PubMed Health⌕ Search

Biomedical subjects

W Weiss

Publications and source records attributed to W Weiss.

At least 37 records · Page 2Linked to original sources

Development of insulin-dependent diabetes mellitus in a patient with chronic hepatitis C during therapy with interferon-alpha.

Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis. It has been associated with various forms of autoimmune disease, e.g. autoimmune hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mellitus. Further, an increase of insulin resistance and development of non-insulin-dependent diabetes mellitus has been described after treatment with IFN-alpha. Several studies have investigated the induction of different autoimmune markers by IFN-alpha, but only few specified patients who developed insulin-dependent diabetes mellitus. We report the case of a 37-year-old man with chronic hepatitis C who was treated with IFN-alpha plus ribavirin. Thirty weeks after the start of treatment, the patient developed insulin-dependent diabetes mellitus and therapy was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of diabetes mellitus, the C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive family history for type 2 diabetes. Several autoimmune markers were investigated before, during and 6 months after withdrawal of antiviral treatment. High titres of glutamic acid decarboxylase (GAD) antibodies were present before therapy. A significant increase in titres of islet cell antibodies, parietal cell antibodies and sperm antibodies was present after 14 weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha therapy, these antibodies had significantly decreased whereas GAD antibodies remained unchanged. There was no clinical sign of any other autoimmune disease. Our data show that, in patients with a predisposition to insulin-dependent diabetes mellitus, the disease may become manifest as a side-effect during therapy with IFN-alpha. Several pathogenetic factors may be involved in this process, and, in addition to IFN-alpha, hepatitis C itself may induce autoimmune mechanisms. We conclude that screening for autoantibodies specific for type 1 diabetes should be performed before the start of IFN-alpha treatment. In patients found to be at increased risk of developing diabetes mellitus type 1, monitoring of titres of these antibodies during therapy could help to assess the individual risk-benefit ratio of IFN-alpha treatment.

Adult↗

Multistage multiantigen heterologous prime boost vaccine for Plasmodium knowlesi malaria provides partial protection in rhesus macaques.

A nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a multicomponent, multistage DNA vaccine for the simian malaria species Plasmodium knowlesi including two preerythrocytic-stage antigens, the circumsporozoite protein (PkCSP) and sporozoite surface protein 2 (PkSSP2), and two blood stage antigens, apical merozoite antigen 1 (PkAMA1) and merozoite surface protein 1 (PkMSP1p42), as well as recombinant canarypox viruses encoding the four antigens (ALVAC-4). The DNA vaccine plasmids expressed the corresponding antigens in vitro and induced antiparasite antibodies in mice. Groups of four rhesus monkeys received three doses of a mixture of the four DNA vaccine plasmids and a plasmid encoding rhesus granulocyte-monocyte colony-stimulating factor, followed by boosting with a single dose of ALVAC-4. Three groups received the priming DNA doses by different routes, either by intramuscular needle injection, by intramuscular injection with a needleless injection device, the Biojector, or by a combination of intramuscular and intradermal routes by Biojector. Animals immunized by any route developed antibody responses against sporozoites and infected erythrocytes and against a recombinant PkCSP protein, as well as gamma interferon-secreting T-cell responses against peptides from PkCSP. Following challenge with 100 P. knowlesi sporozoites, 1 of 12 experimental monkeys was completely protected and the mean parasitemia in the remaining monkeys was significantly lower than that in 4 control monkeys. This model will be important in preclinical vaccine development.

Animals↗

Improving protective immunity induced by DNA-based immunization: priming with antigen and GM-CSF-encoding plasmid DNA and boosting with antigen-expressing recombinant poxvirus.

