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Biomedical subjects

P Weber

Publications and source records attributed to P Weber.

At least 199 records · Page 11Linked to original sources
PubMed1991

The effects of cyclosporin A on eicosanoid excretion in patients with rheumatoid arthritis.

Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephrotoxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24-week period, during which treatment with nonsteroidal antiinflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (+/- SD) serum creatinine level (1.04 +/- 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P less than 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P less than 0.03) in the 2,3-dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.

Adult↗
PubMed1991

Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn's disease.

The presence of antibodies against pancreatic juice (PAB) in patients with Crohn's disease has recently been reported. In our study sera from 273 patients with inflammatory bowel disease (222 with Crohn's disease, 51 with ulcerative colitis) have been examined for PAB and also for antibodies against gut tissues by means of indirect immunofluorescence. PAB were found in 68 of the 222 patients with Crohn's disease (31%), with titres ranging from 1/10 to 1/1280, and in only two patients with ulcerative colitis (4%), with titres of 1/20. None were found in 198 patients with various chronic inflammatory diseases and healthy control subjects. No differences were found between the PAB positive and negative patients when the following parameters were compared: disease activity (Crohn's disease activity index), involvement of bowel segments, incidence of extraintestinal disease, or treatment with anti-inflammatory drugs. Only seven of the patients with Crohn's disease had a history of pancreatic disease and of these, four had detectable pancreatic antibodies. Longitudinal observations of 40 patients with Crohn's disease showed a stable pattern for PAB, independent of disease activity and treatment. Partial characterisation of the PAB antigen, isolated from pancreatic juice, showed a trypsin sensitive macromolecular protein of more than 10(6) daltons not identical with a panel of defined exocrine pancreatic proteins. By contrast, antibodies against goblet cells (GAB) were found in 13 of 51 patients with ulcerative colitis (29%) and in none of the patients with Crohn's disease or control subjects. PAB were found as a highly specific serological marker for Crohn's disease and GAB for ulcerative colitis, but the relevance of PAB and GAB in the pathogenesis in Crohn's disease remains unclear.

Adolescent↗
PubMed1991

Aspirin-induced decline in prostacyclin production in patients with coronary artery disease is due to decreased endoperoxide shift. Analysis of the effects of a combination of aspirin and n-3 fatty acids on the eicosanoid profile.

BACKGROUND: It was the purpose of this study to determine the effects of the combination of aspirin (ASA) and fish oil, which is rich in n-3 polyunsaturated fatty acids, on the eicosanoid profile of patients with coronary artery disease. Specifically, we wanted to determine whether the ASA-induced reduction in prostacyclin production is due to inhibition of endothelial cell cyclooxygenase or to reduced endoperoxide shift from platelets and whether ASA negates the potentially beneficial effects of fish oil on the eicosanoid profile. METHODS AND RESULTS: Fourteen patients with clinically stable but advanced coronary artery disease received 12 g (n = 8) or 16 g (n = 6) of fish oil concentrate containing 6 or 8 g of n-3 fatty acids for 6 weeks. In addition to the fish oil, patients received increasing daily doses of ASA (50 mg, 100 mg, 325 mg, and 1,300 mg; the latter in four divided doses). Each dose was taken for 2 weeks. With fish oil supplementation, red blood cell phospholipid fatty acid content of arachidonic acid (AA) decreased and of eicosapentaenoic acid (EPA) increased so that EPA as a percent of AA increased from 2% to 26%. Serum thromboxane B2, which represents the production of TXA2 by maximally stimulated platelets, was suppressed by 38% on fish oil alone and by 97% or greater on all doses of ASA. Excretion of PGI2-M, the main urinary metabolite of PGI2 (derived from AA), fell from 50 +/- 4 ng/g of creatinine to 42 +/- 2 ng/g on fish oil alone (p = 0.02). On 50 mg of ASA per day, PGI2-M excretion was 26 +/- 2 ng/g of creatinine (p less than 0.001 versus fish oil alone). On 100 mg and 325 mg of ASA per day, PGI2-M was 24 +/- 3 ng/g and 27 +/- 3 ng/g, respectively (p V NS versus value on 50 mg per day). PGI3-M, the main urinary metabolite of PGI3 (derived from EPA), increased from 0.2 +/- 0.1 ng/g of creatinine to 4.9 +/- 0.7 ng/g on fish oil alone (p less than 0.001). In contrast with the marked ASA-induced decline in PGI2-M, PGI3-M excretion was not affected by the addition of ASA, even at the higher doses (4.6 +/- 0.7 ng/g and 4.9 +/- 0.5 ng/g on 325 mg per day and 325 mg four times daily, respectively). CONCLUSIONS: Moderate-dose (325 mg per day or less) ASA taken once daily has no effect on PGI3 production despite significantly reducing PGI2 production. This suggests that endothelial cell cyclooxygenase is minimally inhibited by such doses of ASA and that a large percent of the PGI2 produced in patients with advanced coronary artery disease derives from the transfer of prostaglandin endoperoxides from activated platelets to endothelial cells. The loss of these substrates accounts for the decrease in PGI2 with moderate-dose ASA. Thus, the ASA-induced decrease in PGI2 may in large part be an unavoidable consequence of ASA-induced platelet cyclooxygenase inhibition. ASA does not negate the potentially beneficial effects of n-3 fatty acids on the eicosanoid profile.

