyperamylasemia through the use of an algorithm that can be applied in clinical situations without the need for the integration of radiologic procedures or clinical data. The proposed algorithm was tested for effectiveness in 97 consecutive hospitalized patients with hyperamylasemia (amylase level greater than twice the upper reference limit) for a 2-year period. The majority (52.5%) of these patients had acute pancreatitis. The algorithm assigned the correct diagnostic categories in 95.8% of cases, with a disagreement between patient diagnosis and algorithm-generated diagnosis in only four cases. These four patients (two with acute biliary disease, one with bacterial peritonitis, and one with chronic renal failure) had pancreatic lipase values greater than five times the upper reference limit, so that the algorithm classified their condition as acute pancreatitis. The clinical trial indicated that the proposed decision tree, which requires only knowledge of biochemical data that are readily available, is useful in the evaluation of elevated amylase activity and facilitates arrival at a definitive diagnosis.
4
Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes? The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer.
0
Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. The Macular Photocoagulation Study Group. We graded macular features of 127 fellow eyes of participants in the Macular Photocoagulation Study who had an extrafoveal choroidal neovascular membrane secondary to age-related macular degeneration in the first eye and no initial evidence of the neovascular form of age-related macular degeneration in the fellow eye. Our aims were to determine the relationship of drusen characteristics and retinal pigment epithelial abnormalities to the risk of subsequent development of neovascularization in the fellow eye and the risk of subsequent development of recurrent neovascular membranes after photocoagulation in the first eye. Regression analysis demonstrated that the presence of large drusen and focal hyperpigmentation of the retinal pigment epithelium were independent risk factors for the subsequent development of neovascularization in the fellow eye (relative risk, 2.4 and 2.5, respectively). Only 10% of eyes with no large drusen or any retinal pigment epithelial hyperpigmentation compared with 58% of eyes with both large drusen and retinal pigment epithelial hyperpigmentation developed neovascularization in the fellow eye within 5 years. Using multivariate Cox regression analysis, we noted that the risk of developing recurrent neovascular membranes in the first eye was significantly increased when large drusen (relative risk, 2.8) were noted in the fellow eye at the time of laser treatment in the first eye. Fundus features in the fellow eye appear to help identify patients at high risk of developing visual loss from recurrent neovascular membranes following laser treatment in the first eye and from development of a neovascular membrane in the fellow eye.
4
Idiopathic sclerosing peritonitis in a man. Idiopathic sclerosing peritonitis is a rare disease described in young adolescent women, characterized by fibrosis and adhesions of the peritoneum to loops of the small bowel. Here we describe a 35-year-old man who underwent exploratory laparotomy for repeated small bowel obstruction. Only partial resection of the terminal ileum was possible because of adhesions; recurrent abdominal infections and leakage from anastomosis required further resection, which ultimately resulted in short bowel syndrome and malabsorption. The clinical and pathological findings were characteristic for idiopathic sclerosing peritonitis. We review the relevant literature, to confirm, to the best of our knowledge, that this is the first report of a male patient who has developed this rare disease.
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Eosinophilic fasciitis associated with tryptophan ingestion. A manifestation of eosinophilia-myalgia syndrome. Recently, the ingestion of tryptophan has been associated with eosinophilia-myalgia syndrome, which is characterized by eosinophilia, myalgias, and several less consistently reported findings. We treated 13 patients who exhibited clinical features of eosinophilic fasciitis who were taking high-dose tryptophan before the onset of clinical symptoms. Twelve patients exhibited eosinophilia, with eosinophil counts ranging from 0.13 to 0.88. The remaining patient was taking oral corticosteroids when her eosinophil count was determined. Eight patients complained of myalgias. Other symptoms included arthralgias, pruritus, cutaneous burning, weakness, fever, rashes, malaise, edema, muscle spasms, and alopecia. 5-Hydroxyindoleacetic acid levels were elevated in four of the eight urine specimens that were tested. Our findings suggest that previously diagnosed cases of eosinophilic fasciitis may represent variants of tryptophan-associated eosinophilia-myalgia syndrome. Derangements in the metabolism of tryptophan may play a role in sclerotic diseases.
2
A comparison of host responses of the Mongolian jird to infections of Brugia malayi and B. pahangi. Host responses of jirds receiving a single subcutaneous inoculation of subperiodic Brugia malayi were compared with those of jirds similarly infected with B. pahangi. Parasite burdens, lymphatic lesion severity, granulomatous reactivity, antibody responses to parasite antigens, and complete blood cell counts were assessed at 60 and 150 days post-inoculation. At 60 days post-inoculation, percentages of adults recovered at necropsy and lymphatic lesion severity were greater in B. pahangi-infected jirds. At 150 days post-inoculation, lesion severity and percentages of worms recovered were similar in both infections. No significant differences were noted in either infection in reactivity to homologous or heterologous parasite antigens in any parameter measured. Similarities in the kinetics of the inflammatory reactivities of the 2 infections suggest that previous observations made in the jird-B. pahangi model could be utilized in designing studies using B. malayi. Further, the more marked lesion severity observed in B. pahangi-infected jirds and the relative ease of maintaining B. pahangi in the laboratory support the continued use of this system as a conceptual model for the study of lymphatic lesion pathogenesis.
4
Treatment of squamous cell carcinoma of the anal canal. Progress in the prognosis of patients with squamous cell carcinoma of the anal canal has followed the use of multimodality therapy. From 1977 to 1985, 42 patients with squamous cell carcinoma of the anal canal were treated with mitomycin C (15 mg/m2) and 5-fluorouracil (750 mg/m2) on day 1, 5-FU (750 mg/m2/d) alone on days 2 to 5, and radiation therapy (3000 cGy) on days 7 to 28. They were evaluated 4 to 6 weeks after completion of the chemotherapy/radiation therapy protocol and received local excision, abdominoperineal resection, or both. Patient follow-up times ranged from 7 to 161 months, with a mean follow-up time of 71 months. Pathologic examination showed no residual carcinoma in 19 (45%) patients. The authors could not predict, based on clinical evaluation, which patients would have a complete response. Of the patients with a complete clinical response, 44% had tumor in the pathology specimen. Wide local excision was the most common initial operation (23 of 42 patients; 55%), with five of these patients subsequently requiring abdominoperineal resection. Anal continence was retained in 18 of 42 (43%) patients. Eleven patients experienced recurrent disease: six local recurrences, one distant, and four both local and distant. The 5-year overall survival rate was 82% and the 5-year disease-specific survival rate was 87%. There were no treatment related deaths. Preoperative tumor size was the only factor significantly related to survival. Contrary to other reports, tumor in the pathology specimen did not adversely affect long-term survival. Hence, patients should be treated after chemotherapy/radiation therapy with surgical therapy sufficient to control local disease.
1
Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group Investigators in eight communities collected aortas, right coronary arteries, blood, and associated information from 390 males, 15 to 34 years of age, who died of violent causes. Pathologists at central laboratories graded the arteries for atherosclerotic lesions, and serum lipoprotein cholesterol and thiocyanate concentrations were measured. The percentage of intimal surface involved with atherosclerotic lesions in both the aorta and the right coronary artery was positively associated with serum very low-density lipoprotein + low-density lipoprotein cholesterol concentration and negatively associated with serum high-density lipoprotein cholesterol concentration. The serum thiocyanate concentration, a marker for smoking, was strongly associated with prevalence of raised lesions, particularly in the abdominal aorta. The effect of smoking was not explained by lipoprotein levels. Blacks had more extensive total surface involvement of the aorta after adjustment for lipoprotein cholesterol levels and smoking. These associations indicate that serum lipoprotein cholesterol concentrations and smoking are important determinants of the early stages of atherosclerosis in adolescents and young adults.
3
Unusual presentation of recurrent Wegener's granulomatosis. A 65-year-old woman presented with recurrent Wegener's granulomatosis following two years of immunosuppressive therapy and three years of complete remission. At her initial presentation, she had a characteristic x-ray picture showing multiple nodules with total resolution of these findings at three months. Five years later, at the time of clinical relapse, her chest x-ray film showed bilateral diffuse infiltrative disease. This change in radiologic presentation upon relapse of Wegener's has not previously been reported. Other unusual features include diffuse infiltrates as the pulmonary presentation and the long interval between cessation of therapy and relapse. We review the radiologic manifestations of Wegener's granulomatosis.