Intramuscular immunization with a naked DNA plasmid expressing the Plasmodium yoelii circumsporozoite protein (pPyCSP) protects mice against challenge with P. yoelii sporozoites. This protection can be improved either by coadministration of a plasmid expressing murine GM-CSF (pGMCSF) or by boosting with recombinant poxvirus expressing the PyCSP. We now report that combining these two strategies, by first mixing the priming dose of pPyCSP with pGMCSF and then boosting with recombinant virus, can substantially increase vaccine effectiveness. Not only were immune responses and protection improved but the pPyCSP dose could be lowered from 100 microg to 1 microg with little loss of immunogenicity after boost with recombinant poxvirus. Comparing mice primed by the 1-microg doses of pPyCSP plus 1 microg pGMCSF with mice primed by 1-microg doses of pPyCSP alone, the former were better protected (60% vs 0) and had higher concentrations of Abs (titers of 163, 840 vs 5, 120 by indirect fluorescent Ab test against sporozoites), more ex vivo CTL activity (25% vs 7% specific lysis), and more IFN-gamma-secreting cells by enzyme-linked immunospot assay (1460 vs 280 IFN-gamma spot-forming cells/106 cells). Priming with plasmid vaccine plus pGMCSF and boosting with recombinant poxviruses strongly improves the immunogenicity and protective efficacy of DNA vaccination and allows for significant reduction of dose.

Animals↗

The current state of two-dimensional electrophoresis with immobilized pH gradients.

The original protocol of two-dimensional electrophoresis with immobilized pH gradient (IPG-Dalt; Gorg et al., Electrophoresis 1988, 9, 531-546) is updated. Merits and limits of different methods for sample solubilization, sample application (by cup-loading or ingel rehydration) with respect to the pH interval used for IPG-isoelectric focusing are critically discussed. Guidelines for running conditions of analytical and micropreparative IPG-Dalt, using wide IPGs up to pH 12 for overview patterns, or narrow IPGs for zoom-in gels for optimum resolution and detection of minor components, are stated. Results with extended separation distances as well as automated procedures are demonstrated, and a comparison between protein detection by silver staining and fluorescent dyes is given. A brief trouble shooting guide is also included.

Animals↗

Towards higher resolution: two-dimensional electrophoresis of Saccharomyces cerevisiae proteins using overlapping narrow immobilized pH gradients.

The rising number of proteome projects leads to new challenges for two-dimensional electrophoresis with immobilized pH gradients and different applications of this technique. Not only wide pH gradients such as 4-12 or 3-12 (Görg et al., Electrophoresis 1999, 20, 712-717) which can give an overview of the total protein expressions of cells are in demand but also overlapping narrow immobilized pH gradients are to be used for more specialized and detailed research and micropreparative separations. The advantage of overlapping narrow pH gradients is the gain in higher resolution by stretching the protein pattern in the first dimension. This simplifies computer-aided image analysis and protein identification (e.g., by mass spectrometry). In this study the protein patterns of yeast cells in pH gradients 4-5, 4.5-5.5, 5-6, 5.5-6.7 and 6-9 are presented and compared to the pH 4-7 and 3-10 gradients. This combination allowed us to reveal a total of 2286 yeast protein spots compared to 755 protein spots in the pH 3-10 gradient.

Electrophoresis, Gel, Two-Dimensional↗

Osseous integration of bovine hydroxyapatite ceramic in metaphyseal bone defects of the distal radius.

Hydroxyapatite ceramic made of bovine spongiosa was used as structural support material in a prospective study to correct bone defects experienced after reduction in distal radius fractures. The study took place over a 3-year period (1992-1999) and comprised 14 patients. Osseous integration was analyzed via biopsies and magnetic resonance imaging. Long-term follow-up monitoring involving magnetic resonance imaging in 13 of the 14 patients showed fibrovascular growth within incorporated hydroxyapatite material. Osseous integration was demonstrated in magnetic resonance images by gadolinium uptake and by the presence of osteoid layers and endothelialized vessels. Hydroxyapatite ceramic offers a biologically acceptable alternative to autologous bone when augmenting distal radius fracture fixation.

Adult↗

Asbestosis and lobar site of lung cancer.

OBJECTIVE: To assess the evidence for the hypothesis that lung cancer has a predilection for the lower lobes in workers with asbestosis. METHOD: A review of the available literature with relevant information. RESULTS: Six published reports were analysed. In four studies limited to series of cases with diagnoses of asbestosis, three showed lower lobe predominance of lung cancer whereas the fourth study included cases in which the radiographic readings did not meet the usual criterion of profusion for asbestosis. One cohort study showed lower lobe predominance; the other reported only 33% lower lobe cancers compared with 20% in unexposed controls. CONCLUSION: There is some support for the hypothesis but more studies are needed.

