HLA-DRB1*03, but not the TNFA -308 promoter gene polymorphism, confers protection against fistulising Crohn's disease

Crohn's disease (CD) appears in forms so diverse that it has been hypothesized CD might be a syndrome, with different pathogenic mechanisms leading to the various clinical phenotypes. This may plausibly explain the conflicting and inconclusive results with regard to HLA associations in unselected groups of patients. The power of these association studies may increase when disease heterogeneity is taken into account. As fistulising CD has been proposed as a separate subgroup of patients with CD, we studied the carrier frequencies (CF) of the DRB1 alleles in 35 unrelated Caucasian Dutch CD patients with proven peri-anal fistulas. A striking decrease in the frequency of the DRB1(*)03 allele was found in those patients with peri-anal fistulas when compared with a panel of 2400 healthy controls (HC) (3% vs 25%; P = 0.005; Odds Ratio [OR] = 0.09). The DRB1(*)03 allele is in strong linkage disequilibrium with a polymorphism at position -308 in the promoter region of the gene encoding TNFalpha (TNFA-308(*)2). We investigated whether this allele frequency was decreased as well. Surprisingly, the CF of TNFA-308(*)2 was 29%, not different from the CF of 98 HC (34%; P = 0. 7; OR = 0.8). This study is the first showing a significant negative association between DRB1(*)03 and a particular subgroup of CD patients. Thus, patient selection may largely determine the outcome of genetic association studies in CD, as we previously observed no association with this allele in an unselected population of CD patients. As DRB1(*)03 frequency, but not the closely linked TNFA-308(*)2, was decreased, this suggests recombination between the DRB1 and TNFA loci in this group of patients, and may help to define the biological basis of fistula formation.     

A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues

The long-term clinical effects of soy protein containing various amounts of isoflavones on lipoproteins, mononuclear cell LDL receptor messenger RNA concentrations, and other selected cardiovascular risk factors are not well known. Sixty-six hypercholesterolemic, free-living, postmenopausal women were investigated during a 6-mo parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, all subjects were randomly assigned to 1 of 3 dietary groups (all with 40 g protein): a National Cholesterol Education Program (NCEP) Step 1 diet with protein from casein and nonfat dry milk (control), an NCEP Step 1 diet with protein from isolated soy protein containing moderate amounts of isoflavones (ISP56), or an NCEP Step 1 diet with protein from isolated soy protein containing high amounts of isoflavones (ISP90). Non-HDL cholesterol in both the ISP56 and ISP90 groups was reduced compared with the control group (P < 0.05), whereas total cholesterol was not changed. HDL cholesterol increased in both the ISP56 and ISP90 groups (P < 0.05), whereas the ratio of total to HDL cholesterol decreased significantly in both groups compared with the control (P < 0.05). Mononuclear cell LDL receptor messenger RNA concentrations increased in subjects consuming ISP56 or ISP90 compared with the control (P < 0.05). These results indicate that soy protein, with different amounts of isoflavones, may decrease the risk of cardiovascular disease via improved blood lipid profiles, and that the mechanism by which apolipoprotein B-containing lipoproteins were depressed may be via alterations in LDL receptor quantity or activity.     

Pregnancy following gastric bypass for morbid obesity

BACKGROUND: Women who suffer from morbid obesity are often infertile. If these women are able to become pregnant, they are considered high risk because of the hypertension, diabetes and other associated risk factors. Following the pregnancy is difficult due to limitations of the physical examinations. More costly ultrasound examinations are needed at a higher frequency. Bariatric surgery reduces the woman's weight and the incidence of obesity related co-morbidities. The number of pregnancies and rate of complications during those pregnancies in our post-bariatirc surgical patients were evaluated. METHOD: Our group has been doing bariatric surgery since the early 1980s. We have over 2000 active patients on our current newsletter mailing list. The patients also have a series of networks through support groups. The patients are informed to contact us when they become pregnant so we may assist the obstetrician with their care. Through these various means, we have been able to identify 41 women in our patient population who have become pregnant. Using personal interview, questionnaire, and review of perinatal records, pregnancy-related risks and complications were studied. RESULTS: With over a 95% follow-up rate on the patients identified as having been pregnant following surgery, we found less risk of gestational diabetes, macrosomia, and cesarean section than associated with obesity. There were no patients with clinically significant anemia. CONCLUSION: Since the patients had an operation that restricts their food intake, some basic precautions should be taken when they become pregnant. With this in mind, our patients have done well with their pregnancies. The post-surgical group had fewer pregnancy-related complications than did an internally controlled group that were morbidly obese during their previous pregnancies.     

Electrocardiographic patterns relative to initiating mechanisms of exercise-induced ventricular tachycardia

The initiating mechanisms of exercise-induced ventricular tachycardia were studied in a population of 5842 patients who performed 9064 bicycle exercise tests. Sixty (1%) patients had 194 episodes of ventricular tachycardia during the test. Forty-two percent of these occurred during exercise and 58% during recovery. Two different initiating electrocardiographic patterns were observed. In 17 (28%) patients ventricular tachycardia was initiated by a short-long-short sequence of R-R intervals (group 1). Thirty-eight (63%) patients did not have this pattern of interval changes preceding ventricular tachycardia (group 2). Five (8%) other patients showed both patterns. The clinical characteristics of the groups were different for angina and cardiomyopathy but not for previous myocardial infarction. In group 1 ventricular tachycardia was related to recovery (76%; p < 0.05). In group 2 tachycardia occurrence was equally divided between exercise and recovery. The electrocardiographic differences suggest that different initiating mechanisms are involved in the development of exercise-induced ventricular tachycardia. The present findings may enhance aimed drug therapy in ventricular tachycardia.     

Clinical rheumatology training of Australian medical students. A national survey of 1991 graduates

OBJECTIVE: To describe Australian medical graduates' knowledge, experiences and practical training in rheumatology and their attitudes towards rehabilitation and disability. DESIGN: Cross-sectional survey of all interns at randomly selected hospitals in each State. PARTICIPANTS: 382 Australian interns at 12 hospitals surveyed in the first week of their 1991 internship. RESULTS: New interns demonstrated little experience with soft tissue rheumatism, with only 45% reporting they had examined a patient with bursitis and 22% one with epicondylitis. There was considerable dissatisfaction with the teaching of assessment of low back pain, regardless of the amount of formal rheumatology teaching the graduates had experienced, with only 22% rating it as good or excellent. There was little evidence that students are exposed to the social dimensions of chronic illness; only 32% of students reported that they had been shown how to assess a patient's psychological adjustment to illness. Only 22% felt competent at assessing disability and handicap and less than half of the graduates studied had ever attended a clinic where there was a physiotherapist. Graduates who had never been attached to either a rheumatology ward or an outpatients clinic (17%) were less likely to have examined a patient with gout (P < 0.001), osteoarthritis (P < 0.01), or chronic low back pain (P < 0.05), and were more likely to report dissatisfaction with training in rheumatology. CONCLUSION: This survey suggests that there are significant problems in the training of medical students in musculoskeletal disorders, particularly in relation to the assessment of disability and the appreciation of psychosocial factors.