4
Lower leg subcutaneous blood flow during walking and passive dependency in chronic venous insufficiency. The blood flow in the subcutaneous adipose tissue of the lower leg of eight normal subjects and 19 patients with chronic venous insufficiency was measured. The 133Xe-washout technique was used with portable CdT1(C1) detectors and a data storage unit. Only those patients with ulcers and a systolic blood pressure at the toe of greater than or equal to 60 mm were investigated. In the controls the relative blood flow during sitting was 0.61 (range 0.35-0.80). In the patients it was 0.46 (range 0.22-0.87). This difference was not significant. During walking the blood flow increased in controls as well as in the patients compared to the value determined in the sitting position (P = 0.0078 and P = 0.0028, respectively, Wilcoxon matched-pairs test). The relative blood-flow rate during walking was 0.96 (range 0.60-1.58) in the controls, and 1.04 (range 0.49-1.46) in the patients. The difference between the normal subjects and the patients was not significant (P = 0.79). We conclude from our studies that patients with venous insufficiency are able to increase their blood flow during walking to the same extent as normal controls.
4
Continuous infusion of interpleural bupivacaine maintains effective analgesia after cholecystectomy. Twenty-five patients who had undergone elective cholecystectomy were prospectively randomized to receive via an interpleural catheter either a continuous infusion of 0.25% bupivacaine at 0.125 mL.kg-1.h-1 (n = 13) or repeated bolus injections (n = 12) of 0.5% bupivacaine with epinephrine 1:200,000 at 0.4 mL/kg every sixth hour. Adequacy of pain relief was measured by the amount of patient-controlled analgesia morphine required postoperatively and by patient scores on a visual analog scale obtained every sixth hour. Two venous blood samples for measurements of serum bupivacaine levels were obtained from patients in the continuous group at hours 6 and 24; four blood samples were obtained from patients in the bolus group, both immediately before and 30 min after injections at hours 6 and 24. Among the patients receiving the bolus injections, morphine was required 62 +/- 15 (SEM) times over the 24-h study period with total morphine dosage averaging 30 +/- 15 mg. Corresponding values for patients in the continuous groups were 35 +/- 10 times and 23 +/- 5 mg of morphine. The difference was not, however, statistically significant, but when activity during the 2-h time periods immediately before reinjection were examined, patients in the bolus group required and received significantly more morphine than did those in the continuous group (P less than 0.05). Patients in the continuous group had visual analog scale scores that averaged 2.9 +/- 0.6 over the 24-h study period. Patients within the bolus group had visual analog scale scores before and again 30 min after injection that averaged 5.8 +/- 0.8 and 1.8 +/- 0.5, respectively (P less than 0.05).
4
Infantile systemic hyalinosis: newly recognized disorder of collagen? Four infants with stiff skin and painful joint contractures in the first few months of life are described. Other features included small papules, particularly on the face and trunk, perianal nodules, hyperpigmentation over the metacarpophalangeal joints and over the malleoli, gingival hyperplasia, persistent diarrhea, and failure to thrive. Two of these infants died before the age of 18 months. In each case hyaline material was found in the papillary dermis. Ultrastructurally, there was a distinctive fibrillogranular appearance in which a banding pattern could be observed. This material was also found within membrane-bound vacuoles in macrophages and fibroblasts. It had an appearance and localization identical with that of collagen type VI. These features are similar to those reported in juvenile hyaline fibromatosis. It is believed that these infants have a closely related, but nonetheless distinctive, inherited disorder of collagen.
4
Giant breast hematoma requiring blood transfusion: an unusual complication after an echocardiographic study during thrombolytic therapy. We report on a patient in whom significant bleeding occurred during thrombolytic therapy. The bleeding occurred after an echocardiographic study, and it resulted in blood transfusion.
3
Radioimmunology. Imaging and therapy. Targeting of radioactivity to tumors using antitumor antibodies is evolving from a laboratory curiosity toward a practical diagnostic and therapeutic technique that promises widespread benefits for many common human cancers. The development of the hybridoma technique by Kohler and Milstein for producing monoclonal antibodies is probably the single most important contribution to the development of this field. A large array of monoclonal antibodies against many human tumors have been created and labeled with a variety of radioisotopes; 110 clinical trials have been identified from the literature between the interval of 1978 to the present. These studies are beginning to form the basis for certain conclusions regarding likely benefits for certain combinations of antitumor antibodies and isotopes in specific instances of clinical management in patients with malignant neoplasms. For example, in melanoma, lymphoma, neuroblastoma, and colorectal malignancies, radiolabeled antibodies have demonstrated occult tumors, which could not be disclosed with conventional methodologies. Radioimmunotherapy of malignant lymphoma is achieving durable remissions in patients who have failed conventional forms of therapy. For the most part, these advances have been achieved through intelligent application of known principles of immunochemistry, imaging physics, and tumor immunology. Progress has been slow but steady. In a few instances, the term "magic bullet" is warranted in describing the targeting of a particular radiolabeled antibody to a human tumor. I-131, 3-F8, an IgG3 against the GD2 antigen of neuroblastoma, which was introduced by Cheung, and In-111 T-101, against the CD5 antigen of T-cells, which was developed by Royston, stand out because of the consistency and high concentration of radioactive targeting to human tumors in clinical trials. If certain technical innovations fulfill their initial promise, the future will be bright for radioimmunologic methods of diagnosis and therapy. Genetic engineering will permit the development of "humanized" antibodies with biologic properties that favor tumor localization. New chemical approaches will broaden the range of isotopes available as diagnostic and therapeutic radiolabels. Application of modern imaging methodologies, such as positron emission tomography (PET), will detect more lesions of smaller size and permit quantitative imaging for dosimetry considerations. Greater speed and ease of use of computerized work stations will lead to the broader application of fusion imaging in which radioantibody images will be viewed simultaneously with TCT or MRI for better anatomic correlation of abnormal sites of antigen-reactive tumor deposits.
0
Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent.
2
Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs BACKGROUND AND METHODS: This study was designed to explore the effect of mild cerebral and systemic hypothermia (34 degrees C) on outcome after prolonged cardiac arrest in dogs. After ventricular fibrillation with no flow of 10 min, and standard external CPR with epinephrine (low flow) from ventricular fibrillation time of 10 to 15 min, defibrillation and restoration of spontaneous normotension were between ventricular fibrillation time of 16 and 20 min. This procedure was followed by controlled ventilation to 20 hr postarrest and intensive care to 72 hr postarrest. In control group 1 (n = 10), core temperature was 37.5 degrees C; in control group 2 (n = 10), cooling was started immediately after restoration of spontaneous normotension; and in group 3 (n = 10), cooling was initiated with start of CPR. Cooling was by clinically feasible methods. RESULTS: Best overall performance categories achieved (1 = normal; 5 = brain death) were better in group 2 (p = .012) and group 3 (p = .005) than in group 1. Best neurologic deficit scores were 36 +/- 14% in group 1, 22 +/- 15% in group 2 (p = .02), and 19 +/- 18% in group 3 (p = .01). Brain histopathologic damage scores were also lower (better) in groups 2 (p = .05) and 3 (p = .03). Myocardial damage was the same in all three groups. CONCLUSION: Mild cerebral hypothermia started during or immediately after external CPR improves neurologic recovery.
4
Coccydynia. Aetiology and treatment. A five-year prospective trial involving 120 patients was undertaken to investigate the aetiology and treatment of coccydynia. The cause lies in some localised musculoskeletal abnormality in the coccygeal region. Lumbosacral disc prolapse is not a significant factor. The condition is genuine and distressing and we found no evidence of neurosis in our patients. Physiotherapy was of little help in treatment but 60% of patients responded to local injections of corticosteroid and local anaesthesia. Manipulation and injection was even more successful and cured about 85%. Coccygectomy was required in almost 20% and had a success rate of over 90%.
