[Oral antidiabetic monotherapy and combination treatment with glybenclamide (HB 419) and biguanides of insulin receiving diabetics of the adult type].
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Biomedical subjects
Publications and source records attributed to P Netter.
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Three respiratory-deficient mutants of cytochrome oxidase subunit I in the yeast mitochondrion have been sequenced. They are located in, or near, transmembrane segment VI, the catalytic core of the enzyme. Respiratory-competent revertants have been selected and studied. The mutant V244M was found to revert at the same site in valine (wild-type), isoleucine or threonine. The revertants of the mutant G251R were of three types: glycine (wild-type), serine and threonine at position 251. A search for second-site mutations was carried out but none were found. Among 60 revertants tested, the mutant K265M was found to revert only to the wild-type allele.
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Only a very few studies on the effects of cold on human information processing appear to exist. Therefore, the present experiment was designed to study the effects of the experimentally induced lowering of body core temperature on information processing, while applying a reaction time paradigm. Thirty healthy male volunteers performed a stimulus evaluation-response selection reaction time task after exposure to ambient temperatures of either 28 or 5 degrees C. A 0.5 degree C-decrease in body core temperature resulted in a significant increase in both reaction and movement time indicating a general deteriorating effect of lowering of body core temperature on information processing. Mean reaction times were 538 ms and 549 ms for the control and the cold group, respectively (p < .05). The respective mean movement times were 298 ms and 269 ms (p < .001). Speed of stimulus evaluation was not sensitive to decreases in body core temperature. However, response complexity and body core temperature showed a significant interaction in their effect on movement time (p < .05), indicating that lowering of body core temperature is more likely to affect response-related stages of central information processing rather than stimulus evaluation. Furthermore, movement time appeared to be more sensitive to cold-induced effects on information processing as compared to reaction time. Additional correlational analyses suggest that the observed effects can be considered as independent of changes in skin temperature and experienced levels of thermal discomfort. Taken together, the results indicate that lowering of body core temperature differentially affects various stages of information processing.
Free and bound fractions of salicylates were separated by equilibrium dialysis and measured by spectrofluorimetry in 27 patients with rheumatoid arthritis and in 16 controls. The results showed that in patients with rheumatoid arthritis, the binding of salicylate to proteins decreased in an overproportional manner with the decrease of serum albumin concentrations. This phenomenon was linked with the severity of the inflammatory syndrome. The saturation binding capacity per unit of protein concentration was lower in the patients suffering from active forms of the condition, a finding which suggests that the changes observed are not due only to quantitative changes in the serum albumins. This study confirms the importance of determining free salicylate concentrations in the treatment of patients with inflammatory diseases.
Histamine H2-receptor antagonists are widely used in the treatment of gastrointestinal diseases related to gastric acid hypersecretion. Cimetidine was introduced into medical practice in 1976 and ranitidine, famotidine and nizatidine in 1981, 1985 and 1987, respectively. Haematological adverse effects are relatively uncommon and most have been reported in cases of cimetidine administration. These adverse effects are reviewed under 4 main headings: (a) blood cytopenias and leucocytosis; (b) coagulation disorders related to drug interactions with oral anticoagulants; (c) reduction of dietary iron absorption; and (d) reduction of dietary cobalamin absorption. 85 reported cases of blood cytopenias attributed to these drugs are reviewed, of which 75 (88%) were associated with cimetidine therapy. In postmarketing surveillance studies, the incidence of cimetidine-associated blood cytopenia has been evaluated at about 2.3 per 100,000 patients. Neutropenia and agranulocytosis are by far the most frequently encountered. Whatever the drug or the type of cytopenia, this adverse effect is almost always rapidly reversible when treatment is stopped. Moreover, in several cases other factors such as underlying diseases or additional drugs could have been responsible, at least partly, for the cytopenia. The pathophysiological basis of these adverse effects remains poorly explained. Various mechanisms have been proposed, which in some cases are probably associated: (a) direct toxicity for haemopoietic stem cells; (b) drug-induced immune reactions leading to blood or bone marrow cell damage, and (c) drug interactions, with increased and prolonged action of potentially haematotoxic drugs. Mechanisms (a) and (c) appear to be of particular clinical importance in cases of impaired renal elimination of H2-receptor antagonists. Cimetidine and probably to a lesser extent ranitidine potentiate the action of oral anticoagulants of both coumarin and indanedione structure. This may result in haemorrhagic complications. Such action is a consequence of the reduced hepatic metabolism of oral anticoagulants through a dose-dependent, reversible inhibition of cytochrome P450. Malabsorption of dietary iron and cobalamin appears to result from inhibition of gastric secretion by the H2-receptor antagonists. This is of no clinical importance in short term treatment, but long term use of H2-receptor antagonists may theoretically contribute to the occurrence of iron or cobalamin deficiency anaemia.
The effect of lowering body temperature on plasma epinephrine, norepinephrine, and platelet density distribution and volume was studied in a placebo-controlled double-blind study. Lowering of body core temperature was induced by either exposure to a cold environment at a temperature of 5 degrees C (CT) or by a single dose of the 5-HT1A agonist ipsapirone (IPS). A third group exposed to an ambient temperature of 28 degrees C was given placebo (PLAC). All of the three groups were investigated in a climate chamber. In the CT group the density distribution of blood platelet subpopulations was shifted to an increase in less dense platelets that were more sensitive towards aggregation-inducing agents. The mean platelet volume in this subpopulation was decreased. Epinephrine was not affected, whereas the increase of norepinephrine was correlated with an increase of platelets that were more sensitive to aggregation-inducing agents in the CT group but not in the PLAC and IPS groups.
