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Biomedical subjects

O Adam

Publications and source records attributed to O Adam.

At least 37 records · Page 2Linked to original sources

Factor XIII insufficiency in a patient with severe psoriasis vulgaris, arthritis, and infirmity.

Factor XIII (FXIII) links soluble fibrin monomers and collagen fibres to stable fibrin connections. Deficiency of FXIII, caused by dyspoiesis or increased consumption, results in a bleeding tendency and wound healing complications. Although the decrease of FXIII and successful replacement in patients with wound healing complications after surgery have been described by several authors, it is rarely considered that patients with autoimmune diseases, bleeding or healing complications may suffer from FXIII deficiency. We report a patient with severe psoriasis vulgaris generalisata with large, painful erythemas, bleeding tendency, joint contractions and infirmity, whose FXIII activity was 19%. After successful replacement the bleeding tendency vanished, and a marked improvement of skin and joint mobility allowed mobilisation and administration of physical therapy, whereby some independence and mobility were restored to the patient.

Adult↗

[Selenium concentration in erythrocytes of patients with rheumatoid arthritis. Clinical and laboratory chemistry infection markers during administration of selenium].

PATIENTS AND METHODS: Seventy patients with definitive rheumatoid arthritis were matched to built 2 groups, which were double-blind and randomized allocated to supplementation with sodium-selenit 200 micrograms/d or placebo for 3 months, each. Both groups were given fish oil fatty acids (30 mg/kg body weight), DMARDS were continued throughout the study, while variations in steroids or NSAD were admitted. RESULTS: Selenium concentrations in erythrocytes of patients with rheumatoid arthritis were 85.1 +/- 26 micrograms/l, and significantly lower than found in an average German population (123 +/- 23 micrograms/l). During the observation period of 3 months normal selenium concentrations were not restored, despite supplementation higher than RDA. At the end of the experimental period the selenium supplemented group showed less tender or swollen joints, and morning stiffness. Selen-supplemented patients needed less cortisone and NSAD than controls. In accordance with clinical improvement we found a decrease of laboratory indicators of inflammation (C-reactive protein, alpha 2-globuline, prostaglandin E2). CONCLUSION: No side effects of supplementation with selenium were noted, which can be considered as adjuvant therapy in patients with rheumatoid arthritis.

Adult↗

Mycobacterium smegmatis phosphoinositols-glyceroarabinomannans. Structure and localization of alkali-labile and alkali-stable phosphoinositides.

Lipoarabinomannans from fast growing Mycobacterium sp., namely AraLAMs, stimulate the early events of macrophage activation. The immunological activities of all of these AraLAMs drastically decrease with the loss of the mild alkali groups, which were believed to be restricted to the fatty acid residues from the phosphatidyl-myo-inositol anchor. This report reveals the presence and the structure of mild alkali-labile phosphoinositide units linked via the phosphate to the C-5 of the beta-D-Araf in the AraLAMs of Mycobacterium smegmatis, a fast growing mycobacterial species. Their structure was unambiguously established with a strategy based on both one-dimensional 31P and two-dimensional 1H-31P heteronuclear multiple quantum correlation spectroscopy (HMQC) and HMQC-homonuclear Hartmann-Hahn spectroscopy NMR experiments applied to native AraLAMs and to AraLAMs treated in mild alkali conditions. Next to these alkali-labile phosphoinositides estimated at three per molecule, two other mild alkali-stable phosphoinositide units were identified: the expected (myo-inositol-1)-phosphate-(3-glycerol) unit typifying the well known glycosylphosphatidylinositol anchor of the mannan core and, more surprisingly, one (myo-inositol-1)-phosphate-(5-beta-D-Araf) unit having the same structure as the alkali-labile ones. Moreover, these four phosphoinositide units were found capping the arabinan side chains. Thus, their different behavior toward mild alkaline hydrolysis was explained according to their accessibility to the alkali reagent. This novel class of LAMs, namely phosphoinositols-glyceroarabinomannans (PI-GAMs), are characterized by their phosphoinositide units but also by the absence of fatty acid residues. These PI-GAMs were found to elicit the secretion of tumor necrosis factor-alpha, suggesting that phosphoinositides are the major PI-GAM epitope involved in this process.

Antigens, Bacterial↗

Complete NMR structural elucidation of the capsular polysaccharide adjuvant from Klebsiella I-714.