2
Sudden cardiac death while wearing a Holter monitor. The Holter tapes of 61 patients (46 men, mean age +/- standard deviation 65 +/- 11 years) with sudden cardiac death while being monitored were analyzed. Thirty-eight patients were known to have coronary artery disease, 5 had cardiomyopathy, and 7 had aortic valve disease. Etiology remained unknown in 11 patients. Mean New York Heart Association functional class was 2.5 +/- 0.7. Thirty patients had received antiarrhythmic drugs and 32 had received digitalis. Sudden death occurred at rest in 73%. In the hours before death, repetitive ventricular arrhythmias were found in 50 patients (82%), with atrial fibrillation in 34%. Patients with bradyarrhythmic death (18%) had less complex ventricular activity compared to patients with tachyarrhythmic death (p less than 0.01). Lethal arrhythmias--monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, torsades de pointes, primary ventricular fibrillation, and 1:1 conducting atrial tachycardia--were found in 26 (43%), 15 (25%), 5 (8%), 3 (5%), and 1 patient, respectively. The coupling interval of the final ventricular tachycardia correlated inversely with the initial frequency of ventricular tachycardia (p less than 0.05). For patients with tachyarrhythmic death, an increase of heart rate within the last 3 hours was noted (83 vs 89 beats/min, p less than 0.05). Ventricular premature complexes and the proportion of patients with greater than 2 couplets and greater than 2 triplets increased significantly only within the last hour before death.
4
Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance. It has been widely proposed that conversion of xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD), underlies ischemic/reperfusion injury, although the relationship of this conversion to hypoxia and its physiologic control have not been defined. This study details the time course and control of this enzymatic interconversion. In a functionally intact, isolated perfused rat liver model, mean % XOD activity increased as a function of both the duration (25 to 45% in 3 h) and degree (r = 0.97) of hypoxia. This process was markedly accelerated in ischemic liver by an overnight fast (45 vs. 30% at 2 h), and by imposing a short period of in vivo ischemia (cardiopulmonary arrest 72%). Moreover, only under these conditions was there a significant rise in the XOD activity due to the conformationally altered XDH molecule (XODc, 18%), as well as concomitant morphologic injury. Neither circulating white blood cells nor thrombosis appeared to contribute to the effects of in vivo ischemia on enzyme conversion. Thus, it is apparent that conversion to the free radical-producing state, with high levels of XOD activity and concurrent cellular injury, can be achieved during a relatively short period of hypoxia under certain well-defined physiologic conditions, in a time course consistent with its purported role in modulating reperfusion injury. These data also suggest that the premorbid condition of organ donors (e.g., nutritional status and relative state of hypoxia) is important in achieving optimal organ preservation.
4
Interruption of professional and home activity after laparoscopic cholecystectomy among French and American patients. With a laparoscopic approach, patients can undergo cholecystectomy with a shorter hospitalization, minimal pain, and quicker recovery. It has not been demonstrated, however, that patients actually return to work after laparoscopic cholecystectomy faster than the traditional 4- to 6-week absence from work after a standard open procedure. A survey of 104 French and 84 American patients undergoing laparoscopic cholecystectomy revealed that postoperative discomfort was completely resolved in 2 weeks in 73% of French and 93% of American patients. All but 11 French and 5 American patients were back to normal home activities by 2 weeks after the operation. Of the 35 American and 40 French patients who had professional activity outside the home, 63% and 25%, respectively, returned to work within 14 days. Five (14%) of the American patients and 12 (30%) of the French patients returned to work 4 weeks or more after the operation. The amount of physical activity on the job correlated with the period off work, but, interestingly, at least six patients with very hard physical activity at work (including construction workers) were able to return to full work activity within 1 week. These data suggest that early return to work is possible and that pain resolves quickly after laparoscopic cholecystectomy. The economic benefit of having patients back on the job quickly, however, may be less than expected until cultural norms change with regard to leave of absence after major surgery.
4
p53 mutations in colorectal cancer. Immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in approximately 50% of the malignant tumors examined. Benign adenomas were all negative for p53 overexpression. To determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines. Six of the cell lines expressed high levels of p53 in ELISA, cell-staining, and immunoprecipitation studies. Direct sequencing and chemical-mismatch-cleavage analysis of p53 cDNA by using the polymerase chain reaction in these cell lines showed that all cell lines that expressed high levels of p53 were synthesizing mRNAs that encoded mutant p53 proteins. In two of those four cell lines where p53 expression was lower, point mutations were still detected. Thus, we conclude that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis. Mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer.
0
Magnetic resonance imaging of fourth ventricular epidermoid tumors. Two pathologically proved cases of epidermoid tumor of the fourth ventricle are presented; clinical history and computed tomographic, magnetic resonance imaging, and histopathologic findings are included.
0
Cloning of a gene that is rearranged in patients with choroideraemia Choroideraemia (tapetochoroidal dystrophy, TCD), a common form of X-linked blindness, is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina. Previous studies have assigned the TCD gene to a small segment of the Xq21 band. By making use of reverse genetics strategies we have isolated eight overlapping complementary DNA clones from the same chromosomal region. The corresponding gene is expressed in retina, choroid and retinal pigment epithelium. The cDNAs encompass an open reading frame of 948 base pairs that is structurally altered in eight TCD patients with deletions, and in a female patient with a balanced translocation involving Xq21. These findings provide strong evidence that we have cloned the gene underlying choroideraemia. Elucidation of its function should provide new insights into the molecular mechanisms responsible for this disorder and other hereditary retinopathies.
4
The influence of calcium alginate haemostatic swabs upon operative blood loss in adenotonsillectomy. Although adenotonsillectomy is regarded as a minor procedure, it has been shown that 18% of patients may experience an operative blood loss of 10-20% of the total blood volume. The aim of this study was to determine whether calcium alginate haemostatic swabs reduce operative blood loss in adenotonsillectomy. Seventy-two patients (ages 2-12 years) entered a prospective trial in which the operation was performed either with normal gauze swabs or calcium alginate swabs. Thirty-six children were randomized to each group. The mean blood loss was found to be 34.9 ml (2.07% of total blood volume) and 47.8 ml (2.97% of total blood volume) respectively. Although there was no significant reduction in operative blood loss using calcium alginate, in both groups the blood loss was much smaller than that stated by the majority of previous workers.
4
Bronchobiliary fistula detected by cholescintigraphy. We present a case of a bronchobiliary fistula initially detected by hepatobiliary scintigraphy. The patient developed bilioptysis 18 mo after undergoing a right hepatic lobectomy and resection of the common bile duct for cholangiocarcinoma. The procedure was complicated by the development of a subphrenic abscess that required percutaneous biliary drainage.
4
Edwards' syndrome after the replacement of cryopreserved-thawed embryos. A case of Edwards' syndrome after the replacement of frozen-thawed embryos is reported. The presence of cardiac abnormalities and limb deformities raised the suspicion of chromosomal abnormality. The diagnosis of trisomy 18 was made by cytogenetic analysis of fetal blood from the umbilical vein. The chromosomal nondisjunction might have been spontaneous or because of freezing and thawing. If it occurred as a result of freezing and thawing, it is more likely that this was at the first cleavage division rather than the second meiotic division because the embryos were frozen at the late pronuclear stage. Unfortunately, there were no karyotypic markers in the couple's chromosomes to time the nondisjunction. The wisdom of using donor oocytes in an ovum donation program from patients with long-standing infertility is questioned.