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Life prolongation in cancer patients is attended by a greater frequency of renal lesions associated with chemotherapy, and in the last few years cancer patients cured or in lasting remission have begun to haunt dialysis centres. Before blaming the renal toxicity of cytotoxic drugs, it is necessary to exclude all other causes of renal dysfunction (pre-renal, obstructive, iatrogenic or cancer-related). The renal toxicity of certain drugs, such as cisplatin, cyclophosphamide, ifosfamide, streptozocin, nitrosoureas, methotrexate, mitomycin C and recombinant IL2, is of importance as it is frequent and limits their use. The dangers of anticancerous drugs combinations, concomitant administration of other nephrotoxic drugs (antibiotics, non-steroidal anti-inflammatory agents) and extracellular dehydration created by gastrointestinal disorders must be borne in mind. Careful evaluation of renal function prior to chemotherapy, application of preventive measures with proven efficacy and repeated laboratory tests in short-mid- and long-term should reduce the frequency of renal complications while preserving or even improving therapeutic effectiveness.
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Two cases of pseudo-alcoholic amiodarone-induced hepatitis are reported. The authors mention the different clinical forms of the disease and describe its clinical, biochemical and histological features. They stress the unpredictable and discordant character of its course and the influence of associated pathological factors. The role played by Ito's cells in the genesis of the liver fibrosis observed in amiodarone toxicity is discussed.
Ten patients (average age 51 years) on long-term hemodialysis (average duration 13.5 years) were examined by magnetic resonance (MR) (all cases) and CT (five cases) for cystic radiolucencies of the wrist, shoulders, and hips. MR and CT revealed more lesions of smaller size than plain films and both showed a constant communication with the joint space. Synovial hypertrophy was generally absent or very mild even in the case of large osseous erosions. The MR analysis of the content of the lesions in the wrist was quite variable: low signal on T1- and T2-weighted images (12 of 24), low signal on T1- and high signal on T2-weighted images (10 of 24), and high signal on T1- and T2-weighted images (2 of 24). The patterns of transplanted (four cases) or ungrafted (six cases) patients were indistinguishable. These results suggest an articular origin of the lesions, but different from synovial processes such as rheumatoid arthritis, and confirm their probable multifactorial pathogenesis.
The effects of alcohol tolerance on stress sensitivity to venipuncture and mental arithmetics, on acute ethanol effects, and on ethanol-induced modifications of stress responses were tested in 44 healthy male volunteers selected according to a questionnaire as 22 high (HC) and low (LC) habitual consumers of alcohol each. Plasma epinephrine (E) and norepinephrine (NE), mood check lists, and performance scores were obtained at two mental arithmetic stressors, one applied before and one after their intake of 0.8 g/kg of ethanol or a respective placebo drink. HC were less responsive with both E and NE to venipuncture and to mental stress regarding emotional and NE changes though showing higher E increases. Ethanol blood levels in HC were higher but ethanol-induced NE changes lower than in LC. The E, NE, and emotional stress responses were less reduced and performance less impaired by ethanol in HC than in LC. This was taken as evidence that neither stress nor ethanol sensitivity is increased in alcohol-preferring subjects but that tolerance by chronic intake of moderate doses of alcohol will result in a reduced efficacy of ethanol both on the psychological and biochemical levels, although effects on these two levels have not been found to be intraindividually related.
The discovery of an inducible form of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity explains both therapeutic effects and side-effects of non-steroidal anti-inflammatory drugs (NSAIDs). Selective COX-2 inhibitors have demonstrated in clinical trials a significantly better gastrointestinal tolerability than classical NSAIDs, for the same anti-inflammatory activity. Their tolerability in patients with active ulcer or with a recent history of ulcer as well as in patients suffering from cardiovascular or renal diseases has still to be investigated in detail. Their therapeutic potential in several new indications, including pre-term labour, colorectal cancer and Alzheimer's disease, is currently being investigated.
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We report a study of lymphocyte subsets in experimental arthritis induced in Wistar Furth rats by native human type II collagen and muramyl dipeptide. This experimental arthritis shares similarities with both the spondyloarthropathies and rheumatoid arthritis. Peripheral blood T lymphocytes, primarily the CD4+ cells (p = 0.01), were lower in arthritic rats than in the controls, although the difference in the CD4/CD8 ratio was not statistically significant. Splenic CD4 cells were significantly (p = 0.03) more numerous in arthritic rats, while the numbers of MHC class II positive cells (p = 0.002) and kappa-bearing B-cells (p = 0.0004) were significantly lower. Determination of peripheral blood and spleen lymphocytes subsets could therefore be used for the assessment of arthritis and for the evaluation of therapeutic agents. Thymic T-cell differentiation does not appear to be impaired in this model. These results differ from the peripheral blood disturbances described in the active stages of human rheumatoid arthritis and are more similar to those reported in ankylosing spondylitis patients. However, the absence of alterations in the Peyer's patches suggests that pathogeneic mechanisms involving mucosal areas and exogenous intestinal antigens are not reproduced in this model.