Aged↗
PubMed1991

Prospective study of nosocomial pneumonia and of patient and circuit colonization during mechanical ventilation with circuit changes every 48 hours versus no change.

Circuits on mechanical ventilators with cascade humidifiers are routinely changed every day or every other day, although humidifying cascades have been considered unlikely to increase the risk of respiratory infection because they do not generate aerosols. Moreover, changing ventilator tubings every 24 rather than every 48 h increases the risk of ventilator-associated pneumonia. To study the effects of ventilator circuit changes on the rate of nosocomial pneumonia and on patient and circuit colonization, 73 consecutive patients requiring continuous mechanical ventilation for more than 48 h were randomly assigned to either ventilator circuit changes every 48 h (Group 1, n = 38) or no change (Group 2, n = 35). Patients dying or being weaned before 96 h were not analyzed (Group 1 n = 3; Group 2 n = 7; leaving Group 1 n = 35 and Group 2 n = 28; p = 0.13). Ventilator-associated pneumonia was defined as the occurrence during mechanical ventilation or within 48 h after weaning of a new and persistent infiltrate on chest X-ray, purulent tracheal secretions, and a positive culture of a protected brush specimen (greater than or equal to 10(3) cfu/ml). Bacterial colonization was assessed every 48 h by quantitative cultures of pharyngeal swab, tracheal aspirate, humidifying cascade, and expiratory tubing trap. The two groups were similar in terms of age, indication for and duration of ventilation, and severity of illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Unaltered pulsatile and circadian TSH release in euthyroid patients with endemic goitre.

To evaluate the pathophysiological role of TSH in goitrogenesis we investigated pulsatile TSH secretion in 11 patients with a non-toxic goitre and in 11 healthy controls. Thyroid volume was 40 +/- 10 ml in the goitre group and 15 +/- 4 ml in the controls as measured by ultrasound. Blood was sampled continuously via an indwelling venous catheter at 10-min intervals over 24 h. Neither the mean 24-h serum TSH levels (goitre 1.1 +/- 0.5 vs controls 0.9 +/- 0.4 mU/l) nor the nocturnal surge of TSH were significantly different between the two groups. The average of the TSH pulse frequency (goitre 10.8 +/- 3.7 vs controls 9.6 +/- 3.5 pulses/24-h) and of the TSH pulse amplitude (goitre 0.4 +/- 0.2 vs controls 0.3 +/- 0.1 mU TSH/l) as analysed by DESADE programme (detection of secretory activity by discrete deconvolution) did not differ in the two groups. Furthermore, there was no correlation between the volume of the thyroid gland and the dynamics of the TSH secretion. We conclude that our data do not suggest a relevant pathophysiological role of TSH secretion in the development of non-toxic goitre in man.

Adult↗
PubMed1991

Long-term zidovudine therapy in patients with AIDS and symptomatic and asymptomatic HIV infection.

Zidovudine is the only anti-retroviral drug approved by the FDA for treatment of HIV infection. We have examined the clinical and laboratory efficacy of this drug for 4 years in a cohort of HIV-infected patients from Wisconsin. Overall, we have found that individuals with AIDS will have at least 1 year of symptom reduction while on the drug. Those with asymptomatic HIV infection tolerate the drug and none have progressed to AIDS in the 4 years of study. Zidovudine is an important component in the treatment of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis.

Antibodies against neutrophils have been detected in sera from patients with primary sclerosing cholangitis and inflammatory bowel diseases either by immunofluorescence or by enzyme-linked immunosorbent assay. To assess primary sclerosing cholangitis-specific antibodies, we examined sera from 30 patients with clinically and morphologically well-established primary sclerosing cholangitis by Western blotting against neutrophils and compared these results with those obtained by testing sera from patients with inflammatory bowel diseases. By Western blot using sonified neutrophils, 24 (80%) of 30 primary sclerosing cholangitis sera were positive. Five antigenic determinants at 95, 60, 55, 40 and 30 kD were visualized. Twenty-eight of the primary sclerosing cholangitis sera also showed the characteristic perinuclear fluorescence pattern by immunofluorescence on neutrophils. Thus a serological diagnosis of primary sclerosing cholangitis could be made in 80% of patients based on these two methods. In contrast, only 9% of 23 patients with ulcerative colitis and 10% of 60 patients with Crohn's disease were positive by Western blot, and these patients also showed positive perinuclear fluorescence pattern by immunofluorescence, suggesting an overlap between inflammatory bowel diseases and primary sclerosing cholangitis. Although some patients with classical primary biliary cirrhosis and autoimmune chronic active hepatitis had antibodies against primary sclerosing cholangitis epitopes, none of the patients with obstructive bile duct disorders, collagen diseases, Wegener's granulomatosis or other hepatic and nonhepatic disorders were positive by Western blot, indicating the specificity of these five primary sclerosing cholangitis-related neutrophilic epitopes.

Adolescent↗
PubMed1991

[Biofreezer BF 80--a universally employed apparatus in preservation at very low temperatures].

A computer-controlled freezing apparatus is described which uses liquid nitrogen (LN2) as coolant. The freezing equipment BF 80 consists of a big cryochamber (volume 24 l), a LN2 tank and a computer for the control of the freezing procedure. The biofreezer functions in the range from 40 to -180 degrees C. A complete cooling curve can be composed of up 15 linear segments with freezing rates between 0 and 45 K.min-1. In the computer up to 80 different freezing curves can be stored and activated by simple operations. The reliability of the biofreezer BF 80 was successfully tested for the cryopreservation of lymphocytes.

Cell Survival↗
PubMed1991

[Immunohistologic studies of differential HLA expression in patients with various intestinal diseases].

Histocompatibility antigens (HLA) play an important part in immunoregulation and in cell differentiation. This study analyses the expression of HLA class I and class II antigens (DR, DP, DQ) in intestinal biopsy specimen from patients with Crohn's disease, ulcerative colitis, GvHD, radiation colitis and intestinal adenomas using the indirect immunoperoxidase technique. 92 of 94 inflamed specimen from patients with inflammatory bowel disease showed a neoexpression of HLA II (DR greater than DP greater than DQ) on their epithelial cells. The intensity of HLA-DR neoexpression was significantly dependent on an endoscopic as well as a histological index of inflammation. All 75 non-inflamed specimen except 4 from patients with Crohn's disease did not show any evidence of HLA II display on the epithelium. 4 of 18 intestinal adenomas expressed HLA II on their epithelial cells without any correlation to the type of adenoma or the degree of cell dysplasia. Furthermore all specimen from a patient with intestinal GvHD showed an aberrant epithelial HLA II expression, but not that from radiation colitis. The expression of HLA class I antigens was similar in all biopsies studied. Our results suggest, that the epithelial neoexpression of HLA class II antigens may be an important event in the pathogenesis of various bowel diseases.

Biopsy↗
PubMed1990

[Crohn's disease: disease activity and recurrence following surgery].

The data from 238 patients (108 men, 130 women, mean age 29 [15-71] years), who had undergone operations for Crohn's disease between 1968 and 1988, were analysed retrospectively with the purpose of ascertaining the significance of an endoscopically demonstrated "early recurrence". In 170 patients postoperative colonoscopy had been performed at least once. In 130 patients the activity of the disease in the years before and after operation was compared in terms of such parameters as haemoglobin, erythrocyte sedimentation rate, serum albumin, body weight and the frequency of acute flare-ups of the disease and admissions to hospital. The probability of an endoscopically demonstrable recurrence was 90% after 5 years, while the corresponding figure for a symptomatic recurrence was 40%. This indicates that the routine performance of postoperative colonoscopies is of no value in assessing the prognosis. The probability of a reoperation was 21% after 5 years; in cases where both the ileum and colon were involved the probability was three times as high as in those with isolated involvement of either the small or the large intestine. Post-operatively, a substantial reduction in disease activity of several years' duration was achieved in the overall majority of cases.

Adolescent↗