4
Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits. Previous studies have demonstrated that bupivacaine administered directly into the central nervous system (CNS) is capable of producing signs of bupivacaine cardiovascular toxicity. To investigate the mechanisms by which bupivacaine may act within the CNS to produce cardiovascular toxicity, we studied four groups of halothane-anesthetized rabbits in which infusion of intracerebroventricular (icv) bupivacaine or intravenous (iv) phenylephrine resulted in dysrhythmias and hypertension. In group 1 (n = 5), icv bupivacaine (500 +/- 79 micrograms [mean +/- SEM]) produced dysrhythmias lasting 73 +/- 13 min, whereas icv saline caused no dysrhythmias or hypertension. In group 2 (n = 9), icv bupivacaine-induced hypertension and dysrhythmias were abolished by icv midazolam in 4.4 +/- 0.6 min, and when dysrhythmias and hypertension recurred (22 +/- 0.9 min), hexamethonium (10 mg/kg iv) promptly terminated dysrhythmias and hypertension (14 +/- 1 s). In group 3 (n = 10), icv bupivacaine-induced dysrhythmias and hypertension were not affected by increasing the inspired halothane concentration from 0.8 to 1.6%. In group 4 (n = 6), iv phenylephrine-induced dysrhythmias and hypertension were not affected by icv midazolam. These results suggest that icv bupivacaine produces dysrhythmias and hypertension by increasing autonomic nervous system (ANS) outflow from the brain stem. The finding that peripheral autonomic blockade by hexamethonium rapidly terminated dysrhythmias and hypertension supports this mechanism. We speculate that icv bupivacaine produces an increase in autonomic outflow by blockade of the inhibitory gamma-aminobutyric acid (GABA) neurons that are known to be the principal tonic inhibitors of the ANS.
3
The use of Glisson's capsule flap in reduced orthotopic hepatic transplantation. The technique of graft reduction has increased the donor pool for children in need of orthotopic hepatic transplantation. However, this technique has been associated with increased perioperative blood loss. Further refinements, such as covering the cut surface of the donor hepatic duct with a flap of Glisson's capsule, may help reduce this complication.
4
Parathyroid hormone and cirrhosis of the liver. Fifty patients with liver cirrhosis (36 alcoholic, 1 drug-induced, 7 posthepatitic, and 6 cryptogenic) and normal renal function were investigated to determine whether PTH levels in serum, measured using the common midregion human PTH-(44-68) RIA, are elevated in such patients and whether this is related to impaired liver function rather than to the effect of secondary hyperparathyroidism. Their data were compared with those from 25 control subjects. The median PTH level of 462 +/- 18 ng/L (+/- SEM) was significantly increased (P less than 0.01) in cirrhotics compared with that of 236 +/- 13 ng/L in the control group. Significant correlations were found between PTH levels and parameters of liver function such as prothrombin time (r = -0.40; P less than 0.01), albumin as a percentage of total protein (r = -0.48; P less than 0.01), bilirubin (r = 0.35; P less than 0.05), albumin (r = -0.34; p less than 0.05), and cholesterol (r = -0.32; P less than 0.05), but not for antipyrine clearance, suggesting increasing PTH with decreasing liver function. The median calcium level (2.26 +/- 0.03 mmol/L), corrected for changes in albumin, was near the lower limit of the normal range (2.25-2.60), but corrected calcium and PTH were positively correlated (r = 0.33; P less than 0.05), indicating that the elevation is not reactive to calcium depletion. A negative correlation existed between PTH and 25-hydroxy-cholecalciferol (r = -0.49; P less than 0.05), the main circulating metabolite of vitamin D. Normal values in an immunoradiometric assay that detects the whole sequence of human PTH-(1-84) suggest that fragments rather than the intact hormone are responsible for PTH elevations in cirrhosis. The positive correlation between midregion PTH and corrected calcium is probably an artifact of the correction formula. In conclusion, midregion PTH fragments are increased in patients with liver cirrhosis. The reason for this elevation may well be the impaired liver function rather than secondary hyperparathyroidism.
1
Prochlorperazine and transdermal scopolamine added to a metoclopramide antiemetic regimen. A controlled comparison. Cisplatin-induced nausea and vomiting occurs both acutely and over a prolonged period of time. These symptoms may be incapacitating and are frequently given as a reason to discontinue therapy. We compared prochlorperazine and transdermal scopolamine when added to a standardized metoclopramide antiemetic regimen. Twenty-seven patients receiving cisplatin at 100 mg/m2 were randomly assigned to one of the two treatment arms. Patients were observed during chemotherapy and answered a standard questionnaire 24-26 hours later. Among similar treatment groups no differences were seen regarding the number of emetic events, level of nausea, degree of sedation or overall acceptability of one treatment arm or another. While not superior to prochlorperazine, transdermal scopolamine is a useful antiemetic agent and can be combined with metoclopramide in an attempt to reduce cisplatin-induced nausea and vomiting. Further evaluation of this approach is needed.
4
Are measurements of height made by health visitors sufficiently accurate for routine screening of growth? To find out whether measurements of height made by health visitors are sufficiently accurate for use in routine screening of children we carried out an interobserver and intraobserver reliability study. Height measurements were made on a group of 10 children aged 3 years old and 10 aged 4.5 years old by two sets of four health visitors. They used a Microtoise or wall chart and the measurements were compared with those made by a trained auxologist with a Harpenden stadiometer. For a single assessment of height both pieces of equipment gave reasonably accurate results. In a child aged 3 years, with height measured on the Microtoise as 100 cm, the true height could be expected--with 95% probability--to lie between 99.2 cm-101.8 cm. At the age of 4.5 years, if the measurement was 110 cm, the child's true height could be expected to lie between 108.9 cm and 111.9 cm. The narrowest confidence interval for the growth rate from 3 to 4.5 years was achieved with the Microtoise, taking the mean of three measurements. We conclude that measurements made by health visitors are sufficiently accurate for routine screening of height, and the use of such measurements for the calculation of height velocity could be improved by more structured training.
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Sudden death associated with undiagnosed Graves' disease. Hyperthyroidism may result in multiple symptoms attributable to an excess of thyroid hormone. We report a case of Graves' disease in association with sudden death in a previously healthy, undiagnosed young female. This case illustrates an unusual initial presentation of Graves' disease.
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Tricuspid valve dysplasia or displacement in intrauterine life. In 450 cases of structural heart disease diagnosed prenatally, 38 fetuses (8.5%) had either a dysplastic or a displaced tricuspid valve. The tricuspid valve was dysplastic in 22 fetuses, all of which had evidence of tricuspid regurgitation resulting in right atrial dilation and increased cardiothoracic ratio. An associated abnormality of the pulmonary valve occurred in 16 fetuses. The remaining 16 fetuses had Ebstein's malformation, 14 with evidence of tricuspid incompetence at presentation and 10 with an associated abnormality of the pulmonary valve. Of the 38 cases, the pregnancy was interrupted in 17, spontaneous intrauterine fetal death occurred in 8, 11 infants died postnatally and 2 infants are still alive; additional abnormalities were found in 8 cases (chromosomal anomalies in 2, ventricular septal defects in 2, corrected transposition in 2, the Chiari malformation in 2, supraventricular tachycardia in 1 case and coarctation of the aorta in 1). Fetuses with severe abnormalities are selected for fetal echocardiography by the four chamber screening program and a high rate of natural loss both in intrauterine life and immediately after birth was observed in the 21 cases in which pregnancy was continued. This would explain the higher incidence of tricuspid valve disease in our prenatal compared with postnatal series. Although increased cardiothoracic ratio and associated lesions of the right ventricular outflow tract contribute to the poor outcome in the cases detected prenatally, the absence of these features does not always indicate a good prognosis because progression of disease can occur with advancing gestational age. No absolute measurement or single echocardiographic feature emerged as a consistent predictive factor of prognosis.
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Role of visceral afferent mechanisms in functional bowel disorders. This report analyzes the clinical and physiological evidence supporting a role for altered visceral afferent mechanisms in the pathogenesis of two functional bowel syndromes: noncardiac chest pain and the irritable bowel syndrome. Considerable recent evidence indicates that increased contractility is present only in a minority of patients and that hypercontractile episodes are not temporally related to abdominal pain. In contrast, altered sensation and motor reflexes in response to physiological stimuli, such as mechanical distention or acid, is common when appropriately investigated. The vagal and spinal afferent innervation mediates visceral sensation and is involved in multiple reflex loops regulating gastrointestinal effector function, such as motility and secretion. Sensory input can be modulated peripherally at the afferent nerve terminal, at the level of prevertebral ganglia, the spinal cord, and the brainstem. An up-regulation of afferent mechanisms would result both in altered conscious perception of physiological stimuli and in altered motor reflexes. Current evidence is consistent with an alteration in the peripheral functioning of visceral afferents and/or in the central processing of afferent information in the etiology of altered somatovisceral sensation and motor function observed in patients with functional bowel disease.