The capsular polysaccharide (CPS) produced by the non-pathogenic Klebsiella strain I-714, selected for its immunomodulating activity, has been purified and almost completely detoxified in a previous study [Adam, O., Vercellone, A., Paul, F., Monsan, P. F. & Puzo, G. (1995) Anal. Biochem. 225, 321-327]. The present report concerns the structural elucidation of this CPS by several one-dimensional and two-dimensional 1H-NMR and 13C-NMR experiments performed on the native molecule. It was found to be a high molecular-mass branched polymer constituted by a hexasaccharide repeating unit of following structure: 4)-alpha-L-Rhap-(1-->3)-beta-D-Galp-(1-->2)-alpha-L-Rhap-(1- ->4)-beta-D- GlcpA-(1-->3)-¿alpha-L-Rhap-(1-->2)-¿-alpha-D-Galp-(1. The presence of two glycosidic substitutions on the Galp residue resulted in a strong overlapping of its proton signals, preventing direct assignment of both proton and carbon resonances. However, assignment could be achieved using the two-bond and three-bond 1H-13C heteronuclear coupling observed in the 1H-13C heteronuclear multiple-bond correlation (HMBC) spectrum.

Adjuvants, Immunologic↗

Factors influencing the emigration of physicians from Canada to the United States.

OBJECTIVE: To determine whether location of postgraduate medical training and other factors are associated with the emigration of physicians from Canada to the United States. DESIGN: Case-control study, physicians were surveyed with the use of a questionnaire mailed in May 1994 (with a reminder sent in September 1994), responses to which were accepted until Dec. 31, 1994. PARTICIPANTS: Physicians randomly selected from the CMA database, 4000 with addresses in Canada and 4000 with current addresses in the United States and previous addresses in Canada. OUTCOME MEASURES: Sex, age, location of undergraduate and postgraduate medical training, qualifications, practice location, opinions concerning residence decisions, current satisfaction and plans. RESULTS: The overall response rate was 49.6% (50.0% among physicians in the United States and 49.2% among those in Canada). Age and sex distributions were similar among the 8000 questionnaire recipients and the nearly 4000 respondents. Physicians living in the United States were more likely to be older (mean 53.2 v. 49.6 years of age), male (87% v. 75%) and specialists (79% v. 52%) than those practising in Canada. Postgraduate training in the United States was associated with subsequent emigration (odds ratio 9.2, 95% confidence interval 7.8 to 10.7). However, in rating the importance of nine factors in the decision to emigrate or remain in Canada, there was no significant difference between the two groups in the rating assigned to location of postgraduate training. Professional factors rated most important by most physicians in both groups were professional/clinical autonomy, availability of medical facilities and job availability. Remuneration was considered an equally important factor by those in Canada and in the United States. Six of seven personal/family factors were rated as more important to their choice of practice location by respondents in Canada than by those in the United States. Current satisfaction was significantly higher among respondents in the United States. Most physicians in each group planned to continue practising at their current location. Of Canadian respondents, 22% indicated that they were more likely to move to the United States than they were a year beforehand, whereas 4% of US respondents indicated that they were more likely to return to Canada. CONCLUSIONS: Factors affecting the decision to move to the United States or remain in Canada can be categorized as "push" factors (e.g., government involvement) and "pull" factors (e.g., better geographic climate in the US). Factors can also be categorized by whether they are amenable to change (e.g., availability of medical facilities) or cannot be managed (e.g., proximity of relatives). An understanding of the reasons why physicians immigrate to the United States or remain in Canada is essential to planning physician resources nationally.

Adult↗

[Simultaneous detection of HBs antigens and antibodies: report of a case].

We reported the case of a young woman who presented simultaneously HBs antigen and HBs antibodies in blood. From historical datas, we suspected that the patient was infected by hepatitis B virus and developed a chronic infection. Lately, she received hepatitis B vaccine. Subtypes of the infectious hepatitis B virus and the immunogenic hepatitis B antigen were different and induced independent immunological responses.

Acute Disease↗

Validation of HPLC-amperometric detection to measure serotonin in plasma, platelets, whole blood, and urine.

