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Biomedical subjects

B Weber

Publications and source records attributed to B Weber.

At least 181 records · Page 10Linked to original sources

Gender-specific differences of serum leptin in obese and normal-weight adolescents: studies in type-I diabetes and Turner syndrome.

The influence of exogenous insulin and estrogen substitution on serum leptin-like immunoreactivity was studied longitudinally in patients with type-I diabetes and Turner syndrome using a specific radioimmunoassay. Prepubertal, pubertal and postpubertal samples of 17 patients (9 girls, 8 boys) with type-I diabetes mellitus developing obesity were compared to those of 17 normal-weight controls matched for gender, age and diabetes duration. Six obese and six normal-weight girls with Turner syndrome were studied without hormone substitution, with ethinylestradiol alone, and with cyclic estradiol/gestagen substitution. The mean leptin levels of the girls with diabetes were two times higher than boys at all times, while insulin doses and glycemic control had no influence. In Turner syndrome estrogen substitution led to increased leptin levels only in the obese group. This study revealed that both body weight above normal and female sex steroids seem to be necessary to elevate leptin concentrations, while exogenous insulin has no effect.

Adolescent↗

Heterogeneity in the polyclonal T cell response to birch pollen allergens.

BACKGROUND: Immunodominant epitopes of Bet v 1a had been identified before, using recombinant (r) Bet v 1a-reactive T cell clones generated from peripheral blood mononuclear cells of patients allergic to birch pollen. This study aimed at evaluating the T cell-stimulating capacity of immunodominant Bet v 1a-derived peptides in a polyclonal system corresponding more closely to the situation in patients. METHODS: Short-term T cell lines (TCL) were established in presence of a protein extract of birch pollen (BP extract). TCL proliferation induced by the BP extract, by natural Bet v 1, rBet v 1a, rBet v 2 or 5 selected immunodominant Bet v 1a-derived peptides was determined. RESULTS: Consistent with the knowledge that Bet v 1 is the major IgE-binding allergen of birch pollen, we found comparable T cell reactivity to natural Bet v 1 and the BP extract within the majority of the TCL. Accordingly, the response to rBet v 2 was low compared with the reactivity to the BP extract. The response of the TCL to rBet v 1a proved to be highly heterogeneous. Furthermore, the TCL response to the 5 immunodominant Bet v 1a-derived peptides showed considerable diversity. The proliferative responses of most TCL (with one exception) following stimulation by these peptides were low, in relation to the expansion induced by the BP extract. CONCLUSION: These findings argue against the use of selected peptides derived from Bet v 1a in specific immunotherapy of patients with birch allergy.

Allergens↗

Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls.

There is only sparse and ambiguous information about circadian and pulsatile secretion features of the hypothalamus-pituitary-adrenocortical system in depression. We studied 15 severely depressed (Hamilton Depression Scale 30.4 +/- 6.7) male patients (age 22-72 yr; mean, 47.7 +/- 14.8) and 22 age-matched male controls (age 23-85 yr; mean, 53.1 +/- 18.2). Twenty-four-hour blood sampling from 0800-0800 h with 30-min sampling intervals was performed; from 1800-2400 h, blood was drawn every 10 min. Multivariate analysis of covariance, with the covariate being age, revealed mean 24-h cortisol (315.9 +/- 58.5 vs. 188.2 +/- 27.3 nmol/L) and mean ACTH (7.82 +/- 1.94 vs. 5.79 +/- 1.28 pmol/L) to be significantly increased in depressed patients. The frequency of cortisol (2.6 +/- 0.7 vs. 1.3 +/- 1.0 pulses/6 h) and ACTH (2.6 +/- 1.6 vs. 1.6 +/- 1.4 pulses/6 h) pulses during the evening were higher in patients compared to controls. The flattened circadian cortisol variation and reduced time of quiescence of cortisol secretory activity (140 +/- 116 vs. 305 +/- 184 min) in patients suggest disturbances of circadian functions. We conclude that increased hypothalamus-pituitary-adrenocortical activity in depression is related to a greater frequency of episodic hormone release, and we hypothesize that the observed circadian changes might be partly due to altered mineralocorticoid and glucocorticoid receptor capacity and function.