4
Intraoperative coronary excimer laser angioplasty: preliminary clinical experience. Diffuse coronary artery atherosclerosis is generally recognized as a deterrent to successful revascularization if it cannot be adequately treated. Mechanical endarterectomy can be useful, but it is not the optimal solution owing to the associated higher incidences of perioperative infarction and mortality. The use of laser energy as an endarterectomy tool appears promising. To investigate the application of excimer laser radiation to intraoperative coronary artery endarterectomy, 15 stenotic lesions in 13 patients were treated with excimer irradiation during coronary artery bypass grafting. Eleven (73%) of the lesions were enlarged by the excimer probe (6 of the successes were in calcified lesions). The 4 arteries not enlarged by the excimer laser all demonstrated calcified lesions. There were 3 perforations and 2 dissections, all but 1 in heavily calcified arteries. The results of this phase 1 safety and efficacy study indicate that excimer irradiation can recanalize most arteries, including total and subtotal occlusions and some calcified lesions. Further evaluation with better delivery systems is needed to determine whether the perforation rate can be reduced.
3
Biliary tract disease in rats with experimental small bowel bacterial overgrowth. Small bowel bacterial overgrowth, which develops in surgically created jejunal self-filling blind loops, is associated with hepatic injury in susceptible rat strains. The histological findings are portal tract inflammation and bile duct proliferation and destruction. In this study, evidence of injury to the extrahepatic and intrahepatic bile ducts in susceptible and resistant inbred rats with self-filling blind loops was determined by bile flow rates, histological appearance of cross-sections of bile ducts and cholangiography. Lewis and Wistar rats with self-filling blind loops had thickening of the cross-sectional area of the extrahepatic bile ducts compared with controls and nonsusceptible Buffalo rats (p less than 0.001). Daily metronidazole therapy significantly reduced thickening of bile ducts in Lewis and Wistar rats with self-filling blind loops. Bile flow was increased in Lewis and Wistar rats with blind loops compared with controls (p less than 0.05). Cholangiograms of Lewis and Wistar rats with self-filling blind loops demonstrated extrahepatic ductal dilatation and ectasia with irregular, beaded, rapidly tapering and tortuous intrahepatic ducts. Blinded cholangiographical scores of susceptible rat strains with self-filling blind loops were higher (score = 5.9 +/- 2.3) than those of controls (1.2 +/- 0.4), rats with blind loops treated with metronidazole (0.8 +/- 1.3) and nonsusceptible Buffalo rats with blind loops (0.6 +/- 0.9) (p less than 0.01). Biliary histological and cholangiographical abnormalities found in this rat model resemble features of primary sclerosing cholangitis. This animal model will be useful in exploring mechanisms of the association of hepatobiliary inflammation with intestinal injury and investigating potential therapeutic agents.
1
Ventricular arrhythmias in ischemic heart disease. Ventricular arrhythmias remain the leading cause of death from coronary artery disease. This review summarizes current thinking in several areas relating to the pathophysiology, prognosis, and therapy of ventricular arrhythmias associated with acute and chronic coronary artery disease syndromes. The experimental basis of arrhythmias in the setting of acute myocardial ischemia and chronic myocardial infarction is described, stressing the important pathophysiologic differences between these two conditions. The effects of the autonomic nervous system as a key modulator of ischemic arrhythmogenesis are discussed. Insights, derived from endocardial mapping studies, into the nature of ventricular tachycardia in humans with chronic myocardial infarction are described, including implications for risk stratification and therapy to prevent arrhythmia recurrence. Current therapeutic principles are discussed in the management of ventricular arrhythmias associated with coronary artery disease, including pharmacologic approaches, surgical and catheter ablation, and automatic implantable cardioverting and defibrillating devices.
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The effect of continuous drainage of cerebrospinal fluid in patients with subarachnoid hemorrhage: a retrospective analysis of 108 patients. The effects of continuous drainage of cerebrospinal fluid (CSF) on vasospasm and hydrocephalus were analyzed retrospectively in 108 patients with subarachnoid hemorrhage (SAH) who were operated on for ruptured aneurysms within 48 hours of their onset. Ninety-two of these patients underwent a procedure for CSF drainage (cisternal drainage, ventricular drainage, lumbar drainage, or a combination of these). The duration, the total volume, and the average daily volume of CSF drainage were 10.4 +/- 7.0 days (mean +/- SD). 2034 +/- 1566 ml, and 190 +/- 65.3 ml, respectively. Patients with a greater drainage volume at a lower height of drainage in the early period after SAH developed more cerebral infarctions later (P less than 0.025). The relationship between the total volume of CSF removed and shunt-dependent hydrocephalus was determined to be statistically significant (P less than 0.005). Cerebral infarction and hydrocephalus after SAH were also found to be statistically associated (P less than 0.001). Thus, continuous cerebrospinal fluid drainage should not be performed too readily in patients with SAH, because the removal of a large amount of CSF can induce cerebral vasospasm as well as hydrocephalus.
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Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes BACKGROUND. Giant cell myocarditis has rarely been diagnosed premortem, and little is known about its natural history. In addition, no comparative studies with lymphocytic myocarditis exist. METHODS AND RESULTS. The clinical features, serial change in left ventricular fraction (LVEF), and outcomes of all patients with histologically verified myocarditis were retrospectively evaluated. Ten patients (22%) were found to have giant cell myocarditis (group 1), whereas the remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation, gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics did not differ between groups. Ventricular tachycardia was detected in 90% of group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular block that required pacemaker insertion was also more common in group 1 (60%) than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p = 0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p = 0.02). When the net change between initial and final LVEF was assessed, a significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03), actuarial survival over 4 years was not different for the giant cell group (50%) than for the lymphocytic group (62%). CONCLUSION. Giant cell myocarditis was more prevalent than previously recognized and highly associated with both ventricular tachycardia and pacemaker requirement. The likelihood of an adverse event, either cardiovascular mortality or cardiac transplantation, was significantly greater for patients with giant cell myocarditis than for those with lymphocytic myocarditis, perhaps because of the progressive decline in left ventricular systolic function that was observed in those with giant cell myocarditis.
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Molecular biology of circulatory shock. Part III. Human hepatoblastoma (HepG2) cells demonstrate two patterns of shock-induced gene expression that are independent, exclusive, and prioritized. During shock and resuscitation, parenchymal cells of solid organs are exposed to a rapidly changing microenvironment, which may include a reduced oxygen tension and an increased concentration of certain cytokines including tumor necrosis factor alpha and interleukin-1. In vivo experiments that testedl iver biopsied from pigs undergoing cardiogenic shock and resuscitation demonstrated several patterns of gene expression. To study the independent and additive influences of hypoxia and of cytokines in vitro, human hepatoblastoma (HepG2) cells were perturbed by hypoxia/reoxygenation (H/R), by heat shock, and by the cytokines interleukin-1 and tumor necrosis factor alpha alone and in combination. H/R induces new patterns of protein synthesis and secretion that are indistinguishable from those induced by heat shock and independent of the acute-phase response mediated by the cytokines. The H/R (heat-shock) response has priority over and will extinguish gene expression supported by the cytokines. This previously unrecognized hierarchy of stress gene expression could well form the molecular basis of shock-related cell and organ failure.
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Proliferation characteristics of human colorectal carcinomas measured in vivo. The cell proliferation kinetics of 100 human colonic and rectal adenocarcinomas have been studied in vivo by bromodeoxyuridine infusion and multiparameter flow cytometry. A total of 97 patients, three with synchronous tumours, consented to receive a single bolus dose of 250 mg between 2.4 and 16 h before curative or palliative surgery. By this method, the ploidy pattern, the total and aneuploid labelling indices (LI), the S phase duration (Ts) and the potential doubling time (Tpot) can be estimated. Of the tumours 48 were diploid and 52 were aneuploid. The mean and median total LI of 100 tumours were 9.0 per cent (range 0.7-22.2 per cent). The mean aneuploid LI was 12.1 per cent (median 12.0 per cent, range 2.0-25.5 per cent), and was significantly higher than the total LI (P = 0.01). The labelling index alone is not a sufficient indicator of proliferation, because the Ts also varies within and between tumours. The intertumour range of the Ts varied from 4.0 to 28.6 h. The mean was 14.1 h and the median was 13.1 h. The mean Tpot was 5.9 days (median 3.9 days) with a range of 1.7-21.4 days. No correlation was found between any kinetic parameters and the Dukes' classification or histological classification. The correlation between proliferation and prognosis will be established in due course.