We describe an isocratic liquid-chromatographic method with amperometric detection for determination of serotonin by rapid sample preparation. Platelet-poor plasma and platelets were injected after a single deproteinization step with perchloric acid. Addition of sodium borohydride to whole blood avoids oxidation of serotonin during the deproteinization step without any chromatographic interferences. We purified urinary serotonin by two successive cationic and anionic extraction steps. After urine dilution, urinary 5-hydroxyindoleacetic acid (5-HIAA) was measured under the same chromatographic conditions. Platelet serotonin concentrations correlated more closely with whole-blood serotonin concentrations after correction for platelet number than with concentrations expressed in nmol/L. This suggests that whole-blood serotonin measurements should be corrected for platelet count to eliminate the variability of circulating platelets. Combined determination of serotonin in whole blood and urine and of 5-HIAA in urine provides a useful tool for detecting and monitoring carcinoid tumors.

Adult↗

Low fat diet decreases alpha-tocopherol levels, and stimulates LDL oxidation and eicosanoid biosynthesis in man.

The effects of a conventional 1000 kcal diet, and of a further restriction of dietary fat by a fat substitute, on the concentrations of vitamin A and E in plasma and LDL, the formation of lipid peroxides and eicosanoids were investigated in 10 obese volunteers. In vitro copper catalyzed oxidation of conjugated dienes, lipid peroxides and TBARS activity, measured in LDL samples after week 2 (supplementation with 140 mg/d alpha-tocopherol and 5000 IU retinol-acetat for two weeks), week 6 (conventional diet) and week 10 (fat substitute), increased with vitamin E depletion statistically significant after week 10 compared to the values after week 2. Concomitantly, PGE2 and LTB4, determined by RIA, increased to 344% and 166%, respectively, compared to the values after week 2. PGM, determined as tetranorprostanedioic acid by GC-MS, increased to 120%. Stimulation of lipid peroxidation and eicosanoid formation was more pronounced in persons with initially low (19 - 26 micromol/l plasma) than in those with high (37 - 70 pmol/l plasma) concentrations of alpha-tocopherol. We conclude that fat restricted diets can lead to an unwanted stimulation of lipid peroxidation and eicosanoid formation, which may be relevant in states of disease, e. g. arteriosclerosis or rheumatoid arthritis.

Diet, Fat-Restricted↗

A nondegradative route for the removal of endotoxin from exopolysaccharides.

The potentiality of the Triton X-114 phase separation technique for the removal of lipopolysaccharide (LPS, endotoxin) from Klebsiella sp. I-714 exopolysaccharide (EPS) has been investigated. Classical purification and chemical detoxification methods were evaluated for their effectiveness in removing residual LPS, while preserving structural and functional integrity of EPS. Ultracentrifugation, Detoxi-Gel, and ion-exchange chromatography did not remove endotoxin, except gel filtration chromatography performed at 60 degrees C in sodium deoxycholate buffer. In this case, the bioactivity of the purified EPS fraction was significantly lowered, as was seen after alkaline hydrolysis treatment. Moreover, the acetic acid detoxification procedure hydrolyzed EPS. As an alternative, phase partitioning of EPS in Triton X-114 at low temperature provided a fast, mild, and efficient method for the removal of LPS as shown by a 100-fold reduction in Limulus amebocyte lysate (LAL) activity and only a 2-fold reduction in bioactivity. Gel filtration chromatography performed at 4 degrees C with Triton X-114 buffer and phase partitioning with the more hydrophilic Triton X-100 nonionic detergent at 75 degrees C led to a similar decrease in LAL activity. This novel application of Triton X-114 partitioning is a nondegradative alternative to the chemical detoxification of gram-negative bacterial EPS for vaccine production. Purification of endotoxin-contaminated polysaccharides prior to screening for biological activity should also benefit from this technique. The extraction scheme using Triton X-114 can be easily used in large-scale purification processes.

Cell Extracts↗

Modulation of the endogenous leukotriene production by fish oil and vitamin E.