Adrenal Glands↗

Factors influencing height and weight development in children with diabetes. Results of the Berlin Retinopathy Study.

OBJECTIVE: To investigate the influence of glycemic control and insulin therapy on the longitudinal growth and weight development of children with diabetes. RESEARCH DESIGN AND METHODS: Prospective measurements of standing height and weight were recorded longitudinally in 634 children after IDDM onset (median age at onset, 9 years [range 1-15 years]; median diabetes duration at final examination, 11 years [range 1-19]; 3,236 patient-years on two or three injections daily; 399 patient-years on multiple injection therapy [MIT]). RESULTS: Normal development was found until puberty, with a tendency toward stunted growth and overweight (weight > 97th centile) thereafter. Female sex (P < 0.01) and MIT (P < 0.01) were associated with overweight. Final height was evaluated in a subgroup of 197 young adults followed until age 18 years. Relative growth was calculated as the difference between the standard deviation scores (SDSs) at manifestation (median 0.2 [range -3.5 to 2.9]) and at 18 years of age (reduction of -0.5 [-2.5 to 1.8]), equivalent to a median loss of 2.9 cm in boys and 2.3 cm in girls. Significant linear correlations with the change in height SDS after diabetes manifestation were found for age at manifestation (r = 0.21, P < 0.001) and prepubertal (r = -0.40, P < 0.001) and postpubertal HbA1c (r = -0.15, P < 0.001). While children with poorer relative growth also had a higher BMI (P < 0.05), no influences of sex, prevalence of limited joint mobility, or presence of retinopathy were found. CONCLUSIONS: Female sex and MIT are associated with diabetes-related obesity. Prepubertal and postpubertal glycemic control appear to be of importance for the diabetes-associated relative growth deficit.

Adolescent↗

Prevalence of latex-specific IgE antibodies in atopic and nonatopic children with type I diabetes.

OBJECTIVE: The potential induction of allergic sensitization to latex from insulin vial tops stimulated an investigation of the prevalence of specific IgE antibodies to latex in serum and the relationship to atopic disease in children with diabetes. RESEARCH DESIGN AND METHODS: In a cross-sectional study, serum samples of 112 children with type I diabetes (age: 15 [5-18] years; diabetes duration: 6 [1-14] years; median [range]) were investigated for total IgE, IgE screening for inhalational and nutritional allergens, and specific IgE antibodies to latex. RESULTS: Specific IgE antibodies for inhalational and/or nutritional allergens was found in 42 (38%) children (atopic group). Seven children (6%) exhibited specific IgE antibodies (0.61 [0.40-3.84] kU/I) to latex in serum although none reported clinical symptoms of latex allergy. All latex-sensitized children were found in the atopic group. This prevalence of latex sensitization of 17% (7/42) in atopic children with diabetes is comparable with the frequency described in atopic children without diabetes. These seven patients had higher serum total IgE antibody levels (328 [113-1,000] kU/I) than atopic patients without latex sensitization (n = 35; 124 [24-857] kU/I; P < 0.05) or patients without atopy (n = 70; 33 [2-339] kU/I; P < 0.001). No differences in age or diabetes duration were observed between either group. CONCLUSIONS: Sensitization to latex is found exclusively in children with atopic sensitization and appears to be related to atopic disease and not to frequent contact to latex through insulin injections. However, atopic patients may be at risk for reactions secondary to latex from insulin vials and syringes.

Adolescent↗

Psychological aspects in diabetes prevention trials.

Growing understanding of the pathogenetic process of insulin-dependent diabetes mellitus diabetes has favoured attempts to predict the clinical manifestation of the metabolic disorder in people at risk by some easily measurable marker or markers and, subsequently, to prevent its onset. This complicated process includes the screening procedure based on the assumption of an eventually positive finding, the detection of islet cell antibody positivity, metabolic tests for the evaluation of the actual state of energy metabolism, the categorization of the respective individual's risk to develop diabetes, the commencement of some placebo-controlled interventive measure, and finally the chance to fail to prevent the disease. Every step in this process may constitute both a threat and a severe burden to the affected individual and his/her family, eventually arousing conflicts and depression, and hopefully also attempts to deal and cope with them. The coping procedure, however, may be greatly influenced by various pre-existing primary and acquired secondary factors. Because at present prevention trials are justified only in families already exposed to this disease, the latter may depend upon the impact of diabetes in one (or more) member(s) of the family, and upon their acquired competence to cope with the various challenges it brings. On the other hand, personal characteristics, such as individual maturity, emotional stability and the integrity of one's self-image in spite of this threat, and the competence of the family to support the threatened member may be important codeterminants of the individual's response to disease prediction and preventive activities. In order to understand the impact of disease prediction and prevention on the individual better, but also to increase his coping potential by competent advice, future prevention trials should be accompanied by psychological research and competent offers of support for the affected individuals and their families.

Clinical Trials as Topic↗

Is your healthcare information system physician friendly?

An organization's healthcare information system (HIS) can be used as a tool to improve relationships with its physicians by facilitating physician work processes and research. An effective HIS should provide census reports tailored to individual physician needs, allow physicians access to information via dedicated personal computers (PCs) or terminals, and should have features, such as screen design and graphical interfaces that are easy to understand and use. In addition, the HIS should provide comprehensive reports, have online ordering capability, and respond quickly to the needs of busy physicians. A good HIS also supports physician-related activities occurring outside the hospital. For example, physician office managers should be able to access billing information, such as patient demographics and procedure codes, contained in the HIS. And, physicians should be able to retrieve archived information from their offices or homes. Critical to physicians' successful use of an organization's HIS is administration's attitude and support. An organization that places a priority on physician issues and needs can make even a basic HIS an effective tool for its physicians, while a sophisticated HIS that does not address physician needs will not maximize return on the investment.

Computer Graphics↗

Follow-up of four HIV-infected individuals after administration of hepatitis C virus and GBV-C/hepatitis G virus contaminated intravenous immunoglobulin: evidence for HCV but not for GBV-C/HGV transmission.

In 1994, hepatitis C virus (HCV) infection was transmitted to four HIV seropositive patients attending the Department of Angiology, University Clinics, Frankfurt am Main, by the administration of Gammagard. The patients were suffering from thrombocytopenia and received betweeen 20 and 30 g of the contaminated lot 93F21AB11. GBV-C/HGV RNA could be amplified from the Gammagard lot 93F21AB11 using 5'NCR and NS5 primer pairs. All the four patients were negative in the GBV-C/HGV RT-PCR prior to therapy and until the end of the follow-up period. GBV-C/HGV IgG antibodies to the putative envelope (E2) were detected using the E2 HGV-env kit (Boehringer-Mannheim, Germany) in Gammagard lot 93F21AB11 and in one patient before donation of immunoglobulin. Anti-E2 seroconversion was observed in one recipient, the other two patients remained anti-E2 seronegative until the end of the observation period. It is concluded that there is no direct evidence for transmission of GBV-C/HGV by contaminated intravenous immunoglobulin since GBV-C/HGV RNA was not detected in the recipients up to 1 year after administration.

Adult↗

Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study.

The French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) conducted a multicenter phase II study of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to evaluate the efficacy and side effects of this combination in pretreated advanced ovarian cancer. Patients with progressive ovarian carcinoma during or after platinum-based chemotherapy received paclitaxel 175 mg/m2 intravenously over 3 hours followed by intravenous carboplatin over 30 minutes every 4 weeks. The dose of carboplatin was calculated using a projected area under the concentration-time curve of 5 mg/mL x min. Of the 50 patients entered, 50 were evaluable for toxicity and 42 for response. There were eight complete and 10 partial responses, for an overall response rate of 43% (95% confidence interval, 28% to 56%). Overall response rates in platinum refractory patients and in those with early (> or = 3 and < 12 months) and late (> or = 12 months) relapse was 28%, 33%, and 71%, respectively. Median response duration, progression-free survival, and overall survivals were 8, 6, and 14 months, respectively. The most frequent and severe toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 30% and 23% of cycles, and granulocyte colony-stimulating factor was administered in 6%. Only one case of neutropenic fever was observed. Grades 3 and 4 thrombocytopenia occurred in 3% and 1% of cycles, respectively. Alopecia and moderate nausea or vomiting were frequent. Transitory peripheral neuropathy was present in 45% of patients but was severe in only one patient. One early death was observed due to progressive disease and possibly to therapy. The combination of paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 5 is an effective therapy in patients previously treated with platinum-based chemotherapy and may be administered safely to outpatients who relapse after one or two lines of chemotherapy.

Adolescent↗

[Diagnosis of Hepatitis B and C: current aspects].

The genetic variability of hepatitis B virus (HBV) is for a DNA virus extremely high. Escape mutants of the pre-core/core gene and S-gene are of clinical and diagnostic importance. HBeAg negative (pre-core) mutants are frequently associated with a more severe prognosis of chronic hepatitis B. One amino acid substitution in the neutralizing epitope of HBsAg is responsible for the failure of active and passive immunization against HBV. S-Gen mutants may be not detected with monoclonal HBsAg tests. Hepatitis C virus (HCV) is even more heterogenous than HBV. At least 6 genotypes may be differentiated. Genetic variability is the cause of reinfections, which in general have a better prognosis than primary infection. Diagnosis of infections with genotypes 4 to 6 is not absolutely reliable. The influence of different genotypes on disease progression needs to be further investigated. A more severe prognosis and higher HCV RNA concentrations are observed in genotype 1b infections. The higher RNA concentration is partly due to an in vitro artefact, since the amplification rate with current primer pairs is optimal for genotype 1.

Emigration and Immigration↗

[Current developments in the laboratory diagnosis of rubella].

Thirty years after the introduction of the hemagglutination inhibition assay (HAI), laboratory diagnosis of rubella virus infection has achieved a high reliability. While the HAI remains the reference standard against which newer assays are compared, routine laboratory diagnosis is based mainly on ELISA tests which permit a more rapid and less cumbersome detection of specific IgG and IgM antibody. Although quantification of immunoglobulin G against rubella virus is performed using WHO standards, the correlation between different ELISAs is relatively poor. Despite substantial improvements in virus isolation and nucleic acid amplification techniques, serology remains the mainstay of diagnosis for both acquired and postnatal diagnosis of congenital infection. Differentiation between primary and re-infection is of critical importance during pregnancy and can be achieved relatively reliably by antibody avidity determination or by immunoblot. While current anti-rubella IgM ELISAs are relatively sensitive, their specificity may be limited by cross reactivity with other viruses, i.e. parvovirus B19 and Epstein-Barr virus. Maternal reinfection with congenital rubella syndrome is very rare, however it may be misdiagnosed in the absence of significant IgG antibody titer change and/or IgM antibody.

Enzyme-Linked Immunosorbent Assay↗

Structure and sequence of the human sulphamidase gene.

Sanfilippo A syndrome (MPS-IIIA) is a mucopolysaccharide lysosomal storage disorder caused by a deficiency in the lysosomal enzyme, sulphamidase (EC 3.10.1.1), which is required for the degradation of heparan sulphate. A genomic clone containing the entire sulphamidase gene was isolated from a chromosome 17-specific gridded cosmid library. The structure of the gene and the sequence of the exon/intron boundaries and the 5' promoter region were determined. The sulphamidase gene is split into 8 exons spanning approximately 11 kb.

Base Sequence↗

Long-term productive human cytomegalovirus infection of a human neuroblastoma cell line.

Human neuroblastoma cell line UKF-NB-4 persistently infected with human cytomegalovirus (HCMV) strain AD169 was established to study the effects of long-term HCMV infection on virus production and phenotypic characteristics of tumour cells. The cells designated UKF-NB-4AD169 were subcultured (80 subcultures) over a period of more than 2 years after initiation of infection. UKF-NB-4AD169 cells continued to produce infectious virus in successive passages, with a titre ranging from 9 x 10(3) to 1 x 10(5) and from 2 x 10(1) to 2 x 10(2) plaque-forming units per 10(6) cells and 1 ml culture medium, respectively; 10-20% of the cells produced HCMV-specific antigens, while 6-13% produced infectious virus progeny. The number of HCMV-specific DNA copies ranged from 9 x 10(4) to 9 x 10(6) per 10(6) cells. Transmission electron microscopy confirmed the productive nature of HCMV infection. UKF-NB-4AD169 cultures proliferated, with population doubling time ranging from 24.5 to 26.6 hr (19.5 to 20.3 hr for UKF-NB-4) and cell viability from 79% to 85% (91-96% for UKF-NB-4). Significantly lower amounts of tyrosine hydroxylase and decreased activity for dopamine-beta-hydroxylase than in uninfected cells were observed in UKF-NB-4AD169 cells. However, the expression of N-myc oncoprotein was significantly increased in persistently infected cultures. Our results show that long-term productive HCMV infection of UKF-NB-4 cell line is associated with the modulation of phenotypic properties, which may be related to the biological behaviour of neuroblastoma cells.

Cell Differentiation↗

Hepatitis C plasma viral load is associated with HCV genotype but not with HIV coinfection.

The influence of human immunodeficiency virus (HIV) coinfection and hepatitis C virus (HCV) genotype distribution on HCV viral load and alanine amino transferase (ALT) levels in chronically infected patients remains unclear. In the present study, serum samples from a group of haemophiliac patients were investigated retrospectively. HCV geno- and subtyping was carried out using the Inno line probe assay (Inno LIPA, Innogenetics, Zwijnaarde, Belgium) in 87 patients positive by HCV RT PCR. Of these patients, 31 (35.6%) were HIV coinfected. HCV RNA was quantified with the HCV Monitor kit (Roche, Basel, Switzerland) in 43 patients (22 HIV-negatives, 21 HIV-positives). The most prevalent genotypes were 1 (n = 52) and 3a (n = 16) followed by genotype 2 (n = 9) and 4 (n = 3). Mixed infections were detected in 7 patients. Of genotype 1 positive samples, 24 and 23 were classified as subtype a and b, respectively. Five samples could not be subtyped. Although higher mean values of ALT were observed in genotype 1 infected patients, there was no statistically significant association between HCV genotype or subtype and liver enzymes (P > 0.05). On the other hand, statistically significant higher HCV RNA titres were observed in haemophiliacs infected with HCV genotype 1 in comparison to those infected with other genotypes (P < 0.01). No relationship was found between the presence of HIV coinfection and viral load of HCV RNA. There was no evidence that HCV infection had a more severe outcome in HIV-positive patients who had been infected with HIV and HCV more than ten years ago, even in those with very low CD4+ cell counts. No clear association between high ALT levels and large amounts of viral RNA was observed. In conclusion, a large viral load is associated with HCV genotype 1 infection; HIV coinfection has no clear effect on the intensity of HCV replication. An ongoing prospective study will evaluate the respective role of viral load, genotype, HIV coinfection and ALT level in the response to interferon therapy.

Alanine Transaminase↗

Salt Enrichment of Municipal Sewage: New Prevention Approaches in Israel

Wastewater irrigation is an environmentally sound wastewater disposal practice, but sewage is more saline than the supplied fresh water and the salts are recycled together with the water. Salts have negative environmental effects on crops, soils, and groundwater. There are no inexpensive ways to remove the salts once they enter sewage, and the prevention of sewage salt enrichment is the most immediately available solution. The body of initiatives presently structured by the Ministry of the Environment of Israel are herein described, with the aim to contribute to the search for a long-term solution of salinity problems in arid countries. The new initiatives are based on: (1) search for new technologies to reduce salt consumption and discharge into sewage; (2) different technologies to cope with different situations; (3) raising the awareness of the public and industry on the environmental implications of salinity pollution; and (4) an elastic legal approach expressed through new state-of-the-art regulations. The main contributor to the salinity of sewage in Israel is the water-softening process followed by the meat koshering process. Some of the adopted technical solutions are: the discharge of the brine into the sea, the substitution of sodium by potassium salts in the ion-exchangers, the construction of centralized systems for the supply of soft water in industrial areas, the precipitation of Ca and Mg in the effluents from ion-exchangers and recycling of the NaCl solution, a reduction of the discharge of salts by the meat koshering process, and new membrane technology for salt recovery.

Journal Article↗

Evaluation of 11 enzyme immunoassays for the detection of immunoglobulin M antibodies to Epstein-Barr virus.

Laboratory diagnosis of Epstein-Barr virus (EBV) infection is based mainly on serological tests. The analysis of the pattern of class-specific immunoglobulin response against defined viral antigens, i.e. virus capsid antigen (VCA), early antigen (EA) and Epstein-Barr nuclear antigen (EBNA), permits the differentiation between primary, latent and secondary (reactivated) EBV infection. In recent months, numerous test kits for the detection of VCA specific IgM antibody have been introduced on the international market. With a panel of well defined sera, the sensitivity and specificity of eleven different commercially available IgM ELISAs was evaluated. A well established, commercially available, indirect immunofluorescence assay (IFA) served as the reference test. Compared to the IFA, the Biotest and Sigma Diagnostic assays had the highest sensitivity for the detection of IgM antibody to VCA or EA. A variable number of false positive results (n = 0-9) was obtained with the EBV-IgM assays by testing potentially cross-reactive serum samples. Up to 19 serum samples from immunocompromised organ transplant recipients were found positive with the Sigma Diagnostics assay. The results of this study show that there are great differences in quality of current EBV-IgM-ELISA test kits. Depending on the clinical setting, it may be important to use a test kit which detects immunoglobulin M reactivity to EA in order to warrant an optimal sensitivity for the serological diagnosis of EBV reactivation in immunocompromised patients. However, since most immunosuppressed patients have serological reactivations, and in most cases these are asymptomatic, the clinical relevance of the detection of EA-IgM is very low.

Antibodies, Viral↗

Lack of correlation between different hepatitis C virus screening and confirmatory assays.

Numerous 2nd and 3rd generation screening and confirmatory assays for the detection of anti-HCV antibodies have been introduced on the international market. The aim of the present study was to compare the performance of five different commercially available screening assays and four 'confirmatory' assays in a panel of serum samples that had tested positive or borderline with a 2nd generation EIA (Abbott HCV EIA 2nd generation). Considerable discrepancies were observed between the different screening assays and confirmatory tests. The antigens from the putative 'core' region of HCV were recognized most frequently by the confirmatory assays. By considering the reactivity to either NS5 (RIBA III and Inno-LIA) or E2/NS1 antigens (Inno-LIA Ab III) no sample could be identified as anti-HCV positive that would otherwise have been regarded as borderline or negative according to its banding pattern with core, NS3 and NS4 proteins. All 24 HCV-RT-PCR positive samples were anti-HCV reactive by the screening EIAs but only 18 and 21 samples were confirmed anti-HCV positive with the RIBA II and III, respectively. A clear association was observed between HCV-RNAemia in serum samples and index values (O.D. sample/O.D. cut-off) of the screening EIAs as well as with the number of reactive proteins in the confirmatory assays. In conclusion, the results of current screening and confirmatory assays are highly divergent. The additional diagnostic significance of the relatively expensive and labour-intensive immunoblots appears to be very limited. For the serological diagnosis of HCV infection and for blood donor screening, confirmatory assays should only be used if there is a borderline result by HCV EIA. The determination of infectivity by qualitative PCR and the follow-up of patients undergoing IFN therapy by HCV-RNA quantification appears to be much more useful.

Hepacivirus↗