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Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery Study (CASS) Quality of life indexes were assessed in 780 patients 10 years after randomization to medical therapy (n = 390) or coronary artery bypass graft surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144 (37%) of the medical group had undergone surgery because of increasing chest pain. At study entry, 22% of medical and surgical patients were angina free; at 1 and 5 years after entry, the frequency of asymptomatic patients was 66% and 63% in the surgical group and 30% and 38% in the medical group. However, by 10 years after entry, the proportion of patients free of angina had fallen to 47% in the surgical group and to 42% in the medical group. Activity limitation and use of beta-blockers and long-acting nitrates were less in the surgical than the medical group at 1 and 5 years after entry but little different from the medical group at 10 years after entry. Throughout follow-up, recreational status, employment status, frequency of heart failure, use of other medications, and hospitalization frequency were similar between the two groups. Thus, indexes of quality of life such as angina relief, increased activity, and reduction in use of antianginal medications initially appear superior in patients with stable manifestations of ischemic heart disease assigned to surgery, but by 10 years after entry, these advantages are much less apparent. Although the observed similarities of the medically and surgically assigned groups at 10 years reflect return of symptoms in the surgical group to some extent, a more important explanation is the performance of late surgery in a large proportion of the medically assigned patients, rendering them asymptomatic.
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Liver and pancreas: improved spin-echo T1 contrast by shorter echo time and fat suppression at 1.5 T. T1-weighted spin-echo magnetic resonance (MR) images have had limited soft-tissue contrast at 1.5 T. The authors investigated the effects of echo-time (TE) minimization and fat suppression on MR images of the liver and pancreas. Two sets of MR images were obtained with identical repetition times and other parameters. In 10 subjects with seven liver lesions, images with TEs of 20 and 12 msec were compared. In 18 additional subjects with seven liver lesions and five pancreatic carcinomas, images with identical TEs but with and without fat suppression were compared. Contrast-to-noise ratios (CNRs) were greater with a TE of 12 msec than with a TE of 20 msec for liver versus spleen (7.6 vs 4.9, P = .014) and liver versus lesion (6.9 vs 3.9, P = .031). In patients without fatty liver, CNR for six lesions versus liver was greater (9.5 vs 6.0, P = .014) with fat suppression. CNR between glandular pancreas and cancer was most conspicuous with fat suppression, but fat planes were less distinct. Minimization of TE improves T1-weighted images significantly. Fat suppression also improves CNR, but the disadvantages of fat suppression do not allow elimination of conventional T1-weighted images.
1
Bradyarrhythmia after heart transplantation. Incidence, time course, and outcome. From June 1980 to April 1989, 72 of 401 (18%) adult recipients of orthotopic heart transplantation developed prolonged (greater than 24 hours) bradyarrhythmias (less than 60 beats/min) within 5 days after transplantation. Junctional bradycardia occurred in 50 (69%) recipients, sinus bradycardia in 18 (25%), and slow ventricular response during atrial fibrillation in four (6%). Fifty-five of 72 (76%) patients had bradyarrhythmias of less than 20 days' duration (less than 7 days, 50 patients; 7-20 days, five patients). Fifty patients returned to sinus rhythm (greater than 60 beats/min) by the time of discharge. Five patients expired within 20 days. Seventeen of 72 (24%) patients had bradyarrhythmia for more than 20 days, which was symptomatic in 11. All 17 patients (junctional bradycardia, 13 patients; sinus bradycardia, four patients) received a permanent pacemaker within 40 days after transplantation. Between 1 and 12 months (mean, 4 +/- 3 months) after pacemaker implantation, 12 patients recovered sinus rhythm (greater than 70 beats/min). The other five patients had intrinsic rates of 32-57 beats/min (mean, 48 +/- 10 beats/min) during 1-9 months (mean, 4 +/- 3 months) of follow-up. The donor ischemic time in bradyarrhythmia patients was 202 +/- 34 minutes, which was significantly longer (p less than 0.01) than the 173 +/- 43 minutes for those patients without bradyarrhythmia. Conclusively, the incidence of posttransplantation bradyarrhythmia is relatively high. It is usually temporary, however, even in patients with a prolonged duration of bradyarrhythmia. A relation appears to exist between donor ischemic time and the incidence of bradyarrhythmia.
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Close correlation of intra-abdominal fat accumulation to hypertension in obese women. The relation between intra-abdominal visceral fat accumulation and blood pressure was investigated in 67 obese women (mean body mass index, 33.6 +/- 3.1; average age, 50 +/- 11 years). As an index of intra-abdominal fat accumulation, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area was determined using a computed tomographic section at the level of the umbilicus. When the obese subjects were divided into a hypertensive group and a normotensive group, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area in the hypertensive group was significantly higher (0.53 +/- 0.33 versus 0.29 +/- 0.12, p less than 0.01). Significant correlations between the ratio of intra-abdominal visceral fat area to subcutaneous fat area and systolic blood pressure (r = 0.62, p less than 0.001) and diastolic blood pressure (r = 0.53, p less than 0.001) also were found. However, no significant difference existed in either the body mass index or the waist-to-hip circumference ratio between the hypertensive and normotensive groups. Plasma renin activity, aldosterone, epinephrine, and norepinephrine levels were not significantly different between the two groups. Moreover, the correlation between the ratio of the intra-abdominal visceral fat area to subcutaneous fat area ratio and blood pressure was found independent of age and body mass index by multiple regression analyses. We conclude that intra-abdominal fat accumulation itself may play an important role in the pathogenesis of hypertension in obesity.
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Sepsis-related cardiogenic shock. To further define cardiovascular abnormalities in patients with septic shock, serial conventional hemodynamic measurements combined with two-dimensional echocardiographic studies were performed at the bedside in 21 patients admitted for an acute episode of sepsis-related circulatory failure. Measurements obtained during the first hours of hospitalization revealed a group of six patients (group 1) with markedly depressed left ventricular function, as evidenced by a low cardiac index (CI) (2.2 +/- 0.8 L/min.m2), reduced left ventricular ejection fraction (LVEF) (21 +/- 8%), and an increased arterial-venous oxygen content difference. Right ventricular systolic function was also severely depressed. These patients were characterized as having sepsis-related cardiogenic shock secondary to profound myocardial depression, which was reversible within 24 to 48 h with inotropic support. The 15 remaining patients (group 2) exhibited an initially increased CI (4.9 +/- 1.8 L/min.m2), with a low systemic vascular resistance. In group 2, LVEF remained within the normal range despite abnormally low peripheral vascular resistance. This finding would suggest the presence of slight to moderate depression of left ventricular systolic function. All patients in this series had a normal left ventricular end-diastolic volume, whether profound myocardial depression was present or not.
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A surgical approach to the cervicothoracic spine. We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care.
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Cytogenetic studies in untreated Hodgkin's disease. Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11-13, 13p11-13, 3q26-28, 6q15-16, and 7q31-35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11-13 (P less than .01), 13p11-13 (P less than .01), 14p11 (P less than .01), 15p11-13 (P less than .02), and 20q12-13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12-13 (P less than .01) and 13p11-13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.
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Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension. Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization.
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Effects of renin inhibition in systemic hypertension. The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension.
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Availability of transplantable organs from brain stem dead donors in intensive care units. OBJECTIVE--By audit from January to June 1989 to quantify, separately for hearts, kidneys, liver, lungs and corneas, the possible increases in transplantable organs from brain stem dead potential donors in intensive care units and to compare them with the increases achieved in October-November 1989, during intense, national publicity about transplantation. DESIGN--Prospective audit of all deaths in intensive care units in England from 1 January to 30 June 1989 and subsequent case study of the impact of publicity on offers and donations during October-November 1989. SETTING--15 regional and special health authorities in England. PATIENTS--5803 patients dying in intensive care units, of whom 497 were confirmed as brain stem dead and had no general medical contraindication to organ donation. MAIN OUTCOME MEASURES--Organ specific suitability for transplantation (as reported by intensive care units); consent for donation of specific suitable organs; and procurement of specific organs reported as suitable for transplantation and offered. RESULTS--In the 497 (8.6%) brain stem dead potential donors were estimated the organ specific suitability for heart as 63%, kidneys 95%, liver 70%, lungs 29%, and corneas 91%. Refusal of relatives (30%) accounted for major losses of suitable organs of all types. For kidneys the loss was equivalent to 44% of brain stem dead actual kidney donors. No discussion of organ donation was the second most important reason for missed kidney donors, the loss being equivalent to 10% of brain stem dead actual donors. Non-procurement or difficulties with allocating organs was the second most notable cause of missed suitable liver and lung donors; 29% (55) of the offered total of 189 liver donors and 27% (21) of 78 offered suitable lung donors in six months. Non-procurement of suitable, offered organs was rare for kidneys and modest, of the order of 13% and 10% respectively, for heart and corneas. Corneal donation from brain stem dead potential donors might be improved nearly as much (that is, a 78% increase in brain stem dead actual corneal donors) by specific measures to promote corneal donation when other organs are offered as by reducing the overall refusal rate. Restricted offers, non-procurement, and no discussion of donation accounted for nearly equal numbers of lost donations of hearts (each equivalent to 15% of donated hearts). During October-November 1989 when there was intense, positive publicity about transplantation the rates of refusal and non-discussion fell compared with during January-June (22%, 36/163 v 30%, 138/460; 7%, 33/497 v 2%, 4/167 respectively). Offers of suitable donors increased significantly (p less than 0.02) compared with the first six months of 1989, most notably for heart donors (80 v 60.1 expected) and kidney donors (122 v 102.1 expected) but only for kidneys was there a noticeable 17% increase in actual donors (118 actual audited donors v 100.8 expected donors; p = 0.09). CONCLUSIONS--Four strategies to increase the supply of transplantable organs from brain stem dead potential donors in intensive care units were identified: (a) reducing refusal of relatives (b) avoiding non-procurement of actually suitable organs (by logistical initiatives) and deterioration of initially suitable organs (by donor care initiatives); (c) converting restricted offers to unrestricted offers; and (d) ensuring discussion with families. Early referral to the transplant team or coordinator gives time for discussion about donor care and agreement on medical suitability for donation of specific organs. Solving some of the logistical problems of non-procurement may be a prerequisite for increased offers to be translated into increased donations. The impact of publicity therefore needs to be measured on offers of suitable donors as well as by actual donations.
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Asymptomatic rhabdomyolysis of unknown etiology. A 7-year-old boy developed rhabdomyolysis with a peak creatine phosphokinase level of 261,400 IU/L after his appendectomy. These abnormalities occurred following a 2-3-day illness consisting of upper respiratory tract symptoms, fever, and abdominal pain mimicking acute appendicitis. At the time of operation, a normal appendix was removed, and mesenteric lymphadenitis was noted. The myoglobinuria and elevation of creatine phosphokinase were transient, and the patient remained asymptomatic. We review various causes of right lower quadrant pain and rhabdomyolysis and address the roles of malignant hyperthermia and infectious agents. The possible cause of the phenomena observed in this patient is discussed.
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Problems of resistant dermatophytes. Recalcitrant fungal infections are defined as infections that are difficult or impossible to eradicate despite seemingly adequate treatment with appropriate oral or parenteral antibiotics. Relative or absolute microbial resistance is only one of the many causes of recalcitrance. Others include failure of the patient to comply with the prescribed treatment regimen, drug degradation in the liver, drug-drug interactions, reabsorption or washout of the drug from the stratum corneum, and failure of the drug to reach the stratum corneum. Excretion in the eccrine sweat is the principal pathway by which griseofulvin and ketoconazole, the two currently available oral antifungal agents, are delivered to the stratum corneum. Measures that promote delivery of these drugs to this site by enhancing sweating and minimizing drug run-off and absorption onto clothing may aid in optimizing the therapeutic response to these agents.
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Closure of refractory perineal Crohn's lesion. Integration of hyperbaric oxygen into case management. A case is reported in which a comprehensive program of hyperbaric oxygen (HBO), surgical debridement and reconstruction, and continuing medical management resulted in complete and sustained closure of an extensive perineal Crohn's lesion refractory to conventional medical and surgical management. It is emphasized that in this case healing occurred in the setting of previous removal of all diseased intestinal tissue and only with the combined use of all three treatment modalities. HBO may be a useful adjunct in the therapy of large nonhealing perineal lesions post-proctocolectomy in patients who are unresponsive to metronidazole or to immunosuppressant therapy or who experience limiting side effects from continued medical therapy.
1
A cost-minimization study of cancer patients requiring a narcotic infusion in hospital and at home. We conducted a retrospective, non-randomized, cost-minimization study, from the perspective of the Ministry of Health, to compare the cost of managing cancer patients who required narcotic infusions, in hospital and at home. Our medical costs averaged $369.72 per inpatient day and $150.24 per outpatient day (saving $219.48 per diem, 1988 Canadian dollars), while narcotic costs were the same for any given patient in both settings. Sensitivity analysis showed that no reasonable changes in the quantity and cost of services reduced our savings by more than 50%. During incremental analysis, savings increased as more outpatient days were managed by our centre, from $0.00 for 318 days, to more than $500,000 for over 2000 days per annum. As this program has been extremely cost effective and preferred by our patients, other hospitals and central funding agencies might consider establishing a regional outpatient narcotic infusion program to reduce their costs.
0
Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits. Platelet-activating factor is a potent mediator of inflammation, which has untoward effects on cerebrovascular and neural elements. While several investigators have reported attenuation of ischemic damage after treatment with antagonists of platelet-activating factor, no study has proved endogenous production of platelet-activating factor in ischemia of the central nervous system. We hypothesized that endogenous production of platelet-activating factor participates in the early pathologic manifestations of deteriorating stroke. In 12 rabbits, we found tissue levels of platelet-activating factor measured by the release of serotonin from washed platelets to be elevated by approximately 20-fold in spinal cord injured by 25 minutes of ischemia and 2 hours of reperfusion (2.80 +/- 0.98 ng/g) compared with that in normal spinal cord (0.15 +/- 0.06 ng/g, p less than 0.01). Given during ischemia to seven rabbits, 10 mg/kg i.p. of a highly selective and potent antagonist of platelet-activating factor (BN 50739) accentuated the early postischemic hyperemia and prevented the delayed hypoperfusion measured by on-line laser-Doppler flowmetry (-35 +/- 7% of baseline [n = 7] without versus 33 +/- 14% with treatment, p less than 0.01) and the edema formation measured as the increase in tissue water content (4.4 +/- 0.7% without [n = 6] versus 2.1 +/- 0.6% with [n = 7]treatment, p less than 0.05) after 2 hours of reperfusion. This neurochemical and pharmacologic evidence emphasizes a new perspective of ischemia-induced phospholipid degradation and suggests an important role for platelet-activating factor in the early manifestations of stroke.
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Prognosis of acute myocardial infarction complicated by primary ventricular fibrillation. Principal Investigators of the SPRINT Study. In 5,839 consecutive patients with acute myocardial infarction (AMI), hospitalized between July 1981 and July 1983 in 14 coronary care units in Israel, the incidence of primary ventricular fibrillation (VF) was 2.1%. Patients with primary VF resembled counterparts without VF in terms of age, gender, frequency of previous AMI and past cigarette smoking habits. The hospital course of patients with primary VF revealed increased incidence of primary atrial fibrillation and atrioventricular block. Increased serum levels of glutamic oxaloacetic transaminase and lactic dehydrogenase were noted among the patients with primary VF. In-hospital mortality rate was 18.8% in 122 patients with primary VF compared with 8.5% in 3,707 patients forming the reference group (p less than 0.01). Adjustment by age using logistic function yielded an estimate of 2.86 for relative mortality odds associated with primary VF, and further adjustment by gender, history of AMI, systemic hypertension, and by enzymatically estimated infarct size slightly reduced the estimated odds, at 2.52 (95% confidence interval, 1.42 to 4.46). Prognosis after discharge from the hospital was independent of primary VF. In conclusion, primary VF exerts an independent, significant effect on in-hospital mortality.
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Risk factors for white matter changes detected by magnetic resonance imaging in the elderly. We found increased age (p = 0.001) and history or evidence of stroke (p = 0.016) to be significant independent multivariate predictors of the presence and severity of leukoencephalopathy on magnetic resonance imaging brain scans in a mixed population of 35 elderly psychiatric patients and 25 neurologically healthy elderly volunteers. These results suggest that subcortical ischemia, as well as age-related changes that may not be vascular in origin, contribute to the emergence of periventricular and other deep white matter hyperintensities that are commonly seen on the magnetic resonance imaging brain scans of older adults.
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Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now.
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Autologous transplantation of adrenal medulla in Parkinson's disease. 18-month results. Eighteen of 19 patients who underwent autologous adrenal medullary transplantation to the right caudate nucleus have been followed up for 18 months. During the course of this study, a statistically significant improvement was noted in percent "on" time, percent "on" time without dyskinesia, activity of daily living (ADL) scores during the "on" stages, and ADL, motor, and Schwab-England scores during the "off" stages. Benefits tended to be maximal at 6 months and to gradually lessen thereafter, although statistically significant improvement in comparison with baseline was still present at 18 months for ADL, motor, and Hoehn-Yahr scores during the "off" stages. Almost all parameters had deteriorated by 18 months compared with 12 months, including those remaining significantly improved in comparison with baseline. These patterns were similar for each of the three participating centers. Complications were largely restricted to the perioperative period.
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The mechanism of heart failure caused by cardiac allograft rejection. Rejection of the cardiac allograft is often associated with reversible myocardial failure, the mechanism of which is not understood. We have examined this phenomenon in a small animal model that provides the opportunity for multimodality study of the rejection process. Heterotopic cardiac transplantation was performed in the Lewis rat with Lewis X Brown-Norway (allografts) or Lewis (isografts) donors. Without immunosuppression, allografts are completely rejected in 6 to 8 days. At 3 days cardiac grafts were explanted and mounted on a modified Langendorff apparatus for functional measurements or submitted for pathologic examination and biochemical determination of high-energy phosphates. Three-day isografts (n = 9) had minimal histologic changes. Pathologic examination of 3-day allografts (n = 13) showed lymphocytic infiltrate and myocyte necrosis, histologic features for which antirejection treatment is usually given clinically. For grafts subjected to functional studies (n = 11), heart rate, cardiac output, coronary flow, and stroke work were determined at baseline and in response to isoproterenol (3 x 10(-8) mol/ml). Three-day allografts (n = 6) and isografts (n = 5) had similar baseline function. The chronotropic response to isoproterenol was similar in allografts and isografts, but allografts had diminished cardiac output and stroke work after isoproterenol. Adenosine triphosphate levels were normal (41.9 nmol/mg) in 3-day allografts (n = 4). We have evaluated functional, biochemical, and pathologic changes associated with myocardial dysfunction during heterotopic cardiac transplant rejection in a small animal. This model reproducibly demonstrates diminished contractile reserve in 3-day allografts with normal baseline function and high-energy stores but histologically significant rejection.
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Use of recombinant human erythropoietin to enhance autologous blood donation in a patient with multiple red cell allo-antibodies and the anemia of chronic disease. We treated a patient with alcohol-induced cirrhosis, intractable pain from a defective hip prosthesis, and multiple red cell allo-antibodies with recombinant human erythropoietin (EPO) in order to facilitate collection of blood for autologous transfusion during an elective total hip revision. This patient had experienced a delayed transfusion reaction 4 months earlier after receiving least incompatible packed red cells for gastrointestinal bleeding. His blood could not be crossmatched because of the development of multiple antibodies to homologous blood given during previous surgery and several episodes of gastrointestinal hemorrhage. Following initiation of EPO therapy, there was a prompt and persistent increase in the reticulocyte count from a baseline of 1.6% to a maximum of 8.6%. This was accompanied by maintenance of the hematocrit between 32% and 38.5% despite withdrawal of seven units of autologous blood over the 45-day treatment period. Poor venous access and availability of blood bank personnel, not hematocrit level, were the limiting factors that determined how frequently blood could be collected. We conclude that EPO stimulated erythropoiesis in this patient with underlying anemia of chronic disease and facilitated harvest of autologous blood for elective surgery.
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Spontaneous reactivation in chronic hepatitis B: patterns and natural history. We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B.
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Changing demographics in the United States. Implications for health professionals. The coming decade will bring dramatic changes in the composition of the American population. Changes in immigration laws, illegal and legal immigration into this country, and the aging of the "baby boomers" will all result in profound changes in the demographics of this country. These demographic changes will necessitate alterations in all aspects of the health care system. This article focuses on the projected changes that will occur in relation to the elderly, Hispanics, Asian Americans, and the economically disadvantaged, and on the related implications for health care professionals. The cancer incidence and mortality rates for each discussed minority group differ from the rates presently reported for white Americans. Thus, health professionals will have to be aware of the differences among these groups and tailor their primary and secondary prevention efforts accordingly. The future task for all health care providers serving minorities and the elderly will be to familiarize themselves with the special health problems of the population with whom they work and with the ethnocultural barriers that deter proper use and delivery of health services.
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Treatment of chronic tinea pedis (athlete's foot type) with topical terbinafine. Twenty-seven patients with chronic tinea pedis, athlete's foot type, were enrolled in a randomized, double-blind trial of topical treatment with terbinafine 1% cream versus its vehicle (placebo). Patients were examined weekly during 4 weeks of twice-daily treatment and at follow-up 2 weeks after the conclusion of therapy. No adverse events were reported in either treatment group. Drug efficacy was evaluated in 22 patients, of whom nine (41%) were treated with terbinafine and 13 (59%) with placebo. Analysis of combined mycologic and clinical results showed that terbinafine was significantly more effective than placebo at the end of therapy (78% vs zero) and at the 2-week follow-up (89% vs zero) (p less than or equal to 0.001 at both intervals.
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Substance P, acetylcholinesterase, and beta-endorphin levels in the plasma and pericardial fluid of patients with and without angina pectoris. We measured substance P-like immunoreactivity (SPLI), beta-endorphin-like immunoreactivity (BELI), acetylcholinesterase activity, and total protein content in pericardial fluid and plasma of patients with angina pectoris and patients with no angina pectoris. SPLI and BELI levels, acetylcholinesterase activity, and total protein content were determined by radioimmunoassay, a colorimetric method, and by the method of Lowry et al. (J Biol Chem 1951; 193:265-75), respectively. In the pericardial fluid, patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 1.69 +/- 0.23 fmol/mg protein, 0.16 +/- 0.13 fmol/mg protein, 0.06 +/- 0.02 units, and 25.7 +/- 3.2 mg/ml, respectively. Patients with no angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.93 +/- 0.17 fmol/mg protein, 0.19 +/- 0.10 fmol/mg protein, 0.16 +/- 0.02 units, and 44.6 +/- 5.3 mg/ml, respectively. SPLI levels were significantly higher (p less than 0.03), and acetylcholinesterase (less than 0.002) and total protein content (less than 0.004) were significantly lower in the pericardial fluid of patients with angina when compared with those of patients with no angina. BELI levels were not significantly different between the two groups. In the plasma, no significant differences were found in SPLI, BELI, acetylcholinesterase, and total protein values between the two groups of patients. Patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.47 +/- 0.26 fmol/mg protein, 0.06 +/- 0.06 fmol/mg protein, 0.29 +/- 0.15 units, and 68.2 +/- 8.7 mg/ml, respectively.
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