We investigated the effects of fish oil and vitamin E on the endogenous leukotriene production. 10 healthy volunteers were supplemented for 1 week with fish oil (containing 40 mg/kg body weight per day of eicosapentaenoic and docosahexaenoic acid), vitamin E (540 mg, i.e., 800 IU of D-alpha-tocopherol per day), or with both agents. Treatment resulted in a significant increase in the eicosapentaenoate concentration in red blood cell membranes and/or in the vitamin E concentration in serum. In addition, nine obese patients were investigated who were on a hypocaloric diet including 10 mg vitamin E/day for 8 weeks. This diet was associated with a significant decrease in serum vitamin E concentration. The urinary concentration of leukotriene E4 plus N-acetylleukotriene E4 served as a measure for the endogenous leukotriene production. Fish oil reduced leukotriene production in eight of the 10 healthy individuals. After vitamin E supplementation, urinary leukotrienes were significantly reduced in all of the healthy volunteers. The combination of vitamin E plus fish oil had no synergistic effect on leukotriene production in the individuals tested. The decrease in serum vitamin E concentration during the hypocaloric, 10 mg vitamin E/day diet was associated with an increase in urinary leukotrienes in 8 of the 9 obese patients. Urinary prostaglandin metabolites, determined as tetranorprostanedioic acid, increased or decreased in parallel with urinary leukotrienes in most individuals; however, changes were less pronounced than those observed with leukotrienes. We conclude that the endogenous leukotriene production can be reduced effectively by high doses of fish oil or vitamin E, whereas vitamin E depletion is associated with an increase in leukotriene generation.

Adult↗

[Renal side-effects of non-steroidal antirheumatic drugs].

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are increasingly used for analgesia, as antirheumatics and to inhibit platelet aggregation. Renal side effects occur mainly in patients at risk, e.g. those with pre-existing renal insufficiency, or when used together with diuretics or a second NSAID. PATIENTS: In these patients, reversible impairment of renal function, disturbance of electrolyte homeostasis, edema and hypertension are quite common. Nephrotic syndrome with or without interstitial nephritis and renal failure is a rare complication of long-term NSAID therapy. Analgesic nephropathy may result from chronic NSAID use. These three renal complications are exemplified by case reports. CONCLUSIONS: Since side effects of NSAIDs are initially reversible, careful observation of patients can prevent chronic illness. Only rarely dialysis or treatment with glucocorticoids is indicated in patients with interstitial nephritis. Given the large number of patients taking NSAIDs, however, renal side effects are rare, and usually have no long-term consequences. Nevertheless, early detection of side effects is of importance for the prevention of long-term medical complications.

Acute Kidney Injury↗

Therapeutic efficacy of oral low-dose cyclosporin A in severe psoriatic arthritis.

Six male patients with severe psoriatic arthritis (PA) unresponsive to various topical and systemic therapies have been treated with oral cyclosporin A (CyA; Sandimmun) solution at daily doses ranging usually from 1.5 to 5.0 mg/kg. In 1 case the dose had to be increased to 7 mg/kg/day. At initiation of CyA therapy skin involvement was between 40 and 90% of total body surface. Initiation of CyA therapy resulted in marked improvement of skin lesions within 2-7 weeks accompanied by impressive relief from arthralgias and improvement of joint function. The requirement for nonsteroidal anti-inflammatory drugs was markedly reduced in all cases. All patients in whom CyA therapy was continued remained clinically stable for several months (follow-up period 2-7 months). Although mild to moderate relapses occurred, rebound phenomena were not observed after discontinuation of treatment. Side effects which comprised serum creatinine increases in 3 out of 6 cases were reversed by adjustment of CyA dosage.

Administration, Oral↗

Cardiovascular effects of n-6 fatty acids.

N-6 fatty acids comprise linoleic, dihomo-gamma-linolenic and arachidonic acid. Each of these polyunsaturated fatty acids display an individual pattern of cardiovascular effects. Moreover, the supplementation of the diet with one of these n-6 fatty acids results in a concomitant effect on the resorption, distribution and metabolism of the other n-6 fatty acids. While linoleic acid is abundant in our diet, the other n-6 fatty acids are only found in minute amounts. Accordingly, the effects with linoleic acid are less impressive, but more complex (e.g. lowering of plasma cholesterol, inhibition of renin) than with both other n-6 fatty acids. Linoleic acid, being no direct prostaglandin precursor, displays a variety of effects on the prostaglandin cascade, while dihomo-gamma-linolenic acid gives rise to 1-series prostaglandins and arachidonic acid to prostaglandins (eicosanoids) of the 2-series. The quality and quantity of prostaglandins formed, contribute essentially to the cardiovascular effects of the individual n-6 fatty acids.

Animals↗