Asbestos↗

Multimicrobial sepsis including Clostridium perfringens after chemoembolization of a single liver metastasis from common bile duct cancer.

A 65-year-old woman underwent resection of a distal common bile duct carcinoma (Whipple's procedure). Twelve months later a single hepatic metastasis was detected and a chemoembolization was performed. Immediately after chemoembolization the patient developed a multimicrobial sepsis including Clostridium perfringens. CT scans depicted pathognomonic signs of gas-containing abscess in the necrotic liver metastasis. She was subsequently treated with broad-spectrum antibiotics, abscess drainage and hyperbaric oxygen therapy. We conclude that antibiotic prophylaxis is recommendable for chemoembolization of liver metastasis in patients with risk factors like intestinal biliary reflux (bilioenteric anastomosis or papillotomy and biliary stenting) and bile duct cancer, otherwise severe sepsis including clostridium bacteremia may occur.

Aged↗

Back to work more quickly after an inguinal hernia repair.

Tension-free hernia repair plus recovery expectancy statements return personnel to work more quickly. On the day of primary inguinal hernia repair, patients were given statements about their likelihood of returning from convalescent leave after 7 days and performing nonstrenuous work. Similar statements were given to them by telephone at 72 hours postoperatively and at a 1-week follow-up appointments. Seventy-four percent of the 73 patients returned to nonstrenuous work within 7 days, and 90% returned to strenuous work within 30 days. In this small sample, 385 work days were saved from the Navy's recommended 14 days of convalescent leave. By combining recovery expectancy statements with an effective surgical procedure, it is possible to avoid prolonged convalescence, thereby enhancing military readiness.

Absenteeism↗

Course of platelet counts in cirrhotic patients after implantation of a transjugular intrahepatic portosystemic shunt--a prospective, controlled study.

BACKGROUND/AIMS: The pathogenesis of thrombocytopenia associated with advanced liver disease is still controversial. To study the impact of portal decompression on this hematologic complication, we conducted a prospective, controlled study to compare the course of platelet counts in patients after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) with matched controls without shunts. METHODS: Fifty-five TIPS patients and 110 controls matched for age, sex, Child-Pugh class, etiology of liver disease and baseline platelet count were included, and followed for 1 year. Follow-up visits were scheduled after 1 month, after 3 months, and at 3-month intervals thereafter. RESULTS: Nonparametric Mann-Whitney U-tests revealed significantly higher platelet counts for TIPS patients as compared to controls from the 1st through the 12th month (p<0.01). During the study period, the median platelet count of TIPS patients increased by 19.7%, from 104.0/nl (IR: 68.0) to 124.5/nl (IR: 41.0). In contrast, during the same period the median platelet count of controls decreased by 17.1%, from 102.5/nl (IR: 66.0) to 85.0/nl (IR: 67.5). In the group of cases with baseline platelet counts < or =100/nl, platelet counts had increased by at least 25% at month 12 in 65% of TIPS patients, but in only 5% of controls (p<0.001). However, normalization of platelet counts, i.e. > or =150/nl, was not achieved in any case. Neither the portosystemic pressure gradient after TIPS implantation, nor the percentage of portosystemic pressure gradient reduction during the procedure was predictive of platelet response. CONCLUSIONS: TIPS implantation increases platelet counts significantly. However, portal hypertension is clearly not the only mechanism contributing to thrombocytopenia in advanced liver disease.

Adult↗

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Adult↗

Asbestosis: a marker for the increased risk of lung cancer among workers exposed to asbestos.

This review examines the hypothesis that excess lung cancer risk in worker cohorts exposed to asbestos occurs only among those with asbestosis. The adequately designed studies in the literature support this hypothesis. The summary relative risk for lung cancer was 1.00 in seven cohorts with no deaths from asbestosis. In addition, there is a high correlation between asbestosis rates and lung cancer rates in 38 cohorts in contrast to a poor correlation between cumulative exposure data and lung cancer relative risks in eight cohorts with adequate data. The evidence indicates that asbestosis is a much better predictor of excess lung cancer risk than measures of exposure and serves as a marker for attributable cases.

Asbestosis↗

Analytical IPG-Dalt.

Explore the source record for details and available documents.

Electrophoresis, Gel, Two-Dimensional↗

Two-dimensional electrophoresis of proteins in an immobilized pH 4-12 gradient.

For checking theoretical two-dimensional (2-D) maps derived from sequenced genomes, indicating that nonnegligible amounts of proteins up to pH 12 are to be expected, a wide-range immobilized pH 4-12 gradient was generated. Depending on the extraction method of sample preparation, proteins with pls up to pH 12 are detected in a single gel. Highly reproducible protein patterns focused to the steady state with round-shaped spots up to pH 12 are obtained with the standard protocol originally described in 1988 (Görg et al., Electrophoresis 1988, 9, 531-546).

Electrophoresis, Gel, Two-Dimensional↗

[Health for all--the last progress assessment before the year 2000].

In the framework of the tri-annual report to WHO of progress towards "Health for all" the specific question concerning reduction of inequity in health is addressed. Regional variations in health status represent an important aspect of that question which is of particular interest in a federal country where major public health competencies are located at the regional level (cantons in Switzerland). Health status is described by both mortality measures (main causes of death) in the population aged 0-64 years and morbidity indicators (rates of disability pensioners) in the same age group. In addition to the comparison of mortality and morbidity rates between cantons an "index of dissimilarity" (DI) was used. For both criteria, changes over a time period of 10 to 12 years were considered. Results show decreasing trends of mortality from all and main causes of death in both sexes. While this tendency goes along with decreasing dissimilarity as to male overall mortality, the corresponding female DI increases, indicating an increase in inequity between the cantons. A similar pattern is observed as to morbidity: although rates of disability pensioners went up for both sexes, this increase resulted in a lower DI-value for men but a higher one for women. The results are discussed against the background of socioeconomic differences (e.g. unemployment) between the cantons studied.

Adolescent↗

Eradication of Helicobacter pylori by a 1-week course of famotidine, amoxicillin and clarithromycin.

OBJECTIVES: The combination of a proton pump inhibitor (PPI) such as omeprazole with amoxicillin and clarithromycin constitutes one of the most effective treatments for the eradication of Helicobacter pylori. Nevertheless, the mechanisms of interaction between these drugs remain unclear. It has been shown that minimal inhibitory concentration values of both antibiotics are considerably lower at neutral pH levels than in an acid environment. Further, omeprazole possesses bacteriostatic activity. To evaluate the significance of these mechanisms we replaced omeprazole with famotidine, a drug which only suppresses acid production, but has no intrinsic antimicrobial activity. METHODS: We evaluated the efficacy of a 1-week course of famotidine 80 mg b.i.d., amoxicillin 1000 mg b.i.d. and clarithromycin 500 mg b.i.d. in a pilot study (20 patients), and then confirmed our results in a larger replication study (87 patients). A total of 107 patients with H. pylori-associated duodenal ulcer (n = 54), gastric ulcer (n = 14) or non-ulcer dyspepsia (n = 39) were included. Endoscopy was performed at baseline and 4-6 weeks after discontinuation of treatment. H. pylori status was assessed by the urease test and histology. RESULTS: H. pylori was successfully eradicated in 94 of 104 patients who completed the study (90.4%; CI 95%, 83.0-95.3%). By intention-to-treat analysis, the eradication rate was 87.9% (CI 95%, 80.1-93.4%). Ulcer healing was observed in 98.1% of duodenal ulcers and 92.9% of gastric ulcers (based on per-protocol analysis). Mild side effects that did not require termination of treatment were reported by seven patients (6.7%). CONCLUSION: A 1-week course of famotidine, amoxicillin and clarithromycin is a highly effective, simple and safe eradication regimen. Our data indicate that acid suppression is the crucial mechanism by which the activity of amoxicillin and clarithromycin against H. pylori is enhanced, whereas additional antimicrobial activity or other specific effects of PPIs seem to be less important.

Adult↗