Pseudomembranous colitis in siblings.
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Biomedical subjects
Publications and source records attributed to L Levy.
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N-Methylformamide (NMF) has been reported to cause liver damage in animals and man. This hepatotoxicity was characterized in BALB/c mice by the release of liver enzymes into the plasma and by histopathological examination of livers after single and repeated administration of NMF. Whereas plasma levels of sorbitol dehydrogenase were elevated dramatically 24 hr after 400 mg/kg given as a single dose, the glutathione content of the livers was not different from controls even after repeated administration. Liver damage was apparent on gross inspection and was defined as periacinar necrosis on histopathology. A dose of 100 mg/kg did not cause damage even after repeated injections on five consecutive days. The hypothesis that NMF is metabolized to a chemically reactive species was tested. Incubation of mouse hepatocytes with 7 mM NMF for 80 min produced a decrease in intracellular glutathione. Exposure of hepatocytes to NMF for 240 min led to the production of breakdown products of lipid peroxides at levels significantly above controls. However, incubation of microsomes or mitochondria with NMF and NADPH did not lead to raised levels of lipid peroxides. The effects described were specific to NMF as incubation of N,N-dimethylformamide, N-hydroxymethylformamide or formamide with hepatocytes did not result in glutathione depletion or increased lipid peroxidation. NMF undergoes extensive metabolism in vivo and the results indicate that NMF forms a chemically reactive metabolite, even though incubation of the drug with liver fractions or hepatocytes did not lead to metabolites at levels which were analytically identifiable.
Tilorone, a synthetic inducer of interferon found earlier to inhibit multiplication of Mycobacterium leprae in the foot pad of the mouse while it enhanced infections of mice by M. lepraemurium and M. marinum, has been shown to exert a dual effect on M. leprae infection of the mouse. When administered continuously, incorporated into the mouse diet in a concentration of 0.015 g per 100 g diet, the drug was usually immunosuppressive, permitting enhanced multiplication of the organisms. When administered in a 3-fold larger concentration beginning during the lag phase or early during logarithmic multiplication, tilorone was antimicrobial; however, when administered in the larger concentration beginning after logarithmic multiplication had been well established, the drug was immunosuppressive. The antimicrobial action of tilorone against M. leprae appears to be a direct action that is weak and slow in onset. The mechanism of the immunosuppressive action remains to be elucidated.
The energy needs, nutritional status and body composition of 6 undernourished adolescents and young adults with cystic fibrosis (3 male and 3 female) were studied prior to and following a 12 day period of refeeding. Nutritional rehabilitation was attempted with continuous naso-gastric feeding of an elemental diet. The energy needs of the patients were shown to be 25-80% higher than in healthy individuals of the same age, sex and size. Lean body mass as judged by measurement of total body potassium and nitrogen was relatively well preserved, but there was significant wasting of adipose tissue. During the short period of refeeding, body weight, fat and potassium all increased significantly, while fat free body mass and total body nitrogen did not change. A model is proposed for the aetiology of undernutrition in the adolescent and young adult cystic with deteriorating lung function. Based on this model and the finding of the short-term N/G refeeding program described in this paper, we have embarked on a long-term supplementation study in malnourished CF patients who do not respond to dietary counselling and oral supplementation.
In an effort to assess the contribution of B-lymphocyte-mediated mechanisms to the immune responses to several mycobacteria, responses to these intracellular pathogens were compared in immunologically normal CBA/CaHN mice and in histocompatible CBA/N (Xid) mice, which exhibit abnormalities of B-lymphocyte function. Swelling in response to local inoculation with Mycobacterium marinum was significantly greater in the hind feet of CBA/CaHN mice than in those of CBA/N mice, but the difference was very small. Survival of mice of both strains after i.v. challenge with M. marinum or i.p. challenge with M. leprae-murium did not differ significantly. Finally, multiplication of M. leprae in the footpads of mice of both strains did not differ significantly. Thus, B-lymphocyte-mediated mechanisms do not appear to be important in the immune responses of mice in experimental infections with these mycobacterial species.
In C57BL mice inoculated with Mycobacterium marinum in the right hind foot pad 2 weeks earlier ("previously infected mice"), inoculation of M. marinum into the left hind foot pad was followed by accelerated enlargement of the left popliteal node. Popliteal-node lymphocytes harvested from previously infected donors, labeled with 3H-uridine in vitro, and infused intravenously into previously infected recipients at the time of reinfection in the left hind foot pad homed on the left popliteal node. Similarly, there was an accelerated increase of the number of labeled lymphocytes in the left popliteal node of previously infected mice infused intravenously with 3H-thymidine 24 or 48 hr after reinfection in the left hind foot pad. Accelerated enlargement of the lymph node and the early accumulation of labeled lymphocytes in the popliteal lymph node draining the foot pad reinfected with M. marinum appeared more likely to have resulted from influx and accumulation of lymphocytes than from local proliferation, especially as the lesion of the left hind foot pad is a very modest one, and the quantity of antigen in the left hind foot pad and draining node is very small. The accumulation of lymphocytes, which is the cause of the accelerated node enlargement, appears to require the presence of both antigen and antigen-reactive lymphocytes.
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Comparison of mild-to-moderate essential hypertension patients treated for 6 weeks by antihypertensive medication versus metronome-conditioned relaxation versus biofeedback versus a mild exercise control procedure showed that those on medication achieved the greatest decrease in blood pressure. The relaxation and biofeedback groups decreased more than the mild exercise group, as predicted, but not significantly more. The differences in benefits of the groups were not a function of group differences in initial blood pressure levels nor in compliance. Nor did the groups differ in the side effects that are usually associated with medications. A second phase of 6 weeks with another treatment or combination of treatments did not add significantly. Some characteristics of patients moderately predicted treatment benefits, for example, high scores on the Jenkins Activity Survey Scales (1) [Type A, S or H], for the relaxation and biofeedback treated patients predicted which patients received greater